GAD3_CAEEL
ID GAD3_CAEEL Reviewed; 1257 AA.
AC Q960A1;
DT 20-JAN-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2013, sequence version 3.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Probable aldehyde oxidase gad-3 {ECO:0000250|UniProtKB:Q06278};
DE EC=1.2.3.1 {ECO:0000250|UniProtKB:Q06278};
GN Name=gad-3 {ECO:0000312|WormBase:B0222.9};
GN ORFNames=B0222.9 {ECO:0000312|WormBase:B0222.9};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24077178; DOI=10.1038/nchembio.1352;
RA Schmeisser K., Mansfeld J., Kuhlow D., Weimer S., Priebe S., Heiland I.,
RA Birringer M., Groth M., Segref A., Kanfi Y., Price N.L., Schmeisser S.,
RA Schuster S., Pfeiffer A.F., Guthke R., Platzer M., Hoppe T., Cohen H.Y.,
RA Zarse K., Sinclair D.A., Ristow M.;
RT "Role of sirtuins in lifespan regulation is linked to methylation of
RT nicotinamide.";
RL Nat. Chem. Biol. 9:693-700(2013).
CC -!- FUNCTION: May be involved in the metabolism of 1-methylnicotinamide
CC (MNA). Linked to regulation of longevity through generation of reactive
CC oxygen species, where it probably functions in a pathway downstream of
CC the sirtuin sir-2.1 and the nicotinamide N-methyltransferase anmt-1.
CC {ECO:0000269|PubMed:24077178}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an aldehyde + H2O + O2 = a carboxylate + H(+) + H2O2;
CC Xref=Rhea:RHEA:16829, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:17478,
CC ChEBI:CHEBI:29067; EC=1.2.3.1;
CC Evidence={ECO:0000250|UniProtKB:Q06278};
CC -!- COFACTOR:
CC Name=[2Fe-2S] cluster; Xref=ChEBI:CHEBI:190135;
CC Evidence={ECO:0000250|UniProtKB:Q06278};
CC Note=Binds 2 [2Fe-2S] clusters per subunit.
CC {ECO:0000250|UniProtKB:Q06278};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:Q06278};
CC Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:Q06278};
CC -!- COFACTOR:
CC Name=Mo-molybdopterin; Xref=ChEBI:CHEBI:71302;
CC Evidence={ECO:0000250|UniProtKB:Q06278};
CC Note=Binds 1 Mo-molybdopterin (Mo-MPT) cofactor per subunit.
CC {ECO:0000250|UniProtKB:Q06278};
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown reduces both the
CC longevity-extending effects and generation of reactive oxygen species
CC when exposed to 1 microM N1-methylnicotinamide.
CC {ECO:0000269|PubMed:24077178}.
CC -!- SIMILARITY: Belongs to the xanthine dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; BX284605; CCD61422.2; -; Genomic_DNA.
DR RefSeq; NP_001294662.1; NM_001307733.1.
DR AlphaFoldDB; Q960A1; -.
DR SMR; Q960A1; -.
DR STRING; 6239.B0222.9; -.
DR EPD; Q960A1; -.
DR PaxDb; Q960A1; -.
DR PeptideAtlas; Q960A1; -.
DR PRIDE; Q960A1; -.
DR EnsemblMetazoa; B0222.9.1; B0222.9.1; WBGene00015057.
DR GeneID; 24104108; -.
DR KEGG; cel:CELE_B0222.9; -.
DR UCSC; B0222.9; c. elegans.
DR CTD; 24104108; -.
DR WormBase; B0222.9; CE48200; WBGene00015057; gad-3.
DR eggNOG; KOG0430; Eukaryota.
DR GeneTree; ENSGT00970000196578; -.
DR HOGENOM; CLU_001681_1_2_1; -.
DR InParanoid; Q960A1; -.
DR OMA; GWSKDHS; -.
DR OrthoDB; 48717at2759; -.
DR BRENDA; 1.2.3.1; 1045.
DR Reactome; R-CEL-964975; Vitamins B6 activation to pyridoxal phosphate.
DR PRO; PR:Q960A1; -.
DR Proteomes; UP000001940; Chromosome V.
DR Bgee; WBGene00015057; Expressed in material anatomical entity and 3 other tissues.
DR GO; GO:0051537; F:2 iron, 2 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0004031; F:aldehyde oxidase activity; IEA:UniProtKB-EC.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; HEP:WormBase.
DR CDD; cd00207; fer2; 1.
DR Gene3D; 3.10.20.30; -; 1.
DR Gene3D; 3.30.465.10; -; 1.
DR InterPro; IPR002888; 2Fe-2S-bd.
DR InterPro; IPR036884; 2Fe-2S-bd_dom_sf.
DR InterPro; IPR036010; 2Fe-2S_ferredoxin-like_sf.
DR InterPro; IPR001041; 2Fe-2S_ferredoxin-type.
DR InterPro; IPR006058; 2Fe2S_fd_BS.
DR InterPro; IPR000674; Ald_Oxase/Xan_DH_a/b.
DR InterPro; IPR036856; Ald_Oxase/Xan_DH_a/b_sf.
DR InterPro; IPR016208; Ald_Oxase/xanthine_DH.
