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lhallee

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A0A0D1DWZ5

RRM4_USTMA

MSDSIYAPHNKHKLEAARAADAAADDAATVSALVEPTDSTAQASHAAEQTIDAHQQAGDVEPERCHPHLTRPLLYLSGVDATMTDKELAGLVFDQVLPVRLKIDRTVGEGQTASGTVEFQTLDKAEKAYATVRPPIQLRINQDASIREPHPSAKPRLVKQLPPTSDDAFVYDLFRPFGPLRRAQCLLTNPAGIHTGFKGMAVLEFYSEQDAQRAESEMHCSEVGGKSISVAIDTATRKVSAAAAEFRPSAAAFVPAGSMSPSAPSFDPYPAGSRSVSTGSAASIYATSGAAPTHDTRNGAQKGARVPLQYSSQASTYVDPCNLFIKNLDPNMESNDLFDTFKRFGHIVSARVMRDDNGKSREFGFVSFTTPDEAQQALQAMDNAKLGTKKIIVRLHEPKTMRQEKLAARYNAANADNSDMSSNSPPTEARKADKRQSRSYFKAGVPSDASGLVDEEQLRSLSTVVRNELLSGEFTRRIPKVSSVTEAQLDDVVGELLSLKLADAVEALNNPISLIQRISDAREQLAQKSASTLTAPSPAPLSAEHPAMLGIQAQRSVSSASSTGEGGASVKERERLLKAVISVTESGAPVEDITDMIASLPKKDRALALFNPEFLKQKVDEAKDILDITDESGEDLSPPRASSGSAPVPLSVQTPASAIFKDASNGQSSISPGAAEAYTLSTLAALPAAEIVRLANSQSSSGLPLPKADPATVKATDDFIDSLQGKAAHDQKQKLGDQLFKKIRTFGVKGAPKLTIHLLDSEDLRALAHLMNSYEDVLKEKVQHKVAAGLNK

mRNA transport [GO:0051028]

cytoplasmic stress granule [GO:0010494]; cytoskeleton [GO:0005856]; cytosol [GO:0005829]; endosome [GO:0005768]; nucleus [GO:0005634]; ribonucleoprotein complex [GO:1990904]

mRNA 3'-UTR binding [GO:0003730]; poly(A) binding [GO:0008143]; poly(U) RNA binding [GO:0008266]

PF00658;PF00076;

3.30.70.330;1.10.1900.10;

Polyadenylate-binding protein type-1 family

SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton {ECO:0000269|PubMed:17105762, ECO:0000269|PubMed:19494833, ECO:0000269|PubMed:25985087}. Endosome {ECO:0000269|PubMed:22357951, ECO:0000269|PubMed:24355572, ECO:0000269|PubMed:25985087}. Note=Assembles into particles that shuttle along microtubules to both poles (PubMed:17105762, PubMed:19494833). Shuttles with RAB5A-positive endosomes along microtubules (PubMed:22357951, PubMed:25985087). {ECO:0000269|PubMed:17105762, ECO:0000269|PubMed:19494833, ECO:0000269|PubMed:22357951, ECO:0000269|PubMed:25985087}.

FUNCTION: Key RNA-binding protein involved in the formation of polar-growing hyphae which is essential for infection by the plant pathogen (PubMed:15643068, PubMed:17105762, PubMed:19494833). During filamentation, assembles into particles that shuttle bidirectionally along microtubules to both poles (PubMed:17105762, PubMed:19494833, PubMed:30738139). The RRM4 transport particles are part of the endosomal mRNP transport that regulates polarity of the infectious hyphae by transporting distinct mRNAs encoding, for example, the ubiquitin fusion protein UBI1, the small G protein RHO3, or the septin CDC3, from the nucleus to cell poles (PubMed:17105762, PubMed:19494833, PubMed:22357951, PubMed:24355572, PubMed:25985087, PubMed:30738139). Recognizes a broad spectrum of cargo mRNAs and precisely binds at stop codons, which constitute landmark sites of translation, suggesting an intimate connection of mRNA transport and translation (PubMed:30552148). Binds also to the specific binding motif UAUG of cargo mRNAs via its third RRM (PubMed:30552148). Plus-end-directed KIN3, a kinesin-3 type motor, mediates anterograde transport of RRM4-containing mRNPs whereas split dynein DYM1-DYN2 functions in retrograde movement of mRNPs (PubMed:22357951). {ECO:0000269|PubMed:15643068, ECO:0000269|PubMed:17105762, ECO:0000269|PubMed:19494833, ECO:0000269|PubMed:22357951, ECO:0000269|PubMed:24355572, ECO:0000269|PubMed:25985087, ECO:0000269|PubMed:30552148, ECO:0000269|PubMed:30738139}.

Ustilago maydis (strain 521 / FGSC 9021) (Corn smut fungus)

A0A0D1E015

UPA1_USTMA

MTIPDPANIIHNDAGTASPHHIWADVGDSTSSSQHEATRSRSDDANGGASASMHAPQHVKANRAAQPTYDSSDLPSFGLSARLTRDSSSFGSKPSSSASDSRRPKFAPYEAENLWATSSTTSHPSKASQSTLSPNASVFKPSRSLQPNHFEPHAVANVHDFDDPLNSAYSSDTVSPRPDHAPLDHEQPQQPSALDPVAVSKVEEQRGDHSIPHQNGLVSAQAQTASDAVSTSKYTTEAADQEEDQDDFVYPGADSPSSGQAAVQDEQQAVTDSQTTKSLTKQESDPEASSTSLSAPAEAEHIVVGSAAEQSLTSSAPAETAVHIDYDTLAQLCSRGPLSDLQSFFHTAQESGLSMFSLSNDPNPGNGLVPLHFAAKDGKTDIVRWLITQAGAIVEMEDREGETALHKAAMAGKLSVASLLLSHGADANAQDADGWTALHNACSRGYLDLVRLLVDRGHAQIDVQGGRGAWTPLMNAASKGHLPVVRHLTAKYHADPFVRNAAGETAFDVAAATFEVYICEILERYEAERWNASKFTTSSPSRSGAIVPGRGPYEPLALHTTIPVILHENQRLDTRLQTLALNGGKPRWSSSSAARAHKPDRRSPSSMPPGPLAPSRTRHVPMRQDDVGLPTRSLPYKLRLRSRVGPAAARRRAAALAAQHTPNPQDCHDDDLASTPTPESVLQARRGTSSVNGASAQHADAESSHFWLCEWQLDTTHPLVDVEHGWQYAQSFDALDDKWSSQPPPPLERLLEGRGLSASVTRAITGGAGFANAQAEQEISSSSWVRRRRWIRVLRRRLDIEFGDDLEACEGATGAGAEHLVLSSESQSNGDGSHGLSTAAIMAAQEAAKSECSQLGPDADYVSRAKALAGPSAASGATPADAMGADRDELARRIARLVMANTELRAAFEDDDVERRSRAEELRKEYALQLGQLREAAGLDEDEDEDAADDDDDEFIYPNSYKDDGASVFTRLVNGETSGTLSRPSLSQRQSSAASMLRNSVAPSEAGTSLAAARSADLAANREFRVPTNEAPNKVVLRHGPTMREQNLQPQWQRDEEAKDCIGCGRHFTFFLRKHHCRRCGRIFCDACSSKRAQLRMAELVVDPSLPSMAASEVLAPTRVCNGCHAELQLPPQLQNMRGADAMMAASRSRGADEVSGRSILETQLEDGAFRSTLAPPSDVSSRASELTECPVCSTTLSALGGSEEQEAHVRNCLENGGGGSMQGGRYLVYKLPEDSPIVGKECSICMEDFVANSTIARLPCLCYFHRGCIDSWFKRGRECPVHARDW

mRNA transport [GO:0051028]

cytoskeleton [GO:0005856]; endosome [GO:0005768]

metal ion binding [GO:0046872]; NF-kappaB binding [GO:0051059]; transferase activity [GO:0016740]

PF00023;PF13637;PF01363;PF13639;

1.25.40.20;3.30.40.10;

UPA1 PAM2 domain-binding protein family

SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton {ECO:0000269|PubMed:25985087}. Endosome {ECO:0000269|PubMed:25985087}. Note=Shuttles with endosomes along microtubules (PubMed:25985087). the FYVE domain mediates endosomal localization and endosomal targeting is crucial for its function during polar growth and CTS1 secretion (PubMed:25985087). {ECO:0000269|PubMed:25985087}.

FUNCTION: FYVE zinc finger domain protein that functions in endosomal targeting and transport of mRNAs, as well as associated ribosomes (PubMed:25985087, PubMed:28422978). The endosomal mRNA transport regulates polarity of the infectious hyphae by transporting a broad spectrum of cargo mRNAs from the nucleus to cell poles (PubMed:25985087). Involved in chitinase CTS1 secretion (PubMed:25985087). Dispensable for general endosomal functions but crucial for endosomal recruitment of RRM4 (PubMed:25985087). {ECO:0000269|PubMed:25985087, ECO:0000269|PubMed:28422978}.

Ustilago maydis (strain 521 / FGSC 9021) (Corn smut fungus)

A0A0D2UG83

H2AY_CAPO3

MAKSKKIVAATSGSRSRSSRAGLAFPVGRVHRLLRKGHFADRIGSGSAVYLAAVLEYLTAEILELAGNAARDNRKTRINPRHIQLAVRNDEELSKLFTGVVIPSGGTLPHIWPALIPNEAKDSSTASASFNAPAKSATVKALAAAKSAGKKPAAVSSSSAAASSSSSASSSSSVAPKKPVRGFTILSKKTLHLGQTLYVVNGDLTEVRCDAVVHPTNGTMSFAGQVGGAIRAAAGAGVDAEVNSYMSEHSQLQVTKAAITSGHNLPSKWIVHVHSPNYSNAATATDALTQTIRNALTLADTKSIKTIAFPSIGSGNNHFPKHIAAQTILQAISAYFMSIMSSSIKEVYFVLFDQESINVYNAELINTN

chromatin organization [GO:0006325]; negative regulation of protein ADP-ribosylation [GO:0010836]; regulation of NAD metabolic process [GO:1902688]

nucleosome [GO:0000786]; nucleus [GO:0005634]

ADP-D-ribose binding [GO:0072570]; ADP-D-ribose modification-dependent protein binding [GO:0160002]; DNA binding [GO:0003677]; protein heterodimerization activity [GO:0046982]; structural constituent of chromatin [GO:0030527]

PF00125;PF16211;PF01661;

1.10.20.10;3.40.220.10;

Histone H2A family

SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O75367}. Chromosome {ECO:0000250|UniProtKB:O75367}.

FUNCTION: Variant histone H2A which replaces conventional H2A in a subset of nucleosomes where it represses transcription. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. {ECO:0000250|UniProtKB:O93327}.; FUNCTION: Specifically binds poly-ADP-ribose and plays a key role in NAD(+) metabolism (PubMed:34887560). Able to bind to the ends of poly-ADP-ribose chains created by PARP1 and cap them (PubMed:34887560). This prevents PARP1 from further addition of ADP-ribose and thus limits the consumption of nuclear NAD(+), allowing the cell to maintain proper NAD(+) levels in both the nucleus and the mitochondria to promote proper mitochondrial respiration (PubMed:34887560). {ECO:0000269|PubMed:34887560}.

Capsaspora owczarzaki (strain ATCC 30864)

A0A0D2Y5A7

ODP2_FUSO4

MLSAALRRRVLAPTHSALRTGFAAHVVRHYASFPEHQVIKMPALSPTMQAGNIGAWQKKPGDSIAPGDVLVEIETDKAQMDFEFQEEGVIAKILKDAGEKDIPVGSPIAVLVEEGTDISAFEKFSIEDAGGDAAKPAAPKKEEKSESKSESASAPEPTPEPQQYQSQGRLQTALDRLPNISASAKRLAREKGISIDGLKGTGKNGQITEEDVKKAISSPAASSAPSATYEDIPISGMRKTIANRLVESTQTNPHFYVTSSISVSKLLKLRQALNSSADGKYKLSVNDFLIKAIAVASRKVPQVNSSWRDGNIRQFNNVDVSVAVSTPTGLITPIVTGVEGRGLEAISSQVKSLAKKARDGKLKPEEYQGGTISISNMGMNPAVDHFTAVINPPQAAILAVGTTKKVAIPAENEAGVEFDDQITLTASFDHKVVDGAVGAEWLKELKQVLENPLELLL

2.3.1.12

COFACTOR: Name=(R)-lipoate; Xref=ChEBI:CHEBI:83088; Evidence={ECO:0000255|PROSITE-ProRule:PRU01066}; Note=Binds 1 lipoyl cofactor covalently. {ECO:0000255|PROSITE-ProRule:PRU01066};

acetyl-CoA biosynthetic process from pyruvate [GO:0006086]; aerobic respiration [GO:0009060]

mitochondrial pyruvate dehydrogenase complex [GO:0005967]; mitochondrion [GO:0005739]

dihydrolipoyllysine-residue acetyltransferase activity [GO:0004742]

PF00198;PF00364;PF02817;

2.40.50.100;3.30.559.10;4.10.320.10;

2-oxoacid dehydrogenase family

PTM: Decrotonylated at 'Lys-148' by SIR5, which inhibits the activity of the pyruvate dehydrogenase complex (PDC). {ECO:0000269|PubMed:34927582}.

SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000269|PubMed:34927582}.

CATALYTIC ACTIVITY: Reaction=acetyl-CoA + N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] = CoA + N(6)-[(R)-S(8)-acetyldihydrolipoyl]-L-lysyl-[protein]; Xref=Rhea:RHEA:17017, Rhea:RHEA-COMP:10475, Rhea:RHEA-COMP:10478, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:83100, ChEBI:CHEBI:83111; EC=2.3.1.12; Evidence={ECO:0000255|RuleBase:RU361137};

FUNCTION: The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2) (PubMed:34927582). High pyruvate dehydrogenase complex activity is required for sufficient energy production during germination of conidia (PubMed:34927582). {ECO:0000269|PubMed:34927582}.

Fusarium oxysporum f. sp. lycopersici (strain 4287 / CBS 123668 / FGSC 9935 / NRRL 34936) (Fusarium vascular wilt of tomato)

A0A0D4WTV1

B1D1_LOXAR

EGAEQDGSERTDGGRPIWNIAHMVNNKQAIDKYLDKGANSVESDVSFDSDGKPEKMLHGIPCDCGRKCLNQMSFTDYLDYMRQLTTPGDPKFRENLILIMLDLKLKSVAANLAYSSGQEVALQMLNTYWKRGESGARAYIVLSIPTIKRVTFVRGFYDKLHSEGFDQYREKVGVDFSGNEDLDETGRILSSQNILDHIWQSDGITNCIFRVMTRLKKAINKRDSNGYMVKVYYWSVDKYTIMRKTLRAGADGMITNFPDRLVSVLNEREFSGKFRLATYDDNPWERYKA

4.6.1.-

COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:Q8I914}; Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000250|UniProtKB:Q8I914};

killing of cells of another organism [GO:0031640]; lipid catabolic process [GO:0016042]

extracellular region [GO:0005576]

lyase activity [GO:0016829]; metal ion binding [GO:0046872]; phosphoric diester hydrolase activity [GO:0008081]; toxin activity [GO:0090729]

3.20.20.190;

Arthropod phospholipase D family, Class II subfamily

SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:25752604}.

CATALYTIC ACTIVITY: Reaction=an N-(acyl)-sphingosylphosphocholine = an N-(acyl)-sphingosyl-1,3-cyclic phosphate + choline; Xref=Rhea:RHEA:60652, ChEBI:CHEBI:15354, ChEBI:CHEBI:64583, ChEBI:CHEBI:143892; Evidence={ECO:0000269|PubMed:25752604}; CATALYTIC ACTIVITY: Reaction=N-hexanoyl-sphing-4-enine-1-phosphocholine = choline + N-(hexanoyl)-sphing-4-enine-1,3-cyclic phosphate; Xref=Rhea:RHEA:60620, ChEBI:CHEBI:15354, ChEBI:CHEBI:78254, ChEBI:CHEBI:143883; Evidence={ECO:0000269|PubMed:25752604}; CATALYTIC ACTIVITY: Reaction=N-(dodecanoyl)-sphing-4-enine-1-phosphocholine = choline + N-dodecanoyl-sphing-4-enine-1,3-cyclic phosphate; Xref=Rhea:RHEA:60636, ChEBI:CHEBI:15354, ChEBI:CHEBI:137334, ChEBI:CHEBI:143884; Evidence={ECO:0000269|PubMed:25752604}; CATALYTIC ACTIVITY: Reaction=an N-(acyl)-sphingosylphosphoethanolamine = an N-(acyl)-sphingosyl-1,3-cyclic phosphate + ethanolamine; Xref=Rhea:RHEA:60648, ChEBI:CHEBI:57603, ChEBI:CHEBI:143891, ChEBI:CHEBI:143892; Evidence={ECO:0000269|PubMed:25752604}; CATALYTIC ACTIVITY: Reaction=N-dodecanoyl-heptadecasphing-4-enine-1-phosphoethanolamine = ethanolamine + N-dodecanoyl-heptadecasphing-4-enine-1,3-cyclic phosphate; Xref=Rhea:RHEA:60616, ChEBI:CHEBI:57603, ChEBI:CHEBI:143864, ChEBI:CHEBI:143865; Evidence={ECO:0000269|PubMed:25752604}; CATALYTIC ACTIVITY: Reaction=a 1-acyl-sn-glycero-3-phosphocholine = a 1-acyl-sn-glycero-2,3-cyclic phosphate + choline; Xref=Rhea:RHEA:60700, ChEBI:CHEBI:15354, ChEBI:CHEBI:58168, ChEBI:CHEBI:143947; Evidence={ECO:0000269|PubMed:25752604}; CATALYTIC ACTIVITY: Reaction=1-tetradecanoyl-sn-glycero-3-phosphocholine = 1-tetradecanoyl-sn-glycero-2,3-cyclic phosphate + choline; Xref=Rhea:RHEA:60604, ChEBI:CHEBI:15354, ChEBI:CHEBI:64489, ChEBI:CHEBI:143882; Evidence={ECO:0000269|PubMed:25752604}; CATALYTIC ACTIVITY: Reaction=1-octanoyl-sn-glycero-3-phosphocholine = 1-octanoyl-sn-glycero-2,3-cyclic phosphate + choline; Xref=Rhea:RHEA:60612, ChEBI:CHEBI:15354, ChEBI:CHEBI:143866, ChEBI:CHEBI:143876; Evidence={ECO:0000269|PubMed:25752604}; CATALYTIC ACTIVITY: Reaction=a 1-acyl-sn-glycero-3-phosphoethanolamine = a 1-acyl-sn-glycero-2,3-cyclic phosphate + ethanolamine; Xref=Rhea:RHEA:60704, ChEBI:CHEBI:57603, ChEBI:CHEBI:64381, ChEBI:CHEBI:143947; Evidence={ECO:0000269|PubMed:25752604}; CATALYTIC ACTIVITY: Reaction=1-tetradecanoyl-sn-glycero-3-phosphoethanolamine = 1-tetradecanoyl-sn-glycero-2,3-cyclic phosphate + ethanolamine; Xref=Rhea:RHEA:60608, ChEBI:CHEBI:57603, ChEBI:CHEBI:84299, ChEBI:CHEBI:143882; Evidence={ECO:0000269|PubMed:25752604};

FUNCTION: Dermonecrotic toxins cleave the phosphodiester linkage between the phosphate and headgroup of certain phospholipids (sphingolipid and lysolipid substrates), forming an alcohol (often choline) and a cyclic phosphate (PubMed:25752604). This toxin acts on sphingomyelin (SM) and on ceramide phosphoethanolamine (CPE) with high activity (PubMed:25752604). It also acts on lysophosphatidylcholine (LPC) and on lysophosphatidylethanolamine (LPE) with moderate activity (PubMed:25752604). It is not active on lysophosphatidylserine (LPS), and lysophosphatidylglycerol (LPG) (PubMed:25752604). It acts by transphosphatidylation, releasing exclusively cyclic phosphate as second products (PubMed:25752604). It is not surprising that spider toxins have affinity for ethanolamine-containing sphingolipids since they are common in insect prey (PubMed:25752604). On mammals, induces dermonecrosis, hemolysis, increased vascular permeability, edema, inflammatory response, and platelet aggregation (By similarity). {ECO:0000250|UniProtKB:P0CE80, ECO:0000269|PubMed:25752604}.

Loxosceles arizonica (Arizona brown spider)

A0A0D4WV12

BIB11_SICTE

GDSRRPIWNIAHMVNDLDLVDEYLDDGANSLELDVEFSKSGTALRTYHGVPCDCFRSCTRSEKFSKYLDYIRQLTTPGNSKFRSRLILLVLDLKLNPLSSSAAYNAGADVARNLLDNYWQRGDSKARAYIVLSLETIAGAEFITGFKDTMKKEGFDEKYYDKIGWDFSGNEDLGKIRDVLESHGIREHIWQGDGITNCLPRDDNRLKQAISRRYSPTYVYADKVYTWSIDKESSIENALRLGVDGVMTNYPARVISVLGEREFSGKLRLATYDDNPWEK

4.6.1.-

COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:25752604, ECO:0000312|PDB:4Q6X}; Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000269|PubMed:25752604, ECO:0000312|PDB:4Q6X};

killing of cells of another organism [GO:0031640]; lipid catabolic process [GO:0016042]

extracellular region [GO:0005576]

lyase activity [GO:0016829]; metal ion binding [GO:0046872]; phosphoric diester hydrolase activity [GO:0008081]; toxin activity [GO:0090729]

PF13653;

3.20.20.190;

Arthropod phospholipase D family, Class II subfamily, Class IIb sub-subfamily

SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:25752604}.

CATALYTIC ACTIVITY: Reaction=an N-(acyl)-sphingosylphosphocholine = an N-(acyl)-sphingosyl-1,3-cyclic phosphate + choline; Xref=Rhea:RHEA:60652, ChEBI:CHEBI:15354, ChEBI:CHEBI:64583, ChEBI:CHEBI:143892; Evidence={ECO:0000269|PubMed:25752604}; CATALYTIC ACTIVITY: Reaction=N-hexanoyl-sphing-4-enine-1-phosphocholine = choline + N-(hexanoyl)-sphing-4-enine-1,3-cyclic phosphate; Xref=Rhea:RHEA:60620, ChEBI:CHEBI:15354, ChEBI:CHEBI:78254, ChEBI:CHEBI:143883; Evidence={ECO:0000269|PubMed:25752604}; CATALYTIC ACTIVITY: Reaction=an N-(acyl)-sphingosylphosphoethanolamine = an N-(acyl)-sphingosyl-1,3-cyclic phosphate + ethanolamine; Xref=Rhea:RHEA:60648, ChEBI:CHEBI:57603, ChEBI:CHEBI:143891, ChEBI:CHEBI:143892; Evidence={ECO:0000269|PubMed:25752604}; CATALYTIC ACTIVITY: Reaction=N-dodecanoyl-heptadecasphing-4-enine-1-phosphoethanolamine = ethanolamine + N-dodecanoyl-heptadecasphing-4-enine-1,3-cyclic phosphate; Xref=Rhea:RHEA:60616, ChEBI:CHEBI:57603, ChEBI:CHEBI:143864, ChEBI:CHEBI:143865; Evidence={ECO:0000269|PubMed:25752604}; CATALYTIC ACTIVITY: Reaction=a 1-acyl-sn-glycero-3-phosphoethanolamine = a 1-acyl-sn-glycero-2,3-cyclic phosphate + ethanolamine; Xref=Rhea:RHEA:60704, ChEBI:CHEBI:57603, ChEBI:CHEBI:64381, ChEBI:CHEBI:143947; Evidence={ECO:0000269|PubMed:25752604}; CATALYTIC ACTIVITY: Reaction=1-tetradecanoyl-sn-glycero-3-phosphoethanolamine = 1-tetradecanoyl-sn-glycero-2,3-cyclic phosphate + ethanolamine; Xref=Rhea:RHEA:60608, ChEBI:CHEBI:57603, ChEBI:CHEBI:84299, ChEBI:CHEBI:143882; Evidence={ECO:0000269|PubMed:25752604};

FUNCTION: Dermonecrotic toxins cleave the phosphodiester linkage between the phosphate and headgroup of certain phospholipids (sphingolipid and lysolipid substrates), forming an alcohol (often choline) and a cyclic phosphate (PubMed:25752604). This toxin acts on lysophosphatidylethanolamine (LPE) and ceramide phosphoethanolamine (CPE) with high activity (PubMed:25752604). This toxin acts on sphingomyelin (SM) with very low activity and is not active on lysophosphatidylserine (LPS), lysophosphatidylcholine (LPC) and lysophosphatidylglycerol (LPG) (PubMed:25752604). It acts by transphosphatidylation, releasing exclusively cyclic phosphate as second products (PubMed:25752604). It is not surprising that spider toxins have affinity for ethanolamine-containing sphingolipids since they are common in insect prey (PubMed:25752604). Induces dermonecrosis, hemolysis, increased vascular permeability, edema, inflammatory response, and platelet aggregation (By similarity). {ECO:0000250|UniProtKB:P0CE80, ECO:0000269|PubMed:25752604}.

Sicarius terrosus (Cave spider)

A0A0D9S1R0

APOE_CHLSB

MKVLWAALLVTFLAGCQAAADAPIKVEQPVEPETEPELRPQTEWQSGQPWELALGRFWDYLRWVQTLSEQVQEELLSPQVTQELTTLMDETMKELKAYKSELEEQLSPVAEETRARLSKELQAAQARLGADMEDVRSRLVQYRSEVQAMLGQSTEELRARLASHLRKLRKRLLRDADDLQKRLAVYQAGAREGAERGVSAIRERLGPLVEQGRVRAATVGSLASQPLQERAQALGERLRARMEEMGSRTRDRLDEVKEQVAEVRAKLEEQAQQISLQAEAFQARLKSWFEPLVEDMQRQWAGLVEKVQAAVGASTAPVPSDNH

cholesterol catabolic process [GO:0006707]; cholesterol efflux [GO:0033344]; chylomicron remnant clearance [GO:0034382]; high-density lipoprotein particle assembly [GO:0034380]; intermediate-density lipoprotein particle clearance [GO:0071831]; lipoprotein biosynthetic process [GO:0042158]; lipoprotein catabolic process [GO:0042159]; melanosome organization [GO:0032438]; negative regulation of amyloid fibril formation [GO:1905907]; negative regulation of neuron apoptotic process [GO:0043524]; neuron projection development [GO:0031175]; positive regulation of amyloid-beta clearance [GO:1900223]; triglyceride-rich lipoprotein particle clearance [GO:0071830]; very-low-density lipoprotein particle clearance [GO:0034447]

chylomicron [GO:0042627]; extracellular exosome [GO:0070062]; extracellular matrix [GO:0031012]; extracellular space [GO:0005615]; high-density lipoprotein particle [GO:0034364]; intermediate-density lipoprotein particle [GO:0034363]; low-density lipoprotein particle [GO:0034362]; multivesicular body, internal vesicle [GO:0097487]; very-low-density lipoprotein particle [GO:0034361]

amyloid-beta binding [GO:0001540]; heparan sulfate proteoglycan binding [GO:0043395]; heparin binding [GO:0008201]; identical protein binding [GO:0042802]; lipid binding [GO:0008289]; low-density lipoprotein particle receptor binding [GO:0050750]; very-low-density lipoprotein particle receptor binding [GO:0070326]

PF01442;

1.20.120.20;

Apolipoprotein A1/A4/E family

PTM: APOE exists as multiple glycosylated and sialylated glycoforms within cells and in plasma. The extent of glycosylation and sialylation are tissue and context specific. {ECO:0000250|UniProtKB:P02649}.; PTM: Glycated in plasma VLDL. {ECO:0000250|UniProtKB:P02649}.; PTM: Phosphorylated by FAM20C in the extracellular medium. {ECO:0000250|UniProtKB:P02649}.

SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P02649}. Secreted, extracellular space {ECO:0000250|UniProtKB:P02649}. Secreted, extracellular space, extracellular matrix {ECO:0000250|UniProtKB:P02649}. Extracellular vesicle {ECO:0000250|UniProtKB:P02649}. Endosome, multivesicular body {ECO:0000250|UniProtKB:P02649}. Note=In the plasma, APOE is associated with chylomicrons, chylomicrons remnants, VLDL, LDL and HDL lipoproteins. Lipid poor oligomeric APOE is associated with the extracellular matrix in a calcium- and heparan-sulfate proteoglycans-dependent manner. Lipidation induces the release from the extracellular matrix. Colocalizes with CD63 and PMEL at exosomes and in intraluminal vesicles within multivesicular endosomes. {ECO:0000250|UniProtKB:P02649}.

FUNCTION: APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids. APOE is a core component of plasma lipoproteins and is involved in their production, conversion and clearance. Apolipoproteins are amphipathic molecules that interact both with lipids of the lipoprotein particle core and the aqueous environment of the plasma. As such, APOE associates with chylomicrons, chylomicron remnants, very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL) but shows a preferential binding to high-density lipoproteins (HDL). It also binds a wide range of cellular receptors including the LDL receptor/LDLR, the LDL receptor-related proteins LRP1, LRP2 and LRP8 and the very low-density lipoprotein receptor/VLDLR that mediate the cellular uptake of the APOE-containing lipoprotein particles. Finally, APOE has also a heparin-binding activity and binds heparan-sulfate proteoglycans on the surface of cells, a property that supports the capture and the receptor-mediated uptake of APOE-containing lipoproteins by cells. A main function of APOE is to mediate lipoprotein clearance through the uptake of chylomicrons, VLDLs, and HDLs by hepatocytes. APOE is also involved in the biosynthesis by the liver of VLDLs as well as their uptake by peripheral tissues ensuring the delivery of triglycerides and energy storage in muscle, heart and adipose tissues. By participating in the lipoprotein-mediated distribution of lipids among tissues, APOE plays a critical role in plasma and tissues lipid homeostasis. APOE is also involved in two steps of reverse cholesterol transport, the HDLs-mediated transport of cholesterol from peripheral tissues to the liver, and thereby plays an important role in cholesterol homeostasis. First, it is functionally associated with ABCA1 in the biogenesis of HDLs in tissues. Second, it is enriched in circulating HDLs and mediates their uptake by hepatocytes. APOE also plays an important role in lipid transport in the central nervous system, regulating neuron survival and sprouting. {ECO:0000250|UniProtKB:P02649}.

Chlorocebus sabaeus (Green monkey) (Cercopithecus sabaeus)

A0A0E3D8M9

JANG_PENJA

MLYFLAETIFGFICQYVPIGFWNGYSPAPTDRYRRLDLKSSQGFRAEPNLAPLPTTKPRRERYYGPNQIIRAPLDYLLSIPGKDIRGKLINAFNEWLQLPDDKLAIVKEVINLLHTASLLIDDIQDGSRLRRGRPVAHEVFGVAQTINAANYAYFLQQERLSEIGDPRAFHIFTNALLDLHRGQGMDLYWREAVVCPTEEEYIRMVIYKTGGLFRLALELMQVQSNSTTDFSELVELLGIIFQIRDDYMNLQSGLYAEKKGSMEDLTEGKFSYPVIHSIHAAPENSMLVDILKQRTEDNVVKVRAVHYMESTGSFQYCRENLARLTKQARHHVKELEVSLGPNRGIHAILDLLHVQQPNEKPLV

2.5.1.-; 2.5.1.1; 2.5.1.10; 2.5.1.29

COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:Q12051}; Note=Binds 3 Mg(2+) ions per subunit. {ECO:0000250|UniProtKB:Q12051};

alcohol biosynthetic process [GO:0046165]; isoprenoid biosynthetic process [GO:0008299]; ketone biosynthetic process [GO:0042181]; mycotoxin biosynthetic process [GO:0043386]

dimethylallyltranstransferase activity [GO:0004161]; farnesyltranstransferase activity [GO:0004311]; geranyltranstransferase activity [GO:0004337]; metal ion binding [GO:0046872]

PF00348;

1.10.600.10;

FPP/GGPP synthase family

CATALYTIC ACTIVITY: Reaction=dimethylallyl diphosphate + isopentenyl diphosphate = (2E)-geranyl diphosphate + diphosphate; Xref=Rhea:RHEA:22408, ChEBI:CHEBI:33019, ChEBI:CHEBI:57623, ChEBI:CHEBI:58057, ChEBI:CHEBI:128769; EC=2.5.1.1; Evidence={ECO:0000250|UniProtKB:Q12051}; CATALYTIC ACTIVITY: Reaction=(2E)-geranyl diphosphate + isopentenyl diphosphate = (2E,6E)-farnesyl diphosphate + diphosphate; Xref=Rhea:RHEA:19361, ChEBI:CHEBI:33019, ChEBI:CHEBI:58057, ChEBI:CHEBI:128769, ChEBI:CHEBI:175763; EC=2.5.1.10; Evidence={ECO:0000250|UniProtKB:Q12051}; CATALYTIC ACTIVITY: Reaction=(2E,6E)-farnesyl diphosphate + isopentenyl diphosphate = (2E,6E,10E)-geranylgeranyl diphosphate + diphosphate; Xref=Rhea:RHEA:17653, ChEBI:CHEBI:33019, ChEBI:CHEBI:58756, ChEBI:CHEBI:128769, ChEBI:CHEBI:175763; EC=2.5.1.29; Evidence={ECO:0000250|UniProtKB:Q12051};

PATHWAY: Secondary metabolite biosynthesis. {ECO:0000269|PubMed:26213965}.; PATHWAY: Secondary metabolite biosynthesis. {ECO:0000305|PubMed:26213965}.

FUNCTION: Geranylgeranyl pyrophosphate synthase; part of the gene cluster that mediates the biosynthesis of the indole diterpenes janthitremanes such as shearinine K or shearinine A (PubMed:26213965). The geranylgeranyl diphosphate (GGPP) synthase janG catalyzes the first step in janthitremane biosynthesis via conversion of farnesyl pyrophosphate and isopentyl pyrophosphate into geranylgeranyl pyrophosphate (GGPP) (PubMed:26213965). Condensation of indole-3-glycerol phosphate with GGPP by the prenyl transferase janC then forms 3-geranylgeranylindole (3-GGI) (PubMed:26213965). Epoxidation by the FAD-dependent monooxygenase janM leads to a epoxidized-GGI that is substrate of the terpene cyclase janB for cyclization to yield paspaline (PubMed:26213965). Paspaline is subsequently converted to 13-desoxypaspaline by the cytochrome P450 monooxygenase janP, via beta-PC-M6 in a series of alpha-face oxidations (Probable). The cytochrome P450 monooxygenase janQ is proposed to carry out sequential beta-face oxidation steps at C-7 and C-13 of 13-desoxypaspaline to form paspalicine and paspalinine respectively (Probable). The indole diterpene prenyltransferase janD may then convert paspalinine into shearinine K which is substrate of janO and/or additional enzymes for oxidation and cyclization to generate shearinine A (Probable). {ECO:0000269|PubMed:26213965, ECO:0000305|PubMed:26213965}.

Penicillium janthinellum (Penicillium vitale)

A0A0E3D8P4

PENG_PENCR

MLFLAPGYIFPNVATPVTVAIDFAQAVKQGAYNVLDLKASPIPNPELFQPPSRIIRGPLNYLLSLPGKDIRGKLIDALNEWFRVPEDKLNIIKEIVVILHTASLLIDDIQDSSELRRGNPVAHRIFGVAQTINSANYAYFLAQAKLADLNDSRAFDIFTKGLLKLHRGQGMELYWRDNLICPTEEEYVEMVSCKTGGLFYLAVQLMQLNSEVTVNFSNFINLLGIIFQIRDDYMNLQSGTMTKTKGFSEDLTEGKFGYPIIHSIHAAPNDSQLIQILKLKTKDEVIKQYAVRYIESTGSFVYCREKLDMYLEEANETFRGLEMLLGPSKGIRAILDFLRTR

2.5.1.-; 2.5.1.1; 2.5.1.10; 2.5.1.29

COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:Q12051}; Note=Binds 3 Mg(2+) ions per subunit. {ECO:0000250|UniProtKB:Q12051};

alcohol biosynthetic process [GO:0046165]; isoprenoid biosynthetic process [GO:0008299]; ketone biosynthetic process [GO:0042181]; mycotoxin biosynthetic process [GO:0043386]

dimethylallyltranstransferase activity [GO:0004161]; farnesyltranstransferase activity [GO:0004311]; geranyltranstransferase activity [GO:0004337]; metal ion binding [GO:0046872]

PF00348;

1.10.600.10;

FPP/GGPP synthase family

CATALYTIC ACTIVITY: Reaction=dimethylallyl diphosphate + isopentenyl diphosphate = (2E)-geranyl diphosphate + diphosphate; Xref=Rhea:RHEA:22408, ChEBI:CHEBI:33019, ChEBI:CHEBI:57623, ChEBI:CHEBI:58057, ChEBI:CHEBI:128769; EC=2.5.1.1; Evidence={ECO:0000250|UniProtKB:Q12051}; CATALYTIC ACTIVITY: Reaction=(2E)-geranyl diphosphate + isopentenyl diphosphate = (2E,6E)-farnesyl diphosphate + diphosphate; Xref=Rhea:RHEA:19361, ChEBI:CHEBI:33019, ChEBI:CHEBI:58057, ChEBI:CHEBI:128769, ChEBI:CHEBI:175763; EC=2.5.1.10; Evidence={ECO:0000250|UniProtKB:Q12051}; CATALYTIC ACTIVITY: Reaction=(2E,6E)-farnesyl diphosphate + isopentenyl diphosphate = (2E,6E,10E)-geranylgeranyl diphosphate + diphosphate; Xref=Rhea:RHEA:17653, ChEBI:CHEBI:33019, ChEBI:CHEBI:58756, ChEBI:CHEBI:128769, ChEBI:CHEBI:175763; EC=2.5.1.29; Evidence={ECO:0000250|UniProtKB:Q12051};

PATHWAY: Secondary metabolite biosynthesis. {ECO:0000305|PubMed:26213965}.

FUNCTION: Geranylgeranyl pyrophosphate synthase; part of the gene cluster that mediates the biosynthesis of the indole diterpenes penitrems (PubMed:26213965). The geranylgeranyl diphosphate (GGPP) synthase penG catalyzes the first step in penitrem biosynthesis via conversion of farnesyl pyrophosphate and isopentyl pyrophosphate into geranylgeranyl pyrophosphate (GGPP) (Probable). Condensation of indole-3-glycerol phosphate with GGPP by the prenyl transferase penC then forms 3-geranylgeranylindole (3-GGI) (Probable). Epoxidation by the FAD-dependent monooxygenase penM leads to a epoxidized-GGI that is substrate of the terpene cyclase penB for cyclization to yield paspaline (Probable). Paspaline is subsequently converted to 13-desoxypaxilline by the cytochrome P450 monooxygenase penP, the latter being then converted to paxilline by the cytochrome P450 monooxygenase penQ (PubMed:26213965). Paxilline is converted to beta-paxitriol via C-10 ketoreduction by the short-chain dehydrogenase PC-15 which can be monoprenylated at the C-20 by the indole diterpene prenyltransferase penD (Probable). A two-step elimination (acetylation and elimination) process performed by the O-acetyltransferase PC-16 and the P.simplicissimum ptmI-ortholog not yet identified in P.crustosum, leads to the production of the prenylated form of penijanthine (Probable). The FAD-linked oxidoreductase ptmO then converts the prenylated form of penijanthine into PC-M5 which is in turn transformed into PC-M4 by the aromatic dimethylallyltransferase PC-22 (Probable). A series of oxidation steps involving 4 cytochrome P450 monooxygenases (PC-21, PC-05, PC-23, PC-20) and a FAD-dependent monooxygenase (PC-14) are required for the transformation of PC-M4 to penitrems A and E. Synthesis of these final products is proposed to proceed via penitrems D and C (PC-21, PC-05, PC-14) and penitrems B and F (PC-21, PC-05, PC-14, PC-23) (Probable). {ECO:0000269|PubMed:26213965, ECO:0000305|PubMed:26213965}.

Penicillium crustosum (Blue mold fungus)

A0A0E3JXD9

DAO_UNKP

MTEQMLDYFIVGAGLGGVAFAEVALQHQKSIFVFAGDKPPSSVAAAGVYNAVILKRFTLVSQAQEQINLLKVFYPEIEKRIQKNIIFDLPTYRRLASVEEQNNFIVASDRPLFQLFLSPKIISDKFKAVISPFGFGLMKQTGYVDTKLLLQSYRNYLQQNGCISAETFNYAELIIHPDFVEYKGQKAKQIIFAEGFQMKHNPFFKDLPLEGAKGELLVIRSENLDVNVLLKAGVFVLPIGNDLYKVGATYNWTDKTNKPTQSAKDELISELKELISCDFEVVEHLAGIRPTVKDRKPLVGRHPFHKNIYLLNGLGTRGVMLAPYLSYKLFDFIESDLPLDSSISIERYYNSITSSNK

1.4.3.3

COFACTOR: Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250|UniProtKB:Q1AYM8};

amino acid catabolic process [GO:0009063]

cytoplasm [GO:0005737]; peptidoglycan-based cell wall [GO:0009274]

D-amino-acid oxidase activity [GO:0003884]

PF01266;

3.30.9.10;3.50.50.60;

DAMOX/DASOX family

SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:A5U3S4}. Secreted, cell wall {ECO:0000250|UniProtKB:A5U3S4}.

CATALYTIC ACTIVITY: Reaction=a D-alpha-amino acid + H2O + O2 = a 2-oxocarboxylate + H2O2 + NH4(+); Xref=Rhea:RHEA:21816, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, ChEBI:CHEBI:35179, ChEBI:CHEBI:59871; EC=1.4.3.3; Evidence={ECO:0000269|PubMed:25900453}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21817; Evidence={ECO:0000269|PubMed:25900453}; CATALYTIC ACTIVITY: Reaction=D-phenylalanine + H2O + O2 = 3-phenylpyruvate + H2O2 + NH4(+); Xref=Rhea:RHEA:70963, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:18005, ChEBI:CHEBI:28938, ChEBI:CHEBI:57981; Evidence={ECO:0000269|PubMed:25900453}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70964; Evidence={ECO:0000269|PubMed:25900453}; CATALYTIC ACTIVITY: Reaction=D-lysine + H2O + O2 = 6-amino-2-oxohexanoate + H2O2 + NH4(+); Xref=Rhea:RHEA:37583, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, ChEBI:CHEBI:32557, ChEBI:CHEBI:58183; EC=1.4.3.3; Evidence={ECO:0000269|PubMed:25900453}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37584; Evidence={ECO:0000269|PubMed:25900453}; CATALYTIC ACTIVITY: Reaction=D-methionine + H2O + O2 = 4-methylsulfanyl-2-oxobutanoate + H2O2 + NH4(+); Xref=Rhea:RHEA:78207, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:16723, ChEBI:CHEBI:28938, ChEBI:CHEBI:57932; Evidence={ECO:0000269|PubMed:25900453}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:78208; Evidence={ECO:0000269|PubMed:25900453}; CATALYTIC ACTIVITY: Reaction=D-arginine + H2O + O2 = 5-guanidino-2-oxopentanoate + H2O2 + NH4(+); Xref=Rhea:RHEA:78219, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, ChEBI:CHEBI:32689, ChEBI:CHEBI:58489; Evidence={ECO:0000269|PubMed:25900453}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:78220; Evidence={ECO:0000269|PubMed:25900453}; CATALYTIC ACTIVITY: Reaction=D-ornithine + H2O + O2 = 5-amino-2-oxopentanoate + H2O2 + NH4(+); Xref=Rhea:RHEA:78255, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, ChEBI:CHEBI:57668, ChEBI:CHEBI:58802; Evidence={ECO:0000269|PubMed:25900453}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:78256; Evidence={ECO:0000269|PubMed:25900453}; CATALYTIC ACTIVITY: Reaction=D-leucine + H2O + O2 = 4-methyl-2-oxopentanoate + H2O2 + NH4(+); Xref=Rhea:RHEA:78211, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:17865, ChEBI:CHEBI:28938, ChEBI:CHEBI:143079; Evidence={ECO:0000269|PubMed:25900453}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:78212; Evidence={ECO:0000269|PubMed:25900453}; CATALYTIC ACTIVITY: Reaction=D-histidine + H2O + O2 = 3-(imidazol-5-yl)pyruvate + H2O2 + NH4(+); Xref=Rhea:RHEA:78227, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, ChEBI:CHEBI:58133, ChEBI:CHEBI:142967; Evidence={ECO:0000269|PubMed:25900453}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:78228; Evidence={ECO:0000269|PubMed:25900453};

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=2.96 mM for D-methionine (at 37 degrees Celsius and at pH 8.0) {ECO:0000269|PubMed:25900453}; Note=kcat is 10.9 sec(-1) with D-methionine as substrate (at 37 degrees Celsius and at pH 8.0). {ECO:0000269|PubMed:25900453};

BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 8. {ECO:0000269|PubMed:25900453};

BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: Optimum temperature is 37 degrees Celsius. {ECO:0000269|PubMed:25900453};

FUNCTION: Catalyzes the oxidative deamination of D-amino acids with broad substrate specificity. {ECO:0000269|PubMed:25900453}.

Unknown prokaryotic organism

A0A0E3KBH3

OFOB_SACSO

MAGLKVEWNDWCPGCGNFGILSAEQQAIQELGLDPKKVVLVSGIGCSGKIPHFIRLPASGVHTLHGRALTFAIGIKLANPSLEVIVNGGDGDQLGIGVGHFVSAGRRNVDLTVIVHNNGVYGLTKGQASPTLKLGVKTKSLPKPNINSDINPIALAISSGYTFVARGYAYDVKHLKEIIKKAIKHKGLAMIDVLQPCPTYNDIHTKEYYDKRVYKLDEDPSWDPIVKKPEEMDDKMSKAILKSMEWGDRTPIGIFYQNELVSTYEQRIAERSPSYLDNPPAHDVIEFEGKPTTDVEDILKERRVT

1.2.7.11

COFACTOR: Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; Evidence={ECO:0000250|UniProtKB:Q96XT4}; Note=Binds 1 [4Fe-4S] cluster per subunit. {ECO:0000250|UniProtKB:Q96XT4}; COFACTOR: Name=thiamine diphosphate; Xref=ChEBI:CHEBI:58937; Evidence={ECO:0000250|UniProtKB:Q96XT4}; Note=Binds 1 thiamine pyrophosphate per subunit. {ECO:0000250|UniProtKB:Q96XT4}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:Q96XT4}; Note=Binds 1 Mg(2+) per subunit. {ECO:0000250|UniProtKB:Q96XT4};

2-oxobutyrate synthase activity [GO:0018491]; 2-oxoglutarate synthase activity [GO:0047553]; 4 iron, 4 sulfur cluster binding [GO:0051539]; magnesium ion binding [GO:0000287]; pyruvate synthase activity [GO:0019164]; thiamine pyrophosphate binding [GO:0030976]

PF12367;PF02775;

3.40.50.970;

CATALYTIC ACTIVITY: Reaction=a 2-oxocarboxylate + CoA + 2 oxidized [2Fe-2S]-[ferredoxin] = an acyl-CoA + CO2 + H(+) + 2 reduced [2Fe-2S]-[ferredoxin]; Xref=Rhea:RHEA:42316, Rhea:RHEA-COMP:10000, Rhea:RHEA-COMP:10001, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:35179, ChEBI:CHEBI:57287, ChEBI:CHEBI:58342; EC=1.2.7.11; Evidence={ECO:0000269|PubMed:16466637};

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=163 uM for 2-oxoglutarate {ECO:0000269|PubMed:16466637}; KM=275 uM for pyruvate {ECO:0000269|PubMed:16466637}; KM=516 uM for 2-oxobutyrate {ECO:0000269|PubMed:16466637}; Note=kcat is 452 min(-1) for 2-oxoglutarate as substrate. kcat is 144 min(-1) for pyruvate as substrate. kcat is 93 min(-1) for 2-oxobutyrate as substrate.;

BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is between 7-8. {ECO:0000269|PubMed:16466637};

BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: Optimum temperature is 70 degrees Celsius. {ECO:0000269|PubMed:16466637};

FUNCTION: Catalyzes the coenzyme A-dependent oxidative decarboxylation of different 2-oxoacids such as 2-oxoglutarate, pyruvate and 2-oxobutyrate to form their CoA derivatives. {ECO:0000269|PubMed:16466637}.

Saccharolobus solfataricus (Sulfolobus solfataricus)

A0A0E3T3B5

AADH2_MALDO

MAIQIPSRQLFIDGEWREPVLKKRIPIINPATEQIIGDIPAATAEDVEIAVEAARKALARNKGRDWALAPGAVRAKYLRAIAAKIAERKSEIAKLEAIDCGKPLDEAAWDIDDVSGCFEYYADLAEGLDAQQKTPISLPMEQFKSHVLKEPIGVVGLITPWNYPLLMATWKVAPALAAGCAAILKPSELASVTCLELADVCREVGLPPGVLNILTGLGHEAGAPLASHPHVDKIAFTGSTMTGSKIMTAAAQLVKPVSLELGGKSPIVVFDDVDIDKAAEWTAFGIFWTNGQICSATSRLIIHENIAAKFLDRLVQWCKNIKIADPLEEGCRLGPVVSGGQYEKILKFIATAKSEGARVLSGGARPEHLKKGFFIEPTIITDVTTSMQIWREEVFGPVLCVKTFSSEDEALELANDSHYGLGAAVISKDLERCERVSKALQAGIVWINCSQPCFCQAPWGGNKRSGFGRELGKWGLDNYLTVKQVTEYVSDDPWGWYKSPSKL

1.2.1.-; 1.2.1.19

cellular detoxification of aldehyde [GO:0110095]; glycine betaine biosynthetic process from choline [GO:0019285]

peroxisome [GO:0005777]

1-pyrroline dehydrogenase activity [GO:0033737]; aminobutyraldehyde dehydrogenase activity [GO:0019145]; metal ion binding [GO:0046872]

PF00171;

Aldehyde dehydrogenase family

SUBCELLULAR LOCATION: Peroxisome {ECO:0000269|PubMed:26296314}.

CATALYTIC ACTIVITY: Reaction=4-aminobutanal + H2O + NAD(+) = 4-aminobutanoate + 2 H(+) + NADH; Xref=Rhea:RHEA:19105, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:58264, ChEBI:CHEBI:59888; EC=1.2.1.19; Evidence={ECO:0000269|PubMed:26296314}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19106; Evidence={ECO:0000269|PubMed:26296314}; CATALYTIC ACTIVITY: Reaction=3-aminopropanal + H2O + NAD(+) = beta-alanine + 2 H(+) + NADH; Xref=Rhea:RHEA:30695, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:57966, ChEBI:CHEBI:58374; Evidence={ECO:0000269|PubMed:26296314}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30696; Evidence={ECO:0000269|PubMed:26296314};

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=160 uM for 4-aminobutanal {ECO:0000269|PubMed:26296314}; KM=8.2 uM for 3-aminopropanal {ECO:0000269|PubMed:26296314}; KM=82.8 uM for NAD(+) with 3-aminopropanal as substrate {ECO:0000269|PubMed:26296314}; Vmax=1.9 umol/min/mg enzyme with 4-aminobutanal as substrate {ECO:0000269|PubMed:26296314}; Vmax=11.2 umol/min/mg enzyme with 3-aminopropanal as substrate {ECO:0000269|PubMed:26296314}; Vmax=20.9 umol/min/mg enzyme toward NAD(+) in presence of 3-aminopropanal {ECO:0000269|PubMed:26296314};

PATHWAY: Amine and polyamine biosynthesis; betaine biosynthesis via choline pathway; betaine from betaine aldehyde: step 1/1. {ECO:0000305}.

BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 9.75 with 4-aminobutanal as substrate. {ECO:0000269|PubMed:26296314};

FUNCTION: Dehydrogenase that catalyzes the oxidation of several aminoaldehydes (PubMed:26296314). Metabolizes and detoxifies aldehyde products of polyamine degradation to non-toxic amino acids (Probable). Catalyzes the oxidation of 4-aminobutanal and 3-aminopropanal to 4-aminobutanoate and beta-alanine, respectively (PubMed:26296314). {ECO:0000269|PubMed:26296314, ECO:0000305}.

Malus domestica (Apple) (Pyrus malus)

A0A0E3T552

AADH1_MALDO

MAIQIPSRLLFIDGEWREPVLKKRIPIINPATEEIIGHIPAATAEDVELAVEAARRALSRNKGRDWASAPGAVRAKYLRAIAAKIGERKPEIAKLEAIDCGKPLDEAAWDIDDVSGCFEYYAELAEGLDAQQKAPISLPMEQFKSHVLKEPIGVVGLITPWNYPLLMATWKVAPALAAGCAAILKPSELASVTCLELADVCREVGLPPGVLNILTGLGHEAGAPLVSHPHVDKIAFTGSTMTGSKIMTAAAQLVKPVSLELGGKSPIVVFDDVDIDKAAEWTAFGCFWTNGQICSATSRLILHENIATEFLDRLLKWCKNIKIADPLEEGCRLGPVVSGGQYEKILKSIETAKSEGARVLSGGDRPEHLKKGFFIEPTIITDVTTSMQIWREEVFGPVLCVKTFSSEDEALELANDTHYGLGAAVISKDLERCDRFSKGLQAGIVWINCSQPCFCQAPWGGNKRSGFGRELGKWGLDNYLTVKQVTEYVSDDPWGWYTSPSKL

1.2.1.-; 1.2.1.19

cellular detoxification of aldehyde [GO:0110095]; glycine betaine biosynthetic process from choline [GO:0019285]

cytosol [GO:0005829]

1-pyrroline dehydrogenase activity [GO:0033737]; aminobutyraldehyde dehydrogenase activity [GO:0019145]; metal ion binding [GO:0046872]

PF00171;

Aldehyde dehydrogenase family

SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:26296314}.

