ID DHB12_HUMAN Reviewed; 312 AA. AC Q53GQ0; A8K9B0; D3DR23; Q96EA9; Q96JU2; Q9Y6G8; DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot. DT 02-OCT-2007, sequence version 2. DT 27-MAR-2024, entry version 170. DE RecName: Full=Very-long-chain 3-oxoacyl-CoA reductase {ECO:0000305}; DE EC=1.1.1.330 {ECO:0000269|PubMed:12482854}; DE AltName: Full=17-beta-hydroxysteroid dehydrogenase 12 {ECO:0000303|PubMed:16166196}; DE Short=17-beta-HSD 12 {ECO:0000303|PubMed:16166196}; DE AltName: Full=3-ketoacyl-CoA reductase {ECO:0000303|PubMed:12482854}; DE Short=KAR {ECO:0000303|PubMed:12482854}; DE AltName: Full=Estradiol 17-beta-dehydrogenase 12 {ECO:0000303|PubMed:16166196}; DE EC=1.1.1.62 {ECO:0000269|PubMed:16166196}; DE AltName: Full=Short chain dehydrogenase/reductase family 12C member 1; GN Name=HSD17B12 {ECO:0000312|HGNC:HGNC:18646}; Synonyms=SDR12C1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Liu T., Zhang J., Fu G., Zhang Q., Ye M., Zhou J., Wu J., Shen Y., Yu M., RA Chen S., Mao M., Chen Z.; RT "Human steroid dehydrogenase homologue, complete cds."; RL Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT LEU-280. RC TISSUE=Liver, Placenta, Thymus, and Thyroid; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT LEU-280. RC TISSUE=Liver; RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., RA Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT LEU-280. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Brain, and Pancreas; 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). RN [7] RP PROTEIN SEQUENCE OF 26-35; 65-72; 104-117; 157-179 AND 207-221, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=B-cell lymphoma; RA Bienvenut W.V.; RL Submitted (JUN-2005) to UniProtKB. RN [8] RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RX PubMed=12482854; DOI=10.1074/jbc.m211684200; RA Moon Y.-A., Horton J.D.; RT "Identification of two mammalian reductases involved in the two-carbon RT fatty acyl elongation cascade."; RL J. Biol. Chem. 278:7335-7343(2003). RN [9] RP TISSUE SPECIFICITY. RX PubMed=16113833; DOI=10.1160/th05-01-0037; RA Gnatenko D.V., Cupit L.D., Huang E.C., Dhundale A., Perrotta P.L., RA Bahou W.F.; RT "Platelets express steroidogenic 17beta-hydroxysteroid dehydrogenases. RT Distinct profiles predict the essential thrombocythemic phenotype."; RL Thromb. Haemost. 94:412-421(2005). RN [10] RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, BIOPHYSICOCHEMICAL PROPERTIES, RP TISSUE SPECIFICITY, AND MUTAGENESIS OF VAL-196 AND PHE-234. RX PubMed=16166196; DOI=10.1210/me.2005-0058; RA Luu-The V., Tremblay P., Labrie F.; RT "Characterization of type 12 17beta-hydroxysteroid dehydrogenase, an RT isoform of type 3 17beta-hydroxysteroid dehydrogenase responsible for RT estradiol formation in women."; RL Mol. Endocrinol. 20:437-443(2006). RN [11] RP INTERACTION WITH ELOVL1 AND LASS2. RX PubMed=20937905; DOI=10.1073/pnas.1005572107; RA Ohno Y., Suto S., Yamanaka M., Mizutani Y., Mitsutake S., Igarashi Y., RA Sassa T., Kihara A.; RT "ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid RT synthesis."; RL Proc. Natl. Acad. Sci. U.S.A. 107:18439-18444(2010). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). 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:0000269|PubMed:12482854, CC ECO:0000269|PubMed:16166196}. 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:0000269|PubMed:12482854}; 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:0000269|PubMed:16166196}; 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:0000269|PubMed:16166196}; 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:0000269|PubMed:12482854}; 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:0000269|PubMed:12482854}; 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:0000269|PubMed:12482854}; 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:0000269|PubMed:12482854}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=3.5 uM for estrone {ECO:0000269|PubMed:16166196}; CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis. CC {ECO:0000269|PubMed:12482854}. CC -!