DR InterPro; IPR008274; AldOxase/xan_DH_Mopterin-bd.
DR InterPro; IPR037165; AldOxase/xan_DH_Mopterin-bd_sf.
DR InterPro; IPR012675; Beta-grasp_dom_sf.
DR InterPro; IPR016166; FAD-bd_PCMH.
DR InterPro; IPR036318; FAD-bd_PCMH-like_sf.
DR InterPro; IPR016169; FAD-bd_PCMH_sub2.
DR InterPro; IPR002346; Mopterin_DH_FAD-bd.
DR PANTHER; PTHR11908; PTHR11908; 1.
DR Pfam; PF01315; Ald_Xan_dh_C; 1.
DR Pfam; PF02738; Ald_Xan_dh_C2; 1.
DR Pfam; PF00941; FAD_binding_5; 1.
DR Pfam; PF00111; Fer2; 1.
DR Pfam; PF01799; Fer2_2; 1.
DR PIRSF; PIRSF000127; Xanthine_DH; 1.
DR SMART; SM01008; Ald_Xan_dh_C; 1.
DR SUPFAM; SSF47741; SSF47741; 1.
DR SUPFAM; SSF54292; SSF54292; 1.
DR SUPFAM; SSF54665; SSF54665; 1.
DR SUPFAM; SSF56003; SSF56003; 1.
DR SUPFAM; SSF56176; SSF56176; 1.
DR PROSITE; PS00197; 2FE2S_FER_1; 1.
DR PROSITE; PS51387; FAD_PCMH; 1.
PE 3: Inferred from homology;
KW 2Fe-2S; Iron; Iron-sulfur; Metal-binding; NAD; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..1257
FT /note="Probable aldehyde oxidase gad-3"
FT /evidence="ECO:0000305"
FT /id="PRO_0000435387"
FT DOMAIN 4..91
FT /note="2Fe-2S ferredoxin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00465"
FT DOMAIN 229..459
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT ACT_SITE 1208
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P47989"
FT BINDING 43
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00465"
FT BINDING 48
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00465"
FT BINDING 51
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00465"
FT BINDING 73
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00465"
SQ SEQUENCE 1257 AA; 137689 MW; 9DEBB49320CE8E29 CRC64;
MPLTGIFFNV NGKDVNEENV DPELTLAYYL RNKLGLRGTK LGCEEGVCGS CTVVLGTWDD
CQNKAVYRAV NACLVPLFHV HKTFVITVEG VGSRDKIHPI QDRMARGHAL QCGFCSPGFV
MSAYALFSNQ PNPTIQQINA AIRANLCRCT GYRPILEALY SFSSESGGCC GGNKTGGGCC
KDKSSSDEDG GYDEKLLSFN DFPKYDPTQE IIFPPSLRVF SDSETPVTLK GDRIELLLPK
NIDQFKKFKK DRTVISSGLI TRFVSTRNPK EFSQKWISTK YVKEFNEITV NKDSVVVGAA
LNIQKMADTL TSSLSINIGK EIDSFIQKFS SPQIANFATW TGAIISGAKS SLSVSDLLIL
FNVLDAKLTL LNNSGELTQV AIEEFAEKKL FATHTIVNAI FSRSLTGFLF CLKLGETSEQ
DSTNFNFAAL VGNQVSRIFV GLGGQPKRLT SLEVHIDALK GLSVSDLCQT TEMSDYKNVK
IALTRFSDFM NHKEKTEEIE GINYLQYFKP KTNESAGRPI ANYFNERAIT GEAFYVNDIQ
AYNAVHLGFV LSTVPHAEIT KIDVSEALQL EGVAGYFGVS DVPGNNTPGL QISNMNFPDD
TTIFADKKVE SVGQVIGVIA ANDVVLARRA AKLVKVEYKE LPSLVNFKEA IEAKSLLGDV
QHFGKDENLV KESLENSSKV LEGECDIGGQ EHYYLETQSS LVIPGEGDEL IVNCSTQGTS
FTQLMVAETM KIPAHKIIVK TKRLGGGFGG KVNNASWIAC MCAIVAKKLN RPTYGFLSRA
DDLAITGKRH EVHAKYRVGI NFDGKIEGIH YQAWLNGGWS KDHSEGVTMV MGLMVDDVYN
MGTIRFDGYP VKTNSNSNTA LRGYGNPQSK LINEGVMRRI ARDVGKSTEE IKRINFALEG
GRRYLGGKIH NDALVECWEY CKKWSEFENR QSGIKQFNKN STAVKRGIAM SSVRFGLPHP
GPTGHGIASL LINLDGSVQL SIGGTEMGQG LNQKMLQVCS EALKRPIDTI TIVDCSTDKV
TNAPETGGSQ NADTNGLAVL ACCKKIMSRL QPIIDKNDGE WEKSIREAYG AYVPLQCTEY
GTVERAKFGV GEMESPYNTT GACAVEMEID TLTGYNRVIR VDIVMDVGES LNPALDIGQI
EGAFIQGYGL VTCEKITFNK TTGQLDQNTA GKYKIPKASD VPKDFRVKLL GINNANGAQV
YSSKGIGEPP LMMSCGAVHS SIMNCIDNWR NENGIHEFVD TISPLSAEKI QELCSKK