CATALYTIC ACTIVITY: Reaction=4-aminobutanal + H2O + NAD(+) = 4-aminobutanoate + 2 H(+) + NADH; Xref=Rhea:RHEA:19105, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:58264, ChEBI:CHEBI:59888; EC=1.2.1.19; Evidence={ECO:0000269|PubMed:26296314}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19106; Evidence={ECO:0000269|PubMed:26296314}; CATALYTIC ACTIVITY: Reaction=3-aminopropanal + H2O + NAD(+) = beta-alanine + 2 H(+) + NADH; Xref=Rhea:RHEA:30695, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:57966, ChEBI:CHEBI:58374; Evidence={ECO:0000269|PubMed:26296314}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30696; Evidence={ECO:0000269|PubMed:26296314};

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=84.8 uM for 4-aminobutanal {ECO:0000269|PubMed:26296314}; KM=16 uM for 3-aminopropanal {ECO:0000269|PubMed:26296314}; KM=33.8 uM for NAD(+) with 3-aminopropanal as substrate {ECO:0000269|PubMed:26296314}; Vmax=1.2 umol/min/mg enzyme with 4-aminobutanal as substrate {ECO:0000269|PubMed:26296314}; Vmax=11.3 umol/min/mg enzyme with 3-aminopropanal as substrate {ECO:0000269|PubMed:26296314}; Vmax=5.4 umol/min/mg enzyme toward NAD(+) in presence of 3-aminopropanal {ECO:0000269|PubMed:26296314};

PATHWAY: Amine and polyamine biosynthesis; betaine biosynthesis via choline pathway; betaine from betaine aldehyde: step 1/1. {ECO:0000305}.

BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 9.75 with 4-aminobutanal as substrate. {ECO:0000269|PubMed:26296314};

FUNCTION: Dehydrogenase that catalyzes the oxidation of several aminoaldehydes (PubMed:26296314). Metabolizes and detoxifies aldehyde products of polyamine degradation to non-toxic amino acids (Probable). Catalyzes the oxidation of 4-aminobutanal and 3-aminopropanal to 4-aminobutanoate and beta-alanine, respectively (PubMed:26296314). {ECO:0000269|PubMed:26296314, ECO:0000305}.

Malus domestica (Apple) (Pyrus malus)

A0A0E4AZP0

FSA1_FUSSF

MDASEPIAVIGSACRFPGGSDSPSKLWELLKEPRDLLSKVPPERYNADAFYHADATHHGTTNVRHSYFLSEDPSSFDNNFFNIQPGEAEAIDPQQRLLMEVVYQGLCSAGQTIEGLRGSPTAVYVGVMCDDWSGIITRDLEVFPRYGATGMARSIMSNRISYFFDWHGPSMTIDTACSSSLVAVHQAIQTLRSGESEVAIAAGANLILTPGMYVAESKLSMLSPSGRSKMWDQDVDGYARGEGIAAVVLKPLSAAIRDNDHIDCIIRATGINQDGRTPGLTMPSATAQADLIRSTYARAGLDINKAEDRPQFFHAHGTGTPAGDPREAEAISRAFYSPDNLSKDDKLYVGSIKTIIGHTEGTAGLASLIGTSLAIQNKVIPPNMHLDVLNPKVAPFYNNLEVPTSALEWPETRSGQPRRASINSFGFGGTNAHAIIEAYEPNATAHVSGALFSPLTFSASSEPSLRSLLMSYSEYLKLNPQISLKDLAYSLQTRRSTLAYRVAITASTAENASKQLDAIVDGEQSSSISTRQLSKSSPKILGIFTGQGTQWPRMGARLLEESPFASKRLAELDDALSSLPADDRPTWTLREMILADSESSRVAEAAISQPLCTAVQVVLVDLLRHAGIELSAVVGHSSGEIGAAYAAGLLTARDAIRVAYYRGLYAKLAQSPNGHKGAMMAVGTTFEDAADFCELEAFQGRIQIAAKNSPSSITLSGDEDAIIEAIEIFKDEGKFARQLKVDTAYHSSHVIPCAKPYLEAMNRCGIETATATKTQWYSSVHGGQIMSADSLTTSYWVDNMTSAVLFSPAVAQAWEEGGPYDLAIEVGPHPALKTPALDTIEAISEGRPPYTGVIARGKDDIQQFSNALGFIWTHLGPGSIAFENFESVVSGSKDRPSFIQDLPNYPFDHAKQFMSMSRVSGWFNSIQEAPHPLLGRRCHDRETSHSVQWRNVLSHKEIPWLQGHQLQGQIIFPATGYISMAVEAIKILAEPSSLGLITIEDLSITRALAFADEDASIETLFELRILSRSETEIQAEFCCYSGIPHTHTATMGLNATAQIKASLGTPTSDQLSNIAVDDYDLRPVSVDRFYDFLARLGYNYSWPFRGTTSIRRKANFATGTLEDQSGSNWEDQLMVHPGMLDSSLQTTFAAFCCPGDERLWALHLPTSFRSIAINPYFTSAGIGKQNSFTYQSVAIEERKTSKVLVELNLLSEETGDTFLQIEGMELVPFSPATPANDAVLFSRFDYRLAGPDGELTAAEYSFKPEDYKMALDCERIAFYYLRRLVETITPEEKANTLVHYRHLVDWAAYVVPQVANGGNPHIPASAQQDTHDDIQQLLKKHYERVDIRLLESVGENLPQVIRDSGNILEHMTKDGMLQDVYEQGFGLNLVNQYIAHMTAQIAHRYPRMNILEIGAGTGGSTREILPRLGSAFSTYTYTDVSGGFFDMAQDRFKDYADRMIFKTFDMNISPASQGFTEGAYDLVIASNVLHATLELEDMMKHVRSFLKPGGFLIILETVNNDCLRVGLPMGSLPGWWLGAEHGRRWGPTLTLPQWDSLLSKCGFGGIDTTTPPVHKILPGHVFCAQALDERIEILRSPMEHLATLPETKSTQLAVIGGQTLKVHRMCDQISRRLSSRYSSISRFNSIEELNDTGLPESCTVLSLTELDEPLFANMTYGKLEALKILWKQGGSILWITSGARAENPHSYMTTGVGRCMRFEYPNITLQALDIKQISDRCPELIVDHLLRLEILDKWSKELRSDELLWSLEPEIYIEEETAIIPRLYPYESGNARYNAERRKVIKQADMETDRVVFAEFEGKWEIQHASPLHIAQELPSSSDISARTIQITHLSPATVNIAPGVSAMAWAGVDTASNEPVVAVTHIAESPVSIPAGWCIPLDKLDPVKTLTGVSATLIASSILERLVKGETLVVHDAPPHIRAALDKLAKPVSIAIFYTSSDEAMSKLGARYIDRRSPLRVIRASLPKSASKFISLSQDFGKDETSKVISMCLPRDCETINTAHLFGPRNVAQQSAFEKDVSSSLKKAFEEVGSQVNTTASTDLISLKDTPNPIADQVRFAILDCTDTPIQASVHPIDDGRIFRADKTFLLIGLTGELGQSLCKWMVEQGARSIVLTSRRPNVSEHFLGSFAETGAIVKALPMDVTDRTSIEACLETIKKTLPPIAGVVNGAMVLRDALFENMPYEDFMKVLNPKVVGSQLLDEMFYDTPLDFFIFFSSTTAVMGNSGQSNYIAGNMYMNALAAQRKKRGVAASSIDISSIIGLGYVERAEDLSEDTFIKMGYKPMSEQDLQKLFAEAIVLGRPDCHEVCELVTGVTPIYTDAQASDQYLKDVKFGHFLMERLDTQTYTGKTSTVPVRVQLADVKTRADAVAIIKESFIVRLRRVLAVGPDEIINEKVTLVEQGVDSLMAVEVRSWFIKELDVDIPVLKILGGMSVPDLVDESLDLLSPSILDVSSLEAGNAHPAKPTTVIPQTPTRVTPPESSQGTSDQDKPHTGSDSSRSPIDTPLTSWDRQDLSPPDKSDDAPNSTDNLTPPRTFPNELPSIMSYGQAGFWFLNDYLVNKKAFNMAVMLKLTGSIRTQPLENAVQLVAERHEILRTRFFWSEDGDERTPMQGINPPTMKLTIKTIADEKEAETELKRLHDEDWDLGSGEGVKIILLRLSDQVHFLLSGMHHIYLDGYSFSVFFKDLESAYINHRLPPLPVESQYRTFALQQRKMYDDGDLLKSIEYYRQSFPKEFAPIRLFPFATTASRQLANEYSQHEAKLSITPDVSAKVRQLARANRSTSFHVYLAALKILLFSLLPDTEELFIGIADANRGDKKFMGSLGFFLNLLPLRFQRGKPRSRVSSAIQTARDAAYGALQHSQLPFDVLLRELNVPRSDKHTPIFQVFMDYRQVVQERSSWGGCKLSDEKWCNAGTGYDVALEVTENINTDTLLSLRLQKQLYSEEHTQVLLRSYLSVLEYMIRGSDKSVDAAPAWSSYDLKVAVDAGKAPEFKSKWPPTVSHQIDQVIQNNPDKIALKDGNGNVLTYAQMGNRIDTISKALIDAGTVQGTVVGVFQEPSADWICSLLAIFKAGAVYVPLDLRNSIPRLASIVKASRPSVIITDITTDDKVDLIGAKFVTKLQLGSLDESTRQDSTEINHAKVGSLAVILFTSGSTGEPKGLMMTHTNLLSYAEVSSKTFARVDEDLVVLQQSPFSFDFSLDQTMAALTNGGYLYVVPASKRGDPDEISKIMVEESVTYTTATPSEYDLWLRYSTETLQQCNSWKYAFSGGEAMSYKLAREFGTLKLTNLHVFNGYGPAETTILSHRIDLKYADPDLPDPLPAGYPLPGFSVCIVDDKMRPVPLGVQGEIVLGGPCIVSGYLNMPESTRDKFLPDTFFGTSGTVYRSGDRGRLCYDGLLFCDGRLEGNTMIKLRGFRVELDEVEKTIVSHSAGALSHAVATVRGTEEGRYLVAHIVFAPEFPEQDREGVMKSLRQMLPLPPYMRPSVFQVLPDIPRTAHLKIDRKAIQDIPVQTTQSEISKSLTASEKRLSELWRRVLPLDPGTLTHESDFFLIGGNSILLVKLQALLREGLWMAPKLVTLMGSSTLGAMASVLEDCGPVNVIHWDEEIKFPNDLQLATPLRAAGKSTDINVLLTGSSGYLGRHLLLSLLKDHRVAQVHCLCRTSSDQQVVNDPGSKANIVQSDLAQHNLGIPESTYSQLATEVDVIIHCAANRSFWDRYEALKADNLDSTKELVKFVVSSGRAIPLHFLSSGAVAKYNSGLTPPADGGDGYVATKWASEVFMKQAADSTNLPVFSHRPVACESAQQSEEETISIVNELMQIVKLLGCRPSFDGVGGFVDVMPVNEIVEAIHETALNSQTGEGLCILEHKAHQRAYVRSFATVVESDDGLSKLPCIPILEWFGRAKKAGFSYFLASQDLILGSQLFSRR

2.3.1.-; 6.3.2.-

amide biosynthetic process [GO:0043604]; fatty acid biosynthetic process [GO:0006633]; heterocycle biosynthetic process [GO:0018130]; methylation [GO:0032259]; organic cyclic compound biosynthetic process [GO:1901362]; organonitrogen compound biosynthetic process [GO:1901566]; toxin biosynthetic process [GO:0009403]

3-oxoacyl-[acyl-carrier-protein] synthase activity [GO:0004315]; fatty acid synthase activity [GO:0004312]; ligase activity [GO:0016874]; methyltransferase activity [GO:0008168]; oxidoreductase activity [GO:0016491]; phosphopantetheine binding [GO:0031177]

PF00698;PF00501;PF00668;PF16197;PF00109;PF02801;PF08659;PF08242;PF07993;PF21089;PF00550;PF14765;

3.30.300.30;3.30.70.3290;3.40.47.10;1.10.1200.10;3.30.559.10;3.40.366.10;3.40.50.12780;3.40.50.720;3.30.559.30;3.10.129.110;3.40.50.150;

NRP synthetase family

CATALYTIC ACTIVITY: Reaction=acetyl-CoA + ATP + 11 H(+) + L-serine + 7 malonyl-CoA + 8 NADPH + 2 S-adenosyl-L-methionine = (5S)-3-[(2E,6R,8E,10E,12E)-2,6-dimethyltetradeca-2,8,10,12-tetraenoyl]-5-(hydroxymethyl)pyrrolidine-2,4-dione + AMP + 7 CO2 + 8 CoA + diphosphate + 6 H2O + 8 NADP(+) + 2 S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:67324, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:33384, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:57384, ChEBI:CHEBI:57783, ChEBI:CHEBI:57856, ChEBI:CHEBI:58349, ChEBI:CHEBI:59789, ChEBI:CHEBI:169938, ChEBI:CHEBI:456215; Evidence={ECO:0000305|PubMed:25770422}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67325; Evidence={ECO:0000305|PubMed:25770422};

PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:25770422}.

FUNCTION: Hybrid PKS-NRPS synthetase; part of the gene cluster that mediates the biosynthesis of HIV-1 integrase inhibitor equisetin and of fusarisetin A, both trans-fused decalin-containing tetramic acids showing also antimicrobial activity (PubMed:25770422). The PKS module of fsa1 together with the enoylreductase fsa3 catalyze the formation of the polyketide unit which is then conjugated to L-serine by the condensation domain of the fsa1 NRPS module (PubMed:25770422). Activity of the Dieckmann cyclase domain (RED) results in release of the Dieckmann product intermediate (PubMed:25770422). Diels-Alderase fsa2 is involved in endo-selective Diels-Alder cycloaddition to form the decalin ring, leading to the production of N-desmethylequisetin also called trichosetin (PubMed:25770422, PubMed:28401214, PubMed:29972614, PubMed:34121297). Subsequent N-methylation is carried out by fsa4 to give equisetin (PubMed:25770422). The enzymatic gene responsible for the conversion of equisetin to fusarisetin A has not been identified yet and is probably located outside of the fsa cluster (PubMed:28401214). {ECO:0000269|PubMed:25770422, ECO:0000269|PubMed:28401214, ECO:0000269|PubMed:29972614, ECO:0000269|PubMed:34121297}.

Fusarium sp. (strain FN080326)

A0A0F5HNH9

IMEF_BACTR

MKEELDAFHQIFTTTKEAIERFMAMLTPVIENAEDDHERLYYHHIYEEEEQRLSRLDVLIPLIEKFQDETDEGLFSPSNNAFNRLLQELNLEKFGLHNFIEHVDLALFSFTDEERQTLLKELRKDAYEGYQYVKEKLAEINARFDHDYADPHAHHDEHRDHLADMPSAGSSHEEVQPVAHKKKGFTVGSLIQ

1.16.3.1

intracellular iron ion homeostasis [GO:0006879]

encapsulin nanocompartment [GO:0140737]

ferroxidase activity [GO:0004322]

SUBCELLULAR LOCATION: Encapsulin nanocompartment {ECO:0000269|PubMed:31194509, ECO:0000269|PubMed:31282860}.

CATALYTIC ACTIVITY: Reaction=4 Fe(2+) + 4 H(+) + O2 = 4 Fe(3+) + 2 H2O; Xref=Rhea:RHEA:11148, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034; EC=1.16.3.1; Evidence={ECO:0000269|PubMed:31282860, ECO:0000305|PubMed:31194509}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11149; Evidence={ECO:0000269|PubMed:31282860};

BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: The empty encapsulin nanocompartment is stable until 86.6 degrees Celsius, when loaded with cargo protein is stable until 88.9 degrees Celsius and when grown in high-iron conditions is stable until 91.8 degrees Celsius. {ECO:0000269|PubMed:31282860};

FUNCTION: Cargo protein of a type 1 encapsulin nanocompartment. A ferritin-like iron-binding protein probably involved in iron mineralization in the encapsulin nanocompartment. Has ferroxidase activity even when encapsulated, the rate is probably controlled by the rate of Fe flux across the nanocompartment pores (PubMed:31282860). Part of the iron-mineralizing encapsulin-associated Firmicute (IMEF) system. 2 different cargo proteins have been identified (IMEF and Fer); when both are expressed in E.coli with the shell protein only IMEF is detected within the nanocompartment. E.coli expressing all 3 genes stores the largest amount of iron and is protected from Fe/H2O2-induced oxidative stress (PubMed:28263314). {ECO:0000269|PubMed:28263314, ECO:0000269|PubMed:31282860}.

Bacillus thermotolerans (Quasibacillus thermotolerans)

A0A0G2JDV3

GBP6_MOUSE

MTQPQMAPICLVENHNEQLSVNQEAIEILDKISQPVVVVAIVGLYRTGKSYLMNCLAGQNHGFPLGSTVQSQTKGIWMWCMPHPTKPEHTLVLLDTEGLGDVEKGDPKNDLWIFALSVLLSSTFIYNSMITINHQALEQLQYVTELTELIRAKSSPNPAGIKNSTEFVSFFPDFVWTVRDFMLELKLNGEDITSDDYLENALKLIPGDKPRMQASNSCRECIRLFFPNRKCFVFDRPTHDKELLQKLDSITEDQLDPKFQEVTKAFVSYIFTYAKIKTLKEGIKVTGNRLGILVTTYVNAINSGAVPCLDDAVTTLAQRENSVAVQKAADHYSEQMAQRLRLPTETLQELLDVHAACEKEAMAVFMEHSFKDENQQFLKKLVELIGENKELFLSKNEEASNKYCQEELDRLSKDFMENISTFFVPCGHKLYMDKREKIEHDYWQVPRKGVKASEVFQSFLQSQAFIESSILQADTALTAGEKAIAEERAQKVAAEKEQELLRQKQKEQQEYMEAQEKSHKENLEQLRRKLEQEREQDIKDHDMMLKKLMKDQKAFLEEGFKKKAEEMNKEIQQLRDVIKDKKRNTDRIKEALLNGFSTVLFHYLVRYLKHL

3.6.5.-

adhesion of symbiont to host [GO:0044406]; cellular response to interferon-beta [GO:0035458]; cellular response to lipopolysaccharide [GO:0071222]; cellular response to type II interferon [GO:0071346]; defense response to Gram-positive bacterium [GO:0050830]; defense response to protozoan [GO:0042832]; response to bacterium [GO:0009617]

cytoplasmic vesicle [GO:0031410]; symbiont-containing vacuole membrane [GO:0020005]

GTP binding [GO:0005525]; GTPase activity [GO:0003924]

PF02263;PF02841;

1.20.1000.10;3.40.50.300;

TRAFAC class dynamin-like GTPase superfamily, GB1/RHD3 GTPase family, GB1 subfamily

SUBCELLULAR LOCATION: Cytoplasmic vesicle {ECO:0000269|PubMed:18025219}.

CATALYTIC ACTIVITY: Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; Evidence={ECO:0000250|UniProtKB:P32455};

FUNCTION: Interferon (IFN)-inducible GTPase that plays important roles in innate immunity against a diverse range of bacterial, viral and protozoan pathogens, such as bacterial pathogens Listeria monocytogenes and Mycobacterium bovis BCG as well as the protozoan pathogen Toxoplasma gondii (PubMed:18025219, PubMed:21551061). Confers protection to several pathogens, including the bacterial pathogens Listeria monocytogenes and Mycobacterium bovis BCG as well as the protozoan pathogen Toxoplasma gondii (PubMed:18025219, PubMed:21551061). {ECO:0000269|PubMed:18025219, ECO:0000269|PubMed:21551061}.

Mus musculus (Mouse)

A0A0G2JTR4

ABR_RAT

MEPLSHRGLPRLSWIDTLYSNFSYGAEDYDAEGHEEQKGPPEGSETMPYIDESPTMSPQLSARSQGGGESISPTPPEGLAPGVEAGKGLEMRKLVLSGFLASEEIYINQLEALLLPMKPLKATATTSQPVLTIQQIETIFYKIQDIYEIHKEFYDNLCPKVQQWDSQVTMGHLFQKLASQLGVYKAFVDNYKVALETAEKCSQSNNQFQKISEELKVKGPKDSKDSHTSVTMEALLYKPIDRVTRSTLVLHDLLKHTPVDHPDYPLLQDALRISQNFLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEMSESSRKLRHVFLFTDVLLCAKLKKTSAGKHQQYDCKWYIPLADLVFPSPEESEASPQVHPFPDHELEDMKVKISALKSEIQKEKANKGQSRAIERLKKKMFENEFLLLLNSPTIPFRIHNRNGKSYLFLLSSDYERSEWREAIQKLQKKDLQAFVLSSVELQVLTGSCFKLRTVHNIPVTSNKDDDESPGLYGFLHVIVHSAKGFKQSANLYCTLEVDSFGYFVSKAKTRVFRDTTEPKWDEEFEIELEGSQSLRILCYEKCYDKTKVNKDNNEIVDKIMGKGQIQLDPQTVESKNWHTDVIEMNGIKVEFSMKFTSRDMSLKRTPSKKQTGVFGVKISVVTKRERSKVPYIVRQCIEEVEKRGIEEVGIYRISGVATDIQALKAVFDANNKDILLMLSDMDINAIAGTLKLYFRELPEPLLTDRLYPAFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATVFGPTLLRPSEVESKAHLTSAADIWSHDVMAQVQVLLYYLQHPPISFAELKRNTLYFSTDV

actin cytoskeleton organization [GO:0030036]; brain development [GO:0007420]; cell migration [GO:0016477]; establishment of localization in cell [GO:0051649]; inner ear morphogenesis [GO:0042472]; intracellular signal transduction [GO:0035556]; macrophage migration [GO:1905517]; modulation of chemical synaptic transmission [GO:0050804]; negative regulation of blood vessel remodeling [GO:0060313]; negative regulation of cellular extravasation [GO:0002692]; negative regulation of inflammatory response [GO:0050728]; negative regulation of macrophage migration [GO:1905522]; negative regulation of neutrophil degranulation [GO:0043314]; neuromuscular process controlling balance [GO:0050885]; neutrophil degranulation [GO:0043312]; phagocytosis [GO:0006909]; positive regulation of phagocytosis [GO:0050766]; regulation of vascular permeability [GO:0043114]; response to lipopolysaccharide [GO:0032496]

axon [GO:0030424]; cytosol [GO:0005829]; dendritic spine [GO:0043197]; glutamatergic synapse [GO:0098978]; membrane [GO:0016020]; plasma membrane [GO:0005886]; postsynaptic density, intracellular component [GO:0099092]; Schaffer collateral - CA1 synapse [GO:0098685]

GTPase activator activity [GO:0005096]; guanyl-nucleotide exchange factor activity [GO:0005085]

PF00168;PF19057;PF00620;PF00621;

2.60.40.150;1.20.900.10;2.30.29.30;1.10.555.10;

SUBCELLULAR LOCATION: Cell projection, dendritic spine {ECO:0000250|UniProtKB:Q5SSL4}. Cell projection, axon {ECO:0000250|UniProtKB:Q5SSL4}. Synapse {ECO:0000269|PubMed:20962234}.

FUNCTION: Protein with a unique structure having two opposing regulatory activities toward small GTP-binding proteins. The C-terminus is a GTPase-activating protein domain which stimulates GTP hydrolysis by RAC1, RAC2 and CDC42. Accelerates the intrinsic rate of GTP hydrolysis of RAC1 or CDC42, leading to down-regulation of the active GTP-bound form. The central Dbl homology (DH) domain functions as guanine nucleotide exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to the GTP-bound form (By similarity). Functions as an important negative regulator of neuronal RAC1 activity (By similarity). Regulates macrophage functions such as CSF-1 directed motility and phagocytosis through the modulation of RAC1 activity (By similarity). {ECO:0000250|UniProtKB:Q12979, ECO:0000250|UniProtKB:Q5SSL4}.

Rattus norvegicus (Rat)

A0A0G2JTY4

NFAC3_RAT

MTTANCGAHDELDFKLVFGEDGAPTPVSQVSRPADLEPDDCASIYIFNVDPPPSTLNSSLGLPHHGLLQSHSSVLSPSFQLQGFKNYEGTDDISESKYSSLSGPKPFECPSIQITSISPNCHQETDAHEDDLHVNDPEREYLERPSRDHLYLPLEPSYRESSLSPSPASSVSSRSWFSDASSCESLSHIYDDVDSELNEAAARFTLGSPLTSPGGSPGGCPGEESWHQQYGPGHSLSPRQSPCHSPRSSITDENWLSPRPASGPSSRPTSPCGKRRHSSAEVCYAGSLSPHHSPVPSPGHSPRGSVTEDTWLTAPVHTGSGLSPAPFPFQYCVETDIPLKTRKTSDDQAAILPGKLEVCSDDQGSLSPSRETSVDDGLGSQYPLKKDSSGDQFLSVPSPFTWSKPKPGHTPIFRTSSLPPLDWPLPTHFGQCELKIEVQPKTHHRAHYETEGSRGAVKASTGGHPVVKLLGYSEKPINLQMFIGTADDRYLRPHAFYQVHRITGKTVATASQEIIIASTKVLEIPLLPENNMSASIDCAGILKLRNSDIELRKGETDIGRKNTRVRLVFRVHIPQPSGKVLSLQIASIPVECSQRSAQELPHIEKYSINSCSVNGGHEMIVTGSNFLPESKIIFLEKGQDGRPHWEAEGKIIREKCQGGHIVLEVPPYHNPAVTSAVQVHFYLCNGKRKKSQSQRFTYTPVLMKQEQREDTDLSSVPSLPVPHSAQTQRPSSDTGHPHDSALSAPRSLICPVQPAYASMITSTHLPQLQCRDEGAGKEQHIIPSSVMHQPFQVTPTSPMGSSYQSIQTNMYNGPTCLPMNPASSQEFDPVLFQQDAALSNLVNLGCQPLSPIPFHSSNSDATGHLLAHSPHSVQTPPHLQSMGYHCSSAGQRSLSSPVAAQVTGQPSSHLQPITYCPSHPGSATAASPAASHALSSSPISGPPSPQLQSMPYQSPSSGTASSPSPVTRMHSGQHSTQAQSTGQGGLSVPSSLVCHSLCDPASFPPGGAAVSIKPEPEDQEPNFATIGLQDITLDDVNEIIGRDMSQITVSQGPEVIRDAPLPGPESPDVMSSNSAQ

blood vessel remodeling [GO:0001974]; branching involved in blood vessel morphogenesis [GO:0001569]; calcineurin-NFAT signaling cascade [GO:0033173]; cardiac muscle hypertrophy in response to stress [GO:0014898]; cellular respiration [GO:0045333]; cellular response to calcium ion [GO:0071277]; cellular response to lithium ion [GO:0071285]; DN4 thymocyte differentiation [GO:1904157]; heart development [GO:0007507]; myotube cell development [GO:0014904]; myotube differentiation [GO:0014902]; negative regulation of miRNA transcription [GO:1902894]; negative regulation of vascular associated smooth muscle cell differentiation [GO:1905064]; positive regulation of apoptotic process [GO:0043065]; positive regulation of artery morphogenesis [GO:1905653]; positive regulation of cardiac muscle hypertrophy [GO:0010613]; positive regulation of DNA-templated transcription [GO:0045893]; positive regulation of nitric oxide biosynthetic process [GO:0045429]; positive regulation of transcription by RNA polymerase II [GO:0045944]; positive thymic T cell selection [GO:0045059]; protein import into nucleus [GO:0006606]; regulation of DNA-templated transcription [GO:0006355]; regulation of store-operated calcium entry [GO:2001256]; regulation of transcription by RNA polymerase II [GO:0006357]; response to hypoxia [GO:0001666]; skeletal muscle fiber development [GO:0048741]; T cell differentiation [GO:0030217]; thymus development [GO:0048538]; transcription by RNA polymerase II [GO:0006366]; vascular associated smooth muscle cell development [GO:0097084]; vascular associated smooth muscle cell differentiation [GO:0035886]

cytoplasm [GO:0005737]; cytosol [GO:0005829]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; transcription regulator complex [GO:0005667]

chromatin binding [GO:0003682]; cis-regulatory region sequence-specific DNA binding [GO:0000987]; DNA binding [GO:0003677]; DNA-binding transcription activator activity, RNA polymerase II-specific [GO:0001228]; DNA-binding transcription factor activity [GO:0003700]; DNA-binding transcription factor activity, RNA polymerase II-specific [GO:0000981]; DNA-binding transcription repressor activity, RNA polymerase II-specific [GO:0001227]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]; sequence-specific DNA binding [GO:0043565]; sequence-specific double-stranded DNA binding [GO:1990837]; transcription cis-regulatory region binding [GO:0000976]

PF16179;PF00554;

2.60.40.10;2.60.40.340;

PTM: Phosphorylated by NFATC-kinase; dephosphorylated by calcineurin. {ECO:0000250|UniProtKB:Q12968}.; PTM: Ubiquitinated by STUB1/CHIP, leading to proteasomal degradation. {ECO:0000250|UniProtKB:Q12968}.

SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19538478, ECO:0000269|PubMed:30980393}. Nucleus {ECO:0000269|PubMed:19538478, ECO:0000269|PubMed:30980393}. Note=The subcellular localization of NFATC plays a key role in the regulation of gene transcription (By similarity). Rapid nuclear exit of NFATC is thought to be one mechanism by which cells distinguish between sustained and transient calcium signals (By similarity). Cytoplasmic when phosphorylated and nuclear after activation, that is controlled by calcineurin-mediated dephosphorylation (By similarity). Translocation to the nucleus is increased in the presence of calcium in pre-osteoblasts (By similarity). Translocates to the nucleus in the presence of EDN1 following colocalization with F-actin filaments, translocation is ROCK-dependent (PubMed:19538478). Translocates to the nucleus in response to lipopolysaccharide treatment of macrophages (By similarity). {ECO:0000250|UniProtKB:P97305, ECO:0000269|PubMed:19538478}.

FUNCTION: Acts as a regulator of transcriptional activation. Binds to the TNFSF11/RANKL promoter region and promotes TNFSF11 transcription (By similarity). Binding to the TNFSF11 promoter region is increased by high levels of Ca(2+) which induce NFATC3 expression and may lead to regulation of TNFSF11 expression in osteoblasts (By similarity). Plays a role in promoting mesenteric arterial wall remodeling in response to the intermittent hypoxia-induced increase in EDN1 and ROCK signaling (By similarity). As a result NFATC3 colocalizes with F-actin filaments, translocates to the nucleus and promotes transcription of the smooth muscle hypertrophy and differentiation marker ACTA2 (By similarity). Promotes lipopolysaccharide-induced apoptosis and hypertrophy in cardiomyocytes (PubMed:30980393). Following JAK/STAT signaling activation and as part of a complex with NFATC4 and STAT3, binds to the alpha-beta E4 promoter region of CRYAB and activates transcription in cardiomyocytes (PubMed:19538478). In conjunction with NFATC4, involved in embryonic heart development via maintenance of cardiomyocyte survival, proliferation and differentiation (By similarity). Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2 (By similarity). Required for thymocyte maturation during DN3 to DN4 transition and during positive selection (By similarity). Positively regulates macrophage-derived polymicrobial clearance, via binding to the promoter region and promoting transcription of NOS2 resulting in subsequent generation of nitric oxide (By similarity). Involved in Ca(2+)-mediated transcriptional responses upon Ca(2+) influx via ORAI1 CRAC channels. {ECO:0000250|UniProtKB:P97305, ECO:0000250|UniProtKB:Q12968, ECO:0000269|PubMed:19538478, ECO:0000269|PubMed:30980393}.

Rattus norvegicus (Rat)

A0A0G2JTZ2

SOX6_RAT

MSSKQATSPFACTVDGEETMTQDLTSREKEEGSDQHPASHLPLHPIMHNKPHSEELPTLVSTIQQDADWDSVLSSQQRMESENNKLCSLYSFRNTSTSPHKPDEGSREREIMNSVTFGTPERRKGSLADVVDTLKQKKLEEMTRTEQEDSSCMEKLLSKDWKEKMERLNTSELLGEIKGTPESLAEKERQLSTMITQLISLREQLLAAHDEQKKLAASQIEKQRQQMDLARQQQEQIARQQQQLLQQQHKINLLQQQIQVQGHMPPLMIPIFPHDQRTLAAAAAAQQGFLFPPGITYKPGDNYPVQFIPSTMAAAAASGLSPLQLQKGHVSHPQINPRLKGISDRLGRNLDPYEHGGGHSYNHKQIEQLYAAQLASMQVSPGAKMPSTPQPPNSAGAVSPTGIKNEKRGTSPVTQVKDETTAQPLNLSSRPKTAEPVKSPTSPTQSLFPASKTSPVNLPNKSSIPSPIGGSLGRGSSLDILSSLNSPALFGDQDTVMKAIQEARKMREQIQREQQQQPHGVDGKLSSMNSMGLSNCRNEKERTRFENLGPQLTGKSSEDGKLGPGVIDLTRPEDAEGSKAMNGSAAKLQQYYCWPTGGATVAEARVYRDARGRASSEPHIKRPMNAFMVWAKDERRKILQAFPDMHNSNISKILGSRWKSMSNQEKQPYYEEQARLSKIHLEKYPNYKYKPRPKRTCIVDGKKLRIGEYKQLMRSRRQEMRQFFTVGQQPQIPITTGTGVVYPGAITMATTTPSPQMTSDCSSTSASPEPSLPVIQSTYGMKMDGASLAGNDMINGEDEMEAYDDYEDDPKSDYSSENEAPEPVSAN

astrocyte differentiation [GO:0048708]; brain development [GO:0007420]; cardiac muscle cell differentiation [GO:0055007]; cartilage condensation [GO:0001502]; cartilage development [GO:0051216]; cell fate commitment [GO:0045165]; cell morphogenesis [GO:0000902]; cellular response to transforming growth factor beta stimulus [GO:0071560]; central nervous system development [GO:0007417]; chondrocyte differentiation [GO:0002062]; erythrocyte development [GO:0048821]; erythrocyte differentiation [GO:0030218]; gene expression [GO:0010467]; hemopoiesis [GO:0030097]; in utero embryonic development [GO:0001701]; negative regulation of cardiac muscle cell differentiation [GO:2000726]; negative regulation of DNA-templated transcription [GO:0045892]; negative regulation of transcription by RNA polymerase II [GO:0000122]; oligodendrocyte cell fate specification [GO:0021778]; oligodendrocyte differentiation [GO:0048709]; positive regulation of cartilage development [GO:0061036]; positive regulation of chondrocyte differentiation [GO:0032332]; positive regulation of DNA-templated transcription [GO:0045893]; positive regulation of mesenchymal stem cell differentiation [GO:2000741]; positive regulation of transcription by RNA polymerase II [GO:0045944]; post-embryonic development [GO:0009791]; regulation of DNA-templated transcription [GO:0006355]; regulation of gene expression [GO:0010468]; regulation of transcription by RNA polymerase II [GO:0006357]; spinal cord oligodendrocyte cell differentiation [GO:0021529]

cytoplasm [GO:0005737]; nucleus [GO:0005634]

cis-regulatory region sequence-specific DNA binding [GO:0000987]; DNA binding [GO:0003677]; DNA-binding transcription factor activity [GO:0003700]; DNA-binding transcription factor activity, RNA polymerase II-specific [GO:0000981]; DNA-binding transcription repressor activity [GO:0001217]; DNA-binding transcription repressor activity, RNA polymerase II-specific [GO:0001227]; protein homodimerization activity [GO:0042803]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]; sequence-specific DNA binding [GO:0043565]; transcription cis-regulatory region binding [GO:0000976]

PF00505;

1.10.30.10;

PTM: Sumoylation inhibits the transcriptional activity. {ECO:0000250|UniProtKB:P35712}.

SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P40645, ECO:0000255|PROSITE-ProRule:PRU00267}. Cytoplasm {ECO:0000250|UniProtKB:P40645}.

FUNCTION: Transcription factor that plays a key role in several developmental processes, including neurogenesis, chondrocytes differentiation and cartilage formation (By similarity). Specifically binds the 5'-AACAAT-3' DNA motif present in enhancers and super-enhancers and promotes expression of genes important for chondrogenesis (By similarity). Required for overt chondrogenesis when condensed prechondrocytes differentiate into early stage chondrocytes: SOX5 and SOX6 cooperatively bind with SOX9 on active enhancers and super-enhancers associated with cartilage-specific genes, and thereby potentiate SOX9's ability to transactivate (PubMed:26150426). Not involved in precartilaginous condensation, the first step in chondrogenesis, during which skeletal progenitors differentiate into prechondrocytes (By similarity). Together with SOX5, required to form and maintain a pool of highly proliferating chondroblasts between epiphyses and metaphyses, to form columnar chondroblasts, delay chondrocyte prehypertrophy but promote hypertrophy, and to delay terminal differentiation of chondrocytes on contact with ossification fronts (By similarity). Binds to the proximal promoter region of the myelin protein MPZ gene, and is thereby involved in the differentiation of oligodendroglia in the developing spinal tube (By similarity). Binds to the gene promoter of MBP and acts as a transcriptional repressor (By similarity). {ECO:0000250|UniProtKB:P40645, ECO:0000269|PubMed:26150426}.

Rattus norvegicus (Rat)

A0A0G2JUG7

IQEC1_RAT

MACRRRYLSSLETGSSLSTDRYSVEGEAPSSETGTSLDSPSAYHQGPLVPGSSLSPDHYEHTSVGAYGLYAGPGPQQRTRRPRLQHSTSVLRKQAEEEAIKRSRSLSESYELSSDLQDKQVEMLERKYGGRLVTRHAARTIQTAFRQYQMNKNFERLRSSMSENRMSRRIVLSNMRMQFSFEGPEKVHSSYFEGKQVSVTNDGSQLGALVPSECGDLSDPALKSPAPSSDFADAITELEDAFSRQVKSLAESIDDALNCRSLHSEEVPASDTARARDTEPKPGLHGMDHRKLDEMTASYSDVTLYIDEEELSPPLPLSQAGDRPSSTESDLRLRSGGAAQDYWALAHKEDKADTDTSCRSTPSLERPEPRLRVEHLPLLTIEPPSDSSVELSDRSDRSSLKRQSAYERSLGGQQGSPKHGPHGGPPKGLPREEPELRPRPPRPLESHLAINGSANRQSKSESDYSDGDNDSINSTSNSNDTINCSSESSSRDSLREQTLSKQTYHKETRNSWDSPAFSNDVIRKRHYRIGLNLFNKKPEKGIQYLIERGFVPDTPVGVAHFLLQRKGLSRQMIGEFLGNRQKQFNRDVLDCVVDEMDFSAMELDEALRKFQAHIRVQGEAQKVERLIEAFSQRYCVCNPGVVRQFRNPDTIFILAFAIILLNTDMYSPNVKPERKMKLEDFVKNLRGVDDGEDIPRETLIGIYERIRKRELKTNEDHVSQVQKVEKLIVGKKPIGSLHHGLGCVLSLPHRRLVCYCRLFEVPDPNKPQKLGLHQREIFLFNDLLVVTKIFQKKKNSVTYSFRQSFSLYGMQVLLFENQYYPNGIRLTSAVPGADIKVLINFNAPNPQDRKKFTDDLRESVAEVQEMEKHRIESELEKQKGVVRPSMSQCSSLKKESGNGTLSRACLDDSYASGEGLKRSALSSSLRDLSEAGKRGRRSSAGSLESNVEFQPFQPSQPPVLCS

actin cytoskeleton organization [GO:0030036]; dendritic spine development [GO:0060996]; positive regulation of focal adhesion disassembly [GO:0120183]; positive regulation of keratinocyte migration [GO:0051549]; positive regulation of synapse assembly [GO:0051965]; postsynaptic modulation of chemical synaptic transmission [GO:0099170]; regulation of ARF protein signal transduction [GO:0032012]; regulation of postsynaptic neurotransmitter receptor internalization [GO:0099149]

glutamatergic synapse [GO:0098978]; nucleus [GO:0005634]; postsynapse [GO:0098794]; postsynaptic density, intracellular component [GO:0099092]; Schaffer collateral - CA1 synapse [GO:0098685]; synaptic vesicle [GO:0008021]

guanyl-nucleotide exchange factor activity [GO:0005085]; lipid binding [GO:0008289]; protein kinase binding [GO:0019901]

PF16453;PF01369;

1.10.220.20;1.10.1000.11;2.30.29.30;

BRAG family

SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q6DN90}. Nucleus {ECO:0000250|UniProtKB:Q6DN90}. Postsynaptic density {ECO:0000250|UniProtKB:Q8R0S2}. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle {ECO:0000250|UniProtKB:Q8R0S2}. Note=At steady state, may be preferentially cytosolic. {ECO:0000250|UniProtKB:Q6DN90}.

FUNCTION: Guanine nucleotide exchange factor for ARF1 and ARF6. Guanine nucleotide exchange factor activity is enhanced by lipid binding. Accelerates GTP binding by ARFs of all three classes. Guanine nucleotide exchange protein for ARF6, mediating internalization of beta-1 integrin. Involved in neuronal development (By similarity). In neurons, plays a role in the control of vesicle formation by endocytoc cargo. Upon long term depression, interacts with GRIA2 and mediates the activation of ARF6 to internalize synaptic AMPAR receptors (PubMed:20547133). {ECO:0000250|UniProtKB:Q6DN90, ECO:0000250|UniProtKB:Q8R0S2, ECO:0000269|PubMed:20547133}.

Rattus norvegicus (Rat)

A0A0G2JV04

GGA3_RAT

MAEAEGESLESWLNKATNPSNRQEDWEYIIGFCDQINKELEGPQIAVRLLAHKIQSPQEWEAVQALTVLEACMKNCGRRLHNEVGKFRFLNELIKVVSPKYLGDRVSEKVKAKVIELLFSWTLALPEEAKIKDAYHMLKRQGIVQSDPPIPMDRTLIPSPPPRPKNPVFDDEEKSKLLAKLLRSKNPDDLQEANQLIKSMVKEDEARIQKVTKRLHTLEEVNNNVKLLHEMLLHYSQEFSSEADKELMKELFDRCENKRRTLFKLASETEDNDNSLGDILQASDNLSRVINSYKTIIEGQIINGEVTTSTVPDSEGNSHCGNQGALIDLAELDTPSSSSPVLAPAPAPPTSGIPILPPPPQTSGPPRSRSSSQAEAPSGPDSTNNALSLLDEELLCLGLSDPAPTAPKESAGNSPWHLFQNEPSSDLDFFSPRLVSAASCPSEGSLLPPPVSTSSLSQAPLPAAFPAPVVPASAVTHSTGSFTFSSGPAPALVPKAEPEGPEYPSSSISHRLDALDQLLEEAKVTSGLVKPVSCFSPGPTASPLLPASTPARPLLPFSTGPGSPLFQSPAFQSQGSPQKGPELSLASVHVPLESIKPSSALPVTAYDKNGFRILFHFAKECPPGRPDVLVVVVSMLNTAPLPVKSIVLQAAVPKSMKVKLQPPSGTELSPFSPIQPPAAITQVMLLANPMKEKVRLRYKLTFALGEQLSTELGEVDQFPPVEQWGNL

endocytic recycling [GO:0032456]; Golgi to plasma membrane protein transport [GO:0043001]; Golgi to plasma membrane transport [GO:0006893]; negative regulation of amyloid-beta formation [GO:1902430]; positive regulation of protein catabolic process [GO:0045732]; protein catabolic process [GO:0030163]; protein destabilization [GO:0031648]; protein localization to cell surface [GO:0034394]; protein localization to lysosome [GO:0061462]; protein targeting to lysosome [GO:0006622]; regulation of protein stability [GO:0031647]

early endosome [GO:0005769]; early endosome membrane [GO:0031901]; lysosome [GO:0005764]; protein-containing complex [GO:0032991]; recycling endosome [GO:0055037]; recycling endosome membrane [GO:0055038]; trans-Golgi network [GO:0005802]

phosphatidylinositol binding [GO:0035091]; protein-containing complex binding [GO:0044877]; small GTPase binding [GO:0031267]; ubiquitin binding [GO:0043130]

PF02883;PF03127;PF18308;PF00790;

1.20.5.170;1.20.58.160;1.25.40.90;2.60.40.1230;

GGA protein family

PTM: Phosphorylated by CK2 and dephosphorylated by PP2A (By similarity). Phosphorylation of GGA3 allows the internal DXXLL motif to bind the VHS domain and to inhibit the recognition of cargo signals. {ECO:0000250}.; PTM: Ubiquitinated. {ECO:0000250|UniProtKB:Q9NZ52}.; PTM: Proteolytically cleaved during apoptosis by CASP3. {ECO:0000250|UniProtKB:Q9NZ52}.

SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane {ECO:0000250|UniProtKB:Q9NZ52}; Peripheral membrane protein {ECO:0000250|UniProtKB:Q9NZ52}. Endosome membrane {ECO:0000250|UniProtKB:Q9NZ52}; Peripheral membrane protein {ECO:0000250|UniProtKB:Q9NZ52}. Early endosome membrane {ECO:0000269|PubMed:26446845}; Peripheral membrane protein {ECO:0000305}. Recycling endosome membrane {ECO:0000269|PubMed:26446845}; Peripheral membrane protein {ECO:0000305}.

FUNCTION: Plays a role in protein sorting and trafficking between the trans-Golgi network (TGN) and endosomes. Mediates the ARF-dependent recruitment of clathrin to the TGN and binds ubiquitinated proteins and membrane cargo molecules with a cytosolic acidic cluster-dileucine (DXXLL) motif. Mediates export of the GPCR receptor ADRA2B to the cell surface. Involved in BACE1 transport and sorting as well as regulation of BACE1 protein levels. Regulates retrograde transport of BACE1 from endosomes to the trans-Golgi network via interaction through the VHS motif and dependent of BACE1 phosphorylation. Modulates BACE1 protein levels independently of the interaction between VHS domain and DXXLL motif through recognition of ubiquitination (By similarity). Key player in a novel DXXLL-mediated endosomal sorting machinery to the recycling pathway that targets NTRK1 to the plasma membrane (PubMed:26446845). {ECO:0000250|UniProtKB:Q9NZ52, ECO:0000269|PubMed:26446845}.

Rattus norvegicus (Rat)

A0A0G2JXN2

TRI46_RAT

MAEGEDMQTFTSIMDALVRISTSMKNMEKELLCPVCQEMYKQPLVLPCTHNVCQACAREVLGQQGYIGHGGDPSSEPTSPASTPSTRSPRLSRRTLPKPDRLDRLLKSGFGTYPGRKRGALHPQTILFPCPACQGDVELGERGLSGLFRNLTLERVVERYRQSVSVGGAILCQLCKPPPLEATKGCSECRATFCNECFKLFHPWGTQKAQHEPTLPTLSFRPKGLMCPDHKEEVTHYCKTCQRLVCQLCRVRRTHSGHKITPVLSAYQALKDKLTKSLAYILGNQDTVQTQICELEETIRHTEVSGQQAKEEVSQLVRGLGAVLEEKRSSLLQAIEECQQERLSRLSAQIHEHQSLLDGSGLVGYAQEVLKETDQPCFVQAAKQLHNRIARATEALQTFRPAASSSFRHCQLDVGREMKLLTELNFLRVPEAPVIDTQRTFAYDQIFLCWRLPPHSPPAWHYTVEFRRTDVPAQPGPTRWQRREEVRGTSALLENPDTGSVYVLRVRGCNKAGYGEYSEDVHLHTPPAPVLHFFLDGRWGASRERLAISKDQRAVRSIPGLPLLLAAERLLTGCHLSVDVVLGDVAVTQGRSYWACAVDPASYLVKVGVGLESKLQESFQGAPDVISPRYDPDSGHDSGAEDAAVEALPPFAFLTIGMGKILLGSGASSNAGLTGRDGPAASCTVPLPPRLGICLDYERGRVSFLDAVSFRGLLECPLDCSGPVCPAFCFIGGGAVQLQEPVGTKPERKVTIGGFAKLD

anterograde synaptic vesicle transport [GO:0048490]; axonogenesis [GO:0007409]; microtubule bundle formation [GO:0001578]; microtubule cytoskeleton organization [GO:0000226]; negative regulation of axon extension [GO:0030517]; neuron migration [GO:0001764]; positive regulation of anterograde dense core granule transport [GO:1901953]; protein localization to axon [GO:0099612]; regulation of protein localization [GO:0032880]

axon cytoplasm [GO:1904115]; axon initial segment [GO:0043194]; cytoskeleton [GO:0005856]; main axon [GO:0044304]; proximal neuron projection [GO:1990769]

zinc ion binding [GO:0008270]

PF18568;PF00643;PF13445;

1.20.5.170;2.60.120.920;4.10.830.40;3.30.160.60;2.60.40.10;3.30.40.10;

TRIM/RBCC family

SUBCELLULAR LOCATION: Cell projection, axon {ECO:0000269|PubMed:26671463}. Cytoplasm, cytoskeleton {ECO:0000269|PubMed:26671463}. Note=Microtubule-associated. Localizes to the proximal part of the axon. {ECO:0000269|PubMed:26671463}.

FUNCTION: Microtubule-associated protein that is involved in the formation of parallel microtubule bundles linked by cross-bridges in the proximal axon. Required for the uniform orientation and maintenance of the parallel microtubule fascicles, which are important for efficient cargo delivery and trafficking in axons. Thereby also required for proper axon specification, the establishment of neuronal polarity and proper neuronal migration. {ECO:0000269|PubMed:26671463}.

Rattus norvegicus (Rat)

A0A0G2JXT6

MTMR6_RAT

MEHIRTTKVEQVKLLDRFSTNNKSLTGTLYLTATHLLFIDAHQKETWILHHHIASVEKLALTTSGCPLVIQCKNFRIVHFIVPRERDCHDIYNSLLQLSKQAKYEDLYAFSYNPKQNDTERLNGWQLIDLAAEYERMGVPNANWQLSDANREYKVCETYPRELYVPRTASRPVIVGSSNFRSKGRLPVLSYCQQGTEAAICRCSQPLSGFSARCLEDEHLLQAISKANPGNRYMYVVDTRPKLRMQSWWDTQKDIGRIIVRISSKIWNDEKIRESDEKKRLNAMANRAAGKGYENEDNYSNIRFQFVGIENIHVMRSSLQKLLEVNGSKGLSVNDFYSGLESSGWLRHIKAVLDAAIFLAKAIVVENASVLVHCSDGWDRTSQVCSLGSLLLDSYYRTMKGFMVLIEKDWISFGHKFSERCGHLDGDPKEVSPVFTQFLECVWHLTEQFPQAFEFNEAFLLQIHEHIHSCQFGNFLGNCQKEREELRLKEKTYSLWPFLLADKKKYLNPLYSSKSQRLTVLEPNTASFNFKFWRNMYHQFDRTLHPRQSVLNIIMNMNEQNKQLEEDVKDLEAKIKQCKSGILTKDLLHAVHPESPSLKTSLCLKEQSLLPVKDTLRAVEGSSPADNRYCDYTEEFSKSEPAVVSLEYGVARMTC

3.1.3.64; 3.1.3.95

endocytosis [GO:0006897]; phosphatidylinositol dephosphorylation [GO:0046856]

cytoplasm [GO:0005737]; endoplasmic reticulum [GO:0005783]; endoplasmic reticulum-Golgi intermediate compartment [GO:0005793]; nuclear envelope [GO:0005635]; perinuclear region of cytoplasm [GO:0048471]; ruffle membrane [GO:0032587]

phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity [GO:0052629]; phosphatidylinositol-3,5-bisphosphate phosphatase activity [GO:0106018]; phosphatidylinositol-3-phosphate phosphatase activity [GO:0004438]

PF06602;PF21098;

2.30.29.30;

Protein-tyrosine phosphatase family, Non-receptor class myotubularin subfamily

SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:23188820}. Endoplasmic reticulum {ECO:0000250|UniProtKB:Q9Y217}. Cell projection, ruffle membrane {ECO:0000250|UniProtKB:Q8VE11}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Endoplasmic reticulum-Golgi intermediate compartment {ECO:0000269|PubMed:23188820}. Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:Q9Y217}. Note=Localizes to ruffles during EGF-induced macropinocytosis (By similarity). Colocalizes with MTMR9 to the perinuclear region (By similarity). Partially localizes to the endoplasmic reticulum (By similarity). Co-localizes with RAB1B to the endoplasmic reticulum-Golgi intermediate compartment and to the peri-Golgi region (PubMed:23188820). {ECO:0000250|UniProtKB:Q8VE11, ECO:0000250|UniProtKB:Q9Y217, ECO:0000269|PubMed:23188820}.

