DHB12_RAT
ID DHB12_RAT Reviewed; 312 AA.
AC Q6P7R8; Q9Z1B9;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Very-long-chain 3-oxoacyl-CoA reductase {ECO:0000305};
DE EC=1.1.1.330 {ECO:0000250|UniProtKB:Q53GQ0};
DE AltName: Full=17-beta-hydroxysteroid dehydrogenase 12 {ECO:0000250|UniProtKB:Q53GQ0};
DE Short=17-beta-HSD 12 {ECO:0000250|UniProtKB:Q53GQ0};
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 {ECO:0000250|UniProtKB:Q53GQ0};
DE EC=1.1.1.62 {ECO:0000250|UniProtKB:Q53GQ0};
GN Name=Hsd17b12 {ECO:0000312|RGD:708367};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Trzyna W.C., Gabbeta V., McHugh K.M.;
RL Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pituitary anterior lobe;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
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 -!- CATALYTIC ACTIVITY:
CC Reaction=3-oxooctadecanoyl-CoA + H(+) + NADPH = (3R)-
CC hydroxyoctadecanoyl-CoA + NADP(+); Xref=Rhea:RHEA:39151,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:71407, ChEBI:CHEBI:76374;
CC Evidence={ECO:0000250|UniProtKB:Q53GQ0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(7Z,10Z,13Z,16Z)-3-oxodocosatetraenoyl-CoA + H(+) + NADPH =
CC (3R)-hydroxy-(7Z,10Z,13Z,16Z)-docosatetraenoyl-CoA + NADP(+);
CC Xref=Rhea:RHEA:39323, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:73852, ChEBI:CHEBI:76415;
CC Evidence={ECO:0000250|UniProtKB:Q53GQ0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(7Z,10Z,13Z,16Z,19Z)-3-oxodocosapentaenoyl-CoA + H(+) + NADPH
CC = (3R)-hydroxy-(7Z,10Z,13Z,16Z,19Z)-docosapentaenoyl-CoA + NADP(+);
CC Xref=Rhea:RHEA:39459, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:73863, ChEBI:CHEBI:76460;
CC Evidence={ECO:0000250|UniProtKB:Q53GQ0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(8Z,11Z,14Z)-3-oxoeicosatrienoyl-CoA + H(+) + NADPH = (3R)-
CC hydroxy-(8Z,11Z,14Z)-eicosatrienoyl-CoA + NADP(+);
CC Xref=Rhea:RHEA:39311, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:71481, ChEBI:CHEBI:76411;
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 -!- DOMAIN: The di-lysine motif confers endoplasmic reticulum localization
CC for type I membrane proteins. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. 17-beta-HSD 3 subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD00504.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; U81186; AAD00504.1; ALT_FRAME; mRNA.
DR EMBL; BC061543; AAH61543.1; -; mRNA.
DR RefSeq; NP_114455.1; NM_032066.1.
DR RefSeq; XP_006234661.1; XM_006234599.3.
DR AlphaFoldDB; Q6P7R8; -.
DR SMR; Q6P7R8; -.
DR BioGRID; 249879; 1.
DR STRING; 10116.ENSRNOP00000012806; -.
DR iPTMnet; Q6P7R8; -.
DR PhosphoSitePlus; Q6P7R8; -.
DR SwissPalm; Q6P7R8; -.
DR jPOST; Q6P7R8; -.
DR PaxDb; Q6P7R8; -.
DR PRIDE; Q6P7R8; -.
DR Ensembl; ENSRNOT00000012806; ENSRNOP00000012806; ENSRNOG00000009630.
DR GeneID; 84013; -.
DR KEGG; rno:84013; -.
DR UCSC; RGD:708367; rat.
DR CTD; 51144; -.
DR RGD; 708367; Hsd17b12.
DR eggNOG; KOG1014; Eukaryota.
DR GeneTree; ENSGT00940000154860; -.
DR InParanoid; Q6P7R8; -.
DR OMA; FLQHWSS; -.
DR OrthoDB; 895581at2759; -.
DR PhylomeDB; Q6P7R8; -.
DR TreeFam; TF314591; -.
DR Reactome; R-RNO-193048; Androgen biosynthesis.
DR Reactome; R-RNO-75876; Synthesis of very long-chain fatty acyl-CoAs.
DR UniPathway; UPA00094; -.
DR UniPathway; UPA00769; -.
DR PRO; PR:Q6P7R8; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000009630; Expressed in liver and 20 other tissues.
DR ExpressionAtlas; Q6P7R8; baseline and differential.
DR Genevisible; Q6P7R8; RN.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0031012; C:extracellular matrix; ISO:RGD.
DR GO; GO:0009923; C:fatty acid elongase complex; ISO:RGD.
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:0005518; F:collagen binding; ISO:RGD.
DR GO; GO:0001968; F:fibronectin binding; ISO:RGD.
DR GO; GO:0008201; F:heparin binding; ISO:RGD.
DR GO; GO:0016509; F:long-chain-3-hydroxyacyl-CoA dehydrogenase activity; ISO:RGD.
DR GO; GO:0050062; F:long-chain-fatty-acyl-CoA reductase activity; ISO:RGD.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0006703; P:estrogen biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0030198; P:extracellular matrix organization; ISO:RGD.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0010811; P:positive regulation of cell-substrate adhesion; ISO:RGD.
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..312
FT /note="Very-long-chain 3-oxoacyl-CoA reductase"
FT /id="PRO_0000248370"
FT TRANSMEM 4..24
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 182..202
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 271..291
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MOTIF 308..312
FT /note="Di-lysine motif"
FT /evidence="ECO:0000250"
FT ACT_SITE 202
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 50..79
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 189
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT CONFLICT 236
FT /note="A -> S (in Ref. 1; AAD00504)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 312 AA; 34841 MW; 8531943458EFC711 CRC64;
MERALPAAGF LYWVGASTIA YLTLRASYSL FRAFQVWCVG NQAFVGPRLG EWAVVTGGTD
GIGKSYAEEL AKRGMKIVLI SRSQDKLKEV SNNIKEKFNV ETRTIAVDFS LDDIYDKIKT
GLSGLEIGVL VNNVGMSYEY PEYFLEIPDL DNTIKKLINI NVLSICKVTR LVLPGMVERS
KGVILNISSA SGMLPVPLLT VYSATKAFVD FFSQCLHEEY KSKGIFVQSV LPFFVATKLA
KIRKPTLDKP SAETFVKSAI KTVGLQTRTT GYVIHAIMGS INSILPRWIY FKTIMGFNKS
LRNRYLKKTK KN
