LE767_CAEEL
ID LE767_CAEEL Reviewed; 316 AA.
AC Q09517; C1P622; S6FCZ1;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 20-JUN-2002, sequence version 2.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Very-long-chain 3-oxooacyl-coA reductase let-767;
DE Short=LET-767 {ECO:0000303|PubMed:17951538, ECO:0000303|PubMed:18390550, ECO:0000303|PubMed:21926990};
DE EC=1.1.1.330 {ECO:0000305|PubMed:18390550, ECO:0000305|PubMed:21926990};
DE AltName: Full=Lethal protein 767;
DE AltName: Full=Short-chain dehydrogenase 10;
DE AltName: Full=Steroid dehydrogenase let-767;
DE EC=1.1.1.- {ECO:0000269|PubMed:17951538};
DE AltName: Full=Steroid-dehydrogenase/3-ketoacyl-CoA-reductase {ECO:0000303|PubMed:21926990};
GN Name=let-767; Synonyms=dhs-10; ORFNames=C56G2.6;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
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]
RP IDENTIFICATION.
RA Kuervers L.M., O'Neil N.J., Baillie D.L.;
RT "Let-767 is a gut-specific dehydrogenase.";
RL (er) Worm Breeder's Gazette 15(3):34(1998).
RN [3]
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, MUTAGENESIS OF GLY-135,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=12905072; DOI=10.1007/s00438-003-0900-9;
RA Kuervers L.M., Jones C.L., O'Neil N.J., Baillie D.L.;
RT "The sterol modifying enzyme LET-767 is essential for growth, reproduction
RT and development in Caenorhabditis elegans.";
RL Mol. Genet. Genomics 270:121-131(2003).
RN [4]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=17951538; DOI=10.1677/joe-07-0248;
RA Desnoyers S., Blanchard P.G., St-Laurent J.F., Gagnon S.N., Baillie D.L.,
RA Luu-The V.;
RT "Caenorhabditis elegans LET-767 is able to metabolize androgens and
RT estrogens and likely shares common ancestor with human types 3 and 12
RT 17beta-hydroxysteroid dehydrogenases.";
RL J. Endocrinol. 195:271-279(2007).
RN [5]
RP FUNCTION AS A 3-OXOACYL-COA REDUCTASE, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=18390550; DOI=10.1074/jbc.m800965200;
RA Entchev E.V., Schwudke D., Zagoriy V., Matyash V., Bogdanova A.,
RA Habermann B., Zhu L., Shevchenko A., Kurzchalia T.V.;
RT "LET-767 is required for the production of branched chain and long chain
RT fatty acids in Caenorhabditis elegans.";
RL J. Biol. Chem. 283:17550-17560(2008).
RN [6]
RP FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=21926990; DOI=10.1038/ncb2328;
RA Zhang H., Abraham N., Khan L.A., Hall D.H., Fleming J.T., Gobel V.;
RT "Apicobasal domain identities of expanding tubular membranes depend on
RT glycosphingolipid biosynthesis.";
RL Nat. Cell Biol. 13:1189-1201(2011).