CATALYTIC ACTIVITY: Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,5-bisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-5-phosphate) + phosphate; Xref=Rhea:RHEA:39019, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57795, ChEBI:CHEBI:57923; EC=3.1.3.95; Evidence={ECO:0000250|UniProtKB:Q9Y217}; CATALYTIC ACTIVITY: Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3-phosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + phosphate; Xref=Rhea:RHEA:12316, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57880, ChEBI:CHEBI:58088; EC=3.1.3.64; Evidence={ECO:0000250|UniProtKB:Q9Y217}; CATALYTIC ACTIVITY: Reaction=1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3,5-bisphosphate) + H2O = 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-5-phosphate) + phosphate; Xref=Rhea:RHEA:45632, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:78911, ChEBI:CHEBI:85342; Evidence={ECO:0000250|UniProtKB:Q9Y217}; CATALYTIC ACTIVITY: Reaction=1,2-dioctanoyl-sn-glycero-3-phospho-(1-D-myo-inositol-3-phosphate) + H2O = 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol) + phosphate; Xref=Rhea:RHEA:42328, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:65221, ChEBI:CHEBI:78934; Evidence={ECO:0000250|UniProtKB:Q9Y217};

FUNCTION: Phosphatase that acts on lipids with a phosphoinositol headgroup. Dephosphorylates phosphatidylinositol 3-phosphate (PtdIns(3)P) and phosphatidylinositol 3,5-bisphosphate. Binds with high affinity to phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) but also to phosphatidylinositol 3-phosphate (PtdIns(3)P), phosphatidylinositol 4-phosphate (PtdIns(4)P), and phosphatidylinositol 5-phosphate (PtdIns(5)P), phosphatidic acid and phosphatidylserine (By similarity). Negatively regulates ER-Golgi protein transport (PubMed:23188820). Probably in association with MTMR9, plays a role in the late stages of macropinocytosis by dephosphorylating phosphatidylinositol 3-phosphate in membrane ruffles. Acts as a negative regulator of KCNN4/KCa3.1 channel activity in CD4(+) T-cells possibly by decreasing intracellular levels of phosphatidylinositol 3-phosphate. Negatively regulates proliferation of reactivated CD4(+) T-cells. In complex with MTMR9, negatively regulates DNA damage-induced apoptosis. The formation of the MTMR6-MTMR9 complex stabilizes both MTMR6 and MTMR9 protein levels (By similarity). {ECO:0000250|UniProtKB:Q9Y217, ECO:0000269|PubMed:23188820}.

Rattus norvegicus (Rat)

A0A0G2JZ79

SIR1_RAT

MIGTDPRTILKDLLPETIPPPELDDMTLWQIVINILSEPPKRKKRKDINTIEDAVKLLQECKKIIVLTGAGVSVSCGIPDFRSRDGIYARLAVDFPDLPDPQAMFDIEYFRKDPRPFFKFAKEIYPGQFQPSLCHKFIALSDKEGKLLRNYTQNIDTLEQVAGIQRIIQCHGSFATASCLICKYKVDCEAVRGDIFNQVVPRCPRCPADEPLAIMKPEIVFFGENLPEQFHRAMKYDKDEVDLLIVIGSSLKVRPVALIPSSIPHEVPQILINREPLPHLHFDVELLGDCDVIINELCHRLGGEYAKLCCNPVKLSEITEKPPRTQKELVHLSELPPTPLHISEDSSSPERTVPQDSSVIATLVDQTIKNKVDDLEVSEPKSCVEEKSQEVQTYRNVESINVENPDFKAVGSSTGDKNERTSVAETVRKCWPNRLAKEQISKRLDGNQYLFVPPNRYIFHGAEVYSDSEDDALSSSSCGSNSDSGTCQSPSLEEPLEDESEIEEFYNGLEDDADRPECAGGSGADGGDQEAVNEAIAMKQELTDVNCTPDKSEHY

2.3.1.-; 2.3.1.286

COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250|UniProtKB:Q8IXJ6}; Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q8IXJ6};

angiogenesis [GO:0001525]; behavioral response to starvation [GO:0042595]; cardiac muscle cell apoptotic process [GO:0010659]; cellular response to amyloid-beta [GO:1904646]; cellular response to antibiotic [GO:0071236]; cellular response to curcumin [GO:1904644]; cellular response to glucose starvation [GO:0042149]; cellular response to hydrogen peroxide [GO:0070301]; cellular response to hypoxia [GO:0071456]; cellular response to ionizing radiation [GO:0071479]; cellular response to leukemia inhibitory factor [GO:1990830]; cellular response to organic cyclic compound [GO:0071407]; cellular response to resveratrol [GO:1904639]; cellular response to rotenone [GO:1904648]; cellular response to starvation [GO:0009267]; cellular response to tumor necrosis factor [GO:0071356]; cellular response to vitamin B3 [GO:0071303]; cholesterol homeostasis [GO:0042632]; chromatin organization [GO:0006325]; circadian regulation of gene expression [GO:0032922]; circadian rhythm [GO:0007623]; DNA damage response [GO:0006974]; DNA repair-dependent chromatin remodeling [GO:0140861]; DNA synthesis involved in DNA repair [GO:0000731]; energy homeostasis [GO:0097009]; fatty acid homeostasis [GO:0055089]; heterochromatin formation [GO:0031507]; intracellular glucose homeostasis [GO:0001678]; intracellular triglyceride homeostasis [GO:0035356]; intrinsic apoptotic signaling pathway in response to DNA damage [GO:0008630]; intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator [GO:0042771]; leptin-mediated signaling pathway [GO:0033210]; macrophage differentiation [GO:0030225]; maintenance of nucleus location [GO:0051658]; muscle organ development [GO:0007517]; negative regulation of androgen receptor signaling pathway [GO:0060766]; negative regulation of apoptotic process [GO:0043066]; negative regulation of canonical NF-kappaB signal transduction [GO:0043124]; negative regulation of cardiac muscle cell apoptotic process [GO:0010667]; negative regulation of cell cycle [GO:0045786]; negative regulation of cellular response to testosterone stimulus [GO:2000655]; negative regulation of cellular senescence [GO:2000773]; negative regulation of DNA damage response, signal transduction by p53 class mediator [GO:0043518]; negative regulation of DNA-templated transcription [GO:0045892]; negative regulation of fat cell differentiation [GO:0045599]; negative regulation of fibroblast apoptotic process [GO:2000270]; negative regulation of gene expression [GO:0010629]; negative regulation of growth hormone secretion [GO:0060125]; negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator [GO:1902166]; negative regulation of neuron apoptotic process [GO:0043524]; negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway [GO:1902176]; negative regulation of peptidyl-lysine acetylation [GO:2000757]; negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction [GO:0051898]; negative regulation of phosphorylation [GO:0042326]; negative regulation of prostaglandin biosynthetic process [GO:0031393]; negative regulation of protein acetylation [GO:1901984]; negative regulation of protein localization to nucleus [GO:1900181]; negative regulation of reactive oxygen species biosynthetic process [GO:1903427]; negative regulation of TOR signaling [GO:0032007]; negative regulation of transcription by RNA polymerase II [GO:0000122]; negative regulation of transforming growth factor beta receptor signaling pathway [GO:0030512]; negative regulation of triglyceride biosynthetic process [GO:0010868]; negative regulation of tumor necrosis factor production [GO:0032720]; neuron apoptotic process [GO:0051402]; ovulation from ovarian follicle [GO:0001542]; positive regulation of adaptive immune response [GO:0002821]; positive regulation of adipose tissue development [GO:1904179]; positive regulation of angiogenesis [GO:0045766]; positive regulation of apoptotic process [GO:0043065]; positive regulation of blood vessel endothelial cell migration [GO:0043536]; positive regulation of cell growth involved in cardiac muscle cell development [GO:0061051]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of cellular senescence [GO:2000774]; positive regulation of cholesterol efflux [GO:0010875]; positive regulation of DNA repair [GO:0045739]; positive regulation of double-strand break repair [GO:2000781]; positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway [GO:1902237]; positive regulation of endothelial cell proliferation [GO:0001938]; positive regulation of gluconeogenesis [GO:0045722]; positive regulation of heart rate [GO:0010460]; positive regulation of insulin receptor signaling pathway [GO:0046628]; positive regulation of insulin secretion involved in cellular response to glucose stimulus [GO:0035774]; positive regulation of macroautophagy [GO:0016239]; positive regulation of macrophage apoptotic process [GO:2000111]; positive regulation of macrophage cytokine production [GO:0060907]; positive regulation of MHC class II biosynthetic process [GO:0045348]; positive regulation of neuron projection development [GO:0010976]; positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction [GO:0051897]; positive regulation of protein deacetylation [GO:0090312]; positive regulation of protein phosphorylation [GO:0001934]; positive regulation of skeletal muscle cell proliferation [GO:0014858]; positive regulation of smooth muscle cell differentiation [GO:0051152]; positive regulation of thyroid-stimulating hormone secretion [GO:2000614]; positive regulation of transcription by RNA polymerase II [GO:0045944]; proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161]; protein depropionylation [GO:0106230]; protein destabilization [GO:0031648]; protein ubiquitination [GO:0016567]; pyrimidine dimer repair by nucleotide-excision repair [GO:0000720]; rDNA heterochromatin formation [GO:0000183]; regulation of apoptotic process [GO:0042981]; regulation of bile acid biosynthetic process [GO:0070857]; regulation of brown fat cell differentiation [GO:0090335]; regulation of cell population proliferation [GO:0042127]; regulation of centrosome duplication [GO:0010824]; regulation of glucose metabolic process [GO:0010906]; regulation of lipid storage [GO:0010883]; regulation of mitotic cell cycle [GO:0007346]; regulation of peroxisome proliferator activated receptor signaling pathway [GO:0035358]; regulation of smooth muscle cell apoptotic process [GO:0034391]; regulation of transcription by glucose [GO:0046015]; response to cocaine [GO:0042220]; response to ethanol [GO:0045471]; response to fluoride [GO:1902617]; response to hydrogen peroxide [GO:0042542]; response to insulin [GO:0032868]; response to kainic acid [GO:1904373]; response to leptin [GO:0044321]; response to mycotoxin [GO:0010046]; response to nutrient levels [GO:0031667]; response to oxidative stress [GO:0006979]; response to resveratrol [GO:1904638]; single strand break repair [GO:0000012]; spermatogenesis [GO:0007283]; stress-induced premature senescence [GO:0090400]; transforming growth factor beta receptor signaling pathway [GO:0007179]; triglyceride mobilization [GO:0006642]; UV-damage excision repair [GO:0070914]; vasodilation [GO:0042311]; white fat cell differentiation [GO:0050872]

axon [GO:0030424]; chromatin [GO:0000785]; chromatin silencing complex [GO:0005677]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; eNoSc complex [GO:0061773]; ESC/E(Z) complex [GO:0035098]; euchromatin [GO:0000791]; growth cone [GO:0030426]; heterochromatin [GO:0000792]; mitochondrion [GO:0005739]; nuclear envelope [GO:0005635]; nuclear inner membrane [GO:0005637]; nucleolus [GO:0005730]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; PML body [GO:0016605]; protein-containing complex [GO:0032991]; rDNA heterochromatin [GO:0033553]

bHLH transcription factor binding [GO:0043425]; deacetylase activity [GO:0019213]; DNA-binding transcription factor binding [GO:0140297]; enzyme binding [GO:0019899]; histone binding [GO:0042393]; histone deacetylase activity [GO:0004407]; histone H3K deacetylase activity [GO:0141050]; histone H4K12 deacetylase activity [GO:0140937]; HLH domain binding [GO:0043398]; identical protein binding [GO:0042802]; keratin filament binding [GO:1990254]; lysine-acetylated histone binding [GO:0070577]; metal ion binding [GO:0046872]; mitogen-activated protein kinase binding [GO:0051019]; NAD+ binding [GO:0070403]; NAD-dependent histone deacetylase activity [GO:0017136]; NAD-dependent histone decrotonylase activity [GO:0160012]; NAD-dependent histone H3K14 deacetylase activity [GO:0032041]; NAD-dependent histone H3K9 deacetylase activity [GO:0046969]; NAD-dependent histone H4K16 deacetylase activity [GO:0046970]; NAD-dependent protein deacetylase activity [GO:0034979]; nuclear receptor binding [GO:0016922]; p53 binding [GO:0002039]; promoter-specific chromatin binding [GO:1990841]; protein domain specific binding [GO:0019904]; protein kinase B binding [GO:0043422]; protein lysine deacetylase activity [GO:0033558]; protein-propionyllysine depropionylase activity [GO:0106231]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]; transcription coactivator activity [GO:0003713]; transcription corepressor activity [GO:0003714]

PF02146;

3.30.1600.10;3.40.50.1220;

Sirtuin family, Class I subfamily

PTM: Methylated on multiple lysine residues; methylation is enhanced after DNA damage and is dispensable for deacetylase activity toward p53/TP53. {ECO:0000250|UniProtKB:Q96EB6}.; PTM: Phosphorylated. Phosphorylated by STK4/MST1, resulting in inhibition of SIRT1-mediated p53/TP53 deacetylation. Phosphorylation by MAPK8/JNK1 at Thr-338 leads to increased nuclear localization and enzymatic activity. Phosphorylation at Thr-338 by DYRK1A and DYRK3 activates deacetylase activity and promotes cell survival. Phosphorylated by CaMK2, leading to increased p53/TP53 and NF-kappa-B p65/RELA deacetylation activity (By similarity). {ECO:0000250|UniProtKB:Q923E4, ECO:0000250|UniProtKB:Q96EB6}.; PTM: S-nitrosylated by GAPDH, leading to inhibit the NAD-dependent protein deacetylase activity. {ECO:0000250|UniProtKB:Q923E4}.; PTM: Acetylated at various Lys residues. Deacetylated via an autocatalytic mechanism. Autodeacetylation at Lys-46 promotes its protein deacetylase activity. {ECO:0000250|UniProtKB:Q923E4}.; PTM: Ubiquitinated; leading to degradation. Deubiquitinated by USP22; leading to stabilization. {ECO:0000250|UniProtKB:Q96EB6}.

SUBCELLULAR LOCATION: Nucleus, PML body {ECO:0000250|UniProtKB:Q96EB6}. Cytoplasm {ECO:0000250|UniProtKB:Q96EB6}. Nucleus {ECO:0000250|UniProtKB:Q96EB6}. Note=Recruited to the nuclear bodies via its interaction with PML. Colocalized with APEX1 in the nucleus. May be found in nucleolus, nuclear euchromatin, heterochromatin and inner membrane (By similarity). Shuttles between nucleus and cytoplasm (By similarity). Colocalizes in the nucleus with XBP1 isoform 2 (By similarity). {ECO:0000250|UniProtKB:Q923E4, ECO:0000250|UniProtKB:Q96EB6}.

CATALYTIC ACTIVITY: Reaction=H2O + N(6)-acetyl-L-lysyl-[protein] + NAD(+) = 2''-O-acetyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide; Xref=Rhea:RHEA:43636, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:10731, ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969, ChEBI:CHEBI:57540, ChEBI:CHEBI:61930, ChEBI:CHEBI:83767; EC=2.3.1.286; Evidence={ECO:0000250|UniProtKB:Q96EB6, ECO:0000255|PROSITE-ProRule:PRU00236}; CATALYTIC ACTIVITY: Reaction=H2O + N(6)-propanoyl-L-lysyl-[protein] + NAD(+) = 3''-O-propanoyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide; Xref=Rhea:RHEA:23500, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:13758, ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969, ChEBI:CHEBI:57540, ChEBI:CHEBI:138019, ChEBI:CHEBI:145015; Evidence={ECO:0000250|UniProtKB:Q923E4}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23501; Evidence={ECO:0000250|UniProtKB:Q923E4}; CATALYTIC ACTIVITY: Reaction=H2O + N(6)-(2E)-butenoyl-L-lysyl-[protein] + NAD(+) = 2''-O-(2E)-but-2-enoyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide; Xref=Rhea:RHEA:69332, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:13707, ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969, ChEBI:CHEBI:57540, ChEBI:CHEBI:137954, ChEBI:CHEBI:183235; Evidence={ECO:0000250|UniProtKB:Q96EB6}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69333; Evidence={ECO:0000250|UniProtKB:Q96EB6};

FUNCTION: NAD-dependent protein deacetylase that links transcriptional regulation directly to intracellular energetics and participates in the coordination of several separated cellular functions such as cell cycle, response to DNA damage, metabolism, apoptosis and autophagy. Can modulate chromatin function through deacetylation of histones and can promote alterations in the methylation of histones and DNA, leading to transcriptional repression. Deacetylates a broad range of transcription factors and coregulators, thereby regulating target gene expression positively and negatively. Serves as a sensor of the cytosolic ratio of NAD(+)/NADH which is altered by glucose deprivation and metabolic changes associated with caloric restriction. Is essential in skeletal muscle cell differentiation and in response to low nutrients mediates the inhibitory effect on skeletal myoblast differentiation which also involves 5'-AMP-activated protein kinase (AMPK) and nicotinamide phosphoribosyltransferase (NAMPT). Component of the eNoSC (energy-dependent nucleolar silencing) complex, a complex that mediates silencing of rDNA in response to intracellular energy status and acts by recruiting histone-modifying enzymes. The eNoSC complex is able to sense the energy status of cell: upon glucose starvation, elevation of NAD(+)/NADP(+) ratio activates SIRT1, leading to histone H3 deacetylation followed by dimethylation of H3 at 'Lys-9' (H3K9me2) by SUV39H1 and the formation of silent chromatin in the rDNA locus. Deacetylates 'Lys-266' of SUV39H1, leading to its activation. Inhibits skeletal muscle differentiation by deacetylating PCAF and MYOD1. Deacetylates H2A and 'Lys-26' of H1-4. Deacetylates 'Lys-16' of histone H4 (in vitro). Involved in NR0B2/SHP corepression function through chromatin remodeling: Recruited to LRH1 target gene promoters by NR0B2/SHP thereby stimulating histone H3 and H4 deacetylation leading to transcriptional repression. Proposed to contribute to genomic integrity via positive regulation of telomere length; however, reports on localization to pericentromeric heterochromatin are conflicting. Proposed to play a role in constitutive heterochromatin (CH) formation and/or maintenance through regulation of the available pool of nuclear SUV39H1. Upon oxidative/metabolic stress decreases SUV39H1 degradation by inhibiting SUV39H1 polyubiquitination by MDM2. This increase in SUV39H1 levels enhances SUV39H1 turnover in CH, which in turn seems to accelerate renewal of the heterochromatin which correlates with greater genomic integrity during stress response. Deacetylates 'Lys-382' of p53/TP53 and impairs its ability to induce transcription-dependent proapoptotic program and modulate cell senescence. Deacetylates TAF1B and thereby represses rDNA transcription by the RNA polymerase I. Deacetylates MYC, promotes the association of MYC with MAX and decreases MYC stability leading to compromised transformational capability. Deacetylates FOXO3 in response to oxidative stress thereby increasing its ability to induce cell cycle arrest and resistance to oxidative stress but inhibiting FOXO3-mediated induction of apoptosis transcriptional activity; also leading to FOXO3 ubiquitination and protesomal degradation. Appears to have a similar effect on MLLT7/FOXO4 in regulation of transcriptional activity and apoptosis. Deacetylates DNMT1; thereby impairs DNMT1 methyltransferase-independent transcription repressor activity, modulates DNMT1 cell cycle regulatory function and DNMT1-mediated gene silencing. Deacetylates RELA/NF-kappa-B p65 thereby inhibiting its transactivating potential and augments apoptosis in response to TNF-alpha. Deacetylates HIF1A, KAT5/TIP60, RB1 and HIC1. Deacetylates FOXO1 resulting in its nuclear retention and enhancement of its transcriptional activity leading to increased gluconeogenesis in liver. Inhibits E2F1 transcriptional activity and apoptotic function, possibly by deacetylation. Involved in HES1- and HEY2-mediated transcriptional repression. In cooperation with MYCN seems to be involved in transcriptional repression of DUSP6/MAPK3 leading to MYCN stabilization by phosphorylation at 'Ser-62'. Deacetylates MEF2D. Required for antagonist-mediated transcription suppression of AR-dependent genes which may be linked to local deacetylation of histone H3. Represses HNF1A-mediated transcription. Required for the repression of ESRRG by CREBZF. Deacetylates NR1H3 AND NR1H2 and deacetylation of NR1H3 at 'Lys-434' positively regulates transcription of NR1H3:RXR target genes, promotes NR1H3 proteasomal degradation and results in cholesterol efflux; a promoter clearing mechanism after reach round of transcription is proposed. Involved in lipid metabolism: deacetylates LPIN1, thereby inhibiting diacylglycerol synthesis. Implicated in regulation of adipogenesis and fat mobilization in white adipocytes by repression of PPARG which probably involves association with NCOR1 and SMRT/NCOR2. Deacetylates p300/EP300 and PRMT1. Deacetylates ACSS2 leading to its activation, and HMGCS1 deacetylation. Involved in liver and muscle metabolism. Through deacetylation and activation of PPARGC1A is required to activate fatty acid oxidation in skeletal muscle under low-glucose conditions and is involved in glucose homeostasis. Involved in regulation of PPARA and fatty acid beta-oxidation in liver. Involved in positive regulation of insulin secretion in pancreatic beta cells in response to glucose; the function seems to imply transcriptional repression of UCP2. Proposed to deacetylate IRS2 thereby facilitating its insulin-induced tyrosine phosphorylation. Deacetylates SREBF1 isoform SREBP-1C thereby decreasing its stability and transactivation in lipogenic gene expression. Involved in DNA damage response by repressing genes which are involved in DNA repair, such as XPC and TP73, deacetylating XRCC6/Ku70, and facilitating recruitment of additional factors to sites of damaged DNA, such as SIRT1-deacetylated NBN can recruit ATM to initiate DNA repair and SIRT1-deacetylated XPA interacts with RPA2. Also involved in DNA repair of DNA double-strand breaks by homologous recombination and specifically single-strand annealing independently of XRCC6/Ku70 and NBN. Promotes DNA double-strand breaks by mediating deacetylation of SIRT6. Transcriptional suppression of XPC probably involves an E2F4:RBL2 suppressor complex and protein kinase B (AKT) signaling. Transcriptional suppression of TP73 probably involves E2F4 and PCAF. Deacetylates WRN thereby regulating its helicase and exonuclease activities and regulates WRN nuclear translocation in response to DNA damage. Deacetylates APEX1 at 'Lys-6' and 'Lys-7' and stimulates cellular AP endonuclease activity by promoting the association of APEX1 to XRCC1. Catalyzes deacetylation of ERCC4/XPF, thereby impairing interaction with ERCC1 and nucleotide excision repair (NER). Increases p53/TP53-mediated transcription-independent apoptosis by blocking nuclear translocation of cytoplasmic p53/TP53 and probably redirecting it to mitochondria. Deacetylates XRCC6/Ku70 at 'Lys-539' and 'Lys-542' causing it to sequester BAX away from mitochondria thereby inhibiting stress-induced apoptosis. Is involved in autophagy, presumably by deacetylating ATG5, ATG7 and MAP1LC3B/ATG8. Deacetylates AKT1 which leads to enhanced binding of AKT1 and PDK1 to PIP3 and promotes their activation. Proposed to play role in regulation of STK11/LBK1-dependent AMPK signaling pathways implicated in cellular senescence which seems to involve the regulation of the acetylation status of STK11/LBK1. Can deacetylate STK11/LBK1 and thereby increase its activity, cytoplasmic localization and association with STRAD; however, the relevance of such activity in normal cells is unclear. In endothelial cells is shown to inhibit STK11/LBK1 activity and to promote its degradation. Deacetylates SMAD7 at 'Lys-64' and 'Lys-70' thereby promoting its degradation. Deacetylates CIITA and augments its MHC class II transactivation and contributes to its stability. Deacetylates MECOM/EVI1. Deacetylates PML at 'Lys-487' and this deacetylation promotes PML control of PER2 nuclear localization. During the neurogenic transition, represses selective NOTCH1-target genes through histone deacetylation in a BCL6-dependent manner and leading to neuronal differentiation. Regulates the circadian expression of several core clock genes, including BMAL1, RORC, PER2 and CRY1 and plays a critical role in maintaining a controlled rhythmicity in histone acetylation, thereby contributing to circadian chromatin remodeling. Deacetylates BMAL1 and histones at the circadian gene promoters in order to facilitate repression by inhibitory components of the circadian oscillator. Deacetylates PER2, facilitating its ubiquitination and degradation by the proteasome. Protects cardiomyocytes against palmitate-induced apoptosis. Deacetylates XBP1 isoform 2; deacetylation decreases protein stability of XBP1 isoform 2 and inhibits its transcriptional activity. Deacetylates PCK1 and directs its activity toward phosphoenolpyruvate production promoting gluconeogenesis. Involved in the CCAR2-mediated regulation of PCK1 and NR1D1. Deacetylates CTNB1 at 'Lys-49'. In POMC (pro-opiomelanocortin) neurons, required for leptin-induced activation of PI3K signaling. In addition to protein deacetylase activity, also acts as a protein-lysine deacylase by mediating protein depropionylation and decrotonylation. Mediates depropionylation of Osterix (SP7). Catalyzes decrotonylation of histones; it however does not represent a major histone decrotonylase. Deacetylates SOX9; promoting SOX9 nuclear localization and transactivation activity. Involved in the regulation of centrosome duplication. Deacetylates CENATAC in G1 phase, allowing for SASS6 accumulation on the centrosome and subsequent procentriole assembly (By similarity). Deacetylates NDC80/HEC1 (By similarity). {ECO:0000250|UniProtKB:Q923E4, ECO:0000250|UniProtKB:Q96EB6}.

Rattus norvegicus (Rat)

A0A0G2K047

ACSS3_RAT

MKPSWLQCRKVTGAGTLGAPLPGSPSVRGAGVARRALVAGFGGRGCRALTTSSGGGEYKTHFAASVADPERFWGKAAEQISWYKPWTKTLENRYPPSTSWFVEGMLNICYNAIDRHIENGQGDKIAIIYDSPVTDTKATISYKEVLEQVSKLAGVLVKQGVKKGDTVVIYMPMIPQAIYAMLACARIGAIHSLIFGGFASKELSTRIDHVKPKVVVTASFGIEPGRKVEYMPLLEEALRIGQHKPDRLLIYNRPNMEKVPLMSGRDLDWEEEMAKAQSHDCVPVLSEHPLYILYTSGTTGLPKGVVRPTGGYAVMLNWTMSSIYGLKPGEVWWAASDLGWVVGHSYICYGPLLHGNTTVLYEGKPVGTPDAGAYFRVLAEHGVAALFTAPTAIRAIRQQDPGAALGKQYSLTRFKTLFVAGERCDVETLEWSKKVFRVPVLDHWWQTETGSPITASCIGLGNSKTPPPGQAGKCVPGYNVMILDDNMQKLKARSLGNIVVKLPLPPGAFSGLWKNQEAFKHLYFEKFPGYYDTMDAGYMDEEGYLYVMSRVDDVINVAGHRISAGAIEESVLSHGTVTDCAVVGKEDPLKGHVPLALCVLKKDVNATEEQVLEEIVKHVRQSIGPVAAFRNAVFVKQLPKTRSGKIPRSTLSALVNGKPYKVTPTIEDPSIFGHIEEVLKQAL

6.2.1.1; 6.2.1.17

lipid metabolic process [GO:0006629]

mitochondrial matrix [GO:0005759]

acetate-CoA ligase activity [GO:0003987]; ATP binding [GO:0005524]; butyrate-CoA ligase activity [GO:0047760]; propionate-CoA ligase activity [GO:0050218]

PF16177;PF00501;PF13193;

3.30.300.30;3.40.50.12780;

ATP-dependent AMP-binding enzyme family

SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000269|PubMed:28003429}.

CATALYTIC ACTIVITY: Reaction=acetate + ATP + CoA = acetyl-CoA + AMP + diphosphate; Xref=Rhea:RHEA:23176, ChEBI:CHEBI:30089, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:456215; EC=6.2.1.1; Evidence={ECO:0000269|PubMed:28003429}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23177; Evidence={ECO:0000305|PubMed:28003429}; CATALYTIC ACTIVITY: Reaction=ATP + CoA + propanoate = AMP + diphosphate + propanoyl-CoA; Xref=Rhea:RHEA:20373, ChEBI:CHEBI:17272, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:57392, ChEBI:CHEBI:456215; EC=6.2.1.17; Evidence={ECO:0000269|PubMed:28003429}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20374; Evidence={ECO:0000305|PubMed:28003429}; CATALYTIC ACTIVITY: Reaction=ATP + butanoate + CoA = AMP + butanoyl-CoA + diphosphate; Xref=Rhea:RHEA:46172, ChEBI:CHEBI:17968, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:57371, ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:28003429}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46173; Evidence={ECO:0000305|PubMed:28003429};

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=5.4 mM for acetate {ECO:0000269|PubMed:28003429}; KM=3.7 mM for butyrate {ECO:0000269|PubMed:28003429}; KM=0.19 mM for propionate {ECO:0000269|PubMed:28003429};

FUNCTION: Catalyzes the synthesis of acetyl-CoA from short-chain fatty acids (PubMed:28003429). Propionate is the preferred substrate but can also utilize acetate and butyrate with a much lower affinity (PubMed:28003429). {ECO:0000269|PubMed:28003429}.

Rattus norvegicus (Rat)

A0A0G2K1Q8

ABCA3_RAT

MVVLRQLRLLLWKNYTLKKRKVLVTVLELFLPLLFSGILIWLRLKIQSENVPNATVYPDQHIQELPLFFSFPPPGGSWELAYVPSHSDAARTITEAVRREFMIKMRVHGFSSEKDFEDYVRYDNHSSNVLAAVVFEHTFNHSKDPLPLAVRYHLRFSYTRRNYMWTQTGNLFLKETEGWHTASLFPLFPSPGPREPSSPDGGEPGYIREGFLAVQHAVDKAIMHYHANASAHQLFQKLTVITKRFPFPPYISDPFLIAIQYQLPLLLMLSFTYTSLTIIRAVVQEKEKKLKEYMRMMGLSSWLHWSAWFLMFLLFSLIVVSFMTLLFCVKVKKDIAVLSNSDPSLVLAFLLCFAISSISFSFMVSTFFSKANMAATVGGFLYFFTYTPYFFVAPRYNWMTLSQKLLSCLLSNVAMAMGAQLIGKFEAKGTGIQWCDLLNPVNVDDDFCFGQVLGMLLLDSVLYGLVTWYVEAVFPGQFGVPQPWYFFLMPSYWCGNPRTVVGKEEEGGDPEKAFRTEYFEAEPEDLAAGIKIKHLSKVFQVGNKDKMGIRDLTLNLYEGQITVLLGHNGAGKTTTMSMLTGLFPPTSGHAYIRGYEISQDMVQIRKSLGLCPQHDVLFDNLTVAEHLYFYAQLKGLSVQKCPEEVKQMLHTLGLEDKRDSRSKFLSGGMKRKLAIGIALIAGSKVLMLDEPTSGMDAVSRRAIWDLLQQQKSDRTVLLTTHFMDEADLLGDRIAILAKGELQCCGSSLFLKQKYGAGYHMTLVKEPHCNPEGISQLVHHHVPNAMLESHAGAELSFILPKESTHRFESLFAKLEKKQKELGIASFGASVTTMEEVFLRVGKLVDTSMDIQAIQLPALQYQHERRASDWALDSNLCGVMDPTNGIGALIEEEEVLVKLNTGLALHCQQFWAMFLKKAAYSWREWRMVAAQILVPVTCLTLALLAINYTSEIFDDPPLKLSLNEYGTTVVPFSVPGTSRLGQQLSEHLRDMLQAERQEPREVLGDLEEFLVFRASVEGGGFNERCLVATSFKDSGERTVVTALFNNQAYHSPATALAIVDNLLFKLLCGPRASIEISNYPQPRSTLQVAKDQFNEGRKGFDIALNLLIAMAFLASTFSILAVSERAVQAKHVQFVSGVHVATFWLSALLWDLISFLVPSLLLLVVFRAFDVHAFTRDGHMADLLLLLMLYGWAIIPLMYLLSFFFSAASTAYTRLTIFNILSGIATFIVVTIMRIPAVKLEELSRTLDHVFLVLPNHCLGMAVSNFYENYETRRYCTSSEVATHYCKKYNIQYQENFYAWSTPGIGKFVTSMAASGGIYLTLLFLIETNLLWRLRTFVCAFRRRWTLAELQNRTSVLPEDQDVADERSRVLVPSLDSMLDTPLIINELSKVYDQRAPLLAVDRISLAVQKGECFGLLGFNGAGKTTTFKMLTGEETITSGDAFVGGYSISSDIGKVRQRMGYCPQFDALLDHMTGREMLVMYARLRGIPERLIDACVENTLRGLLLEPHANKLVKTYSGGNKRKLSTGIALIGEPAVIFLDEPSTGMDPVARRLLWDTVARARESGKAIVITSHSMEECEALCTRLAIMVQGQFKCLGSPQHLKSKFGSGYSLQAKVRSEGKQEVLEEFKAFVDLTFPGSVLEDEHQDMVHYHLPGCDLSWAKVFGILEKAKEKYGVDDYSVSQISLEQVFLSFAHLQPPTTEDGR

7.6.2.1; 7.6.2.2

lipid transport [GO:0006869]; lung development [GO:0030324]; organelle assembly [GO:0070925]; phosphatidylcholine metabolic process [GO:0046470]; phosphatidylglycerol metabolic process [GO:0046471]; phospholipid homeostasis [GO:0055091]; phospholipid transport [GO:0015914]; positive regulation of cholesterol efflux [GO:0010875]; positive regulation of phospholipid efflux [GO:1902995]; positive regulation of phospholipid transport [GO:2001140]; positive regulation of protein homooligomerization [GO:0032464]; regulation of lipid biosynthetic process [GO:0046890]; regulation of lipid transport [GO:0032368]; regulation of phosphatidylcholine metabolic process [GO:0150172]; response to glucocorticoid [GO:0051384]; surfactant homeostasis [GO:0043129]; xenobiotic export from cell [GO:0046618]; xenobiotic transmembrane transport [GO:0006855]; xenobiotic transport [GO:0042908]

alveolar lamellar body [GO:0097208]; alveolar lamellar body membrane [GO:0097233]; cytoplasmic vesicle membrane [GO:0030659]; intracellular membrane-bounded organelle [GO:0043231]; lamellar body [GO:0042599]; lamellar body membrane [GO:0097232]; late endosome [GO:0005770]; lysosomal membrane [GO:0005765]; multivesicular body membrane [GO:0032585]; plasma membrane [GO:0005886]

ABC-type xenobiotic transporter activity [GO:0008559]; ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; ATPase-coupled transmembrane transporter activity [GO:0042626]; lipid transporter activity [GO:0005319]; phosphatidylcholine flippase activity [GO:0140345]; phosphatidylcholine transfer activity [GO:0120019]

PF12698;PF00005;

3.40.50.300;

PTM: N-glycosylated. Localization at intracellular vesicles is accompanied by processing of oligosaccharide from high mannose type to complex type. N-linked glycosylation at Asn-124 and Asn-140 is required for stability and efficient anterograde trafficking and prevents from proteasomal degradation. {ECO:0000250|UniProtKB:Q99758}.; PTM: Proteolytically cleaved by CTSL and to a lower extent by CTSB within multivesicular bodies (MVB) and lamellar bodies (LB) leading to a mature form of 150 kDa. {ECO:0000250|UniProtKB:Q99758}.

SUBCELLULAR LOCATION: Endosome, multivesicular body membrane {ECO:0000250|UniProtKB:Q99758}; Multi-pass membrane protein {ECO:0000250|UniProtKB:Q99758}. Cytoplasmic vesicle membrane {ECO:0000250|UniProtKB:Q99758}. Late endosome membrane {ECO:0000250|UniProtKB:Q99758}. Lysosome membrane {ECO:0000250|UniProtKB:Q99758}. Note=Localized in the limiting membrane of lamellar bodies in lung alveolar type II cells. Trafficks via the Golgi, sorting vesicles (SVs) and late endosome/multivesicular body network directly to the outer membrane of lamellar bodies in AT2 lung epithelial cells or to lysosomes and lysosomal-related organelles (LROs) in other cells where undergoes proteolytic cleavage and oligosaccharide processing from high mannose type to complex type. Oligomers formation takes place in a post-endoplasmic reticulum compartment. {ECO:0000250|UniProtKB:Q99758}.

CATALYTIC ACTIVITY: Reaction=ATP + H2O + xenobioticSide 1 = ADP + phosphate + xenobioticSide 2.; EC=7.6.2.2; Evidence={ECO:0000250|UniProtKB:Q99758}; CATALYTIC ACTIVITY: Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine(in) + ATP + H2O = a 1,2-diacyl-sn-glycero-3-phosphocholine(out) + ADP + H(+) + phosphate; Xref=Rhea:RHEA:66272, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57643, ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:Q99758}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66273; Evidence={ECO:0000250|UniProtKB:Q99758}; CATALYTIC ACTIVITY: Reaction=ATP + H2O + phospholipidSide 1 = ADP + phosphate + phospholipidSide 2.; EC=7.6.2.1; Evidence={ECO:0000250|UniProtKB:Q99758}; CATALYTIC ACTIVITY: Reaction=1,2-dihexadecanoyl-sn-glycero-3-phosphocholine(in) + ATP + H2O = 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine(out) + ADP + H(+) + phosphate; Xref=Rhea:RHEA:66340, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:72999, ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:Q99758}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66341; Evidence={ECO:0000250|UniProtKB:Q99758}; CATALYTIC ACTIVITY: Reaction=ATP + cholesterol(in) + H2O = ADP + cholesterol(out) + H(+) + phosphate; Xref=Rhea:RHEA:39051, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16113, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:Q99758}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39052; Evidence={ECO:0000250|UniProtKB:Q99758}; CATALYTIC ACTIVITY: Reaction=1,2-diacyl-sn-glycero-3-phospho-(1'-sn-glycerol)(in) + ATP + H2O = 1,2-diacyl-sn-glycero-3-phospho-(1'-sn-glycerol)(out) + ADP + H(+) + phosphate; Xref=Rhea:RHEA:66344, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:64716, ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:Q8R420}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66345; Evidence={ECO:0000250|UniProtKB:Q8R420};

FUNCTION: Catalyzes the ATP-dependent transport of phospholipids such as phosphatidylcholine and phosphoglycerol from the cytoplasm into the lumen side of lamellar bodies, in turn participates in the lamellar bodies biogenesis and homeostasis of pulmonary surfactant. Transports preferentially phosphatidylcholine containing short acyl chains. In addition plays a role as an efflux transporter of miltefosine across macrophage membranes and free cholesterol (FC) through intralumenal vesicles by removing FC from the cell as a component of surfactant and protects cells from free cholesterol toxicity. {ECO:0000250|UniProtKB:Q99758}.

Rattus norvegicus (Rat)

A0A0G2K2P5

ZO1_RAT

MSARAAAAKSTAMEETAIWEQHTVTLHRAPGFGFGIAISGGRDNPHFQSGETSIVISDVLKGGPAEGQLQENDRVAMVNGVSMDNVEHAFAVQQLRKSGKNAKITIRRKKKVQIPVSHPDPDPVSDNEDDSYDEDVHDPRSGRGALANRRGEKSWARDRSASRDRSLSPRSDRRSVASSQPAKPTKVTLVKSRKNEEYGLRLASHIFVKEISQDSLAARDGNIQEGDVVLKINGTVTENMSLTDAKTLIERSKGKLKMVVQRDERATLLNVPDLSDSIHSANASERDDISEIQSLASDHSVRSHDRPPRRSQSRSPDQRSEPSDHSTQSPQQPSNGSLRSREEERMSKPGAVSTPVKHVDDHTPKAVEEVTVEKHEKQTPTLPEPKPVYAQVGQPDVDLPVSPSDGVLPNSTHEDGILRPSMKLVKFRKGDSVGLRLAGGNDVGIFVAGVLEDSPAAKEGLEEGDQILRVNNVDFTNIIREEAVLFLLDLPKGEEVTILAQKKKDVYRRIVESDVGDSFYIRTHFEYEKESPYGLSFNKGEVFRVVDTLYNGKLGSWLAIRIGKNHKEVERGIVPNKNRAEQLASVQYTLPKTAGGDRADFWRFRGLRSSKRNLRKSREDLSAQPVQTKFPAYERVVLREAGFLRPVTIFGPIADVAREKLAREEPDIYQIAKSEPRDAGTDHRSSGIIRLHTIKQIIDQDKHALLDVTPNAVDRLNYAQWYPIVVFLNPDSKQGVKTMRMRLCPESRKSARKLYERSHKLRKNNHHLFTTTINLNSMNDGWYGALKEAIQQQQNQLVWVSEGKADGATSDDLDLHDDRLSYLSAPGSEYSMYSTDSRHTSDYEDTDTEGGAYTDQELDETLNDEVGTPPESAITRSSEPVREDSSGMHHENQTYPPYSPQAQPQAIHRIDSPGLKTASQQKAEASSPVPYLSPETNPASSASAVKHNVNLTNVNLEEPTPAPPTSHVSQADCLGAPSPEAPHTMLRDEGVSLPSHVDPAKVYRKEPYPEEMMRQNHILKQPALGHPGQRLDKEPNPAYDPQLPYVEKQASRDLEQPPYRYESSSYTDQFSRNYDHRLRFEDRVPTYEDQWSYYDDKQPYPTRPFDTQHPRDLDSRQHPEEASERGYFQRFEEPAPLPYDSRPRYEQLPRTSTLRHEEQPTSGYEVHNRYRPEAQPYAPAGPKSSEPKQYFDQYPRSYEQVPPPGFTSKTGHYEPLHGAAVVPPLIPSSQHKPEVLPSATKPQPPPPALTEEEEDPAMKPQSVLTRVKMFENKRSASLENKKDVNDTASFKPPEVASKPPSASLVGPKPVSQTQFSEHDKTLYRLPEPQKPQAKPPEDIVRSNHYDPEEDEEYYRKQLSYFDRRSFESKPPAHIPAGHHSEPAKPVHSQSQPNFSSYSSKGKPETDAMDRSFSEKRYDPTQAMPPPPPLPSQYSQPVPPLSNSSLHIHSKAAQSEGNSVSLDFQNSYISKPDPPPSQSKPATFRPPTREDPPQTFYPQKSFPDKASVNGAEQTQKTITPAYNRFTPKPYTSSARPFERKFESPKFNHNLLPSETVHKPELSSKPPPSPKTLMKAHSSTQPPEFDSGVETFSVHTDKPKYQINNISTMPKAVPVSPSAVEEDEDEDGHTVVATARGIFNSNGGVLSSIETGVSIIIPQGAIPEGIEQEIYFKVCRDNSILPPLDKEKGETLLSPLVMCGPHGLKFLKPVELRLPHCASMTPDGWSFALKSSDSSSGDPKTWQNKCLPGDPNYLVGANCVSVLIDHF

actin cytoskeleton organization [GO:0030036]; actomyosin structure organization [GO:0031032]; adherens junction maintenance [GO:0034334]; blastocyst formation [GO:0001825]; cell-cell adhesion [GO:0098609]; cell-cell junction organization [GO:0045216]; cellular response to glucose stimulus [GO:0071333]; establishment of endothelial intestinal barrier [GO:0090557]; negative regulation of apoptotic process [GO:0043066]; negative regulation of stress fiber assembly [GO:0051497]; negative regulation of vascular permeability [GO:0043116]; phosphorylation [GO:0016310]; positive regulation of blood-brain barrier permeability [GO:1905605]; positive regulation of cell migration [GO:0030335]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of cell-cell adhesion mediated by cadherin [GO:2000049]; positive regulation of sprouting angiogenesis [GO:1903672]; protein localization to adherens junction [GO:0071896]; protein localization to bicellular tight junction [GO:1902396]; protein localization to cell-cell junction [GO:0150105]; regulation of bicellular tight junction assembly [GO:2000810]; regulation of cell junction assembly [GO:1901888]; regulation of cytoskeleton organization [GO:0051493]; response to ethanol [GO:0045471]; response to lipopolysaccharide [GO:0032496]; response to magnetism [GO:0071000]; response to xenobiotic stimulus [GO:0009410]; sensory perception of sound [GO:0007605]

adherens junction [GO:0005912]; apical junction complex [GO:0043296]; apical part of cell [GO:0045177]; apical plasma membrane [GO:0016324]; apicolateral plasma membrane [GO:0016327]; basolateral plasma membrane [GO:0016323]; bicellular tight junction [GO:0005923]; cell junction [GO:0030054]; cell-cell junction [GO:0005911]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; gap junction [GO:0005921]; intercalated disc [GO:0014704]; intercellular canaliculus [GO:0046581]; membrane [GO:0016020]; nucleus [GO:0005634]; plasma membrane [GO:0005886]; protein-containing complex [GO:0032991]; tight junction [GO:0070160]

ATP binding [GO:0005524]; beta-catenin binding [GO:0008013]; cell adhesion molecule binding [GO:0050839]; connexin binding [GO:0071253]; kinase activity [GO:0016301]; protein domain specific binding [GO:0019904]; transmembrane transporter binding [GO:0044325]

PF00625;PF00595;PF07653;PF00791;

2.30.42.10;2.60.220.30;3.40.50.300;2.30.30.40;

MAGUK family

PTM: Phosphorylated at tyrosine redidues in response to epidermal growth factor (EGF) (By similarity). This response is dependent on an intact actin microfilament system (By similarity). Dephosphorylated by Ptprj (By similarity). {ECO:0000250|UniProtKB:Q07157}.

SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q07157}; Peripheral membrane protein {ECO:0000250|UniProtKB:Q07157}; Cytoplasmic side {ECO:0000250|UniProtKB:Q07157}. Cell junction, tight junction {ECO:0000269|PubMed:3528172, ECO:0000269|PubMed:9707407}. Cell junction {ECO:0000250|UniProtKB:P12830}. Cell junction, gap junction {ECO:0000250|UniProtKB:Q07157}. Note=Moves from the cytoplasm to the cell membrane concurrently with cell-cell contact (By similarity). Distributed over the entire lateral surface of the plasma membrane and other actin-rich structures (By similarity). Detected at the leading edge of migrating and wounded cells (By similarity). Colocalizes with SPEF1 at sites of cell-cell contact in intestinal epithelial cells (By similarity). {ECO:0000250|UniProtKB:Q07157, ECO:0000269|PubMed:3528172, ECO:0000269|PubMed:9707407}.

FUNCTION: TjpP1, Tjp2, and Tjp3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskeleton (PubMed:9707407). The tight junction acts to limit movement of substances through the paracellular space and as a boundary between the compositionally distinct apical and basolateral plasma membrane domains of epithelial and endothelial cells. Necessary for lumenogenesis, and particularly efficient epithelial polarization and barrier formation (By similarity). Plays a role in the regulation of cell migration by targeting Cdc42bpb to the leading edge of migrating cells (By similarity). Plays an important role in podosome formation and associated function, thus regulating cell adhesion and matrix remodeling (By similarity). With Tjp2 and Tjp3, participates in the junctional retention and stability of the transcription factor Dbpa, but is not involved in its shuttling to the nucleus (By similarity). {ECO:0000250|UniProtKB:O97758, ECO:0000250|UniProtKB:Q07157, ECO:0000269|PubMed:9707407}.

Rattus norvegicus (Rat)

A0A0G2K309

ORNT1_RAT

MKSNPAIQAAIDLTAGAAGGTACVLTGQPFDTMKVKMQTFPDLYRGLTDCCLRTYSQVGFRGFYKGTSPALIANIAENSVLFMCYGFCQQVVRKVVGLDRQAKLSDLQNAAAGSFASAFAALVLCPTELVKCRLQTMYEMETSGKIAASQNTVWSVVKEIFRKDGPLGFYHGLSSTLLREVPGYFFFFGGYELSRSFFASGRSKDELGPIPLMLSGGFGGICLWLAVYPVDCIKSRIQVLSMTGKQTGLIRTFLSIVKNEGITALYSGLKPTMIRAFPANGALFLAYEYSRKLMMSQLEAC

L-arginine transmembrane transport [GO:1903826]; L-lysine transmembrane transport [GO:1903401]; mitochondrial L-ornithine transmembrane transport [GO:1990575]

mitochondrial inner membrane [GO:0005743]; mitochondrion [GO:0005739]

antiporter activity [GO:0015297]; L-arginine transmembrane transporter activity [GO:0061459]; L-lysine transmembrane transporter activity [GO:0015189]; L-ornithine transmembrane transporter activity [GO:0000064]

PF00153;

1.50.40.10;

Mitochondrial carrier (TC 2.A.29) family

SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000250|UniProtKB:Q12375}; Multi-pass membrane protein {ECO:0000255}. Mitochondrion membrane {ECO:0000269|PubMed:15057822}; Multi-pass membrane protein {ECO:0000255}.

CATALYTIC ACTIVITY: Reaction=H(+)(in) + L-citrulline(in) + L-ornithine(out) = H(+)(out) + L-citrulline(out) + L-ornithine(in); Xref=Rhea:RHEA:70787, ChEBI:CHEBI:15378, ChEBI:CHEBI:46911, ChEBI:CHEBI:57743; Evidence={ECO:0000269|PubMed:10417335, ECO:0000269|PubMed:9359400}; CATALYTIC ACTIVITY: Reaction=L-arginine(out) + L-ornithine(in) = L-arginine(in) + L-ornithine(out); Xref=Rhea:RHEA:34991, ChEBI:CHEBI:32682, ChEBI:CHEBI:46911; Evidence={ECO:0000250|UniProtKB:Q9Y619}; CATALYTIC ACTIVITY: Reaction=L-lysine(in) + L-ornithine(out) = L-lysine(out) + L-ornithine(in); Xref=Rhea:RHEA:70799, ChEBI:CHEBI:32551, ChEBI:CHEBI:46911; Evidence={ECO:0000250|UniProtKB:Q9Y619}; CATALYTIC ACTIVITY: Reaction=H(+)(in) + L-ornithine(out) = H(+)(out) + L-ornithine(in); Xref=Rhea:RHEA:70791, ChEBI:CHEBI:15378, ChEBI:CHEBI:46911; Evidence={ECO:0000269|PubMed:10417335}; CATALYTIC ACTIVITY: Reaction=H(+)(in) + L-lysine(out) = H(+)(out) + L-lysine(in); Xref=Rhea:RHEA:70795, ChEBI:CHEBI:15378, ChEBI:CHEBI:32551; Evidence={ECO:0000269|PubMed:10417335};

FUNCTION: Mitochondrial ornithine-citrulline antiporter. Catalyzes the exchange between cytosolic ornithine and mitochondrial citrulline plus an H(+), the proton compensates the positive charge of ornithine thus leading to an electroneutral transport. Plays a crucial role in the urea cycle, by connecting the cytosolic and the intramitochondrial reactions of the urea cycle (PubMed:10417335, PubMed:9359400). Lysine and arginine are also transported by the antiport mechanism (By similarity). In addition, catalyzes an electroneutral exchange of ornithine or lysine for H(+), a reaction driven by the pH gradient across the inner membrane (PubMed:10417335). {ECO:0000250|UniProtKB:Q9Y619, ECO:0000269|PubMed:10417335, ECO:0000269|PubMed:9359400}.