- PATHWAY: Steroid biosynthesis; estrogen biosynthesis. CC {ECO:0000269|PubMed:16166196}. CC -!- SUBUNIT: Interacts with ELOVL1 and LASS2. CC {ECO:0000269|PubMed:20937905}. CC -!- INTERACTION: CC Q53GQ0; P28329-3: CHAT; NbExp=3; IntAct=EBI-2963255, EBI-25837549; CC Q53GQ0; P22607: FGFR3; NbExp=4; IntAct=EBI-2963255, EBI-348399; CC Q53GQ0; P06396: GSN; NbExp=3; IntAct=EBI-2963255, EBI-351506; CC Q53GQ0; P01112: HRAS; NbExp=3; IntAct=EBI-2963255, EBI-350145; CC Q53GQ0; Q9UMX0: UBQLN1; NbExp=6; IntAct=EBI-2963255, EBI-741480; CC Q53GQ0; Q9UMX0-2: UBQLN1; NbExp=3; IntAct=EBI-2963255, EBI-10173939; CC Q53GQ0; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-2963255, EBI-947187; CC Q53GQ0; PRO_0000037541 [Q9WMX2]; Xeno; NbExp=2; IntAct=EBI-2963255, EBI-6863754; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:12482854}; Multi-pass membrane protein CC {ECO:0000269|PubMed:12482854}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q53GQ0-1; Sequence=Displayed; CC Name=2; CC IsoId=Q53GQ0-2; Sequence=VSP_056380, VSP_056381; CC -!- TISSUE SPECIFICITY: Expressed in most tissues tested. Highly expressed CC in the ovary and mammary. Expressed in platelets. CC {ECO:0000269|PubMed:12482854, ECO:0000269|PubMed:16113833, CC ECO:0000269|PubMed:16166196}. 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=AK027882; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF078850; AAD44482.1; -; mRNA. DR EMBL; AK027882; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AK074952; BAG52039.1; -; mRNA. DR EMBL; AK075216; BAG52086.1; -; mRNA. DR EMBL; AK222881; BAD96601.1; -; mRNA. DR EMBL; AK292625; BAF85314.1; -; mRNA. DR EMBL; AC023085; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC068205; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC087521; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471064; EAW68082.1; -; Genomic_DNA. DR EMBL; CH471064; EAW68087.1; -; Genomic_DNA. DR EMBL; CH471064; EAW68088.1; -; Genomic_DNA. DR EMBL; BC012043; AAH12043.1; -; mRNA. DR EMBL; BC012536; AAH12536.1; -; mRNA. DR CCDS; CCDS7905.1; -. [Q53GQ0-1] DR RefSeq; NP_057226.1; NM_016142.2. [Q53GQ0-1] DR AlphaFoldDB; Q53GQ0; -. DR SMR; Q53GQ0; -. DR BioGRID; 119328; 222. DR IntAct; Q53GQ0; 78. DR MINT; Q53GQ0; -. DR STRING; 9606.ENSP00000278353; -. DR ChEMBL; CHEMBL5998; -. DR SwissLipids; SLP:000000433; -. DR GlyGen; Q53GQ0; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q53GQ0; -. DR PhosphoSitePlus; Q53GQ0; -. DR SwissPalm; Q53GQ0; -. DR BioMuta; HSD17B12; -. DR DMDM; 158931120; -. DR EPD; Q53GQ0; -. DR jPOST; Q53GQ0; -. DR MassIVE; Q53GQ0; -. DR MaxQB; Q53GQ0; -. DR PaxDb; 9606-ENSP00000278353; -. DR PeptideAtlas; Q53GQ0; -. DR ProteomicsDB; 62486; -. [Q53GQ0-1] DR ProteomicsDB; 76390; -. DR Pumba; Q53GQ0; -. DR Antibodypedia; 3090; 216 antibodies from 24 providers. DR DNASU; 51144; -. DR Ensembl; ENST00000278353.10; ENSP00000278353.4; ENSG00000149084.13. [Q53GQ0-1] DR Ensembl; ENST00000395700.4; ENSP00000379052.4; ENSG00000149084.13. [Q53GQ0-2] DR GeneID; 51144; -. DR KEGG; hsa:51144; -. DR MANE-Select; ENST00000278353.10; ENSP00000278353.4; NM_016142.3; NP_057226.1. DR UCSC; uc001mxq.5; human. [Q53GQ0-1] DR AGR; HGNC:18646; -. DR CTD; 51144; -. DR DisGeNET; 51144; -. DR GeneCards; HSD17B12; -. DR HGNC; HGNC:18646; HSD17B12. DR HPA; ENSG00000149084; Low tissue specificity. DR MIM; 609574; gene. DR neXtProt; NX_Q53GQ0; -. DR OpenTargets; ENSG00000149084; -. DR PharmGKB; PA38618; -. DR VEuPathDB; HostDB:ENSG00000149084; -. DR eggNOG; KOG1014; Eukaryota. DR GeneTree; ENSGT00940000154860; -. DR