CC -!- FUNCTION: Required for branched-chain fatty acid synthesis (such as
CC (omega-1)-methyl-fatty acids) (PubMed:18390550). Catalyzes the
CC reduction of the 3-keto-fatty acyl-CoA intermediate that is formed in
CC each cycle of fatty acid elongation (PubMed:18390550). Very long-chain
CC fatty acids (VLCFAs) serve as precursors for ceramide and sphingolipids
CC (PubMed:12905072, PubMed:18390550, PubMed:21926990). Involved in
CC hormone production as it metabolizes 4-androstendione (androst-4-ene-
CC 3,17-dione) into testosterone and estrone into estradiol (17beta-
CC estradiol) in vitro, but the physiological steroid substrate is unknown
CC (PubMed:17951538). {ECO:0000269|PubMed:12905072,
CC ECO:0000269|PubMed:17951538, ECO:0000269|PubMed:18390550,
CC ECO:0000269|PubMed:21926990}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a very-long-chain (3R)-3-hydroxyacyl-CoA + NADP(+) = a very-
CC long-chain 3-oxoacyl-CoA + H(+) + NADPH; Xref=Rhea:RHEA:48680,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:85440, ChEBI:CHEBI:90725; EC=1.1.1.330;
CC Evidence={ECO:0000305|PubMed:18390550, ECO:0000305|PubMed:21926990};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:48682;
CC Evidence={ECO:0000305|PubMed:18390550, ECO:0000305|PubMed:21926990};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(omega-1)-methyl-(3R)-hydroxy-fatty acyl-CoA + NADP(+) =
CC (omega-1)-methyl-3-oxo-fatty acyl-CoA + H(+) + NADPH;
CC Xref=Rhea:RHEA:69216, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:183086, ChEBI:CHEBI:183087;
CC Evidence={ECO:0000269|PubMed:18390550};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:69218;
CC Evidence={ECO:0000305|PubMed:18390550};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 17beta-hydroxy steroid + NADP(+) = a 17-oxo steroid + H(+) +
CC NADPH; Xref=Rhea:RHEA:69284, ChEBI:CHEBI:15378, ChEBI:CHEBI:19168,
CC ChEBI:CHEBI:35343, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000269|PubMed:17951538};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:69286;
CC Evidence={ECO:0000305|PubMed:17951538};
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis.
CC {ECO:0000269|PubMed:18390550, ECO:0000269|PubMed:21926990}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=3;
CC Name=1;
CC IsoId=Q09517-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q09517-2; Sequence=VSP_061063;
CC Name=3;
CC IsoId=Q09517-3; Sequence=VSP_061063, VSP_061064;
CC -!- TISSUE SPECIFICITY: Expressed in the gut of larva and adult.
CC {ECO:0000269|PubMed:12905072}.
CC -!- DEVELOPMENTAL STAGE: Expressed from first larval stage to adult.
CC {ECO:0000269|PubMed:12905072}.
CC -!- DISRUPTION PHENOTYPE: Worms exhibit slow and retarded growth,
CC reproductive and molting defects, defects in embryogenesis, and
CC hypersensitivity to cholesterol limitation (PubMed:12905072). Increased
CC polarity and tubulogenesis defects in an allelic series of let-767
CC (PubMed:21926990). {ECO:0000269|PubMed:12905072,
CC ECO:0000269|PubMed:21926990}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. 17-beta-HSD 3 subfamily. {ECO:0000305}.
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DR EMBL; FO080744; CCD66337.1; -; Genomic_DNA.
DR EMBL; BX284603; CCD66339.1; -; Genomic_DNA.
DR EMBL; BX284603; CDG24102.1; -; Genomic_DNA.
DR PIR; T15867; T15867.
DR RefSeq; NP_001254935.1; NM_001268006.1. [Q09517-2]
DR RefSeq; NP_001254936.1; NM_001268007.1. [Q09517-1]
DR RefSeq; NP_001293606.1; NM_001306677.1. [Q09517-3]
DR AlphaFoldDB; Q09517; -.
DR SMR; Q09517; -.
DR BioGRID; 41115; 7.
DR STRING; 6239.C56G2.6c; -.
DR SwissLipids; SLP:000000030; -.
DR SwissLipids; SLP:000000178; -.
DR iPTMnet; Q09517; -.
DR EPD; Q09517; -.
DR PaxDb; Q09517; -.
DR PeptideAtlas; Q09517; -.
DR EnsemblMetazoa; C56G2.6a.1; C56G2.6a.1; WBGene00002891. [Q09517-1]
DR EnsemblMetazoa; C56G2.6a.2; C56G2.6a.2; WBGene00002891. [Q09517-1]
DR EnsemblMetazoa; C56G2.6b.1; C56G2.6b.1; WBGene00002891. [Q09517-2]
DR EnsemblMetazoa; C56G2.6c.1; C56G2.6c.1; WBGene00002891. [Q09517-3]
DR GeneID; 175895; -.
DR KEGG; cel:CELE_C56G2.6; -.
DR UCSC; C56G2.6.2; c. elegans. [Q09517-1]
DR CTD; 175895; -.
DR WormBase; C56G2.6a; CE30639; WBGene00002891; let-767.
DR WormBase; C56G2.6b; CE01875; WBGene00002891; let-767.