Rattus norvegicus (Rat)

A0A0G2K344

PK3CA_RAT

MPPRPSSGELWGIHLMPPRILVECLLPNGMIVTLECLREATLVTIKHELFKEARKYPLHQLLQDESSYIFVSVTQEAEREEFFDETRRLCDLRLFQPFLKVIEPVGNREEKILNREIGFVIGMPVCEFDMVKDPEVQDFRRNILNVCKEAVDLRDLNSPHSRAMYVYPPNVESSPELPKHIYNKLDKGQIIVVIWVIVSPNNDKQKYTLKINHDCVPEQVIAEAIRKKTRSMLLSSEQLKLCVLEYQGKYILKVCGCDEYFLEKYPLSQYKYIRSCIMLGRMPNLMLMAKESLYSQLPIDSFTMPSYSRRISTATPYMNGETATKSLWVINSALRIKILCATYVNVNIRDIDKIYVRTGIYHGGEPLCDNVNTQRVPCSNPRWNEWLNYDIYIPDLPRAARLCLSICSVKGRKGAKEEHCPLAWGNINLFDYTDTLVSGKMALNLWPVPHGLEDLLNPIGVTGSNPNKETPCLELEFDWFSSVVKFPDMSVIEEHANWSVSREAGFSYSHTGLSNRLARDNELRENDKEQLRALCTRDPLSEITEQEKDFLWSHRHYCVTIPEILPKLLLSVKWNSRDEVAQMYCLVKDWPPIKPEQAMELLDCNYPDPMVRSFAVRCLEKYLTDDKLSQYLIQLVQVLKYEQYLDNLLVRFLLKKALTNQRIGHFFFWHLKSEMHNKTVSQRFGLLLESYCRACGMYLKHLNRQVEAMEKLINLTDILKQEKKDETQKVQMKFLVEQMRQPDFMDALQGFLSPLNPAHQLGNLRLEECRIMSSAKRPLWLNWENPDIMSELLFQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNSHTIMQIQCKGGLKGALQFNSHTLHQWLKDKNKGEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDFGHFLDHKKKKFGYKRERVPFVLTQDFLIVISKGAQEYTKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQSFDDIAYIRKTLALDKTEQEALEYFTKQMNDAHHGGWTTKMDWIFHTIKQHALN

2.7.1.137; 2.7.1.153; 2.7.11.1

actin cytoskeleton organization [GO:0030036]; adipose tissue development [GO:0060612]; angiogenesis [GO:0001525]; autosome genomic imprinting [GO:0141068]; cardiac muscle cell contraction [GO:0086003]; cell migration [GO:0016477]; cellular response to glucose stimulus [GO:0071333]; cellular response to hydrostatic pressure [GO:0071464]; cellular response to insulin stimulus [GO:0032869]; energy homeostasis [GO:0097009]; glucose metabolic process [GO:0006006]; insulin receptor signaling pathway [GO:0008286]; insulin-like growth factor receptor signaling pathway [GO:0048009]; liver development [GO:0001889]; negative regulation of actin filament depolymerization [GO:0030835]; negative regulation of anoikis [GO:2000811]; negative regulation of fibroblast apoptotic process [GO:2000270]; negative regulation of gene expression [GO:0010629]; negative regulation of neuron apoptotic process [GO:0043524]; phagocytosis [GO:0006909]; phosphatidylinositol 3-kinase/protein kinase B signal transduction [GO:0043491]; phosphatidylinositol phosphate biosynthetic process [GO:0046854]; phosphatidylinositol-3-phosphate biosynthetic process [GO:0036092]; phosphatidylinositol-mediated signaling [GO:0048015]; phosphorylation [GO:0016310]; positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction [GO:0051897]; positive regulation of protein localization to membrane [GO:1905477]; positive regulation of smooth muscle cell proliferation [GO:0048661]; regulation of actin filament organization [GO:0110053]; regulation of cellular respiration [GO:0043457]; regulation of gene expression [GO:0010468]; regulation of multicellular organism growth [GO:0040014]; regulation of protein phosphorylation [GO:0001932]; relaxation of cardiac muscle [GO:0055119]; response to activity [GO:0014823]; response to butyrate [GO:1903544]; response to dexamethasone [GO:0071548]; response to leucine [GO:0043201]; response to muscle inactivity [GO:0014870]; response to muscle stretch [GO:0035994]; vascular endothelial growth factor signaling pathway [GO:0038084]

cytoplasm [GO:0005737]; cytosol [GO:0005829]; intercalated disc [GO:0014704]; lamellipodium [GO:0030027]; phosphatidylinositol 3-kinase complex [GO:0005942]; phosphatidylinositol 3-kinase complex, class IA [GO:0005943]; phosphatidylinositol 3-kinase complex, class IB [GO:0005944]; plasma membrane [GO:0005886]

1-phosphatidylinositol-3-kinase activity [GO:0016303]; 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity [GO:0046934]; 1-phosphatidylinositol-4-phosphate 3-kinase activity [GO:0035005]; ATP binding [GO:0005524]; insulin receptor substrate binding [GO:0043560]; kinase activity [GO:0016301]; protein kinase activator activity [GO:0030295]; protein serine kinase activity [GO:0106310]; protein serine/threonine kinase activity [GO:0004674]

PF00454;PF00792;PF02192;PF00794;PF00613;

2.60.40.150;1.10.1070.11;1.25.40.70;

PI3/PI4-kinase family

CATALYTIC ACTIVITY: Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) + ADP + H(+); Xref=Rhea:RHEA:21292, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57836, ChEBI:CHEBI:58456, ChEBI:CHEBI:456216; EC=2.7.1.153; Evidence={ECO:0000250|UniProtKB:P42336}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21293; Evidence={ECO:0000250|UniProtKB:P42336}; CATALYTIC ACTIVITY: Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3-phosphate) + ADP + H(+); Xref=Rhea:RHEA:12709, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57880, ChEBI:CHEBI:58088, ChEBI:CHEBI:456216; EC=2.7.1.137; Evidence={ECO:0000250|UniProtKB:P42336}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12710; Evidence={ECO:0000250|UniProtKB:P42336}; CATALYTIC ACTIVITY: Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:P32871}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990; Evidence={ECO:0000250|UniProtKB:P32871}; CATALYTIC ACTIVITY: Reaction=1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + ATP = 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) + ADP + H(+); Xref=Rhea:RHEA:55632, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:83416, ChEBI:CHEBI:83419, ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:P42336}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55633; Evidence={ECO:0000250|UniProtKB:P42336}; CATALYTIC ACTIVITY: Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phospho-1D-myo-inositol 4,5-bisphosphate + ATP = 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phospho-(1D-myo-inositol 3,4,5-triphosphate) + ADP + H(+); Xref=Rhea:RHEA:43396, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:77137, ChEBI:CHEBI:83243, ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:P42336}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43397; Evidence={ECO:0000250|UniProtKB:P42336};

PATHWAY: Phospholipid metabolism; phosphatidylinositol phosphate biosynthesis. {ECO:0000250|UniProtKB:P42336}.

FUNCTION: Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides. Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Participates in cellular signaling in response to various growth factors. Involved in the activation of AKT1 upon stimulation by receptor tyrosine kinases ligands such as EGF, insulin, IGF1, VEGFA and PDGF. Involved in signaling via insulin-receptor substrate (IRS) proteins (PubMed:20236230). Essential in endothelial cell migration during vascular development through VEGFA signaling, possibly by regulating RhoA activity. Required for lymphatic vasculature development, possibly by binding to RAS and by activation by EGF and FGF2, but not by PDGF. Regulates invadopodia formation through the PDPK1-AKT1 pathway. Participates in cardiomyogenesis in embryonic stem cells through a AKT1 pathway. Participates in vasculogenesis in embryonic stem cells through PDK1 and protein kinase C pathway. In addition to its lipid kinase activity, it displays a serine-protein kinase activity that results in the autophosphorylation of the p85alpha regulatory subunit as well as phosphorylation of other proteins such as 4EBP1, H-Ras, the IL-3 beta c receptor and possibly others (By similarity). Plays a role in the positive regulation of phagocytosis and pinocytosis (By similarity). {ECO:0000250|UniProtKB:P42336, ECO:0000250|UniProtKB:P42337, ECO:0000269|PubMed:20236230}.

Rattus norvegicus (Rat)

A0A0G2KQY6

S39AE_DANRE

MTLRRASGCRQLTLTIGLALTLGLLQWPIGDVRGQDGASPAQVLQELLTRYGDNASISVPQLRSLLVRLNGGQSEDHDSKTQPTRTNASKCLAADTLAVYGMSEQSRIDERGLQQICPTMIQQLDSQACKTQPNQESESSPRPTEAEVWGYGLLCVTVISLCSLVGASVVPFMRKTFYKRLLLYFIALAIGTLYSNALFQLIPEAFGFDPMEDYYVPKSAVVFGGFYLFFFTEKILKMILKPKDTGGHGHGHSHFPAERYANSNGDLEDGVMEKLQNGEAGGAALPRAEADGRGVGEDDKMLSTGQTVQDTQSSGGGGTGGCYWLKGRAYSDIGTLAWMITLSDGLHNFIDGLAIGASFTASVFQGISTSVAILCEEFPHELGDFVILLNAGMSIQQALFFNFLSACCCYLGMGFGILAGNNFSPNWIFALAGGMFLYIALADMFPEMNEVSREEEEAGGSGFLLTFALQNAGLLTGFAIMLVLTIYSGQIQLG

cellular response to glucose stimulus [GO:0071333]; cellular response to insulin stimulus [GO:0032869]; import across plasma membrane [GO:0098739]; inorganic cation transmembrane transport [GO:0098662]; intracellular zinc ion homeostasis [GO:0006882]; iron import into cell [GO:0033212]; iron ion transmembrane transport [GO:0034755]; manganese ion homeostasis [GO:0055071]; manganese ion transmembrane transport [GO:0071421]; negative regulation of cyclic-nucleotide phosphodiesterase activity [GO:0051344]; positive regulation of G protein-coupled receptor signaling pathway [GO:0045745]; zinc ion import across plasma membrane [GO:0071578]; zinc ion transmembrane transport [GO:0071577]; zinc ion transport [GO:0006829]

apical plasma membrane [GO:0016324]; basolateral plasma membrane [GO:0016323]; early endosome membrane [GO:0031901]; late endosome membrane [GO:0031902]; lysosomal membrane [GO:0005765]; plasma membrane [GO:0005886]

cadmium ion transmembrane transporter activity [GO:0015086]; iron ion transmembrane transporter activity [GO:0005381]; manganese ion transmembrane transporter activity [GO:0005384]; monoatomic anion:monoatomic cation symporter activity [GO:0015296]; monoatomic cation:bicarbonate symporter activity [GO:0140410]; zinc ion transmembrane transporter activity [GO:0005385]

PF02535;

ZIP transporter (TC 2.A.5) family

SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:27231142}; Multi-pass membrane protein {ECO:0000255}. Apical cell membrane {ECO:0000250|UniProtKB:Q15043}; Multi-pass membrane protein {ECO:0000255}. Basolateral cell membrane {ECO:0000250|UniProtKB:Q15043}; Multi-pass membrane protein {ECO:0000255}. Early endosome membrane {ECO:0000250|UniProtKB:Q15043}; Multi-pass membrane protein {ECO:0000255}. Late endosome membrane {ECO:0000250|UniProtKB:Q15043}; Multi-pass membrane protein {ECO:0000255}. Lysosome membrane {ECO:0000250|UniProtKB:Q15043}; Multi-pass membrane protein {ECO:0000255}.

CATALYTIC ACTIVITY: Reaction=2 hydrogencarbonate(out) + Zn(2+)(out) = 2 hydrogencarbonate(in) + Zn(2+)(in); Xref=Rhea:RHEA:62252, ChEBI:CHEBI:17544, ChEBI:CHEBI:29105; Evidence={ECO:0000250|UniProtKB:Q75N73}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62253; Evidence={ECO:0000250|UniProtKB:Q75N73}; CATALYTIC ACTIVITY: Reaction=2 hydrogencarbonate(out) + Mn(2+)(out) = 2 hydrogencarbonate(in) + Mn(2+)(in); Xref=Rhea:RHEA:62260, ChEBI:CHEBI:17544, ChEBI:CHEBI:29035; Evidence={ECO:0000250|UniProtKB:Q75N73}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62261; Evidence={ECO:0000250|UniProtKB:Q75N73}; CATALYTIC ACTIVITY: Reaction=Fe(2+)(out) + 2 hydrogencarbonate(out) = Fe(2+)(in) + 2 hydrogencarbonate(in); Xref=Rhea:RHEA:62368, ChEBI:CHEBI:17544, ChEBI:CHEBI:29033; Evidence={ECO:0000250|UniProtKB:Q75N73}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62369; Evidence={ECO:0000250|UniProtKB:Q75N73}; CATALYTIC ACTIVITY: Reaction=Cd(2+)(out) + 2 hydrogencarbonate(out) = Cd(2+)(in) + 2 hydrogencarbonate(in); Xref=Rhea:RHEA:62256, ChEBI:CHEBI:17544, ChEBI:CHEBI:48775; Evidence={ECO:0000250|UniProtKB:Q75N73}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62257; Evidence={ECO:0000250|UniProtKB:Q75N73};

FUNCTION: Broad-scope metal ion transporter with a preference for zinc uptake. Also mediates cellular uptake of nontransferrin-bound iron. {ECO:0000269|PubMed:27231142}.; FUNCTION: Electroneutral transporter of the plasma membrane mediating the cellular uptake of the divalent metal cations zinc, manganese and iron that are important for tissue homeostasis, metabolism, development and immunity (PubMed:27231142). Functions as an energy-dependent symporter, transporting through the membranes an electroneutral complex composed of a divalent metal cation and two bicarbonate anions (By similarity). Beside these endogenous cellular substrates, can also import cadmium a non-essential metal which is cytotoxic and carcinogenic (By similarity). {ECO:0000250|UniProtKB:Q75N73, ECO:0000269|PubMed:27231142}.

Danio rerio (Zebrafish) (Brachydanio rerio)

A0A0G2KTI4

S12A2_DANRE

MSASPPISAGDYLSAPEPDALKPAGPTPSQSRFQVDLVTESAGDGETTVGFDSSPPEYVAEPPPDGLRDSVSGGEEAKGRFRVVNFAASSPDAAPAETAQNGDTVMSEGSLHSSTGGQQHHHYDTHTNTYYLRTFGHNTIDAVPKIDFYRQTAAPLGEKLIRPTLSELHDELDKEPFEDGFANGEELTPAEESAAKDVSESKGVVKFGWIKGVLVRCMLNIWGVMLFIRMTWIVGQAGIAYSCIIVIMATVVTTITGCSTSAIATNGFVRGGGAYYLISRSLGPEFGGSIGLIFAFANAVAVAMYVVGFAETVVELLMDSGLLMIDQTNDIRVIGTITVILLLGISVAGMEWEAKAQIFLLVILITAIFNYFIGSFIAVDSKKKFGFFSYDAGILAENFGPDFRGQTFFSVFSIFFPAATGILAGANISGDLADPQMAIPKGTLLAILITGLVYVGVAISAGACIVRDATGIESNFTLISNCTDAACKYGYDFSSCRPTVEGEVSSCKFGLHNDFQVMSVVSGFSPLISAGIFSATLSSALASLVSAPKVFQALCKDNIYPGIAIFGKGYGKNNEPLRGYFLTFGIALAFILIAELNVIAPIISNFFLASYALINFSVFHASLANSPGWRPSFKYYNMWASLAGAILCCVVMFIINWWAALLTNVIVLSLYIYVSYKKPDVNWGSSTQALTYHQALTHSLQLCGVADHIKTFRPQCLVMTGAPNSRPAILHLVHAFTKNVGLMLCGHVRISSRRPNFKELNSDMLRYQRWLLNNNSKAFYTCVVAEDLRQGTQYMLQAAGLGRLRPNTLVIGFKNDWRTGDIKEVETYINLIHDAFDFQYGVVILRLREGLDISHIQGQDDSSGMKDVVVSVDISKDSDGDSSKPSSKATSVQNSPAVQKDEDDDGKAHTQPLLKKDKKSPTVPLNVADQRLLDASQQFQQKQGKGTVDVWWLFDDGGLTLLIPYLIANKKKWKDCKIRVFIGGKINRIDHDRRAMATLLSKFRIDFSDITVLGDINTKPKSEGLTEFAEMIEPYKLREDDMEQEAAEKLKSEEPWRITDNELELYKAKGNRQIRLNELLKEHSSTANLIVMSMPLARKGAVSSALYMAWLDTLSKDLPPILLVRGNHQSVLTFYS

cell volume homeostasis [GO:0006884]; chloride ion homeostasis [GO:0055064]; chloride transmembrane transport [GO:1902476]; ear development [GO:0043583]; inner ear morphogenesis [GO:0042472]; potassium ion homeostasis [GO:0055075]; potassium ion import across plasma membrane [GO:1990573]; sodium ion homeostasis [GO:0055078]; sodium ion transmembrane transport [GO:0035725]; swim bladder inflation [GO:0048798]

apical plasma membrane [GO:0016324]; basolateral plasma membrane [GO:0016323]

ammonium transmembrane transporter activity [GO:0008519]; chloride:monoatomic cation symporter activity [GO:0015377]; identical protein binding [GO:0042802]; salt transmembrane transporter activity [GO:1901702]; sodium:potassium:chloride symporter activity [GO:0008511]

PF00324;PF08403;PF03522;

1.20.1740.10;

SLC12A transporter family

PTM: Phosphorylated at Thr-125, Thr-129 and Thr-134 by OXSR1/OSR1 and STK39/SPAK downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4), promoting its activity. {ECO:0000250|UniProtKB:P55013}.

SUBCELLULAR LOCATION: Basolateral cell membrane {ECO:0000269|PubMed:19633174, ECO:0000305|PubMed:31367042}; Multi-pass membrane protein {ECO:0000305|PubMed:31367042}.

CATALYTIC ACTIVITY: Reaction=2 chloride(out) + K(+)(out) + Na(+)(out) = 2 chloride(in) + K(+)(in) + Na(+)(in); Xref=Rhea:RHEA:72395, ChEBI:CHEBI:17996, ChEBI:CHEBI:29101, ChEBI:CHEBI:29103; Evidence={ECO:0000250|UniProtKB:P55011}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:72396; Evidence={ECO:0000250|UniProtKB:P55011};

FUNCTION: Cation-chloride cotransporter which mediates the electroneutral transport of chloride, potassium and/or sodium ions across the membrane (PubMed:31367042). Plays a vital role in the regulation of ionic balance and cell volume (PubMed:31367042). Important for maintenance of endolymph volume in the otic vesicle, probably by regulating ion homeostasis (PubMed:19633174). Also plays a role in normal development of the swim bladder (PubMed:19633174). {ECO:0000269|PubMed:19633174, ECO:0000269|PubMed:31367042}.

Danio rerio (Zebrafish) (Brachydanio rerio)

A0A0G2L7I0

SPRTN_DANRE

MMEDEDFLLALRLQEQFDQETPAAGWPDEDCPSSKRRRVDPSGGLDVIPFTQPRAERPLSIVDESWETLDPNPDVRAMFLQFNDKFFWGKLSGVEVKWSPRMTLCAGVCSYEGRGGLCSIRLSEPLLKLRPRKDLVQTLLHEMIHALLFVTQNNRDRDGHGPEFCKHMNRINQASGTNITIYHSFHDEVDVYRQHWWRCNGPCQNRRPFFGYVKRAMNRPPSARDPWWADHQRSCGGTYTKIKEPENYGKTGKSDKQRDKMPATEMPKKSKPPSSTSSSGSQDIRNIIPFSGRGFVLGGNAQIPTNKQIQSPPKAPPEPLHSPPDSPLLPRLQLNEDNLKRLSSGTSNIPRKRSVGNTNAFINVNGSPVRISNGNGSGGKQRSVRDLFQAIVLKSPDRGASAVGSSKSSTDASTADYRSNSALDAKPSGKTSLITDHLSYTISGPKTLSAESNISKYFGGSAKTDVQDSKLKTFGSPQKSAIGTPGYVSKAFGSNQRPDSTSSGIRNTGSPQRSHASATSGSSFKHFRGPAKPESNFPSPRNIGSPRTSGTTPSGAKKRSWEEHNSERVFDYFQRTVGESATSTDKKREEVRSEAPPPVRDQQANNPPAQITVHCPVCHIRLPESTINDHLDSCLL

3.4.24.-

COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250|UniProtKB:Q9H040};

DNA damage response [GO:0006974]; protein autoprocessing [GO:0016540]; protein-DNA covalent cross-linking repair [GO:0106300]; proteolysis [GO:0006508]

chromatin [GO:0000785]; nucleus [GO:0005634]

double-stranded DNA binding [GO:0003690]; metal ion binding [GO:0046872]; metalloendopeptidase activity [GO:0004222]; polyubiquitin modification-dependent protein binding [GO:0031593]; single-stranded DNA binding [GO:0003697]

PF10263;

3.30.160.60;

Spartan family

PTM: Autocatalytically cleaved in response to double-stranded DNA-binding: autocatalytic cleavage takes place in trans and leads to inactivation. {ECO:0000250|UniProtKB:Q9H040}.

SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9H040}. Chromosome {ECO:0000250|UniProtKB:A0A1L8G2K9}. Note=Localizes to sites of UV damage via the PIP-box. Recruited to stalled replication forks at sites of replication stress. {ECO:0000250|UniProtKB:Q9H040}.

FUNCTION: DNA-dependent metalloendopeptidase that mediates the proteolytic cleavage of covalent DNA-protein cross-links (DPCs) during DNA synthesis, thereby playing a key role in maintaining genomic integrity. DPCs are highly toxic DNA lesions that interfere with essential chromatin transactions, such as replication and transcription, and which are induced by reactive agents, such as UV light or formaldehyde. Associates with the DNA replication machinery and specifically removes DPCs during DNA synthesis. Catalyzes proteolytic cleavage of the hmces DNA-protein cross-link following unfolding by the brip1/fancj helicase. Acts as a pleiotropic protease for DNA-binding proteins cross-linked with DNA, such as top1, top2a, histones H3 and H4. Mediates degradation of DPCs that are not ubiquitinated, while it is not able to degrade ubiquitinated DPCs. SPRTN activation requires polymerase collision with DPCs followed by helicase bypass of DPCs. May also act as a 'reader' of ubiquitinated pcna: facilitates chromatin association of rad18 and is required for efficient pcna monoubiquitination, promoting a feed-forward loop to enhance pcna ubiquitination and translesion DNA synthesis. Acts as a regulator of translesion DNA synthesis by recruiting vcp/p97 to sites of DNA damage. {ECO:0000250|UniProtKB:A0A1L8G2K9, ECO:0000250|UniProtKB:Q9H040}.

Danio rerio (Zebrafish) (Brachydanio rerio)

A0A0G2Q9D6

GYRB_MYCBP

MGKNEARRSALAPDHGTVVCDPLRRLNRMHATPEESIRIVAAQKKKAQDEYGAASITILEGLEAVRKRPGMYIGSTGERGLHHLIWEVVDNAVDEAMAGYATTVNVVLLEDGGVEVADDGRGIPVATHASGIPTVDVVMTQLHAGGKFDSDAYAISGGLHGVGVSVVNALSTRLEVEIKRDGYEWSQVYEKSEPLGLKQGAPTKKTGSTVRFWADPAVFETTEYDFETVARRLQEMAFLNKGLTINLTDERVTQDEVVDEVVSDVAEAPKSASERAAESTAPHKVKSRTFHYPGGLVDFVKHINRTKNAIHSSIVDFSGKGTGHEVEIAMQWNAGYSESVHTFANTINTHEGGTHEEGFRSALTSVVNKYAKDRKLLKDKDPNLTGDDIREGLAAVISVKVSEPQFEGQTKTKLGNTEVKSFVQKVCNEQLTHWFEANPTDSKVVVNKAVSSAQARIAARKARELVRRKSATDIGGLPGKLADCRSTDPRKSELYVVEGDSAGGSAKSGRDSMFQAILPLRGKIINVEKARIDRVLKNTEVQAIITALGTGIHDEFDIGKLRYHKIVLMADADVDGQHISTLLLTLLFRFMRPLIENGHVFLAQPPLYKLKWQRSDPEFAYSDRERDGLLEAGLKAGKKINKEDGIQRYKGLGEMDAKELWETTMDPSVRVLRQVTLDDAAAADELFSILMGEDVDARRSFITRNAKDVRFLDV

5.6.2.2

COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000255|HAMAP-Rule:MF_01898, ECO:0000269|PubMed:7503546}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000255|HAMAP-Rule:MF_01898}; Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000255|HAMAP-Rule:MF_01898}; Note=Binds two Mg(2+) per subunit. The magnesium ions form salt bridges with both the protein and the DNA. Can also accept other divalent metal cations, such as Mn(2+) or Ca(2+). {ECO:0000255|HAMAP-Rule:MF_01898};

DNA topological change [GO:0006265]; DNA-templated DNA replication [GO:0006261]

chromosome [GO:0005694]; cytoplasm [GO:0005737]

ATP binding [GO:0005524]; DNA binding [GO:0003677]; DNA negative supercoiling activity [GO:0034335]; metal ion binding [GO:0046872]

PF00204;PF00986;PF02518;PF01751;

3.30.230.10;3.40.50.670;3.30.565.10;

Type II topoisomerase GyrB family

SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_01898}.

CATALYTIC ACTIVITY: Reaction=ATP-dependent breakage, passage and rejoining of double-stranded DNA.; EC=5.6.2.2; Evidence={ECO:0000255|HAMAP-Rule:MF_01898};

FUNCTION: A type II topoisomerase that negatively supercoils closed circular double-stranded DNA in an ATP-dependent manner and also catalyzes the interconversion of other topological isomers of double-stranded DNA rings, including catenanes and knotted rings. Relaxes negatively supercoiled DNA in an ATP-independent manner. A linear reaction intermediate can be trapped in the presence of the antibiotic ciprofloxacin (PubMed:7503546). Negative supercoiling favors strand separation, and DNA replication, transcription, recombination and repair, all of which involve strand separation. Type II topoisomerases break and join 2 DNA strands simultaneously in an ATP-dependent manner. {ECO:0000269|PubMed:7503546}.

Mycobacterium bovis (strain BCG / Pasteur 1173P2)

A0A0G2Q9F8

GYRA_MYCBP

MTDTTLPPDDSLDRIEPVDIQQEMQRSYIDYAMSVIVGRALPEVRDGLKPVHRRVLYAMFDSGFRPDRSHAKSARSVAETMGNYHPHGDASIYDTLVRMAQPWSLRYPLVDGQGNFGSPGNDPPAAMRYTEARLTPLAMEMLREIDEETVDFIPNYDGRVQEPTVLPSRFPNLLANGSGGIAVGMATNIPPHNLRELADAVFWALENHDADEEETLAAVMGRVKGPDFPTAGLIVGSQGTADAYKTGRGSIRMRGVVEVEEDSRGRTSLVITELPYQVNHDNFITSIAEQVRDGKLAGISNIEDQSSDRVGLRIVIEIKRDAVAKVVINNLYKHTQLQTSFGANMLAIVDGVPRTLRLDQLIRYYVDHQLDVIVRRTTYRLRKANERAHILRGLVKALDALDEVIALIRASETVDIARAGLIELLDIDEIQAQAILDMQLRRLAALERQRIIDDLAKIEAEIADLEDILAKPERQRGIVRDELAEIVDRHGDDRRTRIIAADGDVSDEDLIAREDVVVTITETGYAKRTKTDLYRSQKRGGKGVQGAGLKQDDIVAHFFVCSTHDLILFFTTQGRVYRAKAYDLPEASRTARGQHVANLLAFQPEERIAQVIQIRGYTDAPYLVLATRNGLVKKSKLTDFDSNRSGGIVAVNLRDNDELVGAVLCSADDDLLLVSANGQSIRFSATDEALRPMGRATSGVQGMRFNIDDRLLSLNVVREGTYLLVATSGGYAKRTAIEEYPVQGRGGKGVLTVMYDRRRGRLVGALIVDDDSELYAVTSGGGVIRTAARQVRKAGRQTKGVRLMNLGEGDTLLAIARNAEESGDDNAVDANGADQTGN

5.6.2.2

COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:7503546}; Note=Reaction requires Mg(2+). {ECO:0000269|PubMed:7503546};

DNA topological change [GO:0006265]; DNA-templated DNA replication [GO:0006261]; response to antibiotic [GO:0046677]

chromosome [GO:0005694]; cytoplasm [GO:0005737]; DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) complex [GO:0009330]

ATP binding [GO:0005524]; DNA binding [GO:0003677]; DNA negative supercoiling activity [GO:0034335]

PF03989;PF00521;

3.30.1360.40;2.120.10.90;3.90.199.10;1.10.268.10;

Type II topoisomerase GyrA/ParC subunit family

SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_01897}.

CATALYTIC ACTIVITY: Reaction=ATP-dependent breakage, passage and rejoining of double-stranded DNA.; EC=5.6.2.2; Evidence={ECO:0000255|HAMAP-Rule:MF_01897};

FUNCTION: A type II topoisomerase that negatively supercoils closed circular double-stranded (ds) DNA in an ATP-dependent manner to modulate DNA topology and maintain chromosomes in an underwound state. Also catalyzes the interconversion of other topological isomers of double-stranded DNA rings, including catenanes and knotted rings. Relaxes negatively supercoiled DNA in an ATP-independent manner. A linear reaction intermediate can be trapped in the presence of the antibiotic ciprofloxacin (PubMed:7503546). Negative supercoiling favors strand separation, and DNA replication, transcription, recombination and repair, all of which involve strand separation. Type II topoisomerases break and join 2 DNA strands simultaneously in an ATP-dependent manner. {ECO:0000269|PubMed:7503546}.

Mycobacterium bovis (strain BCG / Pasteur 1173P2)

A0A0G2QC33

ATG4B_RAT

MDAATLTYDTLRFAEFEDFPETSEPVWILGRKYSIFTEKDEILSDVASRLWFTYRRNFPAIGGTGPTSDTGWGCMLRCGQMIFAQALVCRHLGRDWRWTQRKRQPDSYFSVLNAFLDRKDSYYSIHQIAQMGVGEGKSIGQWYGPNTVAQVLKKLAVFDTWSSLAVHIAMDNTVVMEEIRRLCRASLPCAGAAALSMESERHCNGLPAGAEVTNRPLAWRPLVLLIPLRLGLTDINEAYVETLKHCFMMPQSLGVIGGKPNSAHYFIGYVGEELIYLDPHTTQPAVELTDSCFIPDESFHCQHPPCRMGIGELDPSIAVGFFCKTEEDFNDWCQQVKKLSQLGGALPMFELVEQQPSHLACQDVLNLSLDSSDVERLERFFDSEDEDFEILSL

3.4.22.-

aggrephagy [GO:0035973]; autophagosome assembly [GO:0000045]; autophagy [GO:0006914]; cellular response to starvation [GO:0009267]; microautophagy [GO:0016237]; mitophagy [GO:0000423]; otolith mineralization completed early in development [GO:0031173]; piecemeal microautophagy of the nucleus [GO:0034727]; positive regulation of protein catabolic process [GO:0045732]; protein localization to phagophore assembly site [GO:0034497]; protein processing [GO:0016485]; protein transport [GO:0015031]; proteolysis [GO:0006508]

autophagosome membrane [GO:0000421]; cytoplasm [GO:0005737]; cytoplasmic vesicle [GO:0031410]; cytosol [GO:0005829]; endoplasmic reticulum [GO:0005783]; mitochondrion [GO:0005739]

cysteine-type endopeptidase activity [GO:0004197]; cysteine-type peptidase activity [GO:0008234]; endopeptidase activity [GO:0004175]; peptidase activity [GO:0008233]; protein-phosphatidylethanolamide deconjugating activity [GO:0019786]; scaffold protein binding [GO:0097110]

PF20166;PF03416;

Peptidase C54 family

PTM: Phosphorylation at Ser-383 and Ser-392 promotes autophagy by increasing protein delipidation activity without affecting proteolytic activation of ATG8 proteins. Phosphorylation at Ser-316 by ULK1 inhibits autophagy by decreasing both proteolytic activation and delipidation activities. Phosphorylation at Ser-316 is dephosphorylated by protein phosphatase 2A (PP2A). Phosphorylation at Ser-34 by AKT2 promotes its hydrolase activity, leading to increased proteolytic activation and delipidation of ATG8 family proteins. Phosphorylation at Ser-34 by AKT1 promotes mitochondrial localization and inhibition of the F1F0-ATP synthase activity, leading to elevation of mitochondrial reactive oxygen species (ROS). {ECO:0000250|UniProtKB:Q9Y4P1}.; PTM: Ubiquitinated by RNF5, leading to its degradation by the proteasome. {ECO:0000250|UniProtKB:Q9Y4P1}.; PTM: S-nitrosylation in response to high glucose decreases both proteolytic activation and delipidation activities. {ECO:0000269|PubMed:28633005}.; PTM: O-glycosylated by OGT, leading to increase protease activity, thereby promoting the proteolytic activation of ATG8 family proteins. {ECO:0000250|UniProtKB:Q9Y4P1}.; PTM: Forms reversible intrachain disulfide bonds in response to oxidative stress. Forms interchain disulfide bonds, leading to formation of homooligomers in response to oxidation. {ECO:0000250|UniProtKB:Q9Y4P1}.

SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9Y4P1}. Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q9Y4P1}. Cytoplasmic vesicle, autophagosome {ECO:0000250|UniProtKB:Q9Y4P1}. Endoplasmic reticulum {ECO:0000250|UniProtKB:Q9Y4P1}. Mitochondrion {ECO:0000250|UniProtKB:Q9Y4P1}. Note=Mainly localizes to the cytoplasm, including cytosol. A samll potion localizes to mitochondria; phosphorylation at Ser-34 promotes localization to mitochondria. {ECO:0000250|UniProtKB:Q9Y4P1}.

CATALYTIC ACTIVITY: Reaction=[protein]-C-terminal L-amino acid-glycyl-phosphatidylethanolamide + H2O = [protein]-C-terminal L-amino acid-glycine + a 1,2-diacyl-sn-glycero-3-phosphoethanolamine; Xref=Rhea:RHEA:67548, Rhea:RHEA-COMP:17323, Rhea:RHEA-COMP:17324, ChEBI:CHEBI:15377, ChEBI:CHEBI:64612, ChEBI:CHEBI:172940, ChEBI:CHEBI:172941; Evidence={ECO:0000250|UniProtKB:Q9Y4P1}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67549; Evidence={ECO:0000250|UniProtKB:Q9Y4P1}; CATALYTIC ACTIVITY: Reaction=[protein]-C-terminal L-amino acid-glycyl-phosphatidylserine + H2O = [protein]-C-terminal L-amino acid-glycine + a 1,2-diacyl-sn-glycero-3-phospho-L-serine; Xref=Rhea:RHEA:67576, Rhea:RHEA-COMP:17324, Rhea:RHEA-COMP:17326, ChEBI:CHEBI:15377, ChEBI:CHEBI:57262, ChEBI:CHEBI:172940, ChEBI:CHEBI:172942; Evidence={ECO:0000250|UniProtKB:Q9Y4P1}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67577; Evidence={ECO:0000250|UniProtKB:Q9Y4P1};

FUNCTION: Cysteine protease that plays a key role in autophagy by mediating both proteolytic activation and delipidation of ATG8 family proteins. Required for canonical autophagy (macroautophagy), non-canonical autophagy as well as for mitophagy. The protease activity is required for proteolytic activation of ATG8 family proteins: cleaves the C-terminal amino acid of ATG8 proteins MAP1LC3A, MAP1LC3B, MAP1LC3C, GABARAPL1, GABARAPL2 and GABARAP, to reveal a C-terminal glycine. Exposure of the glycine at the C-terminus is essential for ATG8 proteins conjugation to phosphatidylethanolamine (PE) and insertion to membranes, which is necessary for autophagy. Protease activity is also required to counteract formation of high-molecular weight conjugates of ATG8 proteins (ATG8ylation): acts as a deubiquitinating-like enzyme that removes ATG8 conjugated to other proteins, such as ATG3. In addition to the protease activity, also mediates delipidation of ATG8 family proteins. Catalyzes delipidation of PE-conjugated forms of ATG8 proteins during macroautophagy. Also involved in non-canonical autophagy, a parallel pathway involving conjugation of ATG8 proteins to single membranes at endolysosomal compartments, by catalyzing delipidation of ATG8 proteins conjugated to phosphatidylserine (PS). Compared to other members of the family (ATG4A, ATG4C or ATG4C), constitutes the major protein for proteolytic activation of ATG8 proteins, while it displays weaker delipidation activity than other ATG4 paralogs. Involved in phagophore growth during mitophagy independently of its protease activity and of ATG8 proteins: acts by regulating ATG9A trafficking to mitochondria and promoting phagophore-endoplasmic reticulum contacts during the lipid transfer phase of mitophagy. {ECO:0000250|UniProtKB:Q9Y4P1}.

Rattus norvegicus (Rat)

A0A0G2UGT2

LEC_MYTTR

MTTFLIKHKASGKYFHPKGGTSNPPNGTNLVLHSDIHERMYFQFEVVNERWRYIKHVASEKIVHPFGGKADPLNGTNMVLHQDRHDRALFAMDFFNDNIRHKGGKYIHPKGGSKNPSNGNLTVMHGDEHGAMEFIFVSPKNKDKRVLVYA

aggregation of unicellular organisms [GO:0098630]; defense response to fungus [GO:0050832]; defense response to Gram-positive bacterium [GO:0050830]; detection of bacterium [GO:0016045]; erythrocyte aggregation [GO:0034117]; innate immune response [GO:0045087]; protein homooligomerization [GO:0051260]; response to Gram-negative bacterium [GO:0140460]

galactose binding [GO:0005534]; peptidoglycan binding [GO:0042834]

2.80.10.50;

PTM: The N-terminus is blocked. {ECO:0000269|PubMed:26802895}.

BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 9-10 for hemagglutinating activity. The activity is decreased by 25% at pH 6.0 and by 50% at pH 4.0. {ECO:0000269|Ref.2};

BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: Thermally labile. Complete loss of hemagglutinating activity after incubation at 60 degrees Celsius for 30 minutes. {ECO:0000269|Ref.2};

FUNCTION: D-galactose-binding lectin (PubMed:26802895, Ref.2). Binds both alpha and beta anomer of galactose (Gal). Binds strongly to branched beta-Gal-terminated glycans and weakly to unbranched glycans with alpha-Gal on the end of chains (PubMed:31905927). Has strong affinity for both Gal and GalNAc. Binds glycoproteins containing mucin-type chains. Has hemagglutinating activity towards human group A erythrocytes (Ref.2). Has hemagglutinating activity towards rabbit erythrocytes (PubMed:30292806). Agglutinates V.proteolyticus bacteria. Binds strongly to fungi including species from genera Aspergillus, Alternaria, Fusarium and Haematonectria, and to a lesser extent to fungi from genera Trichoderma. Decreases conidia germination and hyphal growth of fungi (PubMed:26802895). At high concentration, stimulates secretion of cytokines TNF-alpha and IFN-gamma from human peripheral blood cells, and at low concentration reduces hyperexpression of cytokine IL-10 in these cells, indicative of immunomodulatory capability. However, has no effect on IL-4 production (Ref.2). Recognizes pathogen-associated molecular patterns (PAMPs) and binds to peptidoglycan from S.aureus, but has only little binding to beta-1,3-glucan from E.gracilis and lipopolysaccharide (LPS) from E.coli (PubMed:31905927). May be involved in innate immunity acting as an antibacterial or antifungal agent recognizing carbohydrate ligands on the surface of pathogens (PubMed:26802895, PubMed:31905927). {ECO:0000269|PubMed:26802895, ECO:0000269|PubMed:30292806, ECO:0000269|PubMed:31905927, ECO:0000269|Ref.2}.

Mytilus trossulus (Blue mussel)

A0A0H2UNG0

PULA_STRPN

MRKTPSHTEKKMVYSIRSLKNGTGSVLIGASLVLLAMATPTISSDESTPTTNEPNNRNTTTLAQPLTDTAAGSGKNESDISSPGNANASLEKTEEKPAASPADPAPQTGQDRSSEPTTSTSPVTTETKAEEPIEDNYFRIHVKKLPEENKDAQGLWTWDDVEKPSENWPNGALSFKDAKKDDYGYYLDVKLKGEQAKKISFLINNTAGKNLTGDKSVEKLVPKMNEAWLDQDYKVFSYEPQPAGTVRVNYYRTDGNYDKKSLWYWGDVKNPSSAQWPDGTDFTATGKYGRYIDIPLNEAAREFGFLLLDESKQGDDVKIRKENYKFTDLKNHSQIFLKDDDESIYTNPYYVHDIRMTGAQHVGTSSIESSFSTLVGAKKEDILKHSNITNHLGNKVTITDVAIDEAGKKVTYSGDFSDTKHPYTVSYNSDQFTTKTSWRLKDETYSYDGKLGADLKEEGKQVDLTLWSPSADKVSVVVYDKNDPDKVVGTVALEKGERGTWKQTLDSTNKLGITDFTGYYYQYQIERQGKTVLALDPYAKSLAAWNSDDSKIDDAHKVAKAAFVDPAKLGPQDLTYGKIHNFKTREDAVIYEAHVRDFTSDPAIAKDLTKPFGTFEAFIEKLDYLKDLGVTHIQLLPVLSYYFVNELKNHERLSDYASSNSNYNWGYDPQNYFSLTGMYSSDPKNPEKRIAEFKNLINEIHKRGMGAILDVVYNHTAKVDLFEDLEPNYYHFMDADGTPRTSFGGGRLGTTHHMTKRLLIDSIKYLVDTYKVDGFRFDMMGDHDAASIEEAYKAARALNPNLIMLGEGWRTYAGDENMPTKAADQDWMKHTDTVAVFSDDIRNNLKSGYPNEGQPAFITGGKRDVNTIFKNLIAQPTNFEADSPGDVIQYIAAHDNLTLFDIIAQSIKKDPSKAENYAEIHRRLRLGNLMVLTAQGTPFIHSGQEYGRTKQFRDPAYKTPVAEDKVPNKSHLLRDKDGNPFDYPYFIHDSYDSSDAVNKFDWTKATDGKAYPENVKSRDYMKGLIALRQSTDAFRLKSLQDIKDRVHLITVPGQNGVEKEDVVIGYQITAPNGDIYAVFVNADEKAREFNLGTAFAHLRNAEVLADENQAGPVGIANPKGLEWTEKGLKLNALTATVLRVSQNGTSHESTAEEKPDSTPSKPEHQNEASHPAHQDPAPEARPDSTKPDAKVADAENKPSQATADSQAEQPAQEAQASSVKEAVRNESVENSSKENIPATPDKQAELPNTGIKNENKLLFAGISLLALLGLGFLLKNKKEN

3.2.1.41

alpha-glucan biosynthetic process [GO:0030979]

cell surface [GO:0009986]; extracellular region [GO:0005576]

amylopectin binding [GO:2001066]; calcium ion binding [GO:0005509]; glycogen binding [GO:2001069]; limit dextrinase activity [GO:0010303]; polysaccharide binding [GO:0030247]; pullulan binding [GO:2001067]; pullulanase activity [GO:0051060]

PF00128;PF02922;PF00746;PF03714;PF18033;PF04650;

2.60.40.1110;2.60.40.1220;3.20.20.80;2.60.40.1180;2.60.40.10;

Glycosyl hydrolase 13 family

SUBCELLULAR LOCATION: Secreted, cell wall {ECO:0000255|PROSITE-ProRule:PRU00477}; Peptidoglycan-anchor {ECO:0000255|PROSITE-ProRule:PRU00477}. Cell surface {ECO:0000250|UniProtKB:Q9F930}. Note=Localizes to cytoplasm in the lung alveolar type II cells of the mouse and human hosts. {ECO:0000269|PubMed:17187076, ECO:0000269|PubMed:21565699}.

CATALYTIC ACTIVITY: Reaction=Hydrolysis of (1->6)-alpha-D-glucosidic linkages in pullulan, amylopectin and glycogen, and in the alpha- and beta-limit dextrins of amylopectin and glycogen.; EC=3.2.1.41; Evidence={ECO:0000269|PubMed:20497336, ECO:0000269|PubMed:21565699};

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=360 uM for para-nitrophenyl-alpha-D-maltopentaoside (pNP-M5) (at 25 degrees Celsius) {ECO:0000269|PubMed:21565699}; Note=kcat is 270 min(-1) for pNP-M5. {ECO:0000269|PubMed:21565699};

FUNCTION: Virulence factor (By similarity). Involved in the degradation of glycogen of the mammalian host cells (PubMed:21565699). Hydrolyzes the alpha-1,6-branchpoints of glycogen (PubMed:20497336, PubMed:21565699). Hydrolyzes pullulan. Does not hydrolyze dextran (PubMed:20497336). Binds to mouse lung alveolar type II cells that are rich in glycogen stores. Is an alpha-glucan-specific carbohydrate-binding protein, which binds to amylose (pure alpha-(1,4)-linked glucose), amylopectin (alpha-(1,4)-linked glucose with alpha-(1,6) branch points), pullulan (linear polymer of mixed alpha-(1,4)- and alpha-(1,6)-linked glucose) and glycogen (similar to amylopectin with more frequent alpha-(1,6) branch points) in vitro. Does not bind to dextran (a linear polymer of alpha-(1,6)-linked glucose) (PubMed:17187076). {ECO:0000250|UniProtKB:A0A0H2ZL64, ECO:0000269|PubMed:17187076, ECO:0000269|PubMed:20497336, ECO:0000269|PubMed:21565699}.

Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4)

A0A0H2URG7

GTFA_STRPN

MTIYNINLGIGWASSGVEYAQAYRAGVFRKLNLSSKFIFTDMILADNIQHLTANIGFDDNQVIWLYNHFTDIKIAPTSVTVDDVLAYFGGEESHREKNGKVLRVFFFDQDKFVTCYLVDENKDLVQHAEYVFKGNLIRKDYFSYTRYCSEYFAPKDNVAVLYQRTFYNEDGTPVYDILMNQGKEEVYHFKDKIFYGKQAFVRAFMKSLNLNKSDLVILDRETGIGQVVFEEAQTAHLAVVVHAEHYSENATNEDYILWNNYYDYQFTNADKVDFFIVSTDRQNEVLQEQFAKYTQHQPKIVTIPVGSIDSLTDSSQGRKPFSLITASRLAKEKHIDWLVKAVIEAHKELPELTFDIYGSGGEDSLLREIIANHQAEDYIQLKGHAELSQIYSQYEVYLTASTSEGFGLTLMEAIGSGLPLIGFDVPYGNQTFIEDGQNGYLIPSSSDHVEDQIKQAYAAKICQLYQENRLEAMRAYSYQIAEGFLTKEILEKWKKTVEEVLHD

2.4.1.-

protein O-linked glycosylation via serine [GO:0018242]

cytoplasm [GO:0005737]; plasma membrane [GO:0005886]; protein N-acetylglucosaminyltransferase complex [GO:0017122]

glycosyltransferase activity [GO:0016757]; nucleotide binding [GO:0000166]

PF00534;

3.40.50.2000;

Glycosyltransferase group 1 family, Glycosyltransferase 4 subfamily

SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_01472}. Cell membrane {ECO:0000250|UniProtKB:A1C3L9, ECO:0000255|HAMAP-Rule:MF_01472}; Peripheral membrane protein {ECO:0000255|HAMAP-Rule:MF_01472}. Note=Cell membrane association requires GtfB. {ECO:0000250|UniProtKB:A1C3L9, ECO:0000255|HAMAP-Rule:MF_01472}.

CATALYTIC ACTIVITY: Reaction=L-seryl-[protein] + UDP-N-acetyl-alpha-D-glucosamine = 3-O-[N-acetyl-alpha-D-glucosaminyl]-L-seryl-[protein] + H(+) + UDP; Xref=Rhea:RHEA:59872, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:15471, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:57705, ChEBI:CHEBI:58223, ChEBI:CHEBI:143279; Evidence={ECO:0000250|UniProtKB:A0A0S4NM89, ECO:0000255|HAMAP-Rule:MF_01472, ECO:0000305|PubMed:24936067};

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: Note=kcat for hydrolysis of UDP-N-acetyl-alpha-D-glucosamine with transfer of GlcNAc to PsrP-SSR1 and generation of UDP is 76.0 min(-1) for GtfA-GtfB and 7.35 min(-1) for GtfA alone. {ECO:0000269|PubMed:24936067};

PATHWAY: Protein modification; protein glycosylation. {ECO:0000255|HAMAP-Rule:MF_01472, ECO:0000269|PubMed:24936067, ECO:0000269|PubMed:28246170}.

FUNCTION: Required for the polymorphic O-glycosylation of serine-rich repeat protein PsrP. Catalyzes the first step in glycosylation by transferring N-acetylglucosamine from UDP-GlcNAc to serine residues in PsrP (PubMed:24936067, PubMed:28246170). Part of the accessory SecA2/SecY2 system specifically required to export serine-rich repeat cell wall proteins encoded upstream in the same operon (Probable). The GtfA-GtfB complex adds GlcNAc from UDP-GlcNAc to PsrP (experimentally characterized with truncated PsrP-SSR1 constructs); this subunit alone has weak N-acetylglucosaminyl transferase activity that is 10-fold stimulated by GtfB. The complex requires at least a 25 residue-long peptide for activity; the in vitro assay has only been seen to glycosylate Ser residues (PubMed:24936067). The alpha linkage was shown in L.reuteri. {ECO:0000250|UniProtKB:A0A0S4NM89, ECO:0000269|PubMed:24936067, ECO:0000269|PubMed:28246170, ECO:0000305|PubMed:16861665}.

Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4)

A0A0H2URJ6

GLYE_STRPN

MRNTKRAVVFAGDYAYIRQIETAMKSLCRHNSHLKIYLLNQDIPQEWFSQIRIYLQEMGGDLIDCKLIGSQFQMNWSNKLPHINHMTFARYFIPDFVTEDKVLYLDSDLIVTGDLTDLFELDLGENYLAAARSCFGAGVGFNAGVLLINNKKWGSETIRQKLIDLTEKEHENVEEGDQSILNMLFKDQYSSLEDQYNFQIGYDYGAATFKHQFIFDIPLEPLPLILHYISQDKPWNQFSVGRLREVWWEYSLMDWSVILNEWFSKSVKYPSKSQIFKLQCVNLTNSWCVEKIDYLAEQLPEVHFHIVAYTNMANELLALTRFPNVTVYPNSLPMLLEQIVIASDLYLDLNHDRKLEDAYEFVLKYKKPMIAFDNTCSENLSEISYEGIYPSSIPKKMVAAIRSYMR

COFACTOR: Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269|PubMed:28246170};

protein glycosylation [GO:0006486]

glycosyltransferase activity [GO:0016757]; metal ion binding [GO:0046872]; nucleotide binding [GO:0000166]

PF01501;

Glycosyltransferase 8 family

PATHWAY: Protein modification; protein glycosylation. {ECO:0000269|PubMed:28246170}.

FUNCTION: Involved in the polymorphic O-glycosylation of the serine-rich repeat protein PsrP. Catalyzes the third step in glycosylation of PsrP in this bacteria. Transfers galactose from UDP-galactose to the terminal glucose moiety of already-glycosylated PsrP (using the short substrate PsrP-GlcNAc-Glc). Has a very marked preference for PsrP substrate that has already been modified by GlcNAc and glucose. Has hydrolytic activity against UDP-galactose but none against UDP-glucose. {ECO:0000269|PubMed:28246170}.; FUNCTION: Also catalyzes the fourth step in glycosylation of PsrP in this bacteria. Can transfer the sugar from UDP-galactose to the terminal sugar moiety of PsrP-GlcNAc-Glc-Glc and of PsrP-GlcNAc-Glc-Gal. {ECO:0000269|PubMed:28246170}.

Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4)

A0A0H2URK1

PSRP_STRPN

MTETVEDKVSHSITGLDILKGIVAAGAVISGTVATQTKVFTNESAVLEKTVEKTDALATNDTVVLGTISTSNSASSTSLSASESASTSASESASTSASTSASTSASESASTSASTSISASSTVVGSQTAAATEATAKKVEEDRKKPASDYVASVTNVNLQSYAKRRKRSVDSIEQLLASIKNAAVFSGNTIVNGAPAINASLNIAKSETKVYTGEGVDSVYRVPIYYKLKVTNDGSKLTFTYTVTYVNPKTNDLGNISSMRPGYSIYNSGTSTQTMLTLGSDLGKPSGVKNYITDKNGRQVLSYNTSTMTTQGSGYTWGNGAQMNGFFAKKGYGLTSSWTVPITGTDTSFTFTPYAARTDRIGINYFNGGGKVVESSTTSQSLSQSKSLSVSASQSASASASTSASASASTSASASASTSASASASTSASVSASTSASASASTSASASASTSASESASTSASASASTSASASASTSASASASTSASESASTSASASASTSASESASTSASASASTSASASASTSASGSASTSTSASASTSASASASTSASASASISASESASTSASESASTSTSASASTSASESASTSASASASTSASASASTSASASASTSASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASVSASTSASASASTSASASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASASISASESASTSASASASTSASASASTSASASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASESASTSASASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASTSASESASTSASASASTSASASASTSASASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASASISASESASTSASASASTSASVSASTSASASASTSASESASTSASASASTSASESASTSASASASTSASASASISASESASTSASASASTSASASASTSASASASTSASESASTSTSASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASVSASTSASESASTSASASASTSASASASTSASESASTSASASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASISASESASTSASASASTSASASASTSASVSASTSASASASTSASASASISASESASTSASASASTSASASASTSASASASTSASASASISASESASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASESASTSASASASTSASASASTSASASASTSASVSASTSASESASTSASASASTSASASASTSASASASTSASESASTSASASASTSASASASTSASESASTSASASASTSASASASTSASASASTSASASASASTSASASASTSASASASTSASASASISASESASTSASESASTSTSASASTSASESASTSASASASTSASASASTSASASASTSASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASASTSASVSASTSASASASTSASASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASASISASESASTSASASASTSASASASTSASASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASESASTSASASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASTSASESASTSASASASTSASASASTSASASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASASISASESASTSASASASTSASVSASTSASASASTSASESASTSASASASTSASESASTSASASASTSASASASISASESASTSASASASTSASASASTSASASASTSASESASTSTSASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASESASTSASASASTSASASASTSASASASTSASVSASTSASESASTSASASASTSASASASTSASASASTSASESASTSASASASTSASASASTSASESASTSASASASTSASASASTSASASASTSASASASASTSASASASTSASASASTSASASASISASESASTSASASASASTSASASASTSASASASTSASASASISASESASTSASESASTSTSASASTSASESASTSASASASTSASASASTSASASASTSASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASASTSASVSASTSASASASTSASASASTSASESASTSASASTSASESASTSASASASTSASASASTSASASASTSASESASTSASASASTSASASASTSASESASTSASASASTSASASASTSASASASTSASESASTSASASASTSASESASTSASASASTSASASASTSASGSASTSTSASASTSASASASTSASASASISASESASTSASESASTSTSASASTSASESASTSASASASTSASASASTSASASASTSASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASVSASTSASASASTSASASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASASISASESASTSASASASTSASASASTSASASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASESASTSASASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASTSASESASTSASASASTSASASASTSASASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASASISASESASTSASASASTSASVSASTSASASASTSASESASTSASASASTSASESASTSASASASTSASASASISASESASTSASASASTSASASASTSASASASTSASESASTSTSASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASVSASTSASESASTSASASASTSASASASTSASESASTSASASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASISASESASTSASASASTSASASASTSASVSASTSASASASTSASASASISASESASTSASASASTSASASASTSASASASTSASASASISASESASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASESASTSASASASTSASASASISASESASTSASASASTSASASASTSASASASTSASESASTSTSASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASVSASTSASESASTSASASASTSASASASTSASESASTSASASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASISASESASTSASASASTSASASASTSASVSASTSASASASTSASASASISASESASTSASASASTSASASASTSASASASTSASASASISASESASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSVSNSANHSNSQVGNTSGSTGKSQKELPNTGTESSIGSVLLGVLAAVTGIGLVAKRRKRDEEE

cell adhesion [GO:0007155]; single-species biofilm formation [GO:0044010]; symbiont-mediated perturbation of host defense response [GO:0052031]

cell surface [GO:0009986]; extracellular region [GO:0005576]; Gram-positive-bacterium-type cell wall [GO:0009275]

DNA binding [GO:0003677]

PF00746;

Serine-rich repeat protein (SRRP) family

PTM: Glycosylated (PubMed:19627498). Only truncated substrates greater than 25 residues long are glycosylated by the Gtf1-Gtf2 complex in vitro; only Ser residues have been seen to be glycosylated. Based on electrophoretic mobility it is probable that most of the Ser residues in SSR1 and SSR2 are O-GlcNAcylated (PubMed:24936067). Subsequent glycosylation by up to 7 sugar transferases (Gtf3 and GlyAT, GlyB, GlyD, GlyE, GlyF and GlyG) is able to generate very high sugar polymorphism (PubMed:28246170). {ECO:0000269|PubMed:19627498, ECO:0000269|PubMed:24936067, ECO:0000269|PubMed:28246170}.; PTM: Can be cleaved by human furin protease; this fragment contributes to self-aggregation and possibly biofilm formation in vitro. {ECO:0000269|PubMed:27582320}.

