DH12A_DANRE
ID DH12A_DANRE Reviewed; 319 AA.
AC Q6P3L6; Q7ZUN4;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Very-long-chain 3-oxoacyl-CoA reductase-A {ECO:0000305};
DE EC=1.1.1.330 {ECO:0000250|UniProtKB:Q53GQ0};
DE AltName: Full=17-beta-hydroxysteroid dehydrogenase 12-A {ECO:0000250|UniProtKB:Q53GQ0};
DE Short=17-beta-HSD 12-A {ECO:0000250|UniProtKB:Q53GQ0};
DE Short=zf3.1;
DE Short=zfHSD17B12A;
DE AltName: Full=3-ketoacyl-CoA reductase {ECO:0000250|UniProtKB:Q53GQ0};
DE Short=KAR {ECO:0000250|UniProtKB:Q53GQ0};
DE AltName: Full=Estradiol 17-beta-dehydrogenase 12-A {ECO:0000250|UniProtKB:Q53GQ0};
DE EC=1.1.1.62 {ECO:0000250|UniProtKB:Q53GQ0};
GN Name=hsd17b12a; ORFNames=zgc:55589;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RX PubMed=15026171; DOI=10.1016/j.mce.2003.11.010;
RA Mindnich R., Deluca D., Adamski J.;
RT "Identification and characterization of 17 beta-hydroxysteroid
RT dehydrogenases in the zebrafish, Danio rerio.";
RL Mol. Cell. Endocrinol. 215:19-30(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=AB;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Catalyzes the second of the four reactions of the long-chain
CC fatty acids elongation cycle. This endoplasmic reticulum-bound
CC enzymatic process, allows the addition of two carbons to the chain of
CC long- and very long-chain fatty acids/VLCFAs per cycle. This enzyme has
CC a 3-ketoacyl-CoA reductase activity, reducing 3-ketoacyl-CoA to 3-
CC hydroxyacyl-CoA, within each cycle of fatty acid elongation. Thereby,
CC it may participate in the production of VLCFAs of different chain
CC lengths that are involved in multiple biological processes as
CC precursors of membrane lipids and lipid mediators. May also catalyze
CC the transformation of estrone (E1) into estradiol (E2) and play a role
CC in estrogen formation. {ECO:0000250|UniProtKB:Q53GQ0}.
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:0000250|UniProtKB:Q53GQ0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-estradiol + NAD(+) = estrone + H(+) + NADH;
CC Xref=Rhea:RHEA:24612, ChEBI:CHEBI:15378, ChEBI:CHEBI:16469,
CC ChEBI:CHEBI:17263, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.62;
CC Evidence={ECO:0000250|UniProtKB:Q53GQ0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-estradiol + NADP(+) = estrone + H(+) + NADPH;
CC Xref=Rhea:RHEA:24616, ChEBI:CHEBI:15378, ChEBI:CHEBI:16469,
CC ChEBI:CHEBI:17263, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.62;
CC Evidence={ECO:0000250|UniProtKB:Q53GQ0};
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis.
CC {ECO:0000250|UniProtKB:Q53GQ0}.
CC -!- PATHWAY: Steroid biosynthesis; estrogen biosynthesis.
CC {ECO:0000250|UniProtKB:Q53GQ0}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q53GQ0}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q53GQ0}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout development. Weakly expressed
CC during early developmental stages from shield to tailbud.
CC {ECO:0000269|PubMed:15026171}.
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; AY551082; AAS58452.1; -; mRNA.
DR EMBL; BC048053; AAH48053.1; -; mRNA.
DR EMBL; BC063943; AAH63943.1; -; mRNA.
DR RefSeq; NP_957175.1; NM_200881.1.
DR AlphaFoldDB; Q6P3L6; -.
DR SMR; Q6P3L6; -.
DR STRING; 7955.ENSDARP00000014003; -.
DR PaxDb; Q6P3L6; -.
DR PRIDE; Q6P3L6; -.
DR Ensembl; ENSDART00000005299; ENSDARP00000014003; ENSDARG00000015709.
DR GeneID; 327417; -.
DR KEGG; dre:327417; -.
DR CTD; 327417; -.
DR ZFIN; ZDB-GENE-030131-5628; hsd17b12a.
DR eggNOG; KOG1014; Eukaryota.
DR GeneTree; ENSGT00940000154860; -.
DR HOGENOM; CLU_010194_38_0_1; -.
DR InParanoid; Q6P3L6; -.
DR OMA; HICYSLF; -.
DR OrthoDB; 895581at2759; -.
DR PhylomeDB; Q6P3L6; -.
DR TreeFam; TF314591; -.
DR Reactome; R-DRE-193048; Androgen biosynthesis.
DR Reactome; R-DRE-75876; Synthesis of very long-chain fatty acyl-CoAs.
DR UniPathway; UPA00094; -.
DR UniPathway; UPA00769; -.
DR PRO; PR:Q6P3L6; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 25.
DR Bgee; ENSDARG00000015709; Expressed in cleaving embryo and 37 other tissues.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0044594; F:17-beta-hydroxysteroid dehydrogenase (NAD+) 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:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0006703; P:estrogen biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-UniPathway.
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 2: Evidence at transcript level;
KW Endoplasmic reticulum; Lipid biosynthesis; Lipid metabolism; Membrane;
KW NADP; Oxidoreductase; Reference proteome; Steroid biosynthesis;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..319
FT /note="Very-long-chain 3-oxoacyl-CoA reductase-A"
FT /id="PRO_0000248371"
FT TRANSMEM 17..37
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 188..208
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 282..302
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ACT_SITE 208
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 56..85
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 195
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT CONFLICT 187
FT /note="K -> E (in Ref. 2; AAH48053)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 319 AA; 35551 MW; BA0892BF0B7A82C8 CRC64;
MESFNVVETL QPAERALFWV GALITASLAL YVVYKTITGF RIWVLGNGDL LSPKLGKWAV
VTGATDGIGK SYAEELARRG FSMMLISRSQ EKLDDVAKSL ESTYKVETKT IAVDFSQIDV
YPKIEKGLAG LEIGILVNNV GISYSYPEFF LHIPDLENFI TTMINVNITS VCQMTRLVLP
RMEARAKGVI LNISSASGMF PVPLLTIYSS TKAFVDFFSR GLQTEYKCKG IIIQSVLPFF
VATKMTKIRK PTLDKPTPER YVAAELNTVG LQDQTNGYFP HAVMGWVTTI LAPIDLVLNL
GLRMNKAQRG GYLRRRKLR