DR WormBase; C56G2.6c; CE48447; WBGene00002891; let-767.
DR eggNOG; KOG1014; Eukaryota.
DR GeneTree; ENSGT00940000165708; -.
DR HOGENOM; CLU_010194_38_0_1; -.
DR InParanoid; Q09517; -.
DR OMA; TIAPMMV; -.
DR OrthoDB; 895581at2759; -.
DR PhylomeDB; Q09517; -.
DR UniPathway; UPA00094; -.
DR PRO; PR:Q09517; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00002891; Expressed in larva and 4 other tissues.
DR ExpressionAtlas; Q09517; baseline and differential.
DR GO; GO:0045179; C:apical cortex; IDA:WormBase.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:WormBase.
DR GO; GO:0072582; F:17-beta-hydroxysteroid dehydrogenase (NADP+) activity; IEA:RHEA.
DR GO; GO:0102339; F:3-oxo-arachidoyl-CoA reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0102340; F:3-oxo-behenoyl-CoA reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0102342; F:3-oxo-cerotoyl-CoA reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0102341; F:3-oxo-lignoceroyl-CoA reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0050062; F:long-chain-fatty-acyl-CoA reductase activity; IDA:WormBase.
DR GO; GO:0030283; F:testosterone dehydrogenase [NAD(P)] activity; IDA:WormBase.
DR GO; GO:0008209; P:androgen metabolic process; IMP:WormBase.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IMP:UniProtKB.
DR GO; GO:0045197; P:establishment or maintenance of epithelial cell apical/basal polarity; IMP:UniProtKB.
DR GO; GO:0008210; P:estrogen metabolic process; IMP:WormBase.
DR GO; GO:0030497; P:fatty acid elongation; IBA:GO_Central.
DR GO; GO:0030540; P:female genitalia development; IMP:UniProtKB.
DR GO; GO:0042759; P:long-chain fatty acid biosynthetic process; IDA:WormBase.
DR GO; GO:0042303; P:molting cycle; IMP:UniProtKB.
DR GO; GO:0018996; P:molting cycle, collagen and cuticulin-based cuticle; IMP:WormBase.
DR GO; GO:0032350; P:regulation of hormone metabolic process; IMP:UniProtKB.
DR GO; GO:0000003; P:reproduction; IMP:UniProtKB.
DR GO; GO:0006694; P:steroid biosynthetic process; IDA:WormBase.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 1: Evidence at protein level;
KW Alternative initiation; Fatty acid biosynthesis; Fatty acid metabolism;
KW Lipid biosynthesis; Lipid metabolism; NADP; Oxidoreductase;
KW Reference proteome; Steroid biosynthesis; Steroid metabolism.
FT CHAIN 1..316
FT /note="Very-long-chain 3-oxooacyl-coA reductase let-767"
FT /id="PRO_0000054578"
FT ACT_SITE 202
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 47..76
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 106
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 189
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 206
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1
FT /note="M -> MESSDNLHDIDNLENGNM (in isoform 2 and isoform
FT 3)"
FT /id="VSP_061063"
FT VAR_SEQ 167
FT /note="L -> LFLTQ (in isoform 3)"
FT /id="VSP_061064"
FT MUTAGEN 135
FT /note="G->R: Arrests at early larval stage."
FT /evidence="ECO:0000269|PubMed:12905072"
SQ SEQUENCE 316 AA; 34309 MW; DA3C6377AC4C12CE CRC64;
MACQCFLVGA GYVALAAVAY RLLTIFSNIL GPYVLLSPID LKKRAGASWA VVTGATDGIG
KAYAFELARR GFNVLLVSRT QSKLDETKKE ILEKYSSIEV RTAAFDFTNA APSAYKDLLA
TLNQVEIGVL INNVGMSYEY PDVLHKVDGG IERLANITTI NTLPPTLLSA GILPQMVARK
AGVIVNVGSS AGANQMALWA VYSATKKYVS WLTAILRKEY EHQGITVQTI APMMVATKMS
KVKRTSFFTP DGAVFAKSAL NTVGNTSDTT GYITHQLQLE LMDLIPTFIR DKILTNMSVG
TRAAALRKKE REAKSQ