SUBCELLULAR LOCATION: Secreted, cell wall {ECO:0000255|PROSITE-ProRule:PRU00477, ECO:0000269|PubMed:19627498}; Peptidoglycan-anchor {ECO:0000255|PROSITE-ProRule:PRU00477}. Cell surface {ECO:0000269|PubMed:19627498}.

FUNCTION: Protein that allows bacteria to adhere to mammalian host cells. Required for full virulence in mouse infection models when infected intranasally (PubMed:16861665). Required for adhesion to host cells in vitro and for persistence in the lower respiratory tract (PubMed:18507531). Binds host keratin 10 (KRT10) on lung cells which mediates adhesion via the C-terminus of the basic region (BR, residues 273-341); glycosylation of either protein is not required for the interaction (PubMed:19627498). A region in the N-terminus (residues 122-166) self aggregates, contributing to mature biofilm formation (PubMed:20714350). The basic region (BR, residues 187-385) also self aggregates; the BR binds DNA which enhances self aggregation (PubMed:27582320). {ECO:0000269|PubMed:16861665, ECO:0000269|PubMed:18507531, ECO:0000269|PubMed:19627498, ECO:0000269|PubMed:20714350, ECO:0000269|PubMed:27582320}.

Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4)

A0A0H2URU9

COMGC_STRPN

MKKMMTFLKKAKVKAFTLVEMLVVLLIISVLFLLFVPNLTKQKEAVNDKGKAAVVKVVESQAELYSLEKNEDASLRKLQADGRITEEQAKAYKEYNDKNGGANRKVND

establishment of competence for transformation [GO:0030420]; protein secretion by the type II secretion system [GO:0015628]

cell surface [GO:0009986]; extracellular region [GO:0005576]; pilus [GO:0009289]; plasma membrane [GO:0005886]; type II protein secretion system complex [GO:0015627]

PF07963;

3.30.700.10;

ComGC family

PTM: Undergoes proteolytic cleavage. {ECO:0000269|PubMed:24550320, ECO:0000269|PubMed:28659339}.

SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P25955}; Single-pass membrane protein {ECO:0000250|UniProtKB:P25955, ECO:0000255}. Cell surface {ECO:0000250|UniProtKB:P25955}. Fimbrium {ECO:0000250|UniProtKB:Q8DN88}. Secreted {ECO:0000269|PubMed:24550320}. Note=The unprocessed form is an integral membrane protein with its C-terminus outside the membrane. Upon cleavage, it is translocated to the outer face of the membrane (By similarity). ComGC release into culture supernatant is probably physiological because it is still observed in an autolysis-deficient lytA mutant background (PubMed:24550320). {ECO:0000250|UniProtKB:P25955, ECO:0000269|PubMed:24550320}.

FUNCTION: Major component of the type IV-like pilus (T4P) that plays a role in transformation (PubMed:28659339). Transformation pili are dynamically extended and retracted, perhaps thereby promoting DNA uptake and transformation (By similarity). Required for transformation (PubMed:24550320). Required for DNA binding (By similarity). {ECO:0000250|UniProtKB:P25955, ECO:0000250|UniProtKB:Q8DN88, ECO:0000269|PubMed:24550320, ECO:0000269|PubMed:28659339}.

Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4)

A0A0H2US87

OSPC3_SHIFL

MKIPEAVNHINVQNNIDLVDGKINPNKDTKALQKNISCVTNSSSSGISEKHLDHCADTVKSFLRKSIAAQSYSKMFSQGTSFKSLNLSIEAPSGARSSFRSLEHLDKVSRHYLSEIIQKTHPLSSDERHLLSIIINSDFNFRHQSNANLSNNTLNIKSFDKIKSENIQTYKNTFSEDIEEIANHDFVFFGVEISNHQETLPLNKTHHTVDFGANAYIIDHDSPYGYMTLTDHFDNAIPPVFYHEHQSFFLDNFKEVVDEVSRYVHGNQGKTDVPIFNTKDMRLGIGLHLIDFIRKSKDQRFREFCYNKNIDPVSLDRIINFVFQLEYHIPRMLSTDNFKKIKLRDISLEDAIKASNYEEINNKVTDKKMAHQALAYSLGNKKADIALYLLSKFNFTKQDVAEMEKMKNNRYCNLYDVEYLLSKDGANYKVLEYFINNGLVDVNKKFQKVNSGDTMLDNAMKSKDSKMIDFLLKNGAILGKRFEI

4.3.99.-

modulation by symbiont of defense-related host calcium ion flux [GO:0052162]; symbiont-mediated perturbation of host programmed cell death [GO:0052040]; symbiont-mediated suppression of host calcium or calmodulin-mediated signal transduction [GO:0075135]; symbiont-mediated suppression of host programmed cell death [GO:0052041]; symbiont-mediated suppression of host signal transduction pathway [GO:0052029]

extracellular region [GO:0005576]; host cell cytoplasm [GO:0030430]

ADP-riboxanase activity [GO:0140740]; calmodulin binding [GO:0005516]; toxin activity [GO:0090729]

PF06128;

OspC family

SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:23684308}. Host cytoplasm {ECO:0000305|PubMed:34409271}. Note=Secreted via the type III secretion system (T3SS). {ECO:0000269|PubMed:23684308}.

CATALYTIC ACTIVITY: Reaction=L-arginyl-[protein] + NAD(+) = ADP-riboxanated L-argininyl-[protein] + H(+) + NH4(+) + nicotinamide; Xref=Rhea:RHEA:69500, Rhea:RHEA-COMP:10532, Rhea:RHEA-COMP:17719, ChEBI:CHEBI:15378, ChEBI:CHEBI:17154, ChEBI:CHEBI:28938, ChEBI:CHEBI:29965, ChEBI:CHEBI:57540, ChEBI:CHEBI:184300; Evidence={ECO:0000269|PubMed:34671164, ECO:0000269|PubMed:35338844, ECO:0000269|PubMed:35568036, ECO:0000269|PubMed:36624349}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69501; Evidence={ECO:0000269|PubMed:34671164, ECO:0000269|PubMed:35338844, ECO:0000269|PubMed:35568036, ECO:0000269|PubMed:36624349};

FUNCTION: ADP-riboxanase effector that inhibits host cell pyroptosis (PubMed:23684308, PubMed:34409271, PubMed:34671164, PubMed:36624349). Acts by mediating arginine ADP-riboxanation of host CASP4/CASP11, blocking CASP4/CASP11 autoprocessing (PubMed:34671164, PubMed:35338844, PubMed:35568036, PubMed:36624349, PubMed:37014865). This prevents CASP4 activation and ability to recognize and cleave GSDMD, thereby inhibiting LPS-induced pyroptosis (PubMed:34671164, PubMed:36624349). ADP-riboxanation takes place in two steps: OspC3 first catalyzes ADP-ribosylation of target Arg, and then initiates a deamination to remove one N-omega group (PubMed:34671164). Independently of its ADP-riboxanase activity, acts as an inhibitor of calcium signaling by inhibiting host calmodulin, preventing activation of the JAK-STAT signaling pathway in response to interferon-beta (PubMed:35568036). Mechanistically, acts by binding to the apo form of calmodulin, preventing calcium-binding and ability to activate host CaMK2 (CAMKII), which is required to stimulate the JAK-STAT signaling pathway in response to interferon-beta (PubMed:35568036). {ECO:0000269|PubMed:23684308, ECO:0000269|PubMed:34409271, ECO:0000269|PubMed:34671164, ECO:0000269|PubMed:35338844, ECO:0000269|PubMed:35568036, ECO:0000269|PubMed:36624349, ECO:0000269|PubMed:37014865}.

Shigella flexneri

A0A0H2USG1

IPA14_SHIFL

MIKSTNIQAIGSGIMHQINNVYSLTPLSLPMELTPSCNEFYLKTWSEWEKNGTPGEQRNIAFNRLKICLQNQEAELNLSELDLKTLPDLPPQITTLEIRKNLLTHLPDLPPMLKVIHAQFNQLESLPALPETLEELNAGDNKIKELPFLPENLTHLRVHNNRLHILPLLPPELKLLVVSGNRLDSIPPFPDKLEGLALANNFIEQLPELPFSMNRAVLMNNNLTTLPESVLRLAQNAFVNVAGNPLSGHTMRTLQQITTGPDYSGPQIFFSMGNSATISAPEHSLADAVTAWFPENKQSDVSQIWHAFEHEEHANTFSAFLDRLSDTVSARNTSGFREQVAAWLEKLSASAELRQQSFAVAADATESCEDRVALTWNNLRKTLLVHQASEGLFDNDTGALLSLGREMFRLEILEDIARDKVRTLHFVDEIEVYLAFQTMLAEKLQLSTAVKEMRFYGVSGVTANDLRTAEAMVRSREENEFTDWFSLWGPWHAVLKRTEADRWAQAEEQKYEMLENEYSQRVADRLKASGLSGDADAEREAGAQVMRETEQQIYRQLTDEVLALRLSENGSNHIA

2.3.2.27

protein ubiquitination [GO:0016567]; symbiont-mediated suppression of host NF-kappaB cascade [GO:0085034]

extracellular region [GO:0005576]; host cell cytoplasm [GO:0030430]

toxin activity [GO:0090729]; ubiquitin protein ligase activity [GO:0061630]

PF14496;PF12468;

1.20.58.90;3.80.10.10;1.20.58.360;1.20.1270.130;

LRR-containing bacterial E3 ligase family

SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q8VSC3}. Host cytoplasm {ECO:0000250|UniProtKB:Q8VSC3}. Note=Secreted via Mxi-Spa type III secretion system (T3SS), and delivered into the host cytoplasm. {ECO:0000250|UniProtKB:Q8VSC3}.

CATALYTIC ACTIVITY: Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27; Evidence={ECO:0000269|PubMed:18997778, ECO:0000269|PubMed:27572974, ECO:0000269|PubMed:35294289};

PATHWAY: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:18997778, ECO:0000269|PubMed:27572974, ECO:0000269|PubMed:35294289}.

FUNCTION: E3 ubiquitin-protein ligase effector that inhibits host cell innate immunity during bacterial infection by catalyzing 'Lys-48'-linked polyubiquitination and subsequent degradation of host RNF31/HOIP and RBCK1/HOIL-1 (PubMed:18997778, PubMed:27572974, PubMed:35294289, PubMed:36610722). Host RNF31/HOIP is the catalytic component of the LUBAC complex, which conjugates linear ('Met-1'-linked) polyubiquitin chains at the surface of bacteria invading the host cytosol to form the ubiquitin coat surrounding bacteria (PubMed:27572974, PubMed:35294289). The bacterial ubiquitin coat acts as an 'eat-me' signal for xenophagy and promotes NF-kappa-B activation (PubMed:27572974, PubMed:28481331). By promoting degradation of host RNF31/HOIP, IpaH1.4 prevents formation of the bacterial ubiquitin coat and activation of host cell innate immunity (PubMed:27572974, PubMed:28481331). {ECO:0000269|PubMed:18997778, ECO:0000269|PubMed:27572974, ECO:0000269|PubMed:28481331, ECO:0000269|PubMed:35294289, ECO:0000269|PubMed:36610722}.

Shigella flexneri

A0A0H2V871

IROE_ECOL6

MYAREYRSTRPHKAIFFHLSCLTLICSAQVYAKPDMRPLGPNIADKGSVFYHFSATSFDSVDGTRHYRVWTAVPNTTAPASGYPILYMLDGNAVMDRLDDELLKQLSEKTPPVIVAVGYQTNLPFDLNSRAYDYTPAAESRKTDLHSGRFSRKSGGSNNFRQLLETRIAPKVEQGLNIDRQRRGLWGHSYGGLFVLDSWLSSSYFRSYYSASPSLGRGYDALLSRVTAVEPLQFCTKHLAIMEGSATQGDNRETHAVGVLSKIHTTLTILKDKGVNAVFWDFPNLGHGPMFNASFRQALLDISGENANYTAGCHELSH

3.1.1.107

plasma membrane [GO:0005886]

carboxylic ester hydrolase activity [GO:0052689]

PF00756;

3.40.50.1820;

Esterase D family

SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000305|PubMed:16076215}; Single-pass membrane protein {ECO:0000255}; Periplasmic side {ECO:0000305|PubMed:16076215}.

CATALYTIC ACTIVITY: Reaction=enterobactin + H2O = N-(2,3-dihydroxybenzoyl)-L-serine trimer; Xref=Rhea:RHEA:60384, ChEBI:CHEBI:15377, ChEBI:CHEBI:77805, ChEBI:CHEBI:143020; EC=3.1.1.107; Evidence={ECO:0000269|PubMed:16076215}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60385; Evidence={ECO:0000269|PubMed:16076215}; CATALYTIC ACTIVITY: Reaction=H2O + monoglucosyl-enterobactin = [N-(2,3-dihydroxybenzoyl)-L-seryl]2-N-(C-5-[deoxy-beta-D-glucosyl]-2,3-dihydroxybenzoyl)-L-serine + H(+); Xref=Rhea:RHEA:60412, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:142958, ChEBI:CHEBI:143023; EC=3.1.1.107; Evidence={ECO:0000269|PubMed:16076215}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60413; Evidence={ECO:0000269|PubMed:16076215}; CATALYTIC ACTIVITY: Reaction=diglucosyl-enterobactin + H2O = H(+) + N-(2,3-dihydroxybenzoyl)-L-seryl-[N-(C-5-[deoxy-beta-D-glucosyl]-2,3-dihydroxybenzoyl)-L-serine]2; Xref=Rhea:RHEA:60416, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:142959, ChEBI:CHEBI:143022; EC=3.1.1.107; Evidence={ECO:0000269|PubMed:16076215}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60417; Evidence={ECO:0000269|PubMed:16076215}; CATALYTIC ACTIVITY: Reaction=H2O + triglucosyl-enterobactin = [N-(C-5-[deoxy-beta-D-glucosyl]-2,3-dihydroxybenzoyl)-L-serine]3 + H(+); Xref=Rhea:RHEA:60420, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:142960, ChEBI:CHEBI:143021; EC=3.1.1.107; Evidence={ECO:0000269|PubMed:16076215}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60421; Evidence={ECO:0000269|PubMed:16076215};

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=16 uM for Ent {ECO:0000269|PubMed:16076215}; KM=3.4 uM for Fe-Ent {ECO:0000269|PubMed:16076215}; KM=29 uM for MGE {ECO:0000269|PubMed:16076215}; KM=4.8 uM for Fe-MGE {ECO:0000269|PubMed:16076215}; KM=39 uM for DGE {ECO:0000269|PubMed:16076215}; KM=4.6 uM for Fe-DGE {ECO:0000269|PubMed:16076215}; KM=155 uM for TGE {ECO:0000269|PubMed:16076215}; Note=kcat is 375 min(-1) with Ent as substrate. kcat is 3.0 min(-1) with Fe-Ent as substrate. kcat is 430 min(-1) with MGE as substrate. kcat is 3.2 min(-1) with Fe-MGE as substrate. kcat is 320 min(-1) with DGE as substrate. kcat is 2.5 min(-1) with Fe-DGE as substrate. kcat is 450 min(-1) with TGE as substrate. {ECO:0000269|PubMed:16076215};

FUNCTION: Catalyzes the hydrolysis of both the apo and Fe3(+)-bound forms of enterobactin (Ent), monoglucosyl-C-Ent (MGE), diglucosyl-C-Ent (DGE) and triglucosyl-C-Ent (TGE). It prefers apo siderophores as substrates and hydrolyzes the Fe3(+)-bound siderophores very inefficiently. Tends to hydrolyze the trilactone just once to produce linearized trimers. May hydrolyze and linearize some or all of apo enterobactins while they are being exported. {ECO:0000269|PubMed:16076215}.

Escherichia coli O6:H1 (strain CFT073 / ATCC 700928 / UPEC)

A0A0H2V8B5

TCPC_ECOL6

MIAYENIEFFICLVNVLGNNMYNILFFIFLSIAIPFLLFLAWKQHLKTKEIRSYLLKEGYNIIFNGEGNSYLAFNISNATFRAGNLTSNDYFQASISYIHDYRWEWKEVEAKKINNIFIIYISNIDFPSQKLFYRNNKSLAEIDWAKLQAIFHQPYEIQNDVMQDNNNTHYDFFISHAKEDKDTFVRPLVDELNRLGVIIWYDEQTLEVGDSLRRNIDLGLRKANYGIVILSHNFLNKKWTQYELDSLINRAVYDDNKIILPIWHNINAQEVSKYSHYLADKMALQTSLYSVKEIARELAEIAYRRR

3.2.2.-; 3.2.2.6

NAD catabolic process [GO:0019677]; negative regulation of MyD88-dependent toll-like receptor signaling pathway [GO:0034125]; signal transduction [GO:0007165]

extracellular region [GO:0005576]; membrane [GO:0016020]

NAD+ nucleosidase activity [GO:0003953]; NAD+ nucleotidase, cyclic ADP-ribose generating [GO:0061809]; NADP+ nucleosidase activity [GO:0050135]

PF13676;

3.40.50.10140;

SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:18327267}. Membrane {ECO:0000255}; Single-pass membrane protein {ECO:0000255}.

CATALYTIC ACTIVITY: Reaction=H2O + NAD(+) = ADP-D-ribose + H(+) + nicotinamide; Xref=Rhea:RHEA:16301, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17154, ChEBI:CHEBI:57540, ChEBI:CHEBI:57967; EC=3.2.2.6; Evidence={ECO:0000269|PubMed:29395922}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16302; Evidence={ECO:0000269|PubMed:29395922}; CATALYTIC ACTIVITY: Reaction=H2O + NADP(+) = ADP-D-ribose 2'-phosphate + H(+) + nicotinamide; Xref=Rhea:RHEA:19849, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17154, ChEBI:CHEBI:58349, ChEBI:CHEBI:58673; Evidence={ECO:0000269|PubMed:29395922}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19850; Evidence={ECO:0000269|PubMed:29395922};

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=196 uM for NAD(+) {ECO:0000269|PubMed:29395922};

FUNCTION: Virulence factor that suppresses host Toll-like receptor (TLR)-mediated cytokine production upon infection, thereby increasing bacterial burden in the urinary tract and promoting renal tissue damage (PubMed:18327267, PubMed:20886104). Acts as a NAD(+) hydrolase (NADase) by catalyzing cleavage of NAD(+) into ADP-D-ribose (ADPR) and nicotinamide (PubMed:29395922). Also able to hydrolyze NADP(+), but not other NAD(+)-related molecules (PubMed:29395922). {ECO:0000269|PubMed:18327267, ECO:0000269|PubMed:20886104, ECO:0000269|PubMed:29395922}.

Escherichia coli O6:H1 (strain CFT073 / ATCC 700928 / UPEC)

A0A0H2VDN9

ESIB_ECOL6

MKKSLLAVMLTGLFALVSLPALGNVNLEQLKQKAESGEAKAQLELGYRYFQGNETTKDLTQAMDWFRRAAEQGYTPAEYVLGLRYMNGEGVPQDYAQAVIWYKKAALKGLPQAQQNLGVMYHEGNGVKVDKAESVKWFRLAAEQGRDSGQQSMGDAYFEGDGVTRDYVMAREWYSKAAEQGNVWSCNQLGYMYSRGLGVERNDAISAQWYRKSATSGDELGQLHLADMYYFGIGVTQDYTQSRVLFSQSAEQGNSIAQFRLGYILEQGLAGAKEPLKALEWYRKSAEQGNSDGQYYLAHLYDKGAEGVAKNREQAISWYTKSAEQGDATAQANLGAIYFRLGSEEEHKKAVEWFRKAAAKGEKAAQFNLGNALLQGKGVKKDEQQAAIWMRKAAEQGLSAAQVQLGEIYYYGLGVERDYVQAWAWFDTASTNDMNLFGTENRNITEKKLTAKQLQQAELLSQQYIEKYAPEAWARMQKLKAQSAVKTGNK

COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:24099525}; Note=The physiological metal is unknown. {ECO:0000305|PubMed:24099525};

ERAD pathway [GO:0036503]; negative regulation of immune response [GO:0050777]; negative regulation of neutrophil activation [GO:1902564]

cell surface [GO:0009986]

IgA binding [GO:0019862]; metal ion binding [GO:0046872]

PF08238;

1.25.40.10;

SUBCELLULAR LOCATION: Cell surface {ECO:0000269|PubMed:23882011}. Note=Accumulates at 1 cell pole in the bladder of mice infected with this strain, in overexpressing bacteria the protein is found all over the cell surface but not in the secreted fraction (PubMed:23882011). Human blood sera from clinical patients with urinary tract infections reacts with antibodies to this protein (PubMed:23882011). {ECO:0000269|PubMed:23882011}.

FUNCTION: Upon host (human neutrophil) infection interferes with productive FCAR signaling, inhibiting secreted IgA (SIgA) effector functions and probably avoiding neutrophil activation. Inhibits the SIgA-mediated oxidative burst by neutrophils, decreases generation of ROS (reactive oxygen species) by neutrophils and reduces chemotaxis by neutrophils, all of which are SIgA effector functions used to stimulate the immune response. Does not block SIgA-binding to its receptor (FCAR) on neutrophils, but it decreases SIgA-stimulated phosphorylation of cytoplasmic proteins, including phospholipase C-gamma and MAP kinases, all actions that may be advantageous to the pathogen. {ECO:0000269|PubMed:23882011}.

Escherichia coli O6:H1 (strain CFT073 / ATCC 700928 / UPEC)

A0A0H2VG78

GLCP_STAES

MKANKYLIFILGALGGLLYGYDNGVISGALLFIHKDIPLNSTTEGIVVSSMLIGAIVGAGSSGPLADKLGRRRLVMLIAIVFIIGALILAASTNLALLIIGRLIIGLAVGGSMSTVPVYLSEMAPTEYRGSLGSLNQLMITIGILAAYLVNYAFADIEGWRWMLGLAVVPSVILLVGIYFMPESPRWLLENRNEEAARQVMKITYDDSEIDKELKEMKEINAISESTWTVIKSPWLGRILIVGCIFAIFQQFIGINAVIFYSSSIFAKAGLGEAASILGSVGIGTINVLVTIVAIFVVDKIDRKKLLVGGNIGMIASLLIMAILIWTIGIASSAWIIIVCLSLFIVFFGISWGPVLWVMLPELFPMRARGAATGISALVLNIGTLIVSLFFPILSDALSTEWVFLIFAFIGVLAMIFVIKFLPETRGRSLEEIEYELRERTGARTE

plasma membrane [GO:0005886]

glucose transmembrane transporter activity [GO:0005355]; symporter activity [GO:0015293]

PF00083;

1.20.1250.20;

Major facilitator superfamily, Sugar transporter (TC 2.A.1.1) family

SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:24127585}; Multi-pass membrane protein {ECO:0000269|PubMed:24127585}.

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=29 uM for glucose {ECO:0000269|PubMed:24127585}; Vmax=160 nmol/min/mg enzyme {ECO:0000269|PubMed:24127585};

FUNCTION: Transporter highly specific for glucose uptake. {ECO:0000269|PubMed:24127585}.

Staphylococcus epidermidis (strain ATCC 12228 / FDA PCI 1200)

A0A0H2WWV6

TARM_STAAC

MKKIFMMVHELDVNKGGMTSSMFNRSKEFYDADIPADIVTFDYKGNYDEIIKALKKQGKMDRRTKMYNVFEYFKQISNNKHFKSNKLLYKHISERLKNTIEIEESKGISRYFDITTGTYIAYIRKSKSEKVIDFFKDNKRIERFSFIDNKVHMKETFNVDNKVCYQVFYDEKGYPYISRNINANNGAVGKTYVLVNKKEFKNNLALCVYYLEKLIKDSKDSIMICDGPGSFPKMFNTNHKNAQKYGVIHVNHHENFDDTGAFKKSEKYIIENANKINGVIVLTEAQRLDILNQFDVENIFTISNFVKIHNAPKHFQTEKIVGHISRMVPTKRIDLLIEVAELVVKKDNAVKFHIYGEGSVKDKIAKMIEDKNLERNVFLKGYTTTPQKCLEDFKLVVSTSQYEGQGLSMIEAMISKRPVVAFDIKYGPSDFIEDNKNGYLIENHNINDMADKILQLVNNDVLAAEFGSKARENIIEKYSTESILEKWLNLFNS

2.4.1.70

cell wall organization [GO:0071555]; teichoic acid biosynthetic process [GO:0019350]

cytoplasm [GO:0005737]

poly(ribitol-phosphate) N-acetylglucosaminyltransferase activity [GO:0047269]

PF00534;

3.40.50.2000;

Glycosyltransferase group 1 family

SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305|PubMed:20185825}.

CATALYTIC ACTIVITY: Reaction=4-O-[(D-ribitylphospho)(n)-di{(2R)-glycerylphospho}]-N-acetyl-beta-D-mannosaminyl-(1->4)-N-acetyl-alpha-D-glucosaminyl di-trans,octa-cis-undecaprenyl diphosphate + n UDP-N-acetyl-alpha-D-glucosamine = 4-O-([2-N-acetyl-alpha-D-glucosaminyl-1-D-ribitylphospho](n)-di{[2R]-1-glycerylphospho})-N-acetyl-beta-D-mannosaminyl-(1->4)-N-acetyl-alpha-D-glucosaminyl di-trans,octa-cis-undecaprenyl diphosphate + n H(+) + n UDP; Xref=Rhea:RHEA:21012, Rhea:RHEA-COMP:12840, Rhea:RHEA-COMP:14256, ChEBI:CHEBI:15378, ChEBI:CHEBI:57705, ChEBI:CHEBI:58223, ChEBI:CHEBI:133896, ChEBI:CHEBI:139145; EC=2.4.1.70; Evidence={ECO:0000269|PubMed:20185825, ECO:0000269|PubMed:25624472, ECO:0000269|PubMed:25697358};

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=65 uM for UDP-GlcNAc {ECO:0000269|PubMed:25624472}; KM=390 uM for WTA {ECO:0000269|PubMed:25624472}; Note=kcat is 126 min(-1). {ECO:0000269|PubMed:25624472};

PATHWAY: Cell wall biogenesis; poly(ribitol phosphate) teichoic acid biosynthesis. {ECO:0000269|PubMed:20185825}.

FUNCTION: Attaches N-acetyl-alpha-D-glucosamine residues to poly(RboP)-wall teichoic acids (WTAs). {ECO:0000269|PubMed:20185825, ECO:0000269|PubMed:25624472, ECO:0000269|PubMed:25697358}.

Staphylococcus aureus (strain COL)

A0A0H2WZ38

GATD_STAAC

MHELTIYHFMSDKLNLYSDIGNIIALRQRAKKRNIKVNVVEINETEGITFDECDIFFIGGGSDREQALATKELSKIKTPLKEAIEDGMPGLTICGGYQFLGKKYITPDGTELEGLGILDFYTESKTNRLTGDIVIESDTFGTIVGFENHGGRTYHDFGTLGHVTFGYGNNDEDKKEGIHYKNLLGTYLHGPILPKNYEITDYLLEKACERKGIPFEPKEIDNEAEIQAKQVLIDRANRQKKSR

3.5.1.2; 6.3.5.13

cell wall organization [GO:0071555]; cobalamin biosynthetic process [GO:0009236]; glutamine metabolic process [GO:0006541]; peptidoglycan biosynthetic process [GO:0009252]; regulation of cell shape [GO:0008360]

carbon-nitrogen ligase activity on lipid II [GO:0140282]; glutaminase activity [GO:0004359]

PF07685;

3.40.50.880;

CobB/CobQ family, GatD subfamily

CATALYTIC ACTIVITY: Reaction=ATP + beta-D-GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)-di-trans,octa-cis-undecaprenyl diphosphate + H2O + L-glutamine = ADP + beta-D-GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-D-isoglutaminyl-L-Lys-D-Ala-D-Ala)-di-trans,octa-cis-undecaprenyl diphosphate + H(+) + L-glutamate + phosphate; Xref=Rhea:RHEA:57928, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29985, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:58359, ChEBI:CHEBI:60033, ChEBI:CHEBI:62233, ChEBI:CHEBI:456216; EC=6.3.5.13; Evidence={ECO:0000250|UniProtKB:A0A0H3JN63, ECO:0000255|HAMAP-Rule:MF_02213}; CATALYTIC ACTIVITY: Reaction=H2O + L-glutamine = L-glutamate + NH4(+); Xref=Rhea:RHEA:15889, ChEBI:CHEBI:15377, ChEBI:CHEBI:28938, ChEBI:CHEBI:29985, ChEBI:CHEBI:58359; EC=3.5.1.2; Evidence={ECO:0000255|HAMAP-Rule:MF_02213, ECO:0000269|PubMed:29593310};

PATHWAY: Cell wall biogenesis; peptidoglycan biosynthesis. {ECO:0000255|HAMAP-Rule:MF_02213, ECO:0000269|PubMed:22303291}.

FUNCTION: The lipid II isoglutaminyl synthase complex catalyzes the formation of alpha-D-isoglutamine in the cell wall lipid II stem peptide (PubMed:22303291). The GatD subunit catalyzes the hydrolysis of glutamine to glutamate and ammonia. The resulting ammonia molecule is channeled to the active site of MurT (PubMed:29593310). {ECO:0000269|PubMed:22303291, ECO:0000269|PubMed:29593310}.

Staphylococcus aureus (strain COL)

A0A0H2Z7X0

TPBB_PSEAB

MNRRRRYTGSNPSLRRVLYRAHLGVALVAVFTAGLAVTLVGLLTLRAYADPNQQLIARSISYTVEAAVVFGDAQAAEESLALIASSEEVSSAIVYDRQGQPLASWHRESTGPLHLLEQQLAHWLLSAPTEQPILHDGQKIGSVEVKGSGGSLLRFLLTGFAGMVLCLLLTALGAFYLSRRLVRGIVGPLDQLAKVAHTVRRERDFEKRVPEAGIAELSQLGEDFNALLDELESWQARLQDENASLAHQAHHDSLTSLPNRAFFEGRLSRALRDASEHREQLAVLFIDSDRFKEINDRLGHAAGDTVLVNIAMRIRGQLRESDLVARLGGDEFAVLLAPLASGADALRIADNIIASMQAPIRLSDGSTVSTSLTIGIALYPEHADTPAALLHDADMAMYIAKRQARGSRRLAELNDPRILQEEKEIDSATPEAPPK

2.7.7.65

COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:Q9I4L5}; Note=Binds 1 Mg(2+) ion per monomer. {ECO:0000250|UniProtKB:Q9I4L5};

signal transduction [GO:0007165]

plasma membrane [GO:0005886]

GTP binding [GO:0005525]; metal ion binding [GO:0046872]; transferase activity [GO:0016740]

PF17152;PF00990;PF00672;

3.30.70.270;6.10.340.10;

PTM: Phosphorylated at both Tyr residues and Ser/Thr residues (PubMed:20946878). Dephosphorylated and inactivated by TpbA (PubMed:20946878). {ECO:0000269|PubMed:20946878}.

SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000255}.

CATALYTIC ACTIVITY: Reaction=2 GTP = 3',3'-c-di-GMP + 2 diphosphate; Xref=Rhea:RHEA:24898, ChEBI:CHEBI:33019, ChEBI:CHEBI:37565, ChEBI:CHEBI:58805; EC=2.7.7.65; Evidence={ECO:0000269|PubMed:20946878}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24899; Evidence={ECO:0000269|PubMed:20946878};

PATHWAY: Purine metabolism; 3',5'-cyclic di-GMP biosynthesis. {ECO:0000305}.

FUNCTION: Catalyzes the synthesis of cyclic-di-GMP (c-di-GMP) via the condensation of 2 GTP molecules (PubMed:20946878). Important for the regulation of biofilm maintenance when exposed to peroxide (PubMed:34694901). {ECO:0000269|PubMed:20946878, ECO:0000269|PubMed:34694901}.; FUNCTION: Part of the YfiB-TpbB-YfiR (or yfiBNR) system, encoding a tripartite signaling module that modulates intracellular c-di-GMP levels. The system is a key regulator of the small colony variant (SCV) phenotype, and plays an important role in biofilm formation and in vivo persistence. The c-di-GMP produced by TpbB/YfiN stimulates the production of the Pel and Psl exopolysaccharides, which promotes surface attachment, generates an SCV phenotype and confers resistance against phagocytosis. {ECO:0000250|UniProtKB:Q9I4L5}.

Pseudomonas aeruginosa (strain UCBPP-PA14)

A0A0H2ZFK2

TPBA_PSEAB

MHRSPLAWLRLLLAAVLGAFLLGGPLHAAETAAPRSPAWAQAVDPSINLYRMSPTLYRSALPNAQSVALLQRLQVKTVVSFIKDDDRAWLGQAPVRVVSLPTHADRVDDAEVLSVLRQLQAAEREGPVLMHCKHGNNRTGLFAAMYRIVVQGWDKQAALEEMQRGGFGDEDDMRDASAYVRGADVDGLRLAMANGECSPSRFALCHVREWMAQALDRP

3.1.3.16; 3.1.3.48

dephosphorylation [GO:0016311]

periplasmic space [GO:0042597]

phosphoprotein phosphatase activity [GO:0004721]

PF03162;

3.90.190.10;

Protein-tyrosine phosphatase family

SUBCELLULAR LOCATION: Periplasm {ECO:0000269|PubMed:19543378}.

CATALYTIC ACTIVITY: Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] + phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA-COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620; EC=3.1.3.48; Evidence={ECO:0000269|PubMed:19543378, ECO:0000269|PubMed:20946878}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10685; Evidence={ECO:0000269|PubMed:19543378, ECO:0000269|PubMed:20946878}; CATALYTIC ACTIVITY: Reaction=H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] + phosphate; Xref=Rhea:RHEA:47004, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15377, ChEBI:CHEBI:30013, ChEBI:CHEBI:43474, ChEBI:CHEBI:61977; EC=3.1.3.16; Evidence={ECO:0000269|PubMed:20946878}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47005; Evidence={ECO:0000269|PubMed:20946878}; CATALYTIC ACTIVITY: Reaction=H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] + phosphate; Xref=Rhea:RHEA:20629, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15377, ChEBI:CHEBI:29999, ChEBI:CHEBI:43474, ChEBI:CHEBI:83421; EC=3.1.3.16; Evidence={ECO:0000305|PubMed:20946878}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20630; Evidence={ECO:0000305|PubMed:20946878};

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=11.21 mM for pNPP {ECO:0000269|PubMed:23524133}; Note=kcat is 0.00162 sec(-1) with pNPP as substrate. {ECO:0000269|PubMed:23524133};

FUNCTION: Phosphatase that regulates diverse phenotypes in P.aeruginosa via regulation of the concentration of cellular c-di-GMP (PubMed:19543378). Acts by dephosphorylating the membrane-anchored diguanylate cyclase TpbB at tyrosine and serine/threonine sites, leading to inactivation of TpbB and reduced c-di-GMP production (PubMed:19543378, PubMed:20946878). The reduced cellular c-di-GMP concentration leads to reduced adhesin expression, reduced extracellular polysaccharide (EPS) production, pellicule production, cell aggregation and biofilm formation, and enhanced swimming and swarming (PubMed:19543378). It affects colony morphology and controls rugose colony formation (PubMed:19543378, PubMed:20946878). TpbA also acts as a positive regulator of extracellular DNA (eDNA, a major component of the biofilm matrix) and cell lysis by reducing c-di-GMP concentrations (PubMed:23766119). In vitro shows phosphatase activity toward p-nitrophenyl phosphate (pNPP), tyrosine phosphopeptides and a threonine phosphopeptide (PubMed:19543378, PubMed:20946878). Does not have phosphodiesterases (PDE) activity, and cannot degrade c-di-GMP (PubMed:20946878). {ECO:0000269|PubMed:19543378, ECO:0000269|PubMed:20946878, ECO:0000269|PubMed:23766119}.

Pseudomonas aeruginosa (strain UCBPP-PA14)

A0A0H2ZL64

PULA_STRP2

MRKTPSHTEKKMVYSIRSLKNGTGSVLIGASLVLLAMATPTISSDESTPTTNEPNNRNTTTLAQPLTDTAADSGKNESDISSPRNANASLEKTEEKPATEPTTSTSPVTTETKAEEPIEDNYFRIHVKKLPEENKDAQGLWTWDDVEKPSENWPNGALSFKDAKKDDYGYYLDVKLKGEQAKKISFLINNTAGKNLTGDKSVEKLVPKMNEAWLDQDYKVFSYEPQPAGTVRVNYYRTDGNYDKKSLWYWGDVKNPSSAQWPDGTDFTATGKYGRYIDIPLNEAAREFGFLLLDESKQGDDVKIRKENYKFTDLKNHSQIFLKDDDESIYTNPYYVHDIRMTGAQHVGTSSIESSFSTLVGAKKEDILKHSNITNHLGNKVTITDVAIDEAGKKVTYSGDFSDTKHPYTVSYNSDQFTTKTSWHLKDETYSYDGKLGADLKEEGKQVDLTLWSPSADKVSVVVYDKNDPDKVVGTVALEKGERGTWKQTLDSTNKLGITDFTGYYYQYQIERQGKTVLALDPYAKSLAAWNSDDAKIDDAHKVAKAAFVDPAKLGPQDLTYGKIHNFKTREDAVIYEAHVRDFTSDPAIAKDLTKPFGTFEAFIEKLDYLKDLGVTHIQLLPVLSYYFVNELKNHERLSDYASSNSNYNWGYDPQNYFSLTGMYSSDPKNPEKRIAEFKNLINEIHKRGMGAILDVVYNHTAKVDIFEDLEPNYYHFMDADGTPRTSFGGGRLGTTHHMTKRLLVDSIKYLVDTYKVDGFRFDMMGDHDAASIEEAYKAARALNPNLIMLGEGWRTYAGDENMPTKAADQDWMKHTDTVAVFSDDIRNNLKSGYPNEGQPAFITGGKRDVNTIFKNLIAQPTNFEADSPGDVIQYIAAHDNLTLFDIIAQSIKKDPSKAENYAEIHRRLRLGNLMVLTAQGTPFIHSGQEYGRTKQFRDPAYKTPVAEDKVPNKSHLLRDKDGNPFDYPYFIHDSYDSSDAVNKFDWTKATDGKAYPENVKSRDYMKGLIALRQSTDAFRLKSLQDIKDRVHLITVPGQNGVEKEDVVIGYQITAPNGDIYAVFVNADEKAREFNLGTAFAHLRNAEVLADENQAGSVGIANPKGLEWTEKGLKLNALTATVLRVSQNGTSHESTAEEKPDSTPSKPEHQDPAPEARPDSTKPDAKVADAENKPSQATADSQAEQPAQEAQASSVKEAVQNESVENSSKKNIPATPDRQAELPNTGIKNENKLLFAGISLLALLGLGFLLKNKKEN

3.2.1.41

carbohydrate metabolic process [GO:0005975]

cell surface [GO:0009986]; extracellular region [GO:0005576]

carbohydrate binding [GO:0030246]; metal ion binding [GO:0046872]; pullulanase activity [GO:0051060]

PF00128;PF02922;PF00746;PF03714;PF18033;PF04650;

2.60.40.1110;2.60.40.1220;3.20.20.80;2.60.40.1180;2.60.40.10;

Glycosyl hydrolase 13 family

SUBCELLULAR LOCATION: Secreted, cell wall {ECO:0000255|PROSITE-ProRule:PRU00477}; Peptidoglycan-anchor {ECO:0000255|PROSITE-ProRule:PRU00477}. Cell surface {ECO:0000250|UniProtKB:Q9F930}. Note=Localizes to cytoplasm in the lung alveolar type II cells of the mouse and human hosts. {ECO:0000250|UniProtKB:A0A0H2UNG0}.

CATALYTIC ACTIVITY: Reaction=Hydrolysis of (1->6)-alpha-D-glucosidic linkages in pullulan, amylopectin and glycogen, and in the alpha- and beta-limit dextrins of amylopectin and glycogen.; EC=3.2.1.41; Evidence={ECO:0000250|UniProtKB:A0A0H2UNG0};

FUNCTION: Virulence factor (PubMed:17041037). Involved in the degradation of glycogen of the mammalian host cells. Hydrolyzes the alpha-1,6-branchpoints of glycogen. Hydrolyzes pullulan. Does not hydrolyze dextran. Binds to mouse lung alveolar type II cells that are rich in glycogen stores. Is an alpha-glucan-specific carbohydrate-binding protein, which binds to amylose (pure alpha-(1,4)-linked glucose), amylopectin (alpha-(1,4)-linked glucose with alpha-(1,6) branch points), pullulan (linear polymer of mixed alpha-(1,4)- and alpha-(1,6)-linked glucose) and glycogen (similar to amylopectin with more frequent alpha-(1,6) branch points) in vitro. Does not bind to dextran (a linear polymer of alpha-(1,6)-linked glucose) (By similarity). {ECO:0000250|UniProtKB:A0A0H2UNG0, ECO:0000269|PubMed:17041037}.

Streptococcus pneumoniae serotype 2 (strain D39 / NCTC 7466)

A0A0H2ZMF9

PBP2A_STRP2

MKLDKLFEKFLSLFKKETSELEDSDSTILRRSRSDRKKLAQVGPIRKFWRRYHLTKIILILGLSAGLLVGIYLFAVAKSTNVNDLQNALKTRTLIFDREEKEAGALSGQKGTYVELTDISKNLQNAVIATEDRSFYKNDGINYGRFFLAIVTAGRSGGGSTITQQLAKNAYLSQDQTVERKAKEFFLALELSKKYSKEQILTMYLNNAYFGNGVWGVEDASKKYFGVSASEVSLDQAATLAGMLKGPELYNPLNSVEDSTNRRDTVLQNMVAAGYIDKNQETEAAEVDMTSQLHDKYEGKISDYRYPSYFDAVVNEAVSKYNLTEEEIVNNGYRIYTELDQNYQANMQIVYENTSLFPRAEDGTFAQSGSVALEPKTGGVRGVVGQVADNDKTGFRNFNYATQSKRSPGSTIKPLVVYTPAVEAGWALNKQLDNHTMQYDSYKVDNYAGIKTSREVPMYQSLAESLNLPAVATVNDLGVDKAFEAGEKFGLNMEKVDRVLGVALGSGVETNPLQMAQAYAAFANEGLMPEAHFISRIENASGQVIASHKNSQKRVIDKSVADKMTSMMLGTFTNGTGISSSPADYVMAGKTGTTEAVFNPEYTSDQWVIGYTPDVVISHWLGFPTTDENHYLAGSTSNGAAHVFRNIANTILPYTPGSTFTVENAYKQNGIAPANTKRQVQTNDNSQTDDNLSDIRGRAQSLVDEASRAISDAKIKEKAQTIWDSIVNLFR

2.4.99.28; 3.4.16.4

cell wall organization [GO:0071555]; peptidoglycan biosynthetic process [GO:0009252]; proteolysis [GO:0006508]; regulation of cell shape [GO:0008360]; response to antibiotic [GO:0046677]

extracellular region [GO:0005576]; plasma membrane [GO:0005886]

acyltransferase activity [GO:0016746]; penicillin binding [GO:0008658]; peptidoglycan glycosyltransferase activity [GO:0008955]; serine-type D-Ala-D-Ala carboxypeptidase activity [GO:0009002]

PF00912;PF00905;

6.20.370.110;1.10.3810.10;3.40.710.10;

Glycosyltransferase 51 family; Transpeptidase family

SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:29487215}; Single-pass type II membrane protein {ECO:0000250|UniProtKB:Q8DNB6}. Secreted, cell wall {ECO:0000305}. Note=Localizes to sites of new peptidoglycan (PG) synthesis at midcell independently of MacP. {ECO:0000269|PubMed:29487215}.

CATALYTIC ACTIVITY: Reaction=Preferential cleavage: (Ac)2-L-Lys-D-Ala-|-D-Ala. Also transpeptidation of peptidyl-alanyl moieties that are N-acyl substituents of D-alanine.; EC=3.4.16.4; Evidence={ECO:0000250|UniProtKB:Q8DNB6}; CATALYTIC ACTIVITY: Reaction=[GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)](n)-di-trans,octa-cis-undecaprenyl diphosphate + beta-D-GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)-di-trans,octa-cis-undecaprenyl diphosphate = [GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)](n+1)-di-trans-octa-cis-undecaprenyl diphosphate + di-trans,octa-cis-undecaprenyl diphosphate + H(+); Xref=Rhea:RHEA:23708, Rhea:RHEA-COMP:9602, Rhea:RHEA-COMP:9603, ChEBI:CHEBI:15378, ChEBI:CHEBI:58405, ChEBI:CHEBI:60033, ChEBI:CHEBI:78435; EC=2.4.99.28; Evidence={ECO:0000250|UniProtKB:Q8DNB6};

PATHWAY: Cell wall biogenesis; peptidoglycan biosynthesis. {ECO:0000305}.

FUNCTION: Cell wall formation. Synthesis of cross-linked peptidoglycan (PG) from the lipid intermediates (By similarity). Binds dansylated lipid II and catalyzes the polymerization of glycan chains. Hydrolyzes S2d (N-benzoyl-D-alanylmercaptoacetic acid) molecule, a synthetic thiolester analog of cell wall stem peptide. Active against bocillin, a fluorescent penicillin. No transpeptidase activity with non-fluorescent lysine-containing lipid II as substrate (By similarity). {ECO:0000250|UniProtKB:P02918, ECO:0000250|UniProtKB:Q8DNB6}.

Streptococcus pneumoniae serotype 2 (strain D39 / NCTC 7466)

A0A0H2ZNH9

WALK_STRP2

MLDLLKQTIFTRDFIFILILLGFILVVTLLLLENRRDNIQLKQINQKVKDLIAGDYSKVLDMQGGSEITNITNNLNDLSEVIRLTQENLEQESKRLNSILFYMTDGVLATNRRGQIIMINDTAKKQLGLVKEDVLNRSILELLKIEENYELRDLITQSPELLLDSQDINGEYLNLRVRFALIRRESGFISGLVAVLHDTTEQEKEERERRLFVSNVSHELRTPLTSVKSYLEALDEGALCETVAPDFIKVSLDETNRMMRMVTDLLHLSRIDNATSHLDVELINFTAFITFILNRFDKMKGQEKEKKYELVRDYPINSIWMEIDTDKMTQVVDNILNNAIKYSPDGGKITVRMKTTEDQMILSISDHGLGIPKQDLPRIFDRFYRVDRARSRAQGGTGLGLSIAKEIIKQHKGFIWAKSEYGKGSTFTIVLPYDKDAVKEEVWEDEVED

2.7.13.3; 3.9.1.-

cellular response to phosphate starvation [GO:0016036]; regulation of DNA-templated transcription [GO:0006355]; signal transduction [GO:0007165]

plasma membrane [GO:0005886]

phosphoprotein phosphatase activity [GO:0004721]; phosphorelay sensor kinase activity [GO:0000155]; protein histidine kinase activity [GO:0004673]

PF02518;PF00512;PF00989;

1.10.287.130;1.10.8.500;3.30.565.10;3.30.450.20;

PTM: Autophosphorylated. {ECO:0000250|UniProtKB:Q8DPL8}.

SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass type III membrane protein {ECO:0000255}.

CATALYTIC ACTIVITY: Reaction=ATP + protein L-histidine = ADP + protein N-phospho-L-histidine.; EC=2.7.13.3; Evidence={ECO:0000269|PubMed:23013245};

FUNCTION: Member of the two-component regulatory system WalK/WalR that regulates genes involved in cell wall metabolism (By similarity). Functions as a sensor protein kinase which is autophosphorylated at a histidine residue and transfers its phosphate group to WalR (By similarity). In turn, WalR binds to the upstream promoter regions of target genes to positively and negatively regulate their expression (By similarity). Required to maintain expression of WalRK regulon genes in exponentially growing cells, including peptidoglycan hydrolase pcsB (PubMed:23013245). Phosphorylates WalR and also capable of dephosphorylation of WalR (PubMed:23013245). WalK phosphatase activity is probably involved in preventing cross-talk from PnpS and other non-cognate sensor kinases during exponential growth (PubMed:23013245). May be considered a potential virulence factor (PubMed:20190050). {ECO:0000250|UniProtKB:Q8DPL8, ECO:0000250|UniProtKB:Q9RDT3, ECO:0000269|PubMed:20190050, ECO:0000269|PubMed:23013245}.

Streptococcus pneumoniae serotype 2 (strain D39 / NCTC 7466)

A0A0H2ZQ76

PCSB_STRP2

MKKKILASLLLSTVMVSQVAVLTTAHAETTDDKIAAQDNKISNLTAQQQEAQKQVDQIQEQVSAIQAEQSNLQAENDRLQAESKKLEGEITELSKNIVSRNQSLEKQARSAQTNGAVTSYINTIVNSKSITEAISRVAAMSEIVSANNKMLEQQKADKKAISEKQVANNDAINTVIANQQKLADDAQALTTKQAELKAAELSLAAEKATAEGEKASLLEQKAAAEAEARAAAVAEAAYKEKRASQQQSVLASANTNLTAQVQAVSESAAAPVRAKVRPTYSTNASSYPIGECTWGVKTLAPWAGDYWGNGAQWATSAAAAGFRTGSTPQVGAIACWNDGGYGHVAVVTAVESTTRIQVSESNYAGNRTIGNHRGWFNPTTTSEGFVTYIYAD

3.2.1.-

cell septum [GO:0030428]; extracellular region [GO:0005576]; plasma membrane [GO:0005886]

hydrolase activity [GO:0016787]

PF05257;

6.10.250.3150;3.90.1720.10;

SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17449619}; Peripheral membrane protein {ECO:0000305|PubMed:22006325}; Extracellular side {ECO:0000305|PubMed:22006325}. Cell septum {ECO:0000269|PubMed:22006325}. Secreted {ECO:0000269|PubMed:17449619}. Note=Localizes to outer membrane surface, probably due to hydrophobic interactions. {ECO:0000305|PubMed:22006325}.

FUNCTION: Peptidoglycan-hydrolase activity (PubMed:24804636). Required in maintaining normal growth and cellular morphology (PubMed:19270090, PubMed:22006325). Involved in splitting of the septum during cell division (By similarity). {ECO:0000250|UniProtKB:Q8DMY4, ECO:0000269|PubMed:19270090, ECO:0000269|PubMed:22006325, ECO:0000269|PubMed:24804636}.

Streptococcus pneumoniae serotype 2 (strain D39 / NCTC 7466)

A0A0H2ZQB9

EGTUB_STRP2

MTNLIATFQDRFGDWLTALSQHLQLSLLTLLLAILLAIPLAVYLRYHEKLADWVLQIAGIFQTIPSLALLGLFIPLMGIGTLPALTALVIYAIFPILQNTITGLKGIDPSLQEAGIAFGMTRWERLKKFEIPLAMPVIMSGIRTAAVLIIGTATLATLIGAGGLGSFILLGIDRNNASLILIGALSSAVLAIAFNFLLKVMEKAKLRTIFSGFALMALLLGLSYSPALLAQKEKENLIIAGKIGPEPEILANMYKLLIEENTSMTATVKPNFGTTSFLYEALKKGDIDIYPEFTGTVTESLLQPSPKVSHEPEQVYQVARDGIAKQDHLAYLKPMSYQNTYAVAVPKKIAQEYGLKTISDLKKVEGQLKAGFTLEFNDREDGNKGLQSMYGLNLNVATMQPALRYQAIHSGDIQITDAYSTDAELERYDLQVLEDDKQLFPPYQGAPLMKEALLKKHPELERVLNTLAGKITESQMSQLNYQVGVEGKSAKQVAKEFLQEQGLLKK

amino acid transport [GO:0006865]; glycine betaine transport [GO:0031460]; quaternary ammonium group transport [GO:0015697]

ATP-binding cassette (ABC) transporter complex [GO:0043190]

ABC-type quaternary ammonium compound transporting activity [GO:0015418]

PF00528;PF04069;

1.10.3720.10;3.40.190.10;

Binding-protein-dependent transport system permease family; OsmX family

SUBCELLULAR LOCATION: Cell membrane {ECO:0000255|RuleBase:RU363032}; Multi-pass membrane protein {ECO:0000255|RuleBase:RU363032}.

FUNCTION: Part of an ABC transporter complex EgtU required for the uptake of ergothioneine (EGT), a natural low-molecular weight (LMW) thiol antioxidant (PubMed:36481738). Responsible for the translocation of the substrate across the membrane (PubMed:36481738). Also contains a C-terminal periplasmic solute-binding domain (SBD) which binds to EGT with sub-micromolar affinity (PubMed:36481738). Binds L-hercynine about 10,000-fold less tightly than EGT (PubMed:36481738). Cannot bind the structurally similar compounds L-histidine, proline-betaine, choline, ectoine, carnitine or dimethylpropiothetin (PubMed:36481738). {ECO:0000269|PubMed:36481738}.