HOGENOM; CLU_010194_38_0_1; -. DR InParanoid; Q53GQ0; -. DR OMA; LVAPGMM; -. DR OrthoDB; 6845at2759; -. DR PhylomeDB; Q53GQ0; -. DR TreeFam; TF314591; -. DR BioCyc; MetaCyc:HS07581-MONOMER; -. DR BRENDA; 1.1.1.62; 2681. DR PathwayCommons; Q53GQ0; -. DR Reactome; R-HSA-193048; Androgen biosynthesis. DR Reactome; R-HSA-75876; Synthesis of very long-chain fatty acyl-CoAs. DR SABIO-RK; Q53GQ0; -. DR SignaLink; Q53GQ0; -. DR UniPathway; UPA00094; -. DR UniPathway; UPA00769; -. DR BioGRID-ORCS; 51144; 379 hits in 1176 CRISPR screens. DR ChiTaRS; HSD17B12; human. DR GeneWiki; HSD17B12; -. DR GenomeRNAi; 51144; -. DR Pharos; Q53GQ0; Tbio. DR PRO; PR:Q53GQ0; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q53GQ0; Protein. DR Bgee; ENSG00000149084; Expressed in endothelial cell and 205 other cell types or tissues. DR ExpressionAtlas; Q53GQ0; baseline and differential. DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0031012; C:extracellular matrix; IEA:Ensembl. DR GO; GO:0009923; C:fatty acid elongase complex; IDA:UniProtKB. DR GO; GO:0005518; F:collagen binding; IEA:Ensembl. DR GO; GO:0004303; F:estradiol 17-beta-dehydrogenase [NAD(P)] activity; IEA:UniProtKB-EC. DR GO; GO:0001968; F:fibronectin binding; IEA:Ensembl. DR GO; GO:0008201; F:heparin binding; IEA:Ensembl. DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central. DR GO; GO:0141040; F:very-long-chain 3-oxoacyl-CoA reductase activity; IDA:UniProtKB. DR GO; GO:0006703; P:estrogen biosynthetic process; IEA:UniProtKB-UniPathway. DR GO; GO:0030198; P:extracellular matrix organization; IEA:Ensembl. DR GO; GO:0019367; P:fatty acid elongation, saturated fatty acid; IDA:UniProtKB. DR GO; GO:0035338; P:long-chain fatty-acyl-CoA biosynthetic process; TAS:Reactome. DR GO; GO:0010811; P:positive regulation of cell-substrate adhesion; IEA:Ensembl. DR CDD; cd05356; 17beta-HSD1_like_SDR_c; 1. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1. DR InterPro; IPR036291; NAD(P)-bd_dom_sf. DR InterPro; IPR020904; Sc_DH/Rdtase_CS. DR InterPro; IPR002347; SDR_fam. DR PANTHER; PTHR43899; RH59310P; 1. DR PANTHER; PTHR43899:SF14; VERY-LONG-CHAIN 3-OXOACYL-COA REDUCTASE; 1. DR Pfam; PF00106; adh_short; 1. DR PIRSF; PIRSF000126; 11-beta-HSD1; 1. DR PRINTS; PR00081; GDHRDH. DR PRINTS; PR00080; SDRFAMILY. DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1. DR PROSITE; PS00061; ADH_SHORT; 1. DR Genevisible; Q53GQ0; HS. PE 1: Evidence at protein level; KW Alternative splicing; Direct protein sequencing; Endoplasmic reticulum; KW Lipid biosynthesis; Lipid metabolism; Membrane; NADP; Oxidoreductase; KW Reference proteome; Steroid biosynthesis; Transmembrane; KW Transmembrane helix. FT CHAIN 1..312 FT /note="Very-long-chain 3-oxoacyl-CoA reductase" FT /id="PRO_0000248368" 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 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 VAR_SEQ 95..98 FT /note="KEKF -> SNYT (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_056380" FT VAR_SEQ 99..312 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_056381" FT VARIANT 280 FT /note="S -> L (in dbSNP:rs11555762)" FT /evidence="ECO:0000269|PubMed:14702039, ECO:0000269|Ref.3, FT ECO:0000269|Ref.5" FT /id="VAR_027277" FT MUTAGEN 196 FT /note="V->W: No effect." FT /evidence="ECO:0000269|PubMed:16166196" FT MUTAGEN 234 FT /note="F->A: Allows the conversion of androstenedione to FT testosterone." FT /evidence="ECO:0000269|PubMed:16166196" SQ SEQUENCE 312 AA; 34324 MW; 8518336D7F514E50 CRC64; MESALPAAGF LYWVGAGTVA YLALRISYSL FTALRVWGVG NEAGVGPGLG EWAVVTGSTD GIGKSYAEEL AKHGMKVVLI SRSKDKLDQV SSEIKEKFKV ETRTIAVDFA SEDIYDKIKT GLAGLEIGIL VNNVGMSYEY PEYFLDVPDL DNVIKKMINI NILSVCKMTQ LVLPGMVERS KGAILNISSG SGMLPVPLLT IYSATKTFVD FFSQCLHEEY RSKGVFVQSV LPYFVATKLA KIRKPTLDKP SPETFVKSAI KTVGLQSRTN GYLIHALMGS IISNLPSWIY LKIVMNMNKS TRAHYLKKTK KN //