Streptococcus pneumoniae serotype 2 (strain D39 / NCTC 7466)

A0A0H2ZQL5

CCRZ_STRP2

MDLGDNELTLTPIPGKSGKAYMGSYPDGKRIFVKMNTSPILPGLAREQIAPQLLWSRRLADGRDMCAQEWLTGKILTPYDMNRKQIVNILTRLHRSRPLMTQLSRLGYAMETPVDLLQSWQETAPDALRKNHFISEVMADLRQTIPGFREDHATIVHGDVRHSNWIETDSGLIYLVDWDSVRLTDRMFDVAHMLCHYISEHQWKEWLTYYGYKYNQTVLSKLYWYGQLSYLSQISKYYMNQDLENVNREIHGLRHFRDKYGKRR

2.7.1.15; 2.7.1.229

cell cycle [GO:0007049]; cell division [GO:0051301]; DNA damage response [GO:0006974]; DNA replication initiation [GO:0006270]; regulation of cell cycle [GO:0051726]

cell division site [GO:0032153]; cytoplasm [GO:0005737]

ATP binding [GO:0005524]; carbohydrate kinase activity [GO:0019200]; phosphotransferase activity, alcohol group as acceptor [GO:0016773]; ribokinase activity [GO:0004747]

PF01636;

3.90.1200.10;

Aminoglycoside phosphotransferase family

SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:34373624}. Note=Localizes at mid-cell, forming a patchy ring. Disassembles from the old septum to assemble at the newly formed division site. Colocalizes with FtsZ during the full cell cycle. Colocalizes with DnaA in newborn cells. {ECO:0000269|PubMed:34373624}.

CATALYTIC ACTIVITY: Reaction=ATP + D-ribose = ADP + D-ribose 5-phosphate + H(+); Xref=Rhea:RHEA:13697, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:47013, ChEBI:CHEBI:78346, ChEBI:CHEBI:456216; EC=2.7.1.15; Evidence={ECO:0000250|UniProtKB:C0SPC1}; CATALYTIC ACTIVITY: Reaction=2-deoxy-D-ribose + ATP = 2-deoxy-D-ribose 5-phosphate + ADP + H(+); Xref=Rhea:RHEA:30871, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:62877, ChEBI:CHEBI:90761, ChEBI:CHEBI:456216; EC=2.7.1.229; Evidence={ECO:0000250|UniProtKB:C0SPC1};

FUNCTION: Plays a role in cell cycle regulation and chromosome integrity. Activates DnaA-dependent chromosomal DNA replication initiation ensuring that the chromosome is replicated at the right time during the cell cycle (PubMed:34373624). May regulate replication initiation through phosphorylation of a possible second messenger or metabolite, and by interacting with replication initiation proteins. Has ATPase activity with D-ribose and 2-deoxy-D-ribose in vitro, but not with choline. Involved in DNA damage response (By similarity). {ECO:0000250|UniProtKB:C0SPC1, ECO:0000269|PubMed:34373624}.

Streptococcus pneumoniae serotype 2 (strain D39 / NCTC 7466)

A0A0H3AIG7

VGRG1_VIBC3

MATLAYSIEVEGLEDETLVVRGFHGQESLSNSVFLGQACYGFRYEVQLASRVSNLTAEQMVDKRAELKLYRNSQLVQRVHGIVRAFSQGDIGHHHTFYQLTLVPALERLSLRHNSRIFQKQTVPEILSILLQEMGINDYAFALKRDGVQREFCVQYRESDIDFLHRLAAEEGLVYSFVHEAGKHTLYFSDASDSLSKLPEPIPYNALVGGAIDTPYIHGLTYRTQAEVSEVQLKDYSFKKPAYSFLQTVQGTELDYQQTRYQHFDAPGRYKDDVNGAAFSQIRLDYLRRHAHTATGQSNEPLLRAGYKFDLQEHLDPAMNRDWVVVSINHQGEQPQALQEDGGSGATTYSNQFSLIPGHLHWRAEPQPKPQVDGPMIATVVGPEGEEIFCDEHGRVKIHFPWDRYSNGNEQSSCWVRVSQGWAGSQYGFIAIPRIGHEVIVEFLNGDPDQPIITGRTYHATNTPPYTLPEHKTKTVLRTETHQGEGFNELSFEDQAGKEQIYLHAQKDFDGLIENDQFTQIKHNQHLTVEWESREAVTGEQVLSIEGSLHVKTGKVRVNEAGTEIHVKAGQKVVIEAGSEITVKAGGSFVKVDPAGVHLSGALVNLNSGGSAGSGSGFGGAMPALPGGLEPAVALAPPQTISYQALLQAEQANVPAVKVCPLAAQEATPAVNSITPPPPPPIAPPMAPPQPIMNPQPTANAQPNLGRSTKATPDFPTHFPKSSIGIENELAGLVVAMPANSAQKFGYVKSAQGDALFMLTKDMNQGSYQRPPSLQDGKNYQNWQTHTVELVSYPCEMDDKAAVETRKQAMLWLATHFTTHIDQSNHQPLAPIQSEDGRFVIEITNAKHVIAAGNGISAESQGQTITMTPSGQQATVGVAAKGFGTSATPELRLLESAPWYQKSLKSQFASLTSAENLDDKELAANVFAYLTSIYLKTAELAKKFGIYINEWDPMSEQITPNANGLTDPKVKNAWEILPRTKPSKIVEILSKSDAKAVMKHIKPQLQSRYSESLSKNVFQYFQDGGEVAGHGINNATVGDKHSPELAILFEFRTVPNELQSYLPKTESTTKSEVKLLDQFDPMKRKTVIQQVESLV

6.3.2.-

COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:22898822}; Note=Binds 2 Mg(2+) ions per subunit. Can also use Mn(2+) ions instead of Mg(2+). {ECO:0000269|PubMed:22898822};

actin filament depolymerization [GO:0030042]; isopeptide cross-linking via N6-(L-isoglutamyl)-L-lysine [GO:0018153]

extracellular region [GO:0005576]; host cell cytosol [GO:0044164]

acid-amino acid ligase activity [GO:0016881]; ATP binding [GO:0005524]; magnesium ion binding [GO:0000287]; toxin activity [GO:0090729]

PF16671;PF04717;PF05954;

2.30.110.50;4.10.220.110;1.10.3680.20;3.55.50.10;2.40.50.230;

VgrG protein family

SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q9KS45}. Host cytoplasm, host cytosol {ECO:0000269|PubMed:22898822}. Note=Secreted via the type VI secretion system. {ECO:0000250|UniProtKB:Q9KS45}.

FUNCTION: Part of the type VI secretion system (T6SS) specialized secretion system, which delivers several virulence factors in both prokaryotic and eukaryotic cells during infection (By similarity). Forms the spike at the tip of the elongating tube probably formed by hemolysin co-regulated protein/Hcp. Allows the delivery of the TseL antibacterial toxin to target cells where it exerts its toxicity (By similarity). Acts also directly as an actin-directed toxin that catalyzes the covalent cross-linking of host cytoplasmic monomeric actin. Mediates the cross-link between 'Lys-50' of one monomer and 'Glu-270' of another actin monomer, resulting in formation of highly toxic actin oligomers that cause cell rounding (PubMed:22898822). The toxin can be highly efficient at very low concentrations by acting on formin homology family proteins: toxic actin oligomers bind with high affinity to formins and adversely affect both nucleation and elongation abilities of formins, causing their potent inhibition in both profilin-dependent and independent manners (PubMed:22898822). Acts as an acid--amino-acid ligase that transfers the gamma-phosphoryl group of ATP to the 'Glu-270' actin residue, resulting in the formation of an activated acyl phosphate intermediate. This intermediate is further hydrolyzed and the energy of hydrolysis is utilized for the formation of the amide bond between actin subunits (PubMed:22898822). {ECO:0000250|UniProtKB:Q9KS45, ECO:0000269|PubMed:22898822}.

Vibrio cholerae serotype O1 (strain ATCC 39541 / Classical Ogawa 395 / O395)

A0A0H3AMJ9

CHEY3_VIBC3

MEAILNKNMKILIVDDFSTMRRIVKNLLRDLGFNNTQEADDGLTALPMLKKGDFDFVVTDWNMPGMQGIDLLKNIRADEELKHLPVLMITAEAKREQIIEAAQAGVNGYIVKPFTAATLKEKLDKIFERL

COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:24066084}; Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000269|PubMed:24066084};

archaeal or bacterial-type flagellum-dependent cell motility [GO:0097588]; chemotaxis [GO:0006935]; phosphorelay signal transduction system [GO:0000160]

cytoplasm [GO:0005737]

metal ion binding [GO:0046872]

PF00072;

3.40.50.2300;

PTM: Phosphorylated by CheA-2 and to a lesser extend by VieS. {ECO:0000269|PubMed:18676667}.

SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.

FUNCTION: Acts as a response regulator to control chemotaxis (PubMed:16321945, PubMed:24066084). Involved in the transmission of sensory signals from the chemoreceptors to the flagellar motors (PubMed:16321945, PubMed:24066084). Switches the flagellar rotation by binding to the flagellar motor switch protein FliM (PubMed:16321945, PubMed:24066084). In its active (phosphorylated or acetylated) form, exhibits enhanced binding to a switch component, FliM, at the flagellar motor which induces a change from counterclockwise to clockwise flagellar rotation (By similarity). {ECO:0000250|UniProtKB:P0AE67, ECO:0000269|PubMed:16321945, ECO:0000269|PubMed:24066084}.

Vibrio cholerae serotype O1 (strain ATCC 39541 / Classical Ogawa 395 / O395)

A0A0H3GDH9

PGDA_LISM4

MKIRWIRLSLVAILIIAVVFIGVIGFQKYQFSKSRNKVIMQMDRLMKDQDGGNFRRLDKKENGVEIISYIPKTTEKKDNEIIQKEIGKATDAEVKKLNRDKETQGIIFYTYQKHRMAEQAISYKAVQSEYVKEGRTKFVLKDKKDICKNIVTDAETGALLTLGEVLIKSNQTKLNLKTAVEEELIKTGDFSLKDVGNLGKIKSLVKWNQTDFEITNSEIILPVKIPGAPEPKKVKVKLADIASSVNKRYLPSSVKVPEVPKAKTNKRIALTFDDGPSSSVTPGVLDTLKRHNVKATFFVLGSSVIQNPGLVKRELEEGHQVGSHSWDHPQLTKQSTQEVYNQILKTQKAVFDQTGYFPTTMRPPYGAVNKQVAEEIGLPIIQWSVDTEDWKYRNAGIVTKKVLAGATDGAIVLMHDIHKTTAASLDTTLTKLKSQGYEFVTIDELYGEKLQIGKQYFDKTDSRMVK

3.5.1.104

COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250|UniProtKB:Q8DP63};

autolysis [GO:0001896]; carbohydrate metabolic process [GO:0005975]; cell wall modification [GO:0042545]; evasion of host immune response [GO:0042783]; evasion of host innate immune recognition [GO:0141043]; negative regulation of lysozyme activity [GO:1903591]

extracellular region [GO:0005576]; Gram-positive-bacterium-type cell wall [GO:0009275]; plasma membrane [GO:0005886]

chitin deacetylase activity [GO:0004099]; lysozyme inhibitor activity [GO:0060241]; N-acetylglucosamine deacetylase activity [GO:0050119]; protein homodimerization activity [GO:0042803]; zinc ion binding [GO:0008270]

PF01522;

3.20.20.370;

SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q8Y9V5}; Single-pass membrane protein {ECO:0000250|UniProtKB:Q8Y9V5, ECO:0000255}; Extracellular side {ECO:0000250|UniProtKB:Q8Y9V5}. Secreted, cell wall {ECO:0000250|UniProtKB:A0A3Q0NBH7}.

CATALYTIC ACTIVITY: Reaction=peptidoglycan-N-acetyl-D-glucosamine + H2O = peptidoglycan-D-glucosamine + acetate.; EC=3.5.1.104; Evidence={ECO:0000250|UniProtKB:A0A3Q0NBH7};

FUNCTION: Catalyzes the deacetylation of N-acetylglucosamine (GlcNAc) residues in peptidoglycan (PG). Deacetylates also N-acetylated PG. Does not deacetylate N-acetylmuramic acid (By similarity). Confers host lysozyme resistance. Critical for virulence and escape from innate immune response of the host (PubMed:21768286, PubMed:25157076). Required for intracellular survival of bacteria in macrophages of the host. Required for successful host colonization. Controls the production of inflammatory mediators in the bone marrow derived macrophages (BMMs) of the infected mouse (PubMed:21768286). Suppresses Toll-like receptor 2 (TLR2)-dependent secretion of interleukin 6 (IL-6) and interferon-beta (IFN-beta) in the macrophages of the infected mouse. May decrease accessibility of pattern recognition receptors (PRRs) such as nucleotide-binding oligomerization domain protein (NOD) 1 of the host to the bacterial cell wall components (By similarity). Protects cells from autolysis induced by lysozyme or by other autolysis-inducing agents (By similarity). {ECO:0000250|UniProtKB:A0A3Q0NBH7, ECO:0000250|UniProtKB:Q8Y9V5, ECO:0000269|PubMed:21768286, ECO:0000269|PubMed:25157076}.

Listeria monocytogenes serotype 1/2a (strain 10403S)

A0A0H3GGY3

PGPH_LISM4

MKLAKKWRDWYIESGKKYLFPLLLVCFAVIAYFLVCQMTKPESYNVKLFQVAEKTIRSPQTVEDTEKTKEERTKASDAVEDVYVYNRETGQNRVALIQSLFAYVNEVNAEAQEKDTKNKEKAKKENKPAPAPTSTEDKLKNLKDKLSSNVSEKITSNISDEVFTTLIEAKSKDFNVMEDVVTTEVEKSMENKIRDENLNSVKIRARDDIELSAIPAYYKNVSKALVSYAIVPNEVYDEEQTDARRKEAAQSVVPVKILQGQVIVQEGQIVDRETYRQLKMLHLLDQKMPVKQYAGFAIFIIALAAILFLYTKKQTQPKAKKMQTMLIFSSVYLVSLFMLFIILFLETQNIANIAFLFPAAFAPMILKILLNEKYAFLSVIFIAVTSLLTFQNDATSGITIFILLSGATSVVMLRDYSRRSAIMLSGFMVGLINMIYVLLLLLINNSTLLQVSTLMALGYAFLGGFGAFILGVGVIPLFETIFGLLTTSRLVELANPNHPLLKKILMKAPGTYHHSMMVANLAEACADKIGANSLLVRVGCFYHDIGKTLRPPYFVENQLQGINPHDRLTPEQSRDIILSHTKDGAEILKENHMPQPIIDIALQHHGTTLLKYFYFKAKETNPDVKEADYRYSGPKPQTKEIAIINISDSVEAAVRSSTEPTMAKITEIIDGIIKDRFLDGQFTECDITIQEIKIIRDTLIATLNGIYHQRIQYPDDKD

3.1.4.59

COFACTOR: Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269|PubMed:25583510}; Note=Able to bind Fe(2+), but has only very weak PDE activity. {ECO:0000269|PubMed:25583510};

plasma membrane [GO:0005886]

cyclic-di-AMP phosphodiesterase activity [GO:0106409]; hydrolase activity [GO:0016787]; metal ion binding [GO:0046872]; nucleotide binding [GO:0000166]

PF07698;PF07697;PF01966;

1.10.3210.10;

PgpH phosphodiesterase family

SUBCELLULAR LOCATION: Cell membrane {ECO:0000255}; Multi-pass membrane protein {ECO:0000255}.

CATALYTIC ACTIVITY: Reaction=3',3'-c-di-AMP + H2O = 5'-O-phosphonoadenylyl-(3'->5')-adenosine + H(+); Xref=Rhea:RHEA:54420, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:71500, ChEBI:CHEBI:138171; EC=3.1.4.59; Evidence={ECO:0000269|PubMed:25583510};

FUNCTION: A phosphodiesterase (PDE) that hydrolyzes cyclic di-3',5'-adenylate (c-di-AMP); there are at least 2 PDEs for c-di-AMP in this bacteria (this and pdeA), this may be the major PDE for growth in liquid culture (PubMed:25583510). During host infection c-di-AMP is secreted into the host cytoplasm which leads to interferon-beta production and secretion by the host (Probable). The cytoplasmic HD domain binds and hydrolyzes c-di-AMP to 5'-pApA; has very low activity against c-di-GMP, does not hydrolyze ppGpp (PubMed:25583510). {ECO:0000269|PubMed:25583510, ECO:0000305}.

Listeria monocytogenes serotype 1/2a (strain 10403S)

A0A0H3JN63

GATD_STAAN

MHELTIYHFMSDKLNLYSDIGNIIALRQRAKKRNIKVNVVEINETEGITFDECDIFFIGGGSDREQALATKELSKIKTPLKEAIEDGMPGLTICGGYQFLGKKYITPDGTELEGLGILDFYTESKTNRLTGDIVIESDTFGTIVGFENHGGRTYHDFGTLGHVTFGYGNNDEDKKEGIHYKNLLGTYLHGPILPKNYEITDYLLEKACERKGIPFEPKEIDNEAEIQAKQVLIDRANRQKKSR

3.5.1.2; 6.3.5.13

cell wall organization [GO:0071555]; cobalamin biosynthetic process [GO:0009236]; glutamine metabolic process [GO:0006541]; peptidoglycan biosynthetic process [GO:0009252]; regulation of cell shape [GO:0008360]

carbon-nitrogen ligase activity on lipid II [GO:0140282]; glutaminase activity [GO:0004359]

PF07685;

3.40.50.880;

CobB/CobQ family, GatD subfamily

CATALYTIC ACTIVITY: Reaction=ATP + beta-D-GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)-di-trans,octa-cis-undecaprenyl diphosphate + H2O + L-glutamine = ADP + beta-D-GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-D-isoglutaminyl-L-Lys-D-Ala-D-Ala)-di-trans,octa-cis-undecaprenyl diphosphate + H(+) + L-glutamate + phosphate; Xref=Rhea:RHEA:57928, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29985, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:58359, ChEBI:CHEBI:60033, ChEBI:CHEBI:62233, ChEBI:CHEBI:456216; EC=6.3.5.13; Evidence={ECO:0000255|HAMAP-Rule:MF_02213, ECO:0000269|PubMed:22291598, ECO:0000269|PubMed:30154570}; CATALYTIC ACTIVITY: Reaction=H2O + L-glutamine = L-glutamate + NH4(+); Xref=Rhea:RHEA:15889, ChEBI:CHEBI:15377, ChEBI:CHEBI:28938, ChEBI:CHEBI:29985, ChEBI:CHEBI:58359; EC=3.5.1.2; Evidence={ECO:0000255|HAMAP-Rule:MF_02213, ECO:0000269|PubMed:22291598};

PATHWAY: Cell wall biogenesis; peptidoglycan biosynthesis. {ECO:0000255|HAMAP-Rule:MF_02213, ECO:0000269|PubMed:22291598}.

BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 7.5-7.8 for isoglutaminyl synthase activity. {ECO:0000269|PubMed:22291598};

FUNCTION: The lipid II isoglutaminyl synthase complex catalyzes the formation of alpha-D-isoglutamine in the cell wall lipid II stem peptide (PubMed:22291598, PubMed:30154570). The GatD subunit catalyzes the hydrolysis of glutamine to glutamate and ammonia. The resulting ammonia molecule is channeled to the active site of MurT (PubMed:22291598). {ECO:0000269|PubMed:22291598, ECO:0000269|PubMed:30154570}.

Staphylococcus aureus (strain N315)

A0A0H3JNB0

TARP_STAAN

MKKVSVIMPTFNNGEKLHRTISSVLNQTMKSTDYELIIIDDHSNDNGETLNVIKKYKGLVRFKQLKKNSGNASVPRNTGLKMSKAEYVFFLDSDDLLHERALEDLYNYGKENNSDLIIGKYGVEGKGRSVPKAIFEKGNVAKADIIDNSIFYALSVLKMFKKSVIDKNKIKFKTFSKTAEDQLFTIEFLMNSKNYSIKTDYEYYIVVNDFESSNHLSVNKSTGNQYFATINEIYKAIYKSPIYKNQEKRHQLAGKYTTRLLRHGQKKNFANSKMKYEDKIEWLNNFSKTINKVPRDSDKYVTQIFNLKLEAIRQNDLLAVMIADKLL

2.4.1.-

COFACTOR: Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269|PubMed:30464342};

cell wall organization [GO:0071555]; teichoic acid biosynthetic process [GO:0019350]

glycosyltransferase activity [GO:0016757]; metal ion binding [GO:0046872]

PF00535;

Glycosyltransferase 2 family

CATALYTIC ACTIVITY: Reaction=4-O-[(D-ribitylphospho)(n)-di{(2R)-glycerylphospho}]-N-acetyl-beta-D-mannosaminyl-(1->4)-N-acetyl-alpha-D-glucosaminyl di-trans,octa-cis-undecaprenyl diphosphate + n UDP-N-acetyl-alpha-D-glucosamine = 4-O-([3-N-acetyl-beta-D-glucosaminyl-1-D-ribitylphospho](n)-di{[2R]-1-glycerylphospho})-N-acetyl-beta-D-mannosaminyl-(1->4)-N-acetyl-alpha-D-glucosaminyl di-trans,octa-cis-undecaprenyl diphosphate + n H(+) + n UDP; Xref=Rhea:RHEA:58948, Rhea:RHEA-COMP:12840, Rhea:RHEA-COMP:15259, ChEBI:CHEBI:15378, ChEBI:CHEBI:57705, ChEBI:CHEBI:58223, ChEBI:CHEBI:133896, ChEBI:CHEBI:142885; Evidence={ECO:0000269|PubMed:30464342};

PATHWAY: Cell wall biogenesis; poly(ribitol phosphate) teichoic acid biosynthesis. {ECO:0000269|PubMed:30464342}.

FUNCTION: Attaches beta-O-GlcNAc (beta-O-N-acetyl-D-glucosamine) residues to the C3 position of poly(RboP)-wall teichoic acids (WTAs). Attenuates immunogenicity of WTA and protects S.aureus against adaptative host defenses by allowing bacteria to evade recognition by preexisting anti-S.aureus antibodies. Also protects the cell from podophage infection. {ECO:0000269|PubMed:30464342}.

Staphylococcus aureus (strain N315)

A0A0H3JPC6

TARS_STAAM

MMKFSVIVPTYNSEKYITELLNSLAKQDFPKTEFEVVVVDDCSTDQTLQIVEKYRNKLNLKVSQLETNSGGPGKPRNVALKQAEGEFVLFVDSDDYINKETLKDAAAFIDEHHSDVLLIKMKGVNGRGVPQSMFKETAPEVTLLNSRIIYTLSPTKIYRTALLKDNDIYFPEELKSAEDQLFTMKAYLNANRISVLSDKAYYYATKREGEHMSSAYVSPEDFYEVMRLIAVEILNADLEEAHKDQILAEFLNRHFSFSRTNGFSLKVKLEEQPQWINALGDFIQAVPERVDALVMSKLRPLLHYARAKDIDNYRTVEESYRQGQYYRFDIVDGKLNIQFNEGEPYFEGIDIAKPKVKMTAFKFDNHKIVTELTLNEFMIGEGHYDVRLKLHSRNKKHTMYVPLSVNANKQYRFNIMLEDIKAYLPKEKIWDVFLEVQIGTEVFEVRVGNQRNKYAYTAETSALIHLNNDFYRLTPYFTKDFNNISLYFTAITLTDSISMKLKGKNKIILTGLDRGYVFEEGMASVVLKDDMIMGMLSQTSENEVEILLSKDIKKRDFKNIVKLNTAHMTYSLK

2.4.1.355

COFACTOR: Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269|PubMed:27973583}; Note=Can also use Mg(2+). {ECO:0000269|PubMed:27973583};

cell wall organization [GO:0071555]; response to antibiotic [GO:0046677]; teichoic acid biosynthetic process [GO:0019350]

glycosyltransferase activity [GO:0016757]; metal ion binding [GO:0046872]

PF00535;PF18674;

Glycosyltransferase 2 family

CATALYTIC ACTIVITY: Reaction=4-O-[(D-ribitylphospho)(n)-di{(2R)-glycerylphospho}]-N-acetyl-beta-D-mannosaminyl-(1->4)-N-acetyl-alpha-D-glucosaminyl di-trans,octa-cis-undecaprenyl diphosphate + n UDP-N-acetyl-alpha-D-glucosamine = 4-O-([2-N-acetyl-beta-D-glucosaminyl-1-D-ribitylphospho](n)-di{[2R]-1-glycerylphospho})-N-acetyl-beta-D-mannosaminyl-(1->4)-N-acetyl-alpha-D-glucosaminyl di-trans,octa-cis-undecaprenyl diphosphate + n H(+) + n UDP; Xref=Rhea:RHEA:55672, Rhea:RHEA-COMP:12840, Rhea:RHEA-COMP:14257, ChEBI:CHEBI:15378, ChEBI:CHEBI:57705, ChEBI:CHEBI:58223, ChEBI:CHEBI:133896, ChEBI:CHEBI:139146; EC=2.4.1.355; Evidence={ECO:0000269|PubMed:27973583};

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=45 uM for UDP-GlcNAc {ECO:0000269|PubMed:27973583}; KM=1240 uM for poly(RboP) {ECO:0000269|PubMed:27973583};

PATHWAY: Cell wall biogenesis; poly(ribitol phosphate) teichoic acid biosynthesis. {ECO:0000269|PubMed:27973583}.

FUNCTION: Attaches beta-O-GlcNAc (beta-O-N-acetyl-D-glucosamine) residues to the C4 position of poly(RboP)-wall teichoic acids (WTAs). Mediates beta-lactam resistance in methicillin resistant Staphylococcus aureus (MRSA) strains. {ECO:0000269|PubMed:27973583}.

Staphylococcus aureus (strain Mu50 / ATCC 700699)

A0A0H3JRU9

PYC_STAAM

MKQIKKLLVANRGEIAIRIFRAAAELDISTVAIYSNEDKSSLHRYKADESYLVGSDLGPAESYLNIERIIDVAKQANVDAIHPGYGFLSENEQFARRCAEEGIKFIGPHLEHLDMFGDKVKARTTAIKADLPVIPGTDGPIKSYELAKEFAEEAGFPLMIKATSGGGGKGMRIVREESELEDAFHRAKSEAEKSFGNSEVYIERYIDNPKHIEVQVIGDEHGNIVHLFERDCSVQRRHQKVVEVAPSVGLSPTLRQRICDAAIQLMENIKYVNAGTVEFLVSGDEFFFIEVNPRVQVEHTITEMVTGIDIVKTQILVAAGADLFGEEINMPQQKDITTLGYAIQCRITTEDPLNDFMPDTGTIIAYRSSGGFGVRLDAGDGFQGAEISPYYDSLLVKLSTHAISFKQAEEKMVRSLREMRIRGVKTNIPFLINVMKNKKFTSGDYTTKFIEETPELFDIQPSLDRGTKTLEYIGNVTINGFPNVEKRPKPDYELASIPTVSSSKIASFSGTKQLLDEVGPKGVAEWVKKQDDVLLTDTTFRDAHQSLLATRVRTKDMINIASKTADVFKDGFSLEMWGGATFDVAYNFLKENPWERLERLRKAIPNVLFQMLLRASNAVGYKNYPDNVIHKFVQESAKAGIDVFRIFDSLNWVDQMKVANEAVQEAGKISEGTICYTGDILNPERSNIYTLEYYVKLAKELEREGFHILAIKDMAGLLKPKAAYELIGELKSAVDLPIHLHTHDTSGNGLLTYKQAIDAGVDIIDTAVASMSGLTSQPSANSLYYALNGFPRHLRTDIEGMESLSHYWSTVRTYYSDFESDIKSPNTEIYQHEMPGGQYSNLSQQAKSLGLGERFDEVKDMYRRVNFLFGDIVKVTPSSKVVGDMALYMVQNDLDEQSVITDGYKLDFPESVVSFFKGEIGQPVNGFNKDLQAVILKGQEALTARPGEYLEPVDFEKVRELLEEEQQGPVTEQDIISYVLYPKVYEQYIQTRNQYGNLSLLDTPTFFFGMRNGETVEIEIDKGKRLIIKLETISEPDENGNRTIYYAMNGQARRIYIKDENVHTNANVKPKADKSNPSHIGAQMPGSVTEVKVSVGETVKANQPLLITEAMKMETTIQAPFDGVIKQVTVNNGDTIATGDLLIEIEKATD

6.4.1.1

COFACTOR: Name=biotin; Xref=ChEBI:CHEBI:57586; Evidence={ECO:0000269|PubMed:19523900, ECO:0000269|PubMed:23286247};

gluconeogenesis [GO:0006094]; pyruvate metabolic process [GO:0006090]

cytoplasm [GO:0005737]

ATP binding [GO:0005524]; identical protein binding [GO:0042802]; metal ion binding [GO:0046872]; pyruvate carboxylase activity [GO:0004736]

PF02785;PF00289;PF00364;PF02786;PF00682;PF02436;

2.40.50.100;3.20.20.70;3.30.470.20;3.10.600.10;

CATALYTIC ACTIVITY: Reaction=ATP + hydrogencarbonate + pyruvate = ADP + H(+) + oxaloacetate + phosphate; Xref=Rhea:RHEA:20844, ChEBI:CHEBI:15361, ChEBI:CHEBI:15378, ChEBI:CHEBI:16452, ChEBI:CHEBI:17544, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=6.4.1.1; Evidence={ECO:0000269|PubMed:19523900, ECO:0000269|PubMed:23286247};

FUNCTION: Catalyzes a 2-step reaction, involving the ATP-dependent carboxylation of the covalently attached biotin in the first step and the transfer of the carboxyl group to pyruvate in the second. {ECO:0000269|PubMed:19523900, ECO:0000269|PubMed:23286247}.

Staphylococcus aureus (strain Mu50 / ATCC 700699)

A0A0H3JUU7

MURT_STAAN

MRQWTAIHLAKLARKASRAVGKRGTDLPGQIARKVDTDVLRKLAEQVDDIVFISGTNGKTTTSNLIGHTLKANNIQIIHNNEGANMAAGITSAFIMQSTPKTKIAVIEIDEGSIPRVLKEVTPSMMVFTNFFRDQMDRFGEIDIMVNNIAETISNKGIKLLLNADDPFVSRLKIASDTIVYYGMKAHAHEFEQSTMNESRYCPNCGRLLQYDYIHYNQIGHYHCQCGFKREQAKYEISSFDVAPFLYLNINDEKYDMKIAGDFNAYNALAAYTVLRELGLNEQTIKNGFETYTSDNGRMQYFKKERKEAMINLAKNPAGMNASLSVGEQLEGEKVYVISLNDNAADGRDTSWIYDADFEKLSKQQIEAIIVTGTRAEELQLRLKLAEVEVPIIVERDIYKATAKTMDYKGFTVAIPNYTSLAPMLEQLNRSFEGGQS

6.3.5.13

cell wall organization [GO:0071555]; peptidoglycan biosynthetic process [GO:0009252]; regulation of cell shape [GO:0008360]

acid-amino acid ligase activity [GO:0016881]; ATP binding [GO:0005524]; carbon-nitrogen ligase activity on lipid II [GO:0140282]; zinc ion binding [GO:0008270]

PF08245;PF08353;

3.40.1190.10;

MurCDEF family, MurT subfamily

CATALYTIC ACTIVITY: Reaction=ATP + beta-D-GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)-di-trans,octa-cis-undecaprenyl diphosphate + H2O + L-glutamine = ADP + beta-D-GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-D-isoglutaminyl-L-Lys-D-Ala-D-Ala)-di-trans,octa-cis-undecaprenyl diphosphate + H(+) + L-glutamate + phosphate; Xref=Rhea:RHEA:57928, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29985, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:58359, ChEBI:CHEBI:60033, ChEBI:CHEBI:62233, ChEBI:CHEBI:456216; EC=6.3.5.13; Evidence={ECO:0000255|HAMAP-Rule:MF_02214, ECO:0000269|PubMed:22291598, ECO:0000269|PubMed:30154570}; CATALYTIC ACTIVITY: Reaction=ATP + beta-D-GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)-di-trans,octa-cis-undecaprenyl diphosphate = ADP + beta-D-GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-O-P-Glu-L-Lys-D-Ala-D-Ala)-di-trans,octa-cis-undecaprenyl diphosphate; Xref=Rhea:RHEA:59488, ChEBI:CHEBI:30616, ChEBI:CHEBI:60033, ChEBI:CHEBI:143132, ChEBI:CHEBI:456216; Evidence={ECO:0000255|HAMAP-Rule:MF_02214, ECO:0000269|PubMed:22291598}; CATALYTIC ACTIVITY: Reaction=beta-D-GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-O-P-Glu-L-Lys-D-Ala-D-Ala)-di-trans,octa-cis-undecaprenyl diphosphate + NH4(+) = beta-D-GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-D-isoglutaminyl-L-Lys-D-Ala-D-Ala)-di-trans,octa-cis-undecaprenyl diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:57932, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, ChEBI:CHEBI:43474, ChEBI:CHEBI:62233, ChEBI:CHEBI:143132; Evidence={ECO:0000255|HAMAP-Rule:MF_02214, ECO:0000269|PubMed:22291598};

PATHWAY: Cell wall biogenesis; peptidoglycan biosynthesis. {ECO:0000255|HAMAP-Rule:MF_02214, ECO:0000269|PubMed:22291598}.

BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 7.5-7.8 for isoglutaminyl synthase activity. {ECO:0000269|PubMed:22291598};

FUNCTION: The lipid II isoglutaminyl synthase complex catalyzes the formation of alpha-D-isoglutamine in the cell wall lipid II stem peptide (PubMed:22291598, PubMed:30154570). The MurT subunit catalyzes the ATP-dependent amidation of D-glutamate residue of lipid II, converting it to an isoglutamine residue (PubMed:22291598). {ECO:0000269|PubMed:22291598, ECO:0000269|PubMed:30154570}.

Staphylococcus aureus (strain N315)

A0A0H3K686

SPA_STAAE

MKKKNIYSIRKLGVGIASVTLGTLLISGGVTPAANAAQHDEAQQNAFYQVLNMPNLNADQRNGFIQSLKDDPSQSANVLGEAQKLNDSQAPKADAQQNNFNKDQQSAFYEILNMPNLNEAQRNGFIQSLKDDPSQSTNVLGEAKKLNESQAPKADNNFNKEQQNAFYEILNMPNLNEEQRNGFIQSLKDDPSQSANLLSEAKKLNESQAPKADNKFNKEQQNAFYEILHLPNLNEEQRNGFIQSLKDDPSQSANLLAEAKKLNDAQAPKADNKFNKEQQNAFYEILHLPNLTEEQRNGFIQSLKDDPSVSKEILAEAKKLNDAQAPKEEDNNKPGKEDNNKPGKEDNNKPGKEDNNKPGKEDGNKPGKEDNKKPGKEDGNKPGKEDNKKPGKEDGNKPGKEDGNKPGKEDGNGVHVVKPGDTVNDIAKANGTTADKIAADNKLADKNMIKPGQELVVDKKQPANHADANKAQALPETGEENPFIGTTVFGGLSLALGAALLAGRRREL

extracellular region [GO:0005576]

immunoglobulin binding [GO:0019865]

PF02216;PF00746;PF01476;PF03373;PF04650;

1.20.5.420;3.10.350.10;

Immunoglobulin-binding protein SpA family

SUBCELLULAR LOCATION: Secreted, cell wall {ECO:0000255|PROSITE-ProRule:PRU00477, ECO:0000269|PubMed:17416657, ECO:0000269|PubMed:24434550}; Peptidoglycan-anchor {ECO:0000255|PROSITE-ProRule:PRU00477, ECO:0000269|PubMed:17416657, ECO:0000269|PubMed:24434550}. Secreted {ECO:0000269|PubMed:24434550}. Note=Released from the cell wall in a glycan-free form by LytM; released early in log growth, almost no release occurs after 3 hours growth (PubMed:24434550). Anchored to the cell wall by sortase A (By similarity). {ECO:0000250|UniProtKB:P02976, ECO:0000269|PubMed:24434550}.

FUNCTION: Plays a role in the inhibition of the host innate and adaptive immune responses. Possesses five immunoglobulin-binding domains that capture both the fragment crystallizable region (Fc region) and the Fab region (part of Ig that identifies antigen) of immunoglobulins (By similarity). In turn, Staphylococcus aureus is protected from phagocytic killing via inhibition of Ig Fc region. In addition, the host elicited B-cell response is prevented due to a decrease of antibody-secreting cell proliferation that enter the bone marrow, thereby decreasing long-term antibody production (PubMed:28031339). Inhibits osteogenesis by preventing osteoblast proliferation and expression of alkaline phosphatase, type I collagen, osteopontin and osteocalcin (PubMed:22792377). Acts directly as a pro-inflammatory factor in the lung through its ability to bind and activate tumor necrosis factor alpha receptor 1/TNFRSF1A (PubMed:15247912, PubMed:16709567). {ECO:0000250|UniProtKB:P02976, ECO:0000269|PubMed:15247912, ECO:0000269|PubMed:16709567, ECO:0000269|PubMed:22792377, ECO:0000269|PubMed:28031339}.

Staphylococcus aureus (strain Newman)

A0A0H3K6J4

LYTM_STAAE

MKKLTAAAIATMGFATFTMAHQADAAETTNTQQAHTQMSTQSQDVSYGTYYTIDSNGDYHHTPDGNWNQAMFDNKEYSYTFVDAQGHTHYFYNCYPKNANANGSGQTYVNPATAGDNNDYTASQSQQHINQYGYQSNVGPDASYYSHSNNNQAYNSHDGNGKVNYPNGTSNQNGGSASKATASGHAKDASWLTSRKQLQPYGQYHGGGAHYGVDYAMPENSPVYSLTDGTVVQAGWSNYGGGNQVTIKEANSNNYQWYMHNNRLTVSAGDKVKAGDQIAYSGSTGNSTAPHVHFQRMSGGIGNQYAVDPTSYLQSR

3.4.24.75

COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:O33599};

cell wall organization [GO:0071555]; proteolysis [GO:0006508]; septum digestion after cytokinesis [GO:0000920]

cell division site [GO:0032153]; cell outer membrane [GO:0009279]; extracellular region [GO:0005576]

metal ion binding [GO:0046872]; metalloendopeptidase activity [GO:0004222]

PF01551;

2.40.50.290;2.70.70.10;

Peptidase M23B family

SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:O33599}.

CATALYTIC ACTIVITY: Reaction=Hydrolysis of the -Gly-|-Gly- bond in the pentaglycine inter-peptide link joining staphylococcal cell wall peptidoglycans.; EC=3.4.24.75; Evidence={ECO:0000305|PubMed:24434550};

FUNCTION: Peptidoglycan hydrolase (autolysin) specifically acting on polyglycine interpeptide bridges of the cell wall peptidoglycan (By similarity). Releases SpA, an immunologically active peptide, from the cell wall (PubMed:24434550). {ECO:0000250|UniProtKB:O33599, ECO:0000269|PubMed:24434550}.

Staphylococcus aureus (strain Newman)

A0A0H3KB22

QUEE_BURM1

MTYAVKEIFYTLQGEGANAGRPAVFCRFAGCNLWSGREEDRAQAVCRFCDTDFVGTDGENGGKFKDADALVATIAGLWPAGEAHRFVVCTGGEPMLQLDQPLVDALHAAGFGIAIETNGSLPVLESIDWICVSPKADAPLVVTKGNELKVVIPQDNQRLADYAKLDFEYFLVQPMDGPSRDLNTKLAIDWCKRHPQWRLSMQTHKYLNIP

4.3.99.3

COFACTOR: Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; Evidence={ECO:0000255|HAMAP-Rule:MF_00917, ECO:0000269|PubMed:24362703}; Note=Binds 1 [4Fe-4S] cluster. The cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine. {ECO:0000255|HAMAP-Rule:MF_00917, ECO:0000269|PubMed:24362703}; COFACTOR: Name=S-adenosyl-L-methionine; Xref=ChEBI:CHEBI:59789; Evidence={ECO:0000255|HAMAP-Rule:MF_00917, ECO:0000269|PubMed:24362703}; Note=Binds 1 S-adenosyl-L-methionine per subunit. {ECO:0000255|HAMAP-Rule:MF_00917, ECO:0000269|PubMed:24362703}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000255|HAMAP-Rule:MF_00917, ECO:0000269|PubMed:24362703};

queuosine biosynthetic process [GO:0008616]

4 iron, 4 sulfur cluster binding [GO:0051539]; carbon-nitrogen lyase activity [GO:0016840]; identical protein binding [GO:0042802]; magnesium ion binding [GO:0000287]; protein homodimerization activity [GO:0042803]; S-adenosyl-L-methionine binding [GO:1904047]

3.20.20.70;

Radical SAM superfamily, 7-carboxy-7-deazaguanine synthase family

CATALYTIC ACTIVITY: Reaction=6-carboxy-5,6,7,8-tetrahydropterin + H(+) = 7-carboxy-7-deazaguanine + NH4(+); Xref=Rhea:RHEA:27974, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, ChEBI:CHEBI:61032, ChEBI:CHEBI:61036; EC=4.3.99.3; Evidence={ECO:0000255|HAMAP-Rule:MF_00917, ECO:0000269|PubMed:24362703};

PATHWAY: Purine metabolism; 7-cyano-7-deazaguanine biosynthesis. {ECO:0000255|HAMAP-Rule:MF_00917, ECO:0000305|PubMed:24362703}.

FUNCTION: Catalyzes the complex heterocyclic radical-mediated conversion of 6-carboxy-5,6,7,8-tetrahydropterin (CPH4) to 7-carboxy-7-deazaguanine (CDG), a step common to the biosynthetic pathways of all 7-deazapurine-containing compounds. {ECO:0000255|HAMAP-Rule:MF_00917, ECO:0000269|PubMed:24362703}.

Burkholderia multivorans (strain ATCC 17616 / 249)

A0A0H3LKL4

6HN3M_BORBR

MQGKPRIAVIGAGLGGTAGAALMARAGFNVRLYEQAPAFSRLGAGIHLGPNVMKIMRRIGIEDELNRQGSHPDYWYSRDWQSGAELARIPLGDYAVSHYGATYLTVHRGDFHALMTAALPAGLLQFNKRLTRVDEDDDVVRLHFADGSVEEAEIVIGADGVNSRLREHLLGAELPKYTGYVAHRAVFPTPLDSGSLPFDMCVKWWSDDRHMMVYFVTGKRDEIYYVTGVPEQQWDMGKSWVPSSKAEMRAAFAGWHPTVQALIEATPEVSKWPLLERDPLPLWSRGRIVLLGDACHPMKPHMAQGAAMAIEDAAMLTRIFEQTGLQDHAAAFRLYEDNRAERASRVQRVSHDNTWLRTNENPDWCFGYDVYAEPLVEGRRAAA

1.14.13.114

COFACTOR: Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000269|PubMed:30810301}; Note=Binds 1 FAD molecule per subunit. {ECO:0000250|UniProtKB:Q88FY2};

aromatic compound catabolic process [GO:0019439]

6-hydroxynicotinate 3-monooxygenase activity [GO:0043731]; FAD binding [GO:0071949]

PF01494;

3.50.50.60;

6-hydroxynicotinate 3-monooxygenase family

CATALYTIC ACTIVITY: Reaction=6-hydroxynicotinate + 2 H(+) + NADH + O2 = 2,5-dihydroxypyridine + CO2 + H2O + NAD(+); Xref=Rhea:RHEA:27333, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16364, ChEBI:CHEBI:16526, ChEBI:CHEBI:57540, ChEBI:CHEBI:57664, ChEBI:CHEBI:57945; EC=1.14.13.114; Evidence={ECO:0000269|PubMed:30810301};

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=85 uM for 6-hydroxynicotinate (at pH 7.5 and 25 degrees Celsius) {ECO:0000269|PubMed:27218267}; KM=6 uM for NADH (at pH 7.5 and 25 degrees Celsius) {ECO:0000269|PubMed:27218267}; KM=118 uM for 6-hydroxynicotinate (at pH 7.5 and 25 degrees Celsius) {ECO:0000269|PubMed:30810301}; KM=600 uM for 4-hydroxybenzoate (at pH 7.5 and 25 degrees Celsius) {ECO:0000269|PubMed:30810301}; KM=3.9 uM for 5-chloro-6-hydroxynicotinate (at pH 7.5 and 25 degrees Celsius) {ECO:0000269|PubMed:30810301}; KM=8.1 uM for NADH (at pH 7.5 and 25 degrees Celsius) {ECO:0000269|PubMed:30810301}; Note=kcat is 4.2 sec(-1) with 6-hydroxynicotinate as substrate (at pH 7.5 and 25 degrees Celsius) (PubMed:27218267). kcat is 5.1 sec(-1) with 6-hydroxynicotinate as substrate. kcat is 0.074 sec(-1) with 4-hydroxybenzoate as substrate. kcat is 2.18 sec(-1) with 5-chloro-6-hydroxynicotinate as substrate (at pH 7.5 and 25 degrees Celsius) (PubMed:30810301). {ECO:0000269|PubMed:27218267, ECO:0000269|PubMed:30810301};

PATHWAY: Cofactor degradation; nicotinate degradation. {ECO:0000305|PubMed:27218267, ECO:0000305|PubMed:30810301}.

BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is around 7-8. {ECO:0000269|PubMed:27218267};

FUNCTION: Flavin-dependent monooxygenase (FMO) that catalyzes the decarboxylative hydroxylation of 6-hydroxynicotinic acid (6-HNA) to 2,5-dihydroxypyridine (2,5-DHP) with concomitant oxidation of NADH, a step in the aerobic nicotinate degradation pathway (PubMed:27218267, PubMed:30810301). Is also active on the non-natural substrate 5-chloro-6-hydroxynicotinate, and is much less efficient on the substrate analog 4-hydroxybenzoate (PubMed:30810301). {ECO:0000269|PubMed:27218267, ECO:0000269|PubMed:30810301}.

Bordetella bronchiseptica (strain ATCC BAA-588 / NCTC 13252 / RB50) (Alcaligenes bronchisepticus)

A0A0H3LM39

ZIP_BORBR

MNQPSSLAADLRGAWHAQAQSHPLITLGLAASAAGVVLLLVAGIVNALTGENRVHVGYAVLGGAAGFAATALGALMALGLRAISARTQDAMLGFAAGMMLAASAFSLILPGLDAAGTIVGPGPAAAAVVALGLGLGVLLMLGLDYFTPHEHERTGHQGPEAARVNRVWLFVLTIILHNLPEGMAIGVSFATGDLRIGLPLTSAIAIQDVPEGLAVALALRAVGLPIGRAVLVAVASGLMEPLGALVGVGISSGFALAYPISMGLAAGAMIFVVSHEVIPETHRNGHETTATVGLMAGFALMMFLDTALG

plasma membrane [GO:0005886]

zinc ion transmembrane transporter activity [GO:0005385]

PF02535;

ZIP transporter (TC 2.A.5) family

SUBCELLULAR LOCATION: Cell inner membrane; Multi-pass membrane protein.

CATALYTIC ACTIVITY: Reaction=Zn(2+)(in) = Zn(2+)(out); Xref=Rhea:RHEA:29351, ChEBI:CHEBI:29105; Evidence={ECO:0000269|PubMed:20876577}; CATALYTIC ACTIVITY: Reaction=Cd(2+)(in) = Cd(2+)(out); Xref=Rhea:RHEA:28707, ChEBI:CHEBI:48775; Evidence={ECO:0000269|PubMed:20876577};

FUNCTION: Selective electrodiffusional channel that mediates the uptake of Zn(2+). Exploits in vivo zinc concentration gradients (maintained by cellular zinc homeostasis) to passively move zinc ions into the cytoplasm. ZIPB-mediated zinc flux is dependent upon pH, but independent of the proton motive force. Is also able to import Cd(2+), but is not permeable to Co(2+), Cu(2+), Fe(2+), Mn(2+) and Ni(2+). {ECO:0000269|PubMed:20876577}.

Bordetella bronchiseptica (strain ATCC BAA-588 / NCTC 13252 / RB50) (Alcaligenes bronchisepticus)

A0A0H3M5A8

PPMNT_MYCBP

MKLGAWVAAQLPTTRTAVRTRLTRLVVSIVAGLLLYASFPPRNCWWAAVVALALLAWVLTHRATTPVGGLGYGLLFGLVFYVSLLPWIGELVGPGPWLALATTCALFPGIFGLFAVVVRLLPGWPIWFAVGWAAQEWLKSILPFGGFPWGSVAFGQAEGPLLPLVQLGGVALLSTGVALVGCGLTAIALEIEKWWRTGGQGDAPPAVVLPAACICLVLFAAIVVWPQVRHAGSGSGGEPTVTVAVVQGNVPRLGLDFNAQRRAVLDNHVEETLRLAADVHAGLAQQPQFVIWPENSSDIDPFVNPDAGQRISAAAEAIGAPILIGTLMDVPGRPRENPEWTNTAIVWNPGTGPADRHDKAIVQPFGEYLPMPWLFRHLSGYADRAGHFVPGNGTGVVRIAGVPVGVATCWEVIFDRAPRKSILGGAQLLTVPSNNATFNKTMSEQQLAFAKVRAVEHDRYVVVAGTTGISAVIAPDGGELIRTDFFQPAYLDSQVRLKTRLTPATRWGPILQWILVGAAAAVVLVAMRQNGWFPRPRRSEPKGENDDSDAPPGRSEASGPPALSESDDELIQPEQGGRHSSGFGRHRATSRSYMTTGQPAPPAPGNRPSQRVLVIIPTFNERENLPVIHRRLTQACPAVHVLVVDDSSPDGTGQLADELAQADPGRTHVMHRTAKNGLGAAYLAGFAWGLSREYSVLVEMDADGSHAPEQLQRLLDAVDAGADLAIGSRYVAGGTVRNWPWRRLVLSKTANTYSRLALGIGIHDITAGYRAYRREALEAIDLDGVDSKGYCFQIDLTWRTVSNGFVVTEVPITFTERELGVSKMSGSNIREALVKVARWGIEGRLSRSDHARARPDIARPGAGGSRVSRADVTE

2.3.1.269; 2.4.1.-; 2.4.1.83

lipoprotein biosynthetic process [GO:0042158]

plasma membrane [GO:0005886]

dolichyl-phosphate beta-D-mannosyltransferase activity [GO:0004582]; hydrolase activity [GO:0016787]; N-acyltransferase activity [GO:0016410]

PF00795;PF00535;PF20154;

3.60.110.10;

CN hydrolase family, Apolipoprotein N-acyltransferase subfamily; Glycosyltransferase 2 family

SUBCELLULAR LOCATION: Cell membrane {ECO:0000255}; Multi-pass membrane protein {ECO:0000255}.

CATALYTIC ACTIVITY: Reaction=a glycerophospholipid + N-terminal S-1,2-diacyl-sn-glyceryl-L-cysteinyl-[lipoprotein] = a 2-acyl-sn-glycero-3-phospholipid + H(+) + N-acyl-S-1,2-diacyl-sn-glyceryl-L-cysteinyl-[lipoprotein]; Xref=Rhea:RHEA:48228, Rhea:RHEA-COMP:14681, Rhea:RHEA-COMP:14684, ChEBI:CHEBI:15378, ChEBI:CHEBI:136912, ChEBI:CHEBI:140656, ChEBI:CHEBI:140657, ChEBI:CHEBI:140660; EC=2.3.1.269; Evidence={ECO:0000269|PubMed:24093492}; CATALYTIC ACTIVITY: Reaction=a dolichyl phosphate + GDP-alpha-D-mannose = a dolichyl beta-D-mannosyl phosphate + GDP; Xref=Rhea:RHEA:21184, Rhea:RHEA-COMP:9517, Rhea:RHEA-COMP:9527, ChEBI:CHEBI:57527, ChEBI:CHEBI:57683, ChEBI:CHEBI:58189, ChEBI:CHEBI:58211; EC=2.4.1.83; Evidence={ECO:0000250|UniProtKB:O53493};

PATHWAY: Protein modification; lipoprotein biosynthesis (N-acyl transfer).

FUNCTION: Catalyzes the phospholipid dependent N-acylation of the N-terminal cysteine of apolipoprotein, the last step in lipoprotein maturation. {ECO:0000269|PubMed:24093492}.; FUNCTION: Transfers mannose from GDP-mannose to lipid acceptors to form polyprenol monophosphomannose (PPM). PMM is an alkai-stable sugar donor which adds mannose-phosphate residues to triacylated-phosphatidyl-myo-inositol mannosides (PIM2), eventually leading to generation of the cell wall glycolipid lipoglycan modulins lipoarabinomannan (LAM) and lipomannan (LM). {ECO:0000250|UniProtKB:O53493}.

Mycobacterium bovis (strain BCG / Pasteur 1173P2)

A0A0H3MDW1

CHXR_CHLT2

MAGPKHVLLVSEHWDLFFQTKELLNPEEYRCTIGQQYKQELSADLVVCEYSLLPREIRSPKSLEGSFVLVLLDFFDEETSVDLLDRGFWYLIRPITPRILKSAISLFLSQHSLHSVPESIRFGPNVFYVLKLTVETPEGSVHLTPSESGILKRLLINKGQLCLRKHLLEEIKNHAKAIVARNVDVHIASLRKKLGAYGSRIVTLRGVGYLFSDDGDKKFSQQDTKLS

phosphorelay signal transduction system [GO:0000160]; positive regulation of DNA-templated transcription [GO:0045893]

DNA binding [GO:0003677]; DNA-binding transcription factor activity [GO:0003700]; identical protein binding [GO:0042802]; protein homodimerization activity [GO:0042803]; sequence-specific DNA binding [GO:0043565]; transcription cis-regulatory region binding [GO:0000976]

PF00486;

3.40.50.2300;1.10.10.10;

FUNCTION: May be a global positive regulator of transcription (PubMed:21057008). Binds a cis-acting element of its own promoter DNA sequence and is hence probably also involved in its own transcription activation (PubMed:21057008, PubMed:21775428, PubMed:24646934). The recognition sequence is 5'-WHGAWNH-N(3-5)-WHGAWNH-3', where W is A/T, H is C/A/T, N is G/C/A/T and the linker length in the middle is 3 to 5 nucleotides (PubMed:21057008). {ECO:0000269|PubMed:21057008, ECO:0000269|PubMed:21775428, ECO:0000269|PubMed:24646934}.

Chlamydia trachomatis serovar L2 (strain ATCC VR-902B / DSM 19102 / 434/Bu)

A0A0H3NK84

SSEK1_SALTS

MIPPLNRYVPALSKNELVKTVTNRDIQFTSFNGKDYPLCFLDEKTPLLFQWFERNPARFGKNDIPIINTEKNPYLNNIIKAATIEKERLIGIFVDGDFFPGQKDAFSKLEYDYENIKVIYRNDIDFSMYDKKLSEIYMENISKQESMPEEKRDCHLLQLLKKELSDIQEGNDSLIKSYLLDKGHGWFDFYRNMAMLKAGQLFLEADKVGCYDLSTNSGCIYLDADMIITEKLGGIYIPDGIAVHVERIDGRASMENGIIAVDRNNHPALLAGLEIMHTKFDADPYSDGVCNGIRKHFNYSLNEDYNSFCDFIEFKHDNIIMNTSQFTQSSWARHVQ

2.4.1.-

COFACTOR: Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269|PubMed:30327479};

extracellular region [GO:0005576]; host cell cytoplasm [GO:0030430]; host cell cytosol [GO:0044164]

manganese ion binding [GO:0030145]; protein-arginine N-acetylglucosaminyltransferase activity [GO:0106362]; toxin activity [GO:0090729]

Glycosyltransferase NleB family

PTM: Auto-glycosylated: arginine GlcNAcylation is required for activity toward death domain-containing host target proteins. {ECO:0000269|PubMed:32432056}.

SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q9L9J3}. Host cytoplasm, host cytosol {ECO:0000305|PubMed:32432056}. Note=Secreted via type III secretion systems 1 and 2 (SPI-1 and SPI-2 T3SS). {ECO:0000250|UniProtKB:Q9L9J3}.

CATALYTIC ACTIVITY: Reaction=L-arginyl-[protein] + UDP-N-acetyl-alpha-D-glucosamine = H(+) + N(omega)-(N-acetyl-beta-D-glucosaminyl)-L-arginyl-[protein] + UDP; Xref=Rhea:RHEA:66632, Rhea:RHEA-COMP:10532, Rhea:RHEA-COMP:17079, ChEBI:CHEBI:15378, ChEBI:CHEBI:29965, ChEBI:CHEBI:57705, ChEBI:CHEBI:58223, ChEBI:CHEBI:167322; Evidence={ECO:0000269|PubMed:30327479, ECO:0000269|PubMed:30902834, ECO:0000269|PubMed:32432056, ECO:0000269|PubMed:32766249}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66633; Evidence={ECO:0000269|PubMed:30327479, ECO:0000269|PubMed:30902834, ECO:0000269|PubMed:32432056, ECO:0000269|PubMed:32766249};

FUNCTION: Protein-arginine N-acetylglucosaminyltransferase effector that disrupts TNF signaling in infected cells, including NF-kappa-B signaling, apoptosis and necroptosis (PubMed:30327479, PubMed:32766249). Acts by catalyzing the transfer of a single N-acetylglucosamine (GlcNAc) to a conserved arginine residue in the death domain of host proteins TRADD and, to a lower extent, FADD: arginine GlcNAcylation prevents homotypic/heterotypic death domain interactions and assembly of the oligomeric TNF-alpha receptor complex, thereby disrupting TNF signaling (PubMed:30327479, PubMed:30902834, PubMed:32766249). Also acts on host proteins without a death domain: catalyzes arginine GlcNAcylation of host GAPDH protein, thereby preventing GAPDH interaction with TRAF2, leading to inhibit NF-kappa-B signaling (By similarity). Catalyzes GlcNAcylation of host tubulin-folding cofactor TBCB, thereby promoting microtubule stability (By similarity). Also mediates auto-GlcNAcylation, which is required for activity toward death domain-containing host target proteins (PubMed:32432056). {ECO:0000250|UniProtKB:Q9L9J3, ECO:0000269|PubMed:30327479, ECO:0000269|PubMed:30902834, ECO:0000269|PubMed:32432056, ECO:0000269|PubMed:32766249}.

Salmonella typhimurium (strain SL1344)

A0A0H3PEK7

TLYA_CAMJJ

MRFDFFVSKRLNISRNKALELIENEEVLLNGKSFKASFDVKNFLENLKKTQDLNPEDILLTDGLKLDLLSEIYVSRAALKLKNFLEENGIEIKHKNCLDIGSSTGGFVQILLENQALKITALDVGNNQLHLSLRTNEKIILHENTDLRTFKSEEKFELITCDVSFISLINLLYYIDNLALKEIILLFKPQFEVGKNIKRDKKGVLKDDKAILKARMDFEKACAKLGWLLKNTQKSSIKGKEGNVEYFYYYIKN

2.1.1.226

cell motility [GO:0048870]; cellular response to antibiotic [GO:0071236]; cytosolic ribosome assembly [GO:0042256]; rRNA 2'-O-methylation [GO:0000451]; viral process [GO:0016032]

RNA binding [GO:0003723]; rRNA methyltransferase activity [GO:0008649]

PF01728;

3.10.290.10;3.40.50.150;

TlyA family

CATALYTIC ACTIVITY: Reaction=cytidine(1920) in 23S rRNA + S-adenosyl-L-methionine = 2'-O-methylcytidine(1920) in 23S rRNA + H(+) + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:43200, Rhea:RHEA-COMP:10403, Rhea:RHEA-COMP:10404, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:74495, ChEBI:CHEBI:82748; EC=2.1.1.226; Evidence={ECO:0000269|PubMed:24796671, ECO:0000269|PubMed:29404277}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43201; Evidence={ECO:0000269|PubMed:24796671, ECO:0000269|PubMed:29404277};

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=4.8 uM for 50S ribosomal subunit (at pH 7.5 and 37 degrees Celsius) {ECO:0000269|PubMed:24796671}; KM=5.8 uM for S-adenosyl-L-methionine (at pH 7.5 and 37 degrees Celsius) {ECO:0000269|PubMed:24796671}; Note=kcat is 0.0048 min(-1) for 50S ribosomal subunit. kcat is 0.0044 min(-1) for S-adenosyl-L-methionine. {ECO:0000269|PubMed:24796671};

BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: High methylation activity of the 50S ribosomal subunit at 37 degrees Celsius. Loss of activity at 42 degrees Celsius. {ECO:0000269|PubMed:24796671};

FUNCTION: Catalyzes the 2'-O-methylation at nucleotide C1920 in 23S rRNA (PubMed:24796671, PubMed:29404277). Enhances motility (PubMed:24796671, PubMed:29404277, PubMed:32134554). Enhances biofilm formation (PubMed:29404277, PubMed:32134554). Involved in the assembly of 70S ribosomes (PubMed:24796671). Involved in virulence by promoting adherence and invasion to host cells (PubMed:18389311, PubMed:23971210, PubMed:32134554). Involved in pathogenicity by modulating secretion of host-protective chemokine interleukin 8 (IL-8) (PubMed:32134554). Involved in susceptibility to antibiotic capreomycin (PubMed:24796671, PubMed:32134554). {ECO:0000269|PubMed:18389311, ECO:0000269|PubMed:23971210, ECO:0000269|PubMed:24796671, ECO:0000269|PubMed:29404277, ECO:0000269|PubMed:32134554}.

Campylobacter jejuni subsp. jejuni serotype O:23/36 (strain 81-176)

A0A0H3PJK4

DLP2_CAMJJ

MQINLLNDFIKAYENTYSVSFDDSFKGRIQELCKELNEPFMHASYALENELKELVFSLDKNVNIAIIGQFSSGKSSLLNLILGRDCLPTGVVPVTFKPTFLRYAKEYFLRVEFEDGSDIITNIEKLAFYTDQRNEVKQAKSLHIFAPIPLLEKITLVDTPGLNANENDTLTTLDELKNIHGAIWLSLIDNAGKKSEEDAIKANLELLGENSICVLNQKDKLSAEELDNVLNYAKSVFLKYFNELIAISCKEAKDEQSYEKSNFQSLLDFLTQLDTTVLKEKFVKRKILNLCEILEDENQLFVGIFDRLLNQFQSYEKHLLLAYENFLKEIEILNHQILEQLKSISERISSEIFASVKEKDAYFYKESKGFLKKDLYTRYDYKAPYISSDDAFLAMFYNSDVMSKEFKKIKNELYKSFEEIKMKLKDFINILEREILLFKAEFSNIQKDHIFQSDKNFSELRAFCNASDEYFLKDFKELLFKSILELDLFFEKLNLKAFTNYENATKLSLAFFSRKINESRVLYELDSSEFVLFYPKKSEIYERVLNELNVYEFETLLINKPILTKIAKNFLEQSQNLIQEKNKFLDLKKAELQKRRAQILNVRESIKED

thylakoid membrane organization [GO:0010027]

cytosol [GO:0005829]

hydrolase activity [GO:0016787]

PF00350;

3.40.50.300;

TRAFAC class dynamin-like GTPase superfamily, Dynamin/Fzo/YdjA family

SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:30131557}.

CATALYTIC ACTIVITY: Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; Evidence={ECO:0000269|PubMed:30131557};

FUNCTION: The heterotetrameric DLP1(2)-DLP2(2) complex tethers liposomes and may mediate their fusion. Initial binding is probably mediated by DLP1, while DLP2 couples DLP1 subunits and increases the effective reach of the complex up to 45 nm. The role of the nucleotide is unknown. This subunit alone very weakly binds to liposomes; GTP, GDP, GMPPCP and GMPPNP do not change heterotetramer binding. Tetramerization is required for GTPase activity, suggesting the GTPase domains (dynamin-type G) from DLP1 and DLP2 must dimerize to reconstitute the GTPase active site. {ECO:0000269|PubMed:30131557}.

Campylobacter jejuni subsp. jejuni serotype O:23/36 (strain 81-176)

A0A0H3PJL7

DLP1_CAMJJ

MKELFQKIWQNELQFLNFDAKFQDKSKLDTAECAIILSVNKDNYERYFLLKEFQELCKKIDLRVDIFSMQNAQICILNLFKSGFISKQDLLKALKILEKISKNTEIFDFILQEKVQSIDQKALFQNDFKELNTINLELQKLSFDENLKSRLQKTLEKFQNLEFNIAITGVMNAGKSSLLNALLKEDFLGVSNIPETANLTVLSYGKSEEAKIYFWDKKEWQNILESSHFNADLKEFIDKLDKSVNIEDFIKDKPLIQNIALCELKNFSSAKNKISALIKKIEIKSHLEFLKNNISIVDTPGLDDVVVQREIVTNEYLRESDFLIHLMNASQSLTQKDADFLVHCLLNSRLSKFLIVLTKADLLSKKDLEEVIVYTKESLKSRLVDLDENLVEKIDFLCVSAKMASDFYKGLASKESLQKSGMQEFENYLFNELYAGEKSKIALRAYKKELHLELKNILSEYEMQNRLIKENKQGVSEENQKLLLELQKQNTLLKEAQDEISNSIAKLKNIDSGIDNLVLLLAKKLKERLIDEFKYLKNNAQKLNLSRILNIVDITTKDGINDILREIKFENIKKIEELKTNLSLKYDFLKDDFDNGFEGFKDGISKNIDSIFQSEKFALLRLKIEKLSNLKSDLYELETNLDTVIFDTFKEFKMSEILNSLNINGAFFEFLNDKLKHYEKNQKSKLESLEKVLQSLKNQDANILNSFEENLEKIEKLKQLEMGLLNAD

mitochondrial fusion [GO:0008053]

cytosol [GO:0005829]

GTP binding [GO:0005525]; GTPase activity [GO:0003924]

PF00350;

3.40.50.300;

TRAFAC class dynamin-like GTPase superfamily, Dynamin/Fzo/YdjA family

SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:30131557}.

CATALYTIC ACTIVITY: Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; Evidence={ECO:0000269|PubMed:30131557};

FUNCTION: The heterotetrameric DLP1(2)-DLP2(2) complex tethers liposomes and may mediate their fusion. Initial binding is probably mediated by DLP1, while DLP2 couples DLP1 subunits and increases the effective reach of the complex up to 45 nm. The role of the nucleotide is unknown. This subunit alone weakly binds to liposomes; GTP, GDP, GMPPCP and GMPPNP do not change heterotetramer binding. Tetramerization is required for GTPase activity, suggesting the GTPase domains (dynamin-type G) from DLP1 and DLP2 must dimerize to reconstitute the GTPase active site. {ECO:0000269|PubMed:30131557}.

Campylobacter jejuni subsp. jejuni serotype O:23/36 (strain 81-176)

A0A0H5BMX5

TCEB1_TULGE

MSIVSFCSSLPAGPHGFKHGRGTRDMVHMPCIVRRTARSPAQACRLLRWNKYHCAAVPTNSSLSPSPTPLDVEIELDLEPFLIKYKSGRIERLGRFGDRTDYVEASLDPATEVTSRDAITDTGVPVRIYLPKVDDSPPNSLRVLVYFHGGAFLVEDSASPPYHNYLNNLASKANILIVSVNYRLAPEYPLPVAYDDCMEALNWVNKHSDGTGQEDWINKHGDFDHLFISGDSAGGNITHNIAMSTDAPKNIEGIALVHPYFFGKVALETELQDPTNLLLHRKLWSFITPESEGLDDPRVNPLGPTAPSLEKIKCKRAVVFVAGEDFHSERGRKYSEKLKSEFKGEVPLLCNHDGVGHVYHLSVDATEEEIESAAAWKMMTDLLKFYKDNDVVLEGSIVESLKAKTTEGIKKMKEIEKGMSERMMEQLVAFYNGKPVPYSS

4.2.99.23

defense response [GO:0006952]

amyloplast [GO:0009501]

carboxylic ester hydrolase activity [GO:0052689]; lyase activity [GO:0016829]

PF07859;

3.40.50.1820;

AB hydrolase superfamily

PTM: Not glycosylated. {ECO:0000269|PubMed:25997073}.

SUBCELLULAR LOCATION: Plastid {ECO:0000269|PubMed:25997073}. Plastid, amyloplast {ECO:0000305}.

CATALYTIC ACTIVITY: Reaction=6-tuliposide B = D-glucose + tulipalin B; Xref=Rhea:RHEA:38655, ChEBI:CHEBI:4167, ChEBI:CHEBI:87123, ChEBI:CHEBI:87124; EC=4.2.99.23; Evidence={ECO:0000269|PubMed:25997073};

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=3 mM for 6-tuliposide A {ECO:0000269|PubMed:25997073}; KM=6.8 mM for 6-tuliposide B {ECO:0000269|PubMed:25997073}; Note=kcat is 8.7 sec(-1) with 6-tuliposide A as substrate. kcat is 2000 sec(-1) with 6-tuliposide B as substrate. {ECO:0000269|PubMed:25997073};

BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 7.0-7.5. {ECO:0000269|PubMed:25997073};

BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: Optimum temperature is 30-40 degrees Celsius. {ECO:0000269|PubMed:25997073};

FUNCTION: Lactone-forming carboxylesterase, specifically catalyzing intramolecular transesterification, but not hydrolysis. Involved in the biosynthesis of tulipalins, defensive chemicals that show antimicrobial activities against a broad range of strains of bacteria and fungi. Substrates are 6-tuliposide B > 6-tuliposide A. {ECO:0000269|PubMed:25997073}.

Tulipa gesneriana (Garden tulip)

A0A0J5ZXG5

PYCC_BURCE

MALADDLKKWVGETFTGKWEVQETTSVPNPEDLRLNSNHAKDLKAATVLYADLDGSTDMVNTKKWQFSAQIYKTFLKCASDIIRDEGGNITAYDGDRVMAVFTGNSKNTSAARCALKINSAVLDIIQPAIAKKWQTDFVLRHVVGIDTSQLRTARIGIRGDNDLVWIGRAANYAAKLTNLAGKPTRITADVYNKLADKLKYANGVDMWAPEHWDDMGIWTYTSTWKWTV

4.6.1.26

COFACTOR: Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269|PubMed:34644530}; Note=Slightly more active with Mn(2+) than with Mg(2+). {ECO:0000269|PubMed:34644530};

cyclic nucleotide biosynthetic process [GO:0009190]; defense response to virus [GO:0051607]; intracellular signal transduction [GO:0035556]

cytoplasm [GO:0005737]

adenylate cyclase activity [GO:0004016]; metal ion binding [GO:0046872]; nucleotide binding [GO:0000166]

PF00211;

3.30.70.1230;

Adenylyl cyclase class-4/guanylyl cyclase family, Pyrimidine cyclase subfamily

SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.

CATALYTIC ACTIVITY: Reaction=UTP = 3',5'-cyclic UMP + diphosphate; Xref=Rhea:RHEA:69603, ChEBI:CHEBI:33019, ChEBI:CHEBI:46398, ChEBI:CHEBI:184387; EC=4.6.1.26; Evidence={ECO:0000269|PubMed:34644530};

BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 7.0-9.5. {ECO:0000269|PubMed:34644530};

FUNCTION: Pycsar (pyrimidine cyclase system for antiphage resistance) provides immunity against bacteriophage. The pyrimidine cyclase (PycC) synthesizes cyclic nucleotides in response to infection; these serve as specific second messenger signals. The signals activate the adjacent effector, leading to bacterial cell death and abortive phage infection. A clade B Pycsar system. {ECO:0000305|PubMed:34644530}.; FUNCTION: The pyrimidine cyclase gene of a two-gene Pycsar system, generates cyclic UMP (cUMP) from UTP, has little to no activity on ATP, CTP or GTP (PubMed:34644530). Expression of this and adjacent effector BcPycTIR (AC A0A0J5WTU0) probably confers resistance to bacteriophage. The genes are probably only expressed in response to bacteriophage infection (Probable). {ECO:0000269|PubMed:34644530, ECO:0000305|PubMed:34644530}.

Burkholderia cepacia (Pseudomonas cepacia)

A0A0J9SZQ5

HXT1_PLAV1

MKKSSKEISSSQSLKNGGSDHFFNTSLMYVLAACLASFIFGYQVSVLNTIKNFIVIEFGWCTGNKVECDDSTLKSSFLLASVFIGAVVGSGFSGYLVQHGRRFSLLVIYNFFILVSILTSITHHFHTILFSRLLSGFGIGLITVSVPMYISEMTHKDKKGAYGVLHQLFITFGIFVAVLLGMAMGEAPDAKSVDALGEFQKIWWRLMFFFPCLISILGIVLLTFFYKEETPYYLFENGKIEESKKILKKIYGTDNVDEPLKAIKDAVEQNEAAKKNSISLMRAMQIPSYRNVILLGCILSGLQQFTGINVLVSNSNELYKEFLSNKLITTLSVIMTVVNFLMTFPAIYIVEKLGRKTLLLCGCAGVICAFLPTAIANQIDSTSAFVKNLSIAATFVMIISFAVSYGPVLWIYLHEMFPSEIKDSAASLASLVNWVCAIIVVFPSDIIIKKSPTILFFIFSGMSILSFLFIFFFIKETKGGEIGTSPYITMEERQKHMGKSAV

dehydroascorbic acid transport [GO:0070837]; glucose import [GO:0046323]

membrane [GO:0016020]

D-glucose transmembrane transporter activity [GO:0055056]

PF00083;

1.20.1250.20;

Major facilitator superfamily, Sugar transporter (TC 2.A.1.1) family

SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q7KWJ5}; Multi-pass membrane protein {ECO:0000255}.

CATALYTIC ACTIVITY: Reaction=D-glucose(out) = D-glucose(in); Xref=Rhea:RHEA:60376, ChEBI:CHEBI:4167; Evidence={ECO:0000269|PubMed:12792024, ECO:0000269|PubMed:15107012}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60377; Evidence={ECO:0000305}; CATALYTIC ACTIVITY: Reaction=D-fructose(out) = D-fructose(in); Xref=Rhea:RHEA:60372, ChEBI:CHEBI:37721; Evidence={ECO:0000250|UniProtKB:Q7KWJ5}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60373; Evidence={ECO:0000305}; CATALYTIC ACTIVITY: Reaction=D-galactose(in) = D-galactose(out); Xref=Rhea:RHEA:34915, ChEBI:CHEBI:4139; Evidence={ECO:0000250|UniProtKB:Q7KWJ5}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:34917; Evidence={ECO:0000305}; CATALYTIC ACTIVITY: Reaction=D-mannose(out) = D-mannose(in); Xref=Rhea:RHEA:78391, ChEBI:CHEBI:4208; Evidence={ECO:0000250|UniProtKB:Q7KWJ5}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:78392; Evidence={ECO:0000305}; CATALYTIC ACTIVITY: Reaction=D-glucosamine(out) = D-glucosamine(in); Xref=Rhea:RHEA:78423, ChEBI:CHEBI:58723; Evidence={ECO:0000250|UniProtKB:Q7KWJ5}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:78424; Evidence={ECO:0000305}; CATALYTIC ACTIVITY: Reaction=D-xylose(out) = D-xylose(in); Xref=Rhea:RHEA:78427, ChEBI:CHEBI:53455; Evidence={ECO:0000250|UniProtKB:Q7KWJ5}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:78428; Evidence={ECO:0000305};

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.85 mM for D-glucose {ECO:0000269|PubMed:12792024}; KM=0.77 mM for D-glucose {ECO:0000269|PubMed:15107012};

FUNCTION: Sodium-independent facilitative hexose transporter (By similarity). Can transport D-glucose and D-fructose (PubMed:12792024, PubMed:15107012). Can transport D-mannose, D-galactose, D-xylose and D-glucosamine (By similarity). {ECO:0000250|UniProtKB:Q700M0, ECO:0000250|UniProtKB:Q7KWJ5, ECO:0000269|PubMed:12792024, ECO:0000269|PubMed:15107012}.

Plasmodium vivax (strain Brazil I)

A0A0J9UVG7

SIR5_FUSO4

MRLLRPTPRLSSIFSSKTATSNLRFFTAMAPHNDVGAFHEALRSSKRILALCGAGLSASSGLPTFRGAGGLWRNHDATSLATLSAFKNDPGLVWLFYNYRRHMCLRAEPNPAHYALAALAEKNKDFLCLTQNVDNLSQQAGHPQDQLRTLHGSLFDIKCTNCDWIQRGNYDDPFCPALAPASVDVEPGKPFPLLDASLPLDPISPDDIPKCPQCKIGFQRPGVVWFGENLDEVMMMGITNWLLEDKVDLMLVIGTSAQVYPAAGYIDKAKRKGARIAVINPEAENEEEMYKVKPGDFAFGKDAAEYLPLLLEPVIGKLETDKKERS

2.3.1.-; 2.3.1.286

COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250|UniProtKB:Q9NXA8}; Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q9NXA8};

negative regulation of cellular respiration [GO:1901856]

chromosome [GO:0005694]; cytosol [GO:0005829]; mitochondrion [GO:0005739]; nucleus [GO:0005634]

metal ion binding [GO:0046872]; NAD+ binding [GO:0070403]; NAD-dependent histone deacetylase activity [GO:0017136]; NAD-dependent histone decrotonylase activity [GO:0160012]; NAD-dependent protein decrotonylase activity [GO:0160011]; protein-malonyllysine demalonylase activity [GO:0036054]; protein-succinyllysine desuccinylase activity [GO:0036055]

PF02146;

3.30.1600.10;3.40.50.1220;

Sirtuin family, Class I subfamily

SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:34927582}. Cytoplasm, cytosol {ECO:0000269|PubMed:34927582}. Nucleus {ECO:0000269|PubMed:34927582}. Chromosome {ECO:0000269|PubMed:34927582}.

CATALYTIC ACTIVITY: Reaction=H2O + N(6)-acetyl-L-lysyl-[protein] + NAD(+) = 2''-O-acetyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide; Xref=Rhea:RHEA:43636, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:10731, ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969, ChEBI:CHEBI:57540, ChEBI:CHEBI:61930, ChEBI:CHEBI:83767; EC=2.3.1.286; Evidence={ECO:0000255|PROSITE-ProRule:PRU00236}; CATALYTIC ACTIVITY: Reaction=H2O + N(6)-(2E)-butenoyl-L-lysyl-[protein] = (2E)-2-butenoate + L-lysyl-[protein]; Xref=Rhea:RHEA:69172, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:13707, ChEBI:CHEBI:15377, ChEBI:CHEBI:29969, ChEBI:CHEBI:35899, ChEBI:CHEBI:137954; Evidence={ECO:0000269|PubMed:34927582};

FUNCTION: NAD-dependent protein-lysine deacylase that decrotonylates the PDC (pyruvate dehydrogenase complex) subunit LAT1 at 'Lys-148' to inhibit PDC activity and consequently ATP production (PubMed:34927582). Also decrotonylates histone H3 crotonylated at 'Lys-18' (H3K18cr), to repress the expression of genes involved in aerobic respiration (PubMed:34927582). May also act as a NAD-dependent deacetylase (By similarity). Does not mediate desuccinylation, demalonylation, or deglutarylation of LAT1 (PubMed:34927582). {ECO:0000250|UniProtKB:P06700, ECO:0000269|PubMed:34927582}.

Fusarium oxysporum f. sp. lycopersici (strain 4287 / CBS 123668 / FGSC 9935 / NRRL 34936) (Fusarium vascular wilt of tomato)

A0A0J9X285

HMPK_ACIB6

MRPTVLCFSGLDPSGGAGLQADIEAIGQSGAHAAIACTALTIQNSQQVFGFEATSKELLLAQANAVVGDLPIKCVKSGMLGTTDNIAALAEFLRAHPDYQYVLDPVLVANSGGSLGDQATLVKAFVELIPLATLITPNTVELRALTGVTDLDQATQKLFEMGAKAVLVKGGHEDTPDFIKNSLYIDGELAASSTCPRLEGEYHGSGCSLASFIAGRLALGDSLKIAVQHAETWLFGVLKNAETPVLNGQKIPKRF

2.7.1.49

thiamine biosynthetic process [GO:0009228]; thiamine diphosphate biosynthetic process [GO:0009229]

cytosol [GO:0005829]

hydroxymethylpyrimidine kinase activity [GO:0008902]; phosphomethylpyrimidine kinase activity [GO:0008972]

PF08543;

3.40.1190.20;

ThiD family

PTM: Crystals show a disulfide bond between Cys-195 and Cys-207 (PubMed:38306231). This disulfide is possibly an artifact of the purification and crystallization conditions (PubMed:38306231). However, as it is adjacent to the conserved GSGC of the oxyanion hole, this disulfide may help to orient the backbone amides toward the oxanion intermediate (PubMed:38306231). {ECO:0000269|PubMed:38306231}.

CATALYTIC ACTIVITY: Reaction=4-amino-5-hydroxymethyl-2-methylpyrimidine + ATP = 4-amino-2-methyl-5-(phosphooxymethyl)pyrimidine + ADP + H(+); Xref=Rhea:RHEA:23096, ChEBI:CHEBI:15378, ChEBI:CHEBI:16892, ChEBI:CHEBI:30616, ChEBI:CHEBI:58354, ChEBI:CHEBI:456216; EC=2.7.1.49; Evidence={ECO:0000269|PubMed:38306231}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23097; Evidence={ECO:0000269|PubMed:38306231};

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=64 uM for HMP {ECO:0000269|PubMed:38306231}; Note=kcat is 0.19 sec(-1) with HMP as substrate. {ECO:0000269|PubMed:38306231};

PATHWAY: Cofactor biosynthesis; thiamine diphosphate biosynthesis. {ECO:0000305}.

FUNCTION: Catalyzes the phosphorylation of hydroxymethylpyrimidine (HMP) to hydroxymethylpyrimidine phosphate (HMP-P) (PubMed:38306231). Unlike other HMPKs, it cannot catalyze the phosphorylation of HMP-P to generate the diphosphate HMP-PP (PubMed:38306231). Shows no activity with pyridoxal, pyridoxamine or pyridoxine (PubMed:38306231). Does not show phosphatase activity (PubMed:38306231). {ECO:0000269|PubMed:38306231}.

Acinetobacter baumannii (strain IS-123)

A0A0K0JFP3

HXK_BRUMA

MLGLLTITSVFRNWRNSLQRKEDYDECHMRGINNENEISGKSEKNFKLDEPPISLETVMAEFKLSNETLRRMMAHMSRNMDKGLEGGPENSTISMLPSFVPELPNGTEEGRFIAMDLGGTNLRVMLMDIKPGEELKTEQFNTRIPNWAMRGTGEQLFDYITKCLAEFLIEKGIENDGLPVGFTFSYPCDQKSLRSATLLRWTKGFETTGVVGEDVVELLEQSIARRGDIKVEVVALINDTVGTMVAAAHESGGECHIGVIIATGTNASYMEDTSKIKYGLSKAIAAYNYPEMIIDTEWGGFGDRSEADYILTQYDKIVDSRSEHPGVNTFDKLVGGKCMGEVVRVVLEKLTRARVLFNGKGSDALFQQDSFPTKYISEILRDESGSYVHTRDILGELGIDHYSFSDMLLLREVCVVVSRRSANLGAAAIACVLNRVRKQNMVVGIDGSTYKYHPFFDFWVHDKLKELVDPGLKFKLLQTADGSGKGAALITAIVARLKKRNLKQQQQQQQQQQQHVTMVEQNVVEQIAETKGSREQFMNGNQKINLVTNDIPIYDSFNGDIENGVIHLSTDH

2.7.1.1

glucose metabolic process [GO:0006006]; glycolytic process [GO:0006096]; hexose metabolic process [GO:0019318]; intracellular glucose homeostasis [GO:0001678]

cytosol [GO:0005829]; mitochondrion [GO:0005739]

ATP binding [GO:0005524]; fructokinase activity [GO:0008865]; glucokinase activity [GO:0004340]; glucose binding [GO:0005536]; mannokinase activity [GO:0019158]

PF00349;PF03727;

3.30.420.40;3.40.367.20;

Hexokinase family

CATALYTIC ACTIVITY: Reaction=a D-hexose + ATP = a D-hexose 6-phosphate + ADP + H(+); Xref=Rhea:RHEA:22740, ChEBI:CHEBI:4194, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:229467, ChEBI:CHEBI:456216; EC=2.7.1.1; Evidence={ECO:0000255|PROSITE-ProRule:PRU01084, ECO:0000269|PubMed:18499511}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22741; Evidence={ECO:0000269|PubMed:18499511}; CATALYTIC ACTIVITY: Reaction=ATP + D-mannose = ADP + D-mannose 6-phosphate + H(+); Xref=Rhea:RHEA:11028, ChEBI:CHEBI:4208, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:58735, ChEBI:CHEBI:456216; EC=2.7.1.1; Evidence={ECO:0000269|PubMed:18499511}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11029; Evidence={ECO:0000269|PubMed:18499511}; CATALYTIC ACTIVITY: Reaction=ATP + D-fructose = ADP + D-fructose 6-phosphate + H(+); Xref=Rhea:RHEA:16125, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:37721, ChEBI:CHEBI:61527, ChEBI:CHEBI:456216; EC=2.7.1.1; Evidence={ECO:0000269|PubMed:18499511}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16126; Evidence={ECO:0000269|PubMed:18499511}; CATALYTIC ACTIVITY: Reaction=ATP + D-glucose = ADP + D-glucose 6-phosphate + H(+); Xref=Rhea:RHEA:17825, ChEBI:CHEBI:4167, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:61548, ChEBI:CHEBI:456216; EC=2.7.1.1; Evidence={ECO:0000269|PubMed:18499511}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17826; Evidence={ECO:0000269|PubMed:18499511};

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.035 mM for glucose {ECO:0000269|PubMed:18499511}; KM=75 mM for fructose {ECO:0000269|PubMed:18499511}; KM=1.09 mM for ATP {ECO:0000269|PubMed:18499511};

PATHWAY: Carbohydrate metabolism; hexose metabolism. {ECO:0000269|PubMed:18499511}.; PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose: step 1/4. {ECO:0000269|PubMed:18499511}.

BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 8.4. {ECO:0000269|PubMed:18499511};

FUNCTION: Active against glucose, fructose, mannose, maltose and galactose. {ECO:0000269|PubMed:18499511}.

Brugia malayi (Filarial nematode worm)

A0A0K0MJN3

FABP4_PYGPA

MCDQFVGTWKFLSSENFEDYMKELGVGFATRKMAGVAKPNVTISINGDVITIKTESTFKNTEVSFRLGEEFDETTADDRKTKNVITLDNGILNQVQKWDGKETVIKRKVMDGNLVVECTMNTVTSKRVYERA

cellular response to linoleic acid [GO:0071399]; long-chain fatty acid transport [GO:0015909]

cytoplasm [GO:0005737]; cytosol [GO:0005829]; nucleus [GO:0005634]

linoleic acid binding [GO:0070539]; long-chain fatty acid transporter activity [GO:0005324]; oleic acid binding [GO:0070538]; stearic acid binding [GO:0070540]

PF00061;

2.40.128.20;

Calycin superfamily, Fatty-acid binding protein (FABP) family

SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P04117}. Nucleus {ECO:0000250|UniProtKB:P04117}. Note=Depending on the nature of the ligand, a conformation change exposes a nuclear localization motif and the protein is transported into the nucleus. Subject to constitutive nuclear export. {ECO:0000250|UniProtKB:P04117}.

FUNCTION: Lipid transport protein in adipocytes. Binds both long chain fatty acids and retinoic acid. Delivers long-chain fatty acids and retinoic acid to their cognate receptors in the nucleus (By similarity). Has the highest binding affinity for linoleic acid and decreasing relative affinity for eicosapentaenoic acid (EPA), alpha-linolenic acid (ALA), docosahexaenoic acid (DHA), oleic acid, palmitic acid and stearic acid, respectively (PubMed:26206084). {ECO:0000250|UniProtKB:P04117, ECO:0000269|PubMed:26206084}.

Pygoscelis papua (Gentoo penguin)

A0A0K0PVW1

UGT10_PANGI

MKSELIFLPVPAFGHLVGMVEMAKLFISRHENLSVTVLISKFFIDTGIDNYNKSLLAKPTPRLTIINLPEIDPQKYLLKPRCAIFPSLIENQKTHVRDVMSRMTQSESTRVVGLLADILFVDIFDIADEFNVPTYVYSPAGAGFLGLAFHLQTLNDDKKQDVTEFRNSDTELLVPSFANPVPAEFLPSIFLEKDGRHDVLLSLYWRCREAKGIIVNTFEELEPYAINSLRMDSMIPPIYPVGPILNLNGEGQNSDEAAVILGWLDDQPPSSVVFLCFGSFGSFPENQVKEIAMGLERSGHRFLWSLRPCISEGETTLQLKYSNLELPAGFLDRTSCVGKVIGWAPQMAILAHEAVGGFVSHCGWNSVLESVWYGMPVATWPMYGEQQLNAFEMVKELGLAVEIEVDYRNEYNKSDFIVKADEIETKIKKLMMDGKNSKIRKKVKEMKEKSRVAMSENGSSYTSLAKLFEEIM

2.4.1.367

response to molecule of fungal origin [GO:0002238]; terpenoid biosynthetic process [GO:0016114]

hydrolase activity [GO:0016787]; UDP-glycosyltransferase activity [GO:0008194]

PF00201;

3.40.50.2000;

UDP-glycosyltransferase family

CATALYTIC ACTIVITY: Reaction=(20S)-protopanaxadiol + UDP-alpha-D-glucose = (20S)-ginsenoside C-K + H(+) + UDP; Xref=Rhea:RHEA:57976, ChEBI:CHEBI:15378, ChEBI:CHEBI:58223, ChEBI:CHEBI:58885, ChEBI:CHEBI:75950, ChEBI:CHEBI:77146; Evidence={ECO:0000269|PubMed:26032089}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:57977; Evidence={ECO:0000269|PubMed:26032089}; CATALYTIC ACTIVITY: Reaction=(20S)-protopanaxatriol + UDP-alpha-D-glucose = (20S)-ginsenoside Rh1 + H(+) + UDP; Xref=Rhea:RHEA:58952, ChEBI:CHEBI:15378, ChEBI:CHEBI:58223, ChEBI:CHEBI:58885, ChEBI:CHEBI:75951, ChEBI:CHEBI:142487; EC=2.4.1.367; Evidence={ECO:0000269|PubMed:26032089}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58953; Evidence={ECO:0000269|PubMed:26032089}; CATALYTIC ACTIVITY: Reaction=(20S)-ginsenoside F1 + UDP-alpha-D-glucose = (20S)-ginsenoside Rg1 + H(+) + UDP; Xref=Rhea:RHEA:58008, ChEBI:CHEBI:15378, ChEBI:CHEBI:58223, ChEBI:CHEBI:58885, ChEBI:CHEBI:67987, ChEBI:CHEBI:77150; EC=2.4.1.367; Evidence={ECO:0000269|PubMed:26032089}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58009; Evidence={ECO:0000269|PubMed:26032089};

PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis. {ECO:0000305}.

FUNCTION: Component of the dammarane-type triterpene saponins (e.g. PPT-type ginsenosides or panaxosides) biosynthetic pathway (PubMed:26032089, PubMed:27746309, PubMed:29378087). Glycosyltransferase that catalyzes the biosynthesis of ginsenoside Rh1 from protopanaxatriol (PPT) and the conversion of ginsenoside F1 to ginsenoside Rg1 (PubMed:26032089, PubMed:27746309). {ECO:0000269|PubMed:26032089, ECO:0000269|PubMed:27746309, ECO:0000303|PubMed:29378087}.

Panax ginseng (Korean ginseng)

A0A0K1YW63

SECP_APICE

MRFQVYILHLCFFILVVLTYLSQGQSYTTTTTTSTTEQPTFLQKIHETFKKVKENAKIHNLYIFDPPTWIYTTTTEKPVESTENFDITNRQLITVPVRCPPNYDFIKGRCREKIP

antibacterial innate immune response [GO:0140367]; antifungal innate immune response [GO:0061760]; defense response to fungus [GO:0050832]; defense response to Gram-negative bacterium [GO:0050829]; defense response to Gram-positive bacterium [GO:0050830]; killing of cells of another organism [GO:0031640]; negative regulation of endopeptidase activity [GO:0010951]; suppression of blood coagulation in another organism [GO:0035899]

extracellular region [GO:0005576]

serine-type endopeptidase inhibitor activity [GO:0004867]

PF17521;

Secapin family

SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:27208884}.

BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: Antibacterial activity against P.aeruginosa is retained between 25 and 90 degrees Celsius. {ECO:0000269|Ref.2};

FUNCTION: Serine protease inhibitor which exhibits antifibrinolytic, antielastolytic and antimicrobial activities (PubMed:27208884). Displays antimicrobial activity against bacteria and fungi (PubMed:27208884). Likely functions in the innate immune response to microbial infection and possibly in the venom, as an antifibrinolytic agent (PubMed:27208884). The recombinant form inhibits trypsin (IC(50)=80.02 nM, Ki=127.25 nM), chymotrypsin (IC(50)=393.78 nM, Ki=432.59 nM), the microbial serine proteases subtilisin A (IC(50)=379.20 nM, Ki=492.77 nM) and proteinase K (IC(50)=189.43 nM, Ki=271.76 nM), plasmin (IC(50)=457.98 nM, Ki=502.91 nM), human elastase (IC(50)=347.81 nM, Ki=469.90 nM) and porcine elastase (IC(50)=94.70 nM, Ki=125.62 nM) (PubMed:27208884). Does not inhibit thrombin (PubMed:27208884). Binds to human plasmin and inhibits the plasmin-mediated degradation of fibrin to fibrin degradation products (PubMed:27208884). Also binds to bacterial and fungal surfaces and exhibits antimicrobial activity against the Gram-positive bacteria B.thuringiensis (MIC=4.21 uM) and P.larvae (MIC=11.13 uM), the Gram-negative bacterium E.coli (MIC=6.50 uM), and the fungus B.bassiana (IC(50)=2.57 uM) (PubMed:27208884). The synthetic peptide also exhibits antimicrobial activity against the Gram-positive bacterium P.larvae (MIC=41.12 uM), the Gram-negative bacterium P.aeruginosa (MIC=65.75 uM), and the fungus B.bassiana (IC(50)=44.27 uM) (Ref.2). In vitro it does not induce an inflammatory response and has no cytotoxic activity against mouse embryo cells (Ref.2). {ECO:0000269|PubMed:27208884, ECO:0000269|Ref.2}.

Apis cerana (Indian honeybee)

A0A0K2JL82

CRED_STRCM

MTRPPAPPPGAPGADELLDCGLLSPVRAGTPVEALVCDSAWLQAMLDAEAALTRAQARTGFLPAAAAEAITAAARADRIDLLAVARGARETANPVVGLVAALTAAVRRDDPAAAEYVHRGSTSQDVLDTGAMLVARRALRLIGDDLDRAADALAALAADHRDTPMAGRTLALHAVPTTFGLKAAGWLELVSEAAGRVARLRDGLPFSLGGAAGTLAGYFGDRTDRGDPAVLLDRLLDAYAAETGLARPVLPWHVLRTPVADLAAVLAFTAGALGKIAVDVQSLARTEVAEVAEPAVEGRGASSAMPHKRNPVLSTLIRSAALQVPALATGLTQCLVSEDERSAGAWHAEWQPLRECLRLTGGAARTAVELAAGLEVDAARMRANLDLTDGRIVSESVAVALTPLLGRQAAKELLTRAAFTAGHEGRTLGEVLGELPELDGVLPKERWEALLDPARATGVAGALVDGALARRRPPAR

4.3.99.5

3,4-dihydroxybenzoate catabolic process [GO:0019619]; antibiotic biosynthetic process [GO:0017000]

lyase activity [GO:0016829]

PF10397;PF00206;

1.10.40.30;1.20.200.10;1.10.275.10;

Class-II fumarase/aspartase family

CATALYTIC ACTIVITY: Reaction=2-nitrobutanedioate = fumarate + H(+) + nitrite; Xref=Rhea:RHEA:69044, ChEBI:CHEBI:15378, ChEBI:CHEBI:16301, ChEBI:CHEBI:29806, ChEBI:CHEBI:180682; EC=4.3.99.5; Evidence={ECO:0000269|PubMed:26689788, ECO:0000269|PubMed:29505698}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69045; Evidence={ECO:0000269|PubMed:26689788};

PATHWAY: Antibiotic biosynthesis. {ECO:0000305|PubMed:26278892, ECO:0000305|PubMed:26689788}.

FUNCTION: Part of a gene cluster involved in the biosynthesis of cremeomycin, a light-sensitive o-diazoquinone with antibacterial and antiproliferative effects (PubMed:26278892, PubMed:26689788). Catalyzes the formation of nitrous acid from nitrosuccinic acid (2-nitrobutanedioate) by elimination of its nitro group (PubMed:26689788, PubMed:29505698). {ECO:0000269|PubMed:26278892, ECO:0000269|PubMed:26689788, ECO:0000269|PubMed:29505698}.

Streptomyces cremeus

A0A0K2S4Q6

CD3CH_HUMAN

MTQRAGAAMLPSALLLLCVPGCLTVSGPSTVMGAVGESLSVQCRYEEKYKTFNKYWCRQPCLPIWHEMVETGGSEGVVRSDQVIITDHPGDLTFTVTLENLTADDAGKYRCGIATILQEDGLSGFLPDPFFQVQVLVSSASSTENSVKTPASPTRPSQCQGSLPSSTCFLLLPLLKVPLLLSILGAILWVNRPWRTPWTES

neutrophil chemotaxis [GO:0030593]

extracellular region [GO:0005576]; plasma membrane [GO:0005886]

transmembrane signaling receptor activity [GO:0004888]

PF07686;

2.60.40.10;

CD300 family

SUBCELLULAR LOCATION: [Isoform 1]: Membrane {ECO:0000255}; Single-pass type I membrane protein {ECO:0000255}.; SUBCELLULAR LOCATION: [Isoform 2]: Secreted {ECO:0000269|PubMed:26221034}.

FUNCTION: May play an important role in innate immunity by mediating a signal for the production of a neutrophil chemoattractant. {ECO:0000269|PubMed:26221034}.

Homo sapiens (Human)

A0A0K3AUE4

SEA2_CAEEL

MGREYKFTGIAAKLNPLNCRLKLEIAEDLDERVPTTSTSCSVASVAAATATINTTAPTVLTKSELQKTLQKTSSSFSSSLATTTTTSSHLNAPVESMEGHSSLASYSHHHPSSSHHHHPGQQQSSSSSSSSHLQDFQSPPSASHPYYHQQQPQHQHQQAQQYGQATGSTNGGGQQQMTSMYGGNDYDQHQLHHQNQQHQASTSTQQFHHPQRPPPPQYDQPSSSTGSSLPPLHTVRYEQLPPPPSNQRTPTQQLQYPVKVVEAGGQAYAQQVQQAQQSNRSGAAGVNSALQPKPLPPLSSITSISSSAAGSSISAPSTSQPSTTSSLITSPPSTSSSSMAPRKTPPNASSSSLIKRQSQDVQEQQRVDFEVARNVSQIMSKNGLKVMHEPLLTGSLPQLAPLAPLPPPKSGVYQCPNCNRNLANARNLQRHRQTCGSAQHAAPQLAAMLQRSPPPCASAPPVAPPTAPSTSFQHHNSTGNLTLSYSSSSSRHQSSLYSPQLEHQDLVGNPNVMLSDGYEYKDDPMLYQGPSGLSDSIWSRDDSFHSEPPSASHDQLDMDHLGFPDPLQDPLHHLDSFDSADHRKETPRECHEPDELMTLDPTPPQCGSERFYGINIDDMPLSLDCDEPLMRSESASLSSSSQGRNTPAAVFTCEACKKSVSSERSLRRHYNTCKMFQTELAASGEERPPTTKRKPATKRPSKKKEASEGPEKNSAILAALRKEPAAPQQPQQLQFQQNYQPSPQFQAPYGGGSLPSISASWLHSASTSAAAAAPERSEMFTSPIVTSAPNPYIHQLPHQQPQQQKSSPLEDLLNEQDESADDDGDSRSSSGTVSNSTTTTTTATTTSSKSTGNPLFTCEHCARQLCSMSNLKRHRATCKVAASSSSNSAASRPPSQPSTPATAPATPMLQASQAPQPLQAPPQSPMETTATVTYTKTTVPPSVANTWNTEKAQLISPKPRSQTIFSEASSSMTVGDALRAQQHQQKMDQQIQIQFQQQQQQRFQHHQQQQQAGRIPPRPPNPILNQVQNPPQQVQHNQHQNQMLNPIRQPLLQSPPPPPPKKGLIEHKNTDLVLITSEPLAERMDAKRRSSEGLVAVTSTPLPPIQLPQRSQAPAPSRQQQQQPPVAYQVQFNGRPLPPMQLPPLQNPHNQQQQHQMLHQSQMNYQQVQQVQQVQHVQQQQNLQNQHHHQQQHHQQNQQQAPGNRSRSHSNVGKMEQEAQRQGSPLDSIITSVPLSIEVHHHIMKPGPLEQGQSSVDSQSTAEPSPRKASQQAYICPECKKTYASRKNVKRHRMAVHKLTLDEILANPEQPALDPLSAVGGAGRRHTVAGLETPDSALKPAPTKRKASEAPSAGVATKKGKAMAASVDEIQVKEEEEDQKEETVGSVERQEPPKKPVADDHKSAIAPLPPANTIMPPPPPYNQASAVPLNPPRTALPPLQLPPLQPLQSESPSWASMSAPPTALIPRTPRSSEFADEEDTRAMAKIAAELKRSAEDWPVLAVIEGVAAEPTNGEDIDEDEILIKRLRQGGVLEDVGDVSDLLRDVQGGVDGEPFSEDMLLEKNLSTASSVGLPSLASPGEQFGYQQYSQHPQQHPQQHPQQHPQQQQQVWNPNYEFQGYMQQQHPPMPVSQQFQQPLLQRPASQPPPARPIVKNSRRPSTTPKPPPNLTCSGCKKILGSDYSLRRHRAGCADVQQALNPEYPRPPKRKAAREAQKINEAEILASMPDPQMVAERSAAVAEAAAAEAAVERIGALPPPSVVHEIVHQVNADRQSMKKHNKTTSPPPAQEAPPTCAPDDPMSSSSSSSTSSASPLQGGAKPSTNQARHYCQFPECGKNFSSEWNLARHTRESCKMTTRAHSYEPTSAADKIDLIFMDKSKRRVSRTFLCTVSSLISYWLGEQGDRLELDTKWEHFQLLLDVHTLKVAITADNINLIAEQSKKYQLEHVIRMADQFMMNTNYTTPPTHVQL

cell differentiation [GO:0030154]; determination of adult lifespan [GO:0008340]; negative regulation of gene expression [GO:0010629]; positive regulation of transcription by RNA polymerase II [GO:0045944]; regulation of development, heterochronic [GO:0040034]; regulation of translation [GO:0006417]; response to heat [GO:0009408]; sex differentiation [GO:0007548]; sex-chromosome dosage compensation [GO:0007549]

cytoplasm [GO:0005737]; mediator complex [GO:0016592]; nucleus [GO:0005634]; PcG protein complex [GO:0031519]; transcription regulator complex [GO:0005667]

DNA-binding transcription factor activity, RNA polymerase II-specific [GO:0000981]; double-stranded RNA binding [GO:0003725]; metal ion binding [GO:0046872]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]; single-stranded RNA binding [GO:0003727]; transcription coactivator activity [GO:0003713]

PF00096;

3.30.160.60;

SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:21471153, ECO:0000269|PubMed:23666922}. Cytoplasm {ECO:0000269|PubMed:21471153}. Note=In embryos, diffusely accumulates in the nucleus at the 20- to 30-cell stage, but nuclear localization decreases after the 200-cell stage (PubMed:23666922). Diffusely localized in the nucleus and cytoplasm during the L3 larval stage (PubMed:21471153). {ECO:0000269|PubMed:21471153, ECO:0000269|PubMed:23666922}.

FUNCTION: RNA-binding protein, which regulates the expression of proteins required to control developmental timing of events during the L2 to L3 larval stage switch (PubMed:21471153). Binds to the 3'UTR of the transcript of the heterochronic protein lin-28 to post-transcriptionally negatively regulate its expression in certain tissue types in the later larval stages (PubMed:21471153). During larval development, controls the timing of seam cell division and terminal differentiation into adult alae (PubMed:21471153). In vitro, it can also bind to DNA through its first zinc finger (PubMed:21471153). May bind directly or indirectly to the promoter of the sex-determining factor xol-1 to activate its transcription (PubMed:23666922). Its activation of xol-1 transcription controls sex determination and X chromosome dosage compensation to promote male development (PubMed:23666922). Through the negative regulation of lin-28 transcript, it also has a role in the fox-1-sex-1-mediated determination of sexual fate (PubMed:21471153). Acts in the intestine to play a role in regulating adult lifespan (PubMed:21471153). {ECO:0000269|PubMed:21471153, ECO:0000269|PubMed:23666922}.

Caenorhabditis elegans

A0A0K3AUJ9

PRDX_CAEEL

MSLAPKMSKAFIGKPAPQFKTQAVVDGEFVDVSLSDYKGKYVVLFFYPLDFTFVCPTEIIAFSDRAEEFKAINTVVLAASTDSVFSHLAWINQPRKHGGLGEMNIPVLADTNHQISRDYGVLKEDEGIAFRGLFIIDPSQNLRQITINDLPVGRSVDETLRLVQAFQFVEKHGEVCPAGWTPGSDTIKPGVKESQEYFKKH

1.11.1.24

cell redox homeostasis [GO:0045454]; cellular response to hydrogen peroxide [GO:0070301]; determination of adult lifespan [GO:0008340]; heat acclimation [GO:0010286]; hydrogen peroxide catabolic process [GO:0042744]; negative regulation of transcription by RNA polymerase II [GO:0000122]; positive regulation of brood size [GO:0090727]; regulation of response to oxidative stress [GO:1902882]; removal of superoxide radicals [GO:0019430]; response to hydrogen peroxide [GO:0042542]; response to metal ion [GO:0010038]; response to oxidative stress [GO:0006979]

cytoplasm [GO:0005737]; cytosol [GO:0005829]

thioredoxin peroxidase activity [GO:0008379]

PF10417;PF00578;

3.40.30.10;

Peroxiredoxin family, AhpC/Prx1 subfamily

PTM: The enzyme can be inactivated by further oxidation of the cysteine sulfenic acid (C(P)-SOH) to sulphinic acid (C(P)-SO2H) instead of its condensation to a disulfide bond. {ECO:0000250|UniProtKB:Q06830}.

SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19064914}.

CATALYTIC ACTIVITY: Reaction=[thioredoxin]-dithiol + a hydroperoxide = [thioredoxin]-disulfide + an alcohol + H2O; Xref=Rhea:RHEA:62620, Rhea:RHEA-COMP:10698, Rhea:RHEA-COMP:10700, ChEBI:CHEBI:15377, ChEBI:CHEBI:29950, ChEBI:CHEBI:30879, ChEBI:CHEBI:35924, ChEBI:CHEBI:50058; EC=1.11.1.24; Evidence={ECO:0000269|PubMed:15099742};

FUNCTION: Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively (PubMed:15099742). In I2 pharyngeal neurons, required for the inhibition of feeding in response to light and hydrogen peroxide (PubMed:25640076). In the intestine, plays a role in protecting cells against oxidative stress by detoxifying peroxides such as hydrogen peroxide (PubMed:15099742, PubMed:19064914, PubMed:20649472). In addition, plays a role in the recovery from oxidative stress induced by hydrogen peroxide (PubMed:20649472). In its hyperoxidized form (induced by hydrogen peroxide), confers protection against heat stress (PubMed:19064914). However, has a low tendency for overoxidation during the normal lifespan (PubMed:20964547). Increases sensitivity to cytotoxity caused by metalloids and heavy metals such as arsenic and cadmium by playing a role in inhibiting the expression of phase II detoxification genes such as gcs-1 in intestinal cells (PubMed:19064914, PubMed:25204677). In addition, in response to arsenite, promotes the secretion of the insulin ligand daf-28 into the pseudocoelom, which negatively regulates the activities of daf-16 and skn-1 (PubMed:25808059). Plays a role in promoting longevity (PubMed:19064914, PubMed:24889636). Plays a role in the mitohormetic pathway by promoting the activation of pmk-1 in response to the drug metformin (PubMed:24889636). {ECO:0000269|PubMed:15099742, ECO:0000269|PubMed:19064914, ECO:0000269|PubMed:20649472, ECO:0000269|PubMed:20964547, ECO:0000269|PubMed:24889636, ECO:0000269|PubMed:25204677, ECO:0000269|PubMed:25640076, ECO:0000269|PubMed:25808059}.

Caenorhabditis elegans

A0A0K3AV08

MLK1_CAEEL

MEQASVPSYVNIPPIAKTRSTSHLAPTPEHHRSVSYEDTTTASTSTDSVPEVRIRSESSQVSRESPPIRASKAFVASYEYEAQKDDELNLPLGAIITLVTVETNEDGWYRGELNGKVGLFPSNYAREVTYKDNLVEFKQDEIMLPVAVRTLSDCQIGHGATATVFKMDIKIKKELQNGRMGEAVGDQMKAALKRFNRHASNFRADVVSTDEQLEQLKREANLVNGLSHNNIVRLLGICLEDPYFGLLLELCEGSSLRNVCRNLNSDAAIPLGVLIDWATQVAEGMEYLTKQGYVHRDLKADNVLVKEEVCLCMDEEMFQYAYCLKCGKRPFDKLQLKITDFGVTRKMTADANRFSTAGTYAWLAPEAFKEGTWSEASDVWSYGVVLWELLTREEPYQGHIPATIAFQIANKGQNLSIGDSCPDRWKKLMQDCWNLEPNFRPKFSTLAISFKQYAKEFKDTHLQRAPSKMAVKELYSECFADKTKEEFEKRFHDLYAGSGDINRKNRHSIAPETKARRLKHHKPKKADITGPTEVKHILSVQKDDKNFRVKTYDQSSTGGTLPRLNERQSTLSLSSPDLFHISNLISGSNTVGHSAHRISRKNAIRHKKNQHRMFESPVVSPTMDDSNTFSTIDNADEVDPNHSKESKKGGTLSRAWAKLPWNKRDSKEDHDERAVAGSISSRSSSTTSSNRLITGQTTRGASAAGLLEIGARSRAQSTADGWEDPNTTKKHKVSPSDKRPVKTTNQTERYVKDLEKDTPLRPAQLPPTHRKSALDQTIPASPNSPDSINNFHPMPLSSRRTTANSSSDGAPCYDALVSHSYGAGHGHKNHFGLSDTIPLFPEEPTHYDMGPGRPFGTNGRAIVNQGGDYYGNISGQNYEGFGHGRSINQSTQYYPVGGGCDDYIPIVQKTVIKPTVGEVGNSPYSENIRCATRNVQNPQYIQCKKNQNPRRIPALPMKIQSESNLVTSGMVFTPRDEQLNGIGNSLSSLSLNEPPDIPAPLPPVVTYPIPASLISPSNRVSMSPPTRMAPVLPLGAMSSPRIMDKEILKNSSVEGTEIY

2.7.11.25

COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:P80192};

axon regeneration [GO:0031103]; defense response to Gram-negative bacterium [GO:0050829]; determination of adult lifespan [GO:0008340]; JNK cascade [GO:0007254]; MAPK cascade [GO:0000165]; p38MAPK cascade [GO:0038066]; phosphorylation [GO:0016310]; positive regulation of axon extension involved in regeneration [GO:0048691]; positive regulation of axon regeneration [GO:0048680]; positive regulation of protein phosphorylation [GO:0001934]; response to copper ion [GO:0046688]; response to starvation [GO:0042594]; signal transduction [GO:0007165]

cytoplasm [GO:0005737]

ATP binding [GO:0005524]; MAP kinase kinase kinase activity [GO:0004709]; metal ion binding [GO:0046872]; protein kinase activity [GO:0004672]; protein kinase binding [GO:0019901]; protein kinase C binding [GO:0005080]; protein serine kinase activity [GO:0106310]; receptor tyrosine kinase binding [GO:0030971]; scaffold protein binding [GO:0097110]

PF07714;PF14604;

2.30.30.40;1.10.510.10;

Protein kinase superfamily, STE Ser/Thr protein kinase family, MAP kinase kinase kinase subfamily

PTM: May be phosphorylated on tyrosine residues by svh-2. {ECO:0000269|PubMed:22388962, ECO:0000269|PubMed:27984580}.; PTM: May be ubiquitinated and targeted for proteasomal degradation by E3 ubiquitin ligase rpm-1. {ECO:0000269|PubMed:21670305}.

CATALYTIC ACTIVITY: Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.25; Evidence={ECO:0000269|PubMed:15116070, ECO:0000269|PubMed:20008556}; CATALYTIC ACTIVITY: Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.25; Evidence={ECO:0000269|PubMed:15116070, ECO:0000269|PubMed:20008556};

FUNCTION: Serine/threonine-protein kinase which, by phosphorylating and activating mek-1, plays an important role in the activation of the JNK pathway composed of mlk-1, mek-1 and kgb-1 (PubMed:15116070, PubMed:20008556). Involved in the response to environmental stress such as heavy metals (PubMed:15116070, PubMed:18809575). By activating the JNK pathway downstream of tyrosine receptor svh-2, plays a role in axon regeneration after injury (PubMed:21670305, PubMed:22388962, PubMed:23072806). {ECO:0000269|PubMed:15116070, ECO:0000269|PubMed:18809575, ECO:0000269|PubMed:20008556, ECO:0000269|PubMed:21670305, ECO:0000269|PubMed:22388962, ECO:0000269|PubMed:23072806}.

Caenorhabditis elegans

A0A0K3AWM6

MOM5_CAEEL

MHRHILILFLFGCLSADQRLSSTSISSMNGFSTTRKCEHITIPMCKNLDYNQTVFPNLLGHTTQSEAGPAIAQFNPLIKVKCSEDIRLFLCTVYAPVCTVLEKPIQPCRELCLSAKNGCESLMKKFGFQWPDQLDCNKFPVTDLCVGKNSSESSNSKNYRSSNDVTFGVSTIANEVVLSPKKCPHHMHTTSGSHFSLPLLSGRLPECSLTCEADNQVPMMFDGRVRRILRIWTAAWSVACFVCSLFTLVTFLVDLSRFAYPVRPILYLAFCYLAISTVYMIGVVGEDGFACGTYGSTPTTLVTQGGENVGCSALAVVHYFFFMSSCAWWLVLCLAWFLAANLKWGAESIAALSPYFHAMCWGVPAVLSVTVLVTNSVDGDVFTGICSVGNLNPSALVYFFFTPIVVSLALGAVLLVCGIWSMIRIRSYIKLQHADVERNISKLEKLMLRIGAFAIMYSLPTAMNAAIMWYQAVNMPAWLEGWLHHRCVRLQDRELFGFTYPVDDCPMDPKVAAPEIIVFLLKYVSQLVVGITCAIWVVSSKTLSSYHKAYLALSSRSPTVPAHVDQVNMR

canonical Wnt signaling pathway [GO:0060070]; embryo development ending in birth or egg hatching [GO:0009792]; embryonic digestive tract morphogenesis [GO:0048557]; embryonic morphogenesis [GO:0048598]; endodermal cell fate specification [GO:0001714]; engulfment of apoptotic cell [GO:0043652]; establishment of mitotic spindle orientation [GO:0000132]; gastrulation [GO:0007369]; interneuron migration [GO:1904936]; left/right axis specification [GO:0070986]; motor neuron migration [GO:0097475]; neuroblast migration [GO:0097402]; neuron migration [GO:0001764]; non-canonical Wnt signaling pathway [GO:0035567]; positive regulation of anterior/posterior axon guidance [GO:1905488]; positive regulation of distal tip cell migration [GO:1903356]; positive regulation of engulfment of apoptotic cell [GO:1901076]; positive regulation of motor neuron migration [GO:1905485]; positive regulation of sensory neuron axon guidance [GO:1905491]; sensory neuron migration [GO:1904937]; Wnt signaling pathway [GO:0016055]; Wnt signaling pathway, regulating spindle positioning [GO:0060069]

early endosome [GO:0005769]; plasma membrane [GO:0005886]

Wnt receptor activity [GO:0042813]; Wnt-protein binding [GO:0017147]

PF01534;PF01392;

1.10.2000.10;1.20.1070.10;

G-protein coupled receptor Fz/Smo family

SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15620652, ECO:0000269|PubMed:24401370}; Multi-pass membrane protein {ECO:0000255}. Early endosome {ECO:0000269|PubMed:15620652, ECO:0000269|PubMed:24401370}. Note=Uniformaly localized along the cell membrane throughout the cell cycle, but occasionally enriched at prophase towards the posterior pole of the cell (PubMed:15620652). Sequestered from the cell membrane to endosomes by plr-1 to prevent Wnt signaling (PubMed:24401370). {ECO:0000269|PubMed:15620652, ECO:0000269|PubMed:24401370}.

FUNCTION: Receptor for Wnt proteins (PubMed:16930586, PubMed:22022276, PubMed:23295860, PubMed:24401370, PubMed:26292279). Most frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of gsk-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes (Probable). A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as pkc seems to be required for Wnt-mediated inactivation of gsk-3 kinase (Probable). Both pathways seem to involve interactions with G-proteins (Probable). Required in embryonic development for the correct positioning and orientation of the mitotic spindles and division planes in blastomere cells (PubMed:20126385, PubMed:9288749, PubMed:9288750). During early embryonic cell divisions, directs the asymmetric positioning of transcription factors such as pop-1 and dsh-2 in daughter cells in order to determine cell fate specification (PubMed:12810601, PubMed:15620652, PubMed:15990090). Acts redundantly with other Wnt receptors such as lin-17 to control vulval precursor cell specification and also the polarity of different cell types including distal tip cells, seam cells, AVG interneurons and P-cells and their descendants (PubMed:16930586, PubMed:20126385, PubMed:22022276, PubMed:23295860, PubMed:24401370, PubMed:26292279). Plays a role in the migration of cell types including distal tip cells and the QR neuroblast descendants, QR.p and QR.pa during larval development (PubMed:20126385, PubMed:25373777, PubMed:26292279). Negatively regulates the unc-6/Netrin receptors unc-5 and unc-40 to control distal tip cell polarity and migration (PubMed:26292279). Acts through ced-5/DOCK180 and ced-10/Rac to control both distal tip cell migration and the phagocytic clearance of apoptotic cell corpses (PubMed:20126385). Furthermore, it is also required for the migration and axon guidance of the different neuronal cell types including CAN, ALM, HSN and the two mechanosensory neurons AVM and PVM (PubMed:16109397, PubMed:16516839, PubMed:25917219). Mediates Wnt receptor cfz-2 in directing ALM migration, but may also act redundantly with the Wnt receptors cfz-2 and mig-1 to direct the migration of other neuronal cell types including CAN and HSN (PubMed:16109397, PubMed:16516839). Mediates Wnt ligand egl-20 in the control of the anterior-posterior axon guidance of AVM and PVM neurons (PubMed:16516839). {ECO:0000269|PubMed:12810601, ECO:0000269|PubMed:15620652, ECO:0000269|PubMed:15990090, ECO:0000269|PubMed:16109397, ECO:0000269|PubMed:16516839, ECO:0000269|PubMed:16930586, ECO:0000269|PubMed:20126385, ECO:0000269|PubMed:22022276, ECO:0000269|PubMed:24401370, ECO:0000269|PubMed:25373777, ECO:0000269|PubMed:25917219, ECO:0000269|PubMed:26292279, ECO:0000269|PubMed:9288749, ECO:0000269|PubMed:9288750, ECO:0000305}.

Caenorhabditis elegans

A0A0K3AXH1

ARID1_CAEEL

MSDDPAFLALGTEVSAKFKGAYCEAKIQKVDRSLKVKVSLKESPFGQMIVQDNDLPNAKFEINELTDVVFQRKFIRCQIQSIKDQSKYHVVFNDGDEKELRRTQLVLKGGKHFAADGNLDSMPLTNPESFSTPVIRGAAKRGAQKIRNAISEASGSRGGAVLLHNDDDENDEEDQEDGENEEDADDDDDDTEEQQQPRERRRAAAISAIGVLKKAIEDTQSEESSADSSEERERARSRRKRKDEASSAVTSDEEDQEDLATTDSENPVINGASSAAALSKTLQRKLEKQAMKREKQRLKEEEREEKLRLKEENREKKRREKARIMELKRLEKVYRTSNARIQENHEKSMTQIISHRSVRYFARFSDLKHRRKKKKLYLHEHRQKVNSRIRNVKLYFAWRFVAHKARLSYFARYALQWWRTSEDQAYSLIRTEKLLRSQRRRDWVGSWLEGLEREKIRFVVIHESYTQARRILKYIERGTEKRTFAERCDIEYEDIESSTVSSHFRDQEWFPAVLFPQVFSDENGSEGRQRIVRHMGNGQLVQVWEDDLVPFDWLPEYSFADVTAMTEKKPVEMRRKFKLAWRFATDYAQNRLDARSIRSILEWKFIRPSSRRLKITPIPVQAPSPNRCGEDHDDLVSTPNESDYDSDATIKNVDAETKDLFVAMLVQFHDAHNSVIDTNPTIQGHEVDLYYLYELAKKTGGPKKVYAANLWSDYAKKLVPAATDAEEELKTIFKNFLESYLAINTKLSWPMESLQPRTERKVVLPGQYSESRKKRTQAIMSQVQTPPTAPGSSKKGRVGSGGTRGRKRKVSSESVQLKKRNRKSSSRATTASPGPSEDRFSFQRPQDSDDVTDVPDDMTDHEDLLPEAATRKKYERKSQTPGRRSLSSRRDDTTPVSSMAAAPPKKGRPRKNTTVTTPVLSVPKSEGRGPRKEDTTTKFVRANVLSHILSGQKLRAFYGDEWFRANAIEDATDCTDEIMDIMLAHQDFFTPDTPRLSPSAIQDLDKVLKKIRAKTHYTGWNQRYDEFMKLEKLMVTVEDQMIARGRFRHLPRGRELKAETLALVEKHFRADDEDDGVPKTLAFYLKIAQEALSLSEKRAVADDDESSDSDTDFEQKPDTSAAAAVNGGKSESEEEEEEKTVVMGGDEEAEEEVKSEDVLVESVDQESPPTTSQGTTTPETAATGGLESESDEPEYPPVPEELVPPPPVLLENFPSTDRFSSGGSSNYPTLSRQGSINSMASPMFSPNSDLSLSGPLTLPRSGPLTMANIRQSPTPDEVVGSLRKRLSQTSESSESSELPPPPSAASKSKRIRRASERSIDSASEHHRMMRSPRILTTQHSSGALIFDISTTQPTDTSGPIEALSVRKPGRRKTVFAASPTLLTSGPLTLSSSAPPPPPASPAPPQHAQKTLGRPRKTPSTSSRKPEEEDEAEQIPTTVVGVTEEASVADSSAKEDLTSEDGSATPQDEKDDSESTTTTDTITPKSIRGGKRRRGGGRFGGSYPVKPAKPGRKPKDPHAEEGADEKDPEDQTPTTMTTSTPTRADSFQTQKNRMAKLMEGKPHDYSFLDLPDFDKIIEEAPKEDINILMEERTYELREIFAQCKADLSALEKRYRQQNEAKRKAEFAAKTASSAAAAQASSSTCSTPRP

defense response to other organism [GO:0098542]; ERAD pathway [GO:0036503]; proteasomal protein catabolic process [GO:0010498]; regulation of DNA-templated transcription [GO:0006355]; regulation of transcription by RNA polymerase II [GO:0006357]; response to endoplasmic reticulum stress [GO:0034976]

nucleus [GO:0005634]; SWI/SNF complex [GO:0016514]; transcription repressor complex [GO:0017053]

DNA binding [GO:0003677]; transcription cis-regulatory region binding [GO:0000976]

PF01388;

2.30.30.140;1.10.150.60;

SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00355, ECO:0000305}.

FUNCTION: DNA-binding protein which modulates activity of several transcription factors (By similarity). Plays a role in the modulation of endoplasmic reticulum (ER) homeostasis during chemical and pathogen stress, including exposure to the Gram-negative bacterium P.aeruginosa (PubMed:30287474). {ECO:0000250|UniProtKB:F8VPQ2, ECO:0000269|PubMed:30287474}.

Caenorhabditis elegans

A0A0K8P6T7

PETH_PISS1

MNFPRASRLMQAAVLGGLMAVSAAATAQTNPYARGPNPTAASLEASAGPFTVRSFTVSRPSGYGAGTVYYPTNAGGTVGAIAIVPGYTARQSSIKWWGPRLASHGFVVITIDTNSTLDQPSSRSSQQMAALRQVASLNGTSSSPIYGKVDTARMGVMGWSMGGGGSLISAANNPSLKAAAPQAPWDSSTNFSSVTVPTLIFACENDSIAPVNSSALPIYDSMSRNAKQFLEINGGSHSCANSGNSNQALIGKKGVAWMKRFMDNDTRYSTFACENPNSTRVSDFRTANCS

3.1.1.101

cellular response to organic substance [GO:0071310]; xenobiotic catabolic process [GO:0042178]

extracellular region [GO:0005576]

acetylesterase activity [GO:0008126]; carboxylic ester hydrolase activity [GO:0052689]

PF01738;

3.40.50.1820;

AB hydrolase superfamily

SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:26965627}.

CATALYTIC ACTIVITY: Reaction=(ethylene terephthalate)(n) + H2O = (ethylene terephthalate)(n-1) + 4-[(2-hydroxyethoxy)carbonyl]benzoate + H(+); Xref=Rhea:RHEA:49528, Rhea:RHEA-COMP:12420, Rhea:RHEA-COMP:12421, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:131701, ChEBI:CHEBI:131704; EC=3.1.1.101; Evidence={ECO:0000269|PubMed:26965627, ECO:0000269|PubMed:29235460, ECO:0000269|PubMed:29374183, ECO:0000269|PubMed:29603535, ECO:0000269|PubMed:29666242, ECO:0000269|PubMed:32269349}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49529; Evidence={ECO:0000269|PubMed:26965627}; CATALYTIC ACTIVITY: Reaction=(2,5-ethylene furandicarboxylate)(n) + 2 H2O = (2,5-ethylene furandicarboxylate)(n-1) + 2,5-dicarboxyfuran + ethylene glycol + 2 H(+); Xref=Rhea:RHEA:42648, Rhea:RHEA-COMP:14671, Rhea:RHEA-COMP:14672, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30742, ChEBI:CHEBI:83389, ChEBI:CHEBI:140646; Evidence={ECO:0000269|PubMed:29666242}; CATALYTIC ACTIVITY: Reaction=an acetyl ester + H2O = acetate + an aliphatic alcohol + H(+); Xref=Rhea:RHEA:12957, ChEBI:CHEBI:2571, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30089, ChEBI:CHEBI:47622; Evidence={ECO:0000269|PubMed:26965627, ECO:0000269|PubMed:30502092}; CATALYTIC ACTIVITY: Reaction=a butanoate ester + H2O = an aliphatic alcohol + butanoate + H(+); Xref=Rhea:RHEA:47348, ChEBI:CHEBI:2571, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17968, ChEBI:CHEBI:50477; Evidence={ECO:0000269|PubMed:26965627, ECO:0000269|PubMed:30502092}; CATALYTIC ACTIVITY: Reaction=a hexanoate ester + H2O = an aliphatic alcohol + H(+) + hexanoate; Xref=Rhea:RHEA:47352, ChEBI:CHEBI:2571, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17120, ChEBI:CHEBI:87656; Evidence={ECO:0000269|PubMed:26965627, ECO:0000269|PubMed:30502092}; CATALYTIC ACTIVITY: Reaction=an octanoate ester + H2O = an aliphatic alcohol + H(+) + octanoate; Xref=Rhea:RHEA:47356, ChEBI:CHEBI:2571, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:25646, ChEBI:CHEBI:87657; Evidence={ECO:0000269|PubMed:26965627, ECO:0000269|PubMed:30502092}; CATALYTIC ACTIVITY: Reaction=a dodecanoate ester + H2O = an aliphatic alcohol + dodecanoate + H(+); Xref=Rhea:RHEA:47364, ChEBI:CHEBI:2571, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:18262, ChEBI:CHEBI:87659; Evidence={ECO:0000269|PubMed:30502092};

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.431 mM for pNP-acetate {ECO:0000269|PubMed:30502092}; KM=0.315 mM for pNP-butanoate {ECO:0000269|PubMed:30502092}; KM=0.053 mM for pNP-hexanoate {ECO:0000269|PubMed:30502092}; KM=0.048 mM for pNP-octanoate {ECO:0000269|PubMed:30502092}; KM=2.283 mM for pNP-dodecanoate {ECO:0000269|PubMed:30502092}; Note=kcat is 1590 sec(-1) for the hydrolysis of pNP-acetate. kcat is 1353 sec(-1) for the hydrolysis of pNP-butanoate. kcat is 1345 sec(-1) for the hydrolysis of pNP-hexanoate. kcat is 519 sec(-1) for the hydrolysis of pNP-octanoate. kcat is 1531 sec(-1) for the hydrolysis of pNP-dodecanoate. {ECO:0000269|PubMed:30502092};

PATHWAY: Xenobiotic degradation. {ECO:0000305|PubMed:26965627}.

BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 9 for PET film hydrolysis (PubMed:26965627). Optimum pH is 9 for PET (commercial drinking bottle) hydrolysis. Optimum pH is 6.5-8.0 for BHET hydrolysis (PubMed:29603535). Optimum pH is 8.0 for the hydrolysis of pNP-esters. The enzyme is active at pH 6-10, has an optimal pH range of 7-9 and it is rapidly inactivated below pH 7.0 or above pH 9.0 (PubMed:30502092). {ECO:0000269|PubMed:26965627, ECO:0000269|PubMed:29603535, ECO:0000269|PubMed:30502092};

BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: Optimum temperature is 40 degrees Celsius for PET film hydrolysis (PubMed:26965627). Optimum temperature is 30 degrees Celsius for PET (commercial drinking bottle) hydrolysis and BHET hydrolysis (PubMed:29603535). Optimum temperature is 35-45 degrees Celsius for the hydrolysis of pNP-esters. Remains active even at 65 degrees Celsius (about 60% of maximum activity) (PubMed:30502092). {ECO:0000269|PubMed:26965627, ECO:0000269|PubMed:29603535, ECO:0000269|PubMed:30502092};

FUNCTION: Involved in the degradation and assimilation of the plastic poly(ethylene terephthalate) (PET), which allows I.sakaiensis to use PET as its major energy and carbon source for growth. Likely acts synergistically with MHETase to depolymerize PET (PubMed:26965627). Catalyzes the hydrolysis of PET to produce mono(2-hydroxyethyl) terephthalate (MHET) as the major product (PubMed:26965627, PubMed:29235460, PubMed:29374183, PubMed:29603535, PubMed:29666242, PubMed:32269349). Also depolymerizes another semiaromatic polyester, poly(ethylene-2,5-furandicarboxylate) (PEF), which is an emerging, bioderived PET replacement with improved gas barrier properties (PubMed:29666242). In contrast, PETase does not degrade aliphatic polyesters such as polylactic acid (PLA) and polybutylene succinate (PBS) (PubMed:29666242). Is also able to hydrolyze bis(hydroxyethyl) terephthalate (BHET) to yield MHET with no further decomposition, but terephthalate (TPA) can also be observed (PubMed:26965627, PubMed:29374183, PubMed:29603535). Shows esterase activity towards p-nitrophenol-linked aliphatic esters (pNP-aliphatic esters) in vitro (PubMed:26965627, PubMed:30502092). {ECO:0000269|PubMed:26965627, ECO:0000269|PubMed:29235460, ECO:0000269|PubMed:29374183, ECO:0000269|PubMed:29603535, ECO:0000269|PubMed:29666242, ECO:0000269|PubMed:30502092, ECO:0000269|PubMed:32269349}.

Piscinibacter sakaiensis (Ideonella sakaiensis)

A0A0K8P8E7

MHETH_PISS1

MQTTVTTMLLASVALAACAGGGSTPLPLPQQQPPQQEPPPPPVPLASRAACEALKDGNGDMVWPNAATVVEVAAWRDAAPATASAAALPEHCEVSGAIAKRTGIDGYPYEIKFRLRMPAEWNGRFFMEGGSGTNGSLSAATGSIGGGQIASALSRNFATIATDGGHDNAVNDNPDALGTVAFGLDPQARLDMGYNSYDQVTQAGKAAVARFYGRAADKSYFIGCSEGGREGMMLSQRFPSHYDGIVAGAPGYQLPKAGISGAWTTQSLAPAAVGLDAQGVPLINKSFSDADLHLLSQAILGTCDALDGLADGIVDNYRACQAAFDPATAANPANGQALQCVGAKTADCLSPVQVTAIKRAMAGPVNSAGTPLYNRWAWDAGMSGLSGTTYNQGWRSWWLGSFNSSANNAQRVSGFSARSWLVDFATPPEPMPMTQVAARMMKFDFDIDPLKIWATSGQFTQSSMDWHGATSTDLAAFRDRGGKMILYHGMSDAAFSALDTADYYERLGAAMPGAAGFARLFLVPGMNHCSGGPGTDRFDMLTPLVAWVERGEAPDQISAWSGTPGYFGVAARTRPLCPYPQIARYKGSGDINTEANFACAAPP

3.1.1.102

cellular response to organic substance [GO:0071310]; xenobiotic catabolic process [GO:0042178]

cell outer membrane [GO:0009279]

carboxylic ester hydrolase activity [GO:0052689]; metal ion binding [GO:0046872]

PF07519;

Tannase family

SUBCELLULAR LOCATION: Cell outer membrane {ECO:0000305|PubMed:26965627}; Lipid-anchor {ECO:0000255|PROSITE-ProRule:PRU00303, ECO:0000305|PubMed:26965627}.

CATALYTIC ACTIVITY: Reaction=4-[(2-hydroxyethoxy)carbonyl]benzoate + H2O = ethylene glycol + H(+) + terephthalate; Xref=Rhea:RHEA:49532, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30043, ChEBI:CHEBI:30742, ChEBI:CHEBI:131704; EC=3.1.1.102; Evidence={ECO:0000269|PubMed:26965627, ECO:0000269|PubMed:30979881}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49533; Evidence={ECO:0000269|PubMed:26965627};

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=7.3 uM for mono(2-hydroxyethyl) terephthalate (at pH 7 and 30 degrees Celsius) {ECO:0000269|PubMed:26965627}; Note=kcat is 31 sec(-1) for the hydrolysis of mono(2-hydroxyethyl) terephthalate (at pH 7 and 30 degrees Celsius). {ECO:0000269|PubMed:26965627};

FUNCTION: Involved in the degradation and assimilation of the plastic poly(ethylene terephthalate) (PET), which allows I.sakaiensis to use PET as its major energy and carbon source for growth. Likely acts synergistically with PETase to depolymerize PET. Catalyzes the hydrolysis of mono(2-hydroxyethyl) terephthalate (MHET) into its two environmentally benign monomers, terephthalate and ethylene glycol. Does not show activity against PET, bis(hydroxyethyl) terephthalate (BHET), pNP-aliphatic esters or typical aromatic ester compounds catalyzed by the tannase family enzymes, such as ethyl gallate and ethyl ferulate. {ECO:0000269|PubMed:26965627}.

Piscinibacter sakaiensis (Ideonella sakaiensis)

A0A0L7KF24

FCLN_PLAFX

MNLTKLMKVFGYINIITNCVQSFTNRADKKRYNVFAKSFINTINTNLYTFKAVMSKTPEWIHEKSPKHNSYDIIEKRYNEEFKMTYTVYQHKKAKTQVISLGTNDPLDVEQAFAFYVKTLTHSGKGIPHILEHSVLSGSKNYNYKNSIGLLEKGTLHTHLNAYTFNDRTVYMAGSMNNKDFFNIMGVYMDSVFQPNVLENKYIFETEGWTYEVEKLKEDEKGKAEIPQMKDYKVSFNGIVYNEMKGALSSPLEDLYHEEMKYMFPDNVHSNNSGGDPKEITNLTYEEFKEFYYKNYNPKKVKVFFFSKNNPTELLNFVDQYLGQLDYSKYRDDAVESVEYQTYKKGPFYIKKKYGDHSEEKENLVSVAWLLNPKVDKTNNHNNNHSNNQSSENNGYSNGSHSSDLSLENPTDYFVLLIINNLLIHTPESVLYKALTDCGLGNNVIDRGLNDSLVQYIFSIGLKGIKRNNEKIKIFDKVHYEVEDVIMNALKKVVKEGFNKSAVEASINNIEFILKEANLKTSKSIDFVFEMTSKLNYNRDPLLIFEFEKYLNIVKNKIKNEPMYLEKFVEKHFINNAHRSVILLEGDENYAQEQENLEKQELKKRIENFNEQEKEQVIKNFEELSKYKNAEESPEHLNKFPIISISDLNKKTLEVPVNVYFTNINENNNIMETYNKLKTNEHMLKDNMDVFLKKYVLKNDKHNTNNNNNNNNNMDYSFTETKYEGNVPILVYEMPTTGIVYLQFVFSLDHLTVDELAYLNLFKTLILENKTNKRSSEDFVILREKNIGSMSANVALYSKDDHLNVTDKYNAQALFNLEMHVLSHKCNDALNIALEAVKESDFSNKKKVIDILKRKINGMKTTFSEKGYAILMKYVKAHLNSKHYAHNIIYGYENYLKLQEQLELAENDFKTLENILVRIRNKIFNKKNLMVSVTSDYGALKHLFVNSNESLKNLVSYFEENDKYINDMQNKVNDPTVMGWNEEIKSKKLFDEEKVKKEFFVLPTFVNSVSMSGILFKPGEYLDPSFTVIVAALKNSYLWDTVRGLNGAYGVFADIEYDGSVVFLSARDPNLEKTLATFRESAKGLRKMADTMTENDLLRYIINTIGTIDKPRRGIELSKLSFLRLISNESEQDRVEFRKRIMNTKKEDFYKFADLLESKVNEFEKNIVIITTKEKANEYIANVDGEFKKVLIE

3.4.24.-

COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000269|PubMed:10542284}; Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q76NL8};

acquisition of nutrients from host [GO:0044002]; protein processing [GO:0016485]

apicoplast [GO:0020011]; chloroplast [GO:0009507]; food vacuole [GO:0020020]; mitochondrial matrix [GO:0005759]; vacuolar membrane [GO:0005774]

metal ion binding [GO:0046872]; metalloendopeptidase activity [GO:0004222]

PF08367;PF00675;PF05193;

3.30.830.10;

Peptidase M16 family

PTM: Does not require processing for targeting to the food vacuole or maturation. {ECO:0000269|PubMed:12798513, ECO:0000269|PubMed:12876284}.

SUBCELLULAR LOCATION: Vacuole membrane {ECO:0000269|PubMed:10542284}; Peripheral membrane protein {ECO:0000269|PubMed:12876284}. Plastid, apicoplast {ECO:0000250|UniProtKB:Q76NL8}. Vesicle {ECO:0000269|PubMed:12876284}. Note=Localizes to the food (or digestive) vacuole, an acidic vacuole where host hemoglobin is digested (PubMed:10542284, PubMed:12876284). During the trophozoite and early to mid-schizont stages, localizes to the apicoplast (By similarity). {ECO:0000250|UniProtKB:Q76NL8, ECO:0000269|PubMed:10542284, ECO:0000269|PubMed:12876284}.

BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 5 (food vacuole) (PubMed:12876284). Optimum pH is 7 (PubMed:12876284). {ECO:0000269|PubMed:12876284};

FUNCTION: In the food vacuole, acts downstream of proteases plasmepsins PMI and PMII and falcipains during the catabolism of host hemoglobin by cleaving peptide fragments of alpha and beta hemoglobin subunits generated by PMI and PMII and falcipains (PubMed:10542284, PubMed:12876284). In the apicoplast, degrades apicoplast transit peptides after their cleavage (By similarity). Prefers bulky hydrophobic amino acids in the P1' position at both acidic and neutral pH (PubMed:12876284). At P2', prefers hydrophobic residues at acidic pH; at neutral pH, these same residues are abundant but prefers Arg (PubMed:12876284). At P3', prefers hydrophobic residues, especially Met, at both pH conditions. At P4' and P5', prefers acidic residues at acidic pH, however, at neutral pH, the enzyme is less selective at these positions (PubMed:12876284). The optimal site cleavage at acidic pH is YNEHS-|-FFMEE and, at neutral pH, MKRHS-|-FRMRG (PubMed:12876284). {ECO:0000250|UniProtKB:Q76NL8, ECO:0000269|PubMed:10542284, ECO:0000269|PubMed:12876284}.

Plasmodium falciparum (isolate HB3)

A0A0L8M630

AMDH_STRVG

MISTVVWGTGNVGRLAIRAVEAHPALQLCAVIVHNPAKVGRDAGELGELDRLLGVEATDDIEAVLAARPRAVVYAASGDVRPDEALADITRAVRSGAVVVSPALYPLYDHRNAPPEFRDPVLAAVTEGGGSLFASGVDPGWGNDVLPLLLSGLGTTIDVIRCQEIFDYSTYDQPDSVRYLVGMGQPMDYEPMMLMPSIPTMVWGGQIRMMARALGVELDEIRETSDRRALDTTVTTRTMGEFGAGTQGAIRFEVQGIVEGEPRIVIEHVTRIHPSCAPDWPVPPDGGDGAHRVVIEGRPRIEVTIEATDEGENRSAGGNATAVGRLVGAIDWLVEAEPGLYDALDIPLRPAIGRLGRKQS

1.4.1.28

lysine biosynthetic process via diaminopimelate [GO:0009089]

4-hydroxy-tetrahydrodipicolinate reductase [GO:0008839]

PF19328;PF01113;

3.40.50.720;

Amine dehydrogenase family

CATALYTIC ACTIVITY: Reaction=a secondary alkyl amine + H2O + NAD(+) = a ketone + H(+) + NADH + NH4(+); Xref=Rhea:RHEA:74175, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17087, ChEBI:CHEBI:28938, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:193112; EC=1.4.1.28; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=a secondary alkyl amine + H2O + NADP(+) = a ketone + H(+) + NADPH + NH4(+); Xref=Rhea:RHEA:74179, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17087, ChEBI:CHEBI:28938, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:193112; EC=1.4.1.28; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=H2O + NAD(+) + serinol = dihydroxyacetone + H(+) + NADH + NH4(+); Xref=Rhea:RHEA:75915, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16016, ChEBI:CHEBI:28938, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:194490; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=H2O + NADP(+) + serinol = dihydroxyacetone + H(+) + NADPH + NH4(+); Xref=Rhea:RHEA:75919, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16016, ChEBI:CHEBI:28938, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:194490; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=2-aminopropan-1-ol + H2O + NAD(+) = H(+) + hydroxyacetone + NADH + NH4(+); Xref=Rhea:RHEA:76795, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:27957, ChEBI:CHEBI:28938, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:195439; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=(R)-1-phenylethylamine + H2O + NAD(+) = acetophenone + H(+) + NADH + NH4(+); Xref=Rhea:RHEA:76867, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:27632, ChEBI:CHEBI:28938, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:141112; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=(S)-1-phenylethylamine + H2O + NAD(+) = acetophenone + H(+) + NADH + NH4(+); Xref=Rhea:RHEA:76871, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:27632, ChEBI:CHEBI:28938, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:141108; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=(2S)-2-aminobutan-1-ol + H2O + NAD(+) = 1-hydroxy-2-butanone + H(+) + NADH + NH4(+); Xref=Rhea:RHEA:76799, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:88390, ChEBI:CHEBI:195442; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=(2S)-2-amino-3-methylbutan-1-ol + H2O + NAD(+) = 1-hydroxy-3-methylbutan-2-one + H(+) + NADH + NH4(+); Xref=Rhea:RHEA:77011, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:195496, ChEBI:CHEBI:195497; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=2-aminopentan-1-ol + H2O + NAD(+) = 1-hydroxypentan-2-one + H(+) + NADH + NH4(+); Xref=Rhea:RHEA:76803, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:89466, ChEBI:CHEBI:195443; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=(S)-leucinol + H2O + NAD(+) = 1-hydroxy-4-methylpentan-2-one + H(+) + NADH + NH4(+); Xref=Rhea:RHEA:77015, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:195498, ChEBI:CHEBI:195499; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=(S)-isoleucinol + H2O + NAD(+) = (3S)-1-hydroxy-3-methylpentan-2-one + H(+) + NADH + NH4(+); Xref=Rhea:RHEA:76807, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:195448, ChEBI:CHEBI:195449; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=(S)-methioninol + H2O + NAD(+) = 1-hydroxy-4-(methythio)butan-2-one + H(+) + NADH + NH4(+); Xref=Rhea:RHEA:76811, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:195450, ChEBI:CHEBI:195451; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=2-aminocyclohexanol + H2O + NAD(+) = 2-hydroxycyclohexan-1-one + H(+) + NADH + NH4(+); Xref=Rhea:RHEA:77019, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17878, ChEBI:CHEBI:28938, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:195500; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=H2O + L-alanine + NAD(+) = H(+) + NADH + NH4(+) + pyruvate; Xref=Rhea:RHEA:18405, ChEBI:CHEBI:15361, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:57972; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=D-alanine + H2O + NAD(+) = H(+) + NADH + NH4(+) + pyruvate; Xref=Rhea:RHEA:76815, ChEBI:CHEBI:15361, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, ChEBI:CHEBI:57416, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=H2O + L-aspartate + NAD(+) = H(+) + NADH + NH4(+) + oxaloacetate; Xref=Rhea:RHEA:11788, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16452, ChEBI:CHEBI:28938, ChEBI:CHEBI:29991, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=D-aspartate + H2O + NAD(+) = H(+) + NADH + NH4(+) + oxaloacetate; Xref=Rhea:RHEA:76819, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16452, ChEBI:CHEBI:28938, ChEBI:CHEBI:29990, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=H2O + L-glutamate + NAD(+) = 2-oxoglutarate + H(+) + NADH + NH4(+); Xref=Rhea:RHEA:15133, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16810, ChEBI:CHEBI:28938, ChEBI:CHEBI:29985, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=D-glutamate + H2O + NAD(+) = 2-oxoglutarate + H(+) + NADH + NH4(+); Xref=Rhea:RHEA:77023, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16810, ChEBI:CHEBI:28938, ChEBI:CHEBI:29986, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=H2O + L-serine + NAD(+) = 3-hydroxypyruvate + H(+) + NADH + NH4(+); Xref=Rhea:RHEA:20884, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17180, ChEBI:CHEBI:28938, ChEBI:CHEBI:33384, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=D-serine + H2O + NAD(+) = 3-hydroxypyruvate + H(+) + NADH + NH4(+); Xref=Rhea:RHEA:77027, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17180, ChEBI:CHEBI:28938, ChEBI:CHEBI:35247, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=H2O + methylamine + NAD(+) = formaldehyde + H(+) + NADH + NH4(+); Xref=Rhea:RHEA:76823, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16842, ChEBI:CHEBI:28938, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:59338; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=ethylamine + H2O + NAD(+) = acetaldehyde + H(+) + NADH + NH4(+); Xref=Rhea:RHEA:76835, ChEBI:CHEBI:15343, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:566789; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=H2O + NAD(+) + propylamine = H(+) + NADH + NH4(+) + propanal; Xref=Rhea:RHEA:76839, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17153, ChEBI:CHEBI:28938, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:566825; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=butylamine + H2O + NAD(+) = butanal + H(+) + NADH + NH4(+); Xref=Rhea:RHEA:76827, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15743, ChEBI:CHEBI:28938, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:195458; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=H2O + hexylamine + NAD(+) = H(+) + hexanal + NADH + NH4(+); Xref=Rhea:RHEA:76831, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:88528, ChEBI:CHEBI:195452; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=H2O + NAD(+) + octylamine = H(+) + NADH + NH4(+) + octanal; Xref=Rhea:RHEA:76843, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17935, ChEBI:CHEBI:28938, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:195453; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=(R)-sec-butylamine + H2O + NAD(+) = butan-2-one + H(+) + NADH + NH4(+); Xref=Rhea:RHEA:76847, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28398, ChEBI:CHEBI:28938, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:195455; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=(S)-sec-butylamine + H2O + NAD(+) = butan-2-one + H(+) + NADH + NH4(+); Xref=Rhea:RHEA:76851, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28398, ChEBI:CHEBI:28938, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:195454; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=2-aminopentane + H2O + NAD(+) = H(+) + NADH + NH4(+) + pentan-2-one; Xref=Rhea:RHEA:76855, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16472, ChEBI:CHEBI:28938, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:195456; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=3-aminopentane + H2O + NAD(+) = H(+) + NADH + NH4(+) + pentan-3-one; Xref=Rhea:RHEA:76859, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:87755, ChEBI:CHEBI:195457; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=(2R)-heptan-2-amine + H2O + NAD(+) = H(+) + heptan-2-one + NADH + NH4(+); Xref=Rhea:RHEA:77031, ChEBI:CHEBI:5672, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:195503; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=(2S)-heptan-2-amine + H2O + NAD(+) = H(+) + heptan-2-one + NADH + NH4(+); Xref=Rhea:RHEA:77035, ChEBI:CHEBI:5672, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:195504; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=benzylamine + H2O + NAD(+) = benzaldehyde + H(+) + NADH + NH4(+); Xref=Rhea:RHEA:76863, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17169, ChEBI:CHEBI:28938, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:225238; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=3-aminobutan-2-ol + H2O + NAD(+) = acetoin + H(+) + NADH + NH4(+); Xref=Rhea:RHEA:76879, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15688, ChEBI:CHEBI:28938, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:195440; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=3-aminobutan-1-ol + H2O + NAD(+) = 4-hydroxybutan-2-one + H(+) + NADH + NH4(+); Xref=Rhea:RHEA:76883, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, ChEBI:CHEBI:41268, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:195441; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=5-hydroxypentan-2-amine + H2O + NAD(+) = 5-hydroxypentan-2-one + H(+) + NADH + NH4(+); Xref=Rhea:RHEA:76887, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:195472, ChEBI:CHEBI:195473; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=4-hydroxyhexan-3-amine + H2O + NAD(+) = 4-hydroxyhexan-3-one + H(+) + NADH + NH4(+); Xref=Rhea:RHEA:77039, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:18351, ChEBI:CHEBI:28938, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:195505; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=5-hydroxyoctan-4-amine + H2O + NAD(+) = 5-hydroxyoctan-4-one + H(+) + NADH + NH4(+); Xref=Rhea:RHEA:77043, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:179933, ChEBI:CHEBI:195506; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=2-hydroxy-1-phenylethan-1-amine + H2O + NAD(+) = 2-hydroxyacetophenone + H(+) + NADH + NH4(+); Xref=Rhea:RHEA:76891, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28341, ChEBI:CHEBI:28938, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:195474; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=H2O + hexan-2-amine + NAD(+) = H(+) + hexan-2-one + NADH + NH4(+); Xref=Rhea:RHEA:76875, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:89206, ChEBI:CHEBI:195475; Evidence={ECO:0000269|Ref.2}; CATALYTIC ACTIVITY: Reaction=4-phenylbutan-2-amine + H2O + NAD(+) = 4-phenylbutan-2-one + H(+) + NADH + NH4(+); Xref=Rhea:RHEA:77047, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:195507, ChEBI:CHEBI:195508; Evidence={ECO:0000269|Ref.2};

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=4 mM for serinol {ECO:0000269|Ref.2}; KM=0.84 mM for NAD(+) {ECO:0000269|Ref.2}; KM=2.2 mM for dihydroxyacetone {ECO:0000269|Ref.2}; KM=0.022 mM for NADH {ECO:0000269|Ref.2}; KM=26.5 mM for NH4(+) {ECO:0000269|Ref.2};

BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 10.0 for the oxidative deamination reaction, while the optimum pH of the reductive amination reaction is rather broad and between 6.5 and 7.0. {ECO:0000269|Ref.2};

BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: Optimum temperature is 30 degrees Celsius for the deaminating reaction. Is not thermostable. {ECO:0000269|Ref.2};

FUNCTION: Catalyzes the reversible oxidative deaminations of a broad range of amines, amino alcohols and amino acids. Catalyzes the reversible dehydrogenation of serinol in the presence of NAD(+) to give dihydroxyacetone, ammonium ion and NADH, while NADP(+) shows a slight activity. Is also able to produce 2-amino-1-propanol and aspartate by the reductive amination of the corresponding keto alcohol (hydroxyacetone) and keto acid (oxaloacetate) in the presence of ammonium ions and NADH, and that of acetophenone from phenylethylamine by the oxidative deamination in the presence of NAD(+). {ECO:0000269|Ref.2}.

Streptomyces virginiae (Streptomyces cinnamonensis)

A0A0M3Q1Q3

GTPS1_THYVU

MRRSGNYQAPVWNNDFIQSFSTDKYKDEKFLKKKEELIAQVKVLLNTKMEAVKQLELIEDLRNLGLTYYFEDEFKKILTSIYNEHKGFKNEQVGDLYFTSLAFRLLRLHGFDVSEDVFNFFKNEDGSDFKASLGENTKDVLELYEASFLIRVGEVTLEQARVFSTKILEKKVEEGIKDEKLLAWIQHSLALPLHWRIQRLEARWFLDAYKARKDMNPIIYELGKIDFHIIQETQLQEVQEVSQWWTNTNLAEKLPFVRDRIVECYFWALGLFEPHEYGYQRKMAAIIITFVTIIDDVYDVYDTLDELQLFTDAIRKWDVESISTLPYYMQVCYLAVFTYASELAYDILKDQGFNSISYLQRSWLSLVEGFFQEAKWYYAGYTPTLAEYLENAKVSISSPTIISQVYFTLPNSTERTVVENVFGYHNILYLSGMILRLADDLGTTQFELKRGDVQKAIQCYMNDNNATEEEGTEHVKYLLREAWQEMNSAMADPDCPLSEDLVFAAANLGRTSQFIYLDGDGHGVQHSEIHNQMGGLIFEPYV

4.2.3.114; 4.2.3.115

COFACTOR: Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250|UniProtKB:E2E2P0}; Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:E2E2P0}; Note=Binds 3 Mg(2+) or Mn(2+) ions per subunit. {ECO:0000250|UniProtKB:E2E2P0};

diterpenoid biosynthetic process [GO:0016102]; response to jasmonic acid [GO:0009753]; response to salicylic acid [GO:0009751]; response to UV-C [GO:0010225]

gamma-terpinene synthase activity [GO:0102903]; magnesium ion binding [GO:0000287]; protein homodimerization activity [GO:0042803]; terpene synthase activity [GO:0010333]

PF01397;PF03936;

1.10.600.10;1.50.10.130;

Terpene synthase family

CATALYTIC ACTIVITY: Reaction=(2E)-geranyl diphosphate = diphosphate + gamma-terpinene; Xref=Rhea:RHEA:32559, ChEBI:CHEBI:10577, ChEBI:CHEBI:33019, ChEBI:CHEBI:58057; EC=4.2.3.114; Evidence={ECO:0000269|PubMed:26750479}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32560; Evidence={ECO:0000269|PubMed:26750479}; CATALYTIC ACTIVITY: Reaction=(2E)-geranyl diphosphate = alpha-terpinene + diphosphate; Xref=Rhea:RHEA:32563, ChEBI:CHEBI:10334, ChEBI:CHEBI:33019, ChEBI:CHEBI:58057; EC=4.2.3.115; Evidence={ECO:0000250|UniProtKB:E2E2P0}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32564; Evidence={ECO:0000250|UniProtKB:E2E2P0};

PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis. {ECO:0000269|PubMed:26750479}.

FUNCTION: Involved in the biosynthesis of phenolic monoterpenes natural products thymol and carvacrol which have a broad range of biological activities acting as antimicrobial compounds, insecticides, antioxidants and pharmaceutical agents (PubMed:26750479). Monoterpene synthase which catalyzes the conversion of geranyl diphosphate (GPP) to gamma-terpinene and the minor products alpha-thujene, alpha-terpinene, myrcene, sabinene, (+)-R-limonene, alpha-pinene and alpha-phellandrene (PubMed:26750479). {ECO:0000269|PubMed:26750479}.

Thymus vulgaris (Thyme)

A0A0N7CSQ4

TX41A_SCOMU

MLKSFCILSVFMVLFLAKFPDLCSGEEISPLKIVVRNSEYLNNPCNGVTCPSGYRCSIVDKQCIKKEK

extracellular region [GO:0005576]

ion channel regulator activity [GO:0099106]; toxin activity [GO:0090729]

Scoloptoxin-04 family

SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:26420335}.

FUNCTION: [Tau-scoloptoxin(04)-Sm1a]: Extremely potent agonist and potentiator of TRPV1 (EC(50)=470-521.5 nM (mouse)) (PubMed:26420335, PubMed:32097697). It strongly promotes the heat activation process by downshifting the activation threshold temperature (PubMed:26420335). It preferably binds to the activated channel and promotes its opening (PubMed:26420335). Holding the channel closed by cooling prevents binding of this toxin, leaving it ineffective (PubMed:26420335). The toxin binds to the charge-rich outer pore region of the channel where it directly interacts with the pore helix and turret, two adjacent structural elements known to be critical for activation gating of TRPV1 (PubMed:26420335). In comparison with Sm1b, induces a TRPV1 desensitization with slower kinetics (20 seconds) (PubMed:32097697). In vivo, induces pain in mice after intraplantar injection (PubMed:26420335). {ECO:0000269|PubMed:26420335, ECO:0000269|PubMed:32097697}.; FUNCTION: [Tau-scoloptoxin(04)-Sm1b]: Potent agonist and probable potentiator of TRPV1 (EC(50)=38.35 uM (mouse)) (PubMed:32097697). Also binds to the outer pore region of TRPV1 (PubMed:32097697). In comparison with Sm1a, induces a TRPV1 desensitization with faster kinetics (2 seconds) and leads to a more complete TRPV1 desensitization (PubMed:32097697). Desensitization is achieved by reducing both the open probability and the single-channel conductance upon prolonged exposure (PubMed:32097697). {ECO:0000269|PubMed:32097697}.

Scolopendra mutilans (Chinese red-headed centipede) (Scolopendra subspinipes mutilans)

A0A0N7KJT8

APL25_ORYSJ

MWDLNDSPAAEAAPPPLSPSADDSGASSSSAAAVVEIPDDADDDSAAVVVVTRQFFPPAVPGGGGDPAPGNARAGWLRLAGAAPPVAATGPAASAAVSKKSRRGPRSRSSQYRGVTFYRRTGRWESHIWDCGKQVYLGGFDTAHAAARAYDRAAIKFRGVEADINFSLEDYEDDLKQMSNLTKEEFVHVLRRQSTGFPRGSSKYRGVTLHKCGRWEARMGQFLGKKYVYLGLFDTEEEAARAYDRAAIKCNGKDAVTNFDPSIYAGEFEPPAAATGDAAEHNLDLSLGSSAGSKRGNVDGGGDDEITGGGGGGAGSDQRVPMAFDLDWQTAAARSTKAKFDQNSNHPQMPPVLQVTHLPFSPRHHHQFLSNGDPGTAGGLSLTIGAGMAGHWPPQQQQGWGNAGGMSWPHPPHPPPPPTNAAAAATATAAAASSRFPPYIATQASTWLQKNGFHSLTRPT

regulation of floral organ abscission [GO:0060860]; regulation of flower development [GO:0009909]; regulation of seed development [GO:0080050]; response to cold [GO:0009409]; seed abscission [GO:0097548]

nucleus [GO:0005634]; transcription regulator complex [GO:0005667]

DNA-binding transcription factor activity [GO:0003700]; transcription cis-regulatory region binding [GO:0000976]

PF00847;

3.30.730.10;

AP2/ERF transcription factor family, AP2 subfamily

SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00366, ECO:0000269|PubMed:22408071}.

FUNCTION: Transcription factor (PubMed:22408071). Involved in spikelet transition and development (Probable) (PubMed:22408071). Prevents lemma and palea elongation as well as grain growth (PubMed:22408071, PubMed:28066457). Required for seed shattering through specifying abscission zone (AZ) development (PubMed:22408071). {ECO:0000269|PubMed:22408071, ECO:0000269|PubMed:28066457, ECO:0000305|PubMed:26631749}.

Oryza sativa subsp. japonica (Rice)