DHB8_HUMAN
ID DHB8_HUMAN Reviewed; 261 AA.
AC Q92506; A6NLX7; Q5STP7; Q9UIQ1;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 24-JAN-2001, sequence version 2.
DT 03-AUG-2022, entry version 204.
DE RecName: Full=(3R)-3-hydroxyacyl-CoA dehydrogenase;
DE EC=1.1.1.n12 {ECO:0000269|PubMed:19571038, ECO:0000269|PubMed:25203508};
DE AltName: Full=17-beta-hydroxysteroid dehydrogenase 8 {ECO:0000303|PubMed:17978863, ECO:0000303|PubMed:25203508};
DE Short=17-beta-HSD 8;
DE Short=HSD17B8 {ECO:0000303|PubMed:25203508};
DE AltName: Full=3-ketoacyl-[acyl-carrier-protein] reductase alpha subunit {ECO:0000303|PubMed:25203508};
DE Short=KAR alpha subunit {ECO:0000303|PubMed:25203508};
DE AltName: Full=3-oxoacyl-[acyl-carrier-protein] reductase;
DE AltName: Full=Estradiol 17-beta-dehydrogenase 8;
DE EC=1.1.1.62 {ECO:0000269|PubMed:17978863};
DE AltName: Full=Protein Ke6;
DE Short=Ke6 {ECO:0000303|PubMed:17978863, ECO:0000303|PubMed:19571038};
DE AltName: Full=Short chain dehydrogenase/reductase family 30C member 1;
DE AltName: Full=Testosterone 17-beta-dehydrogenase 8;
DE EC=1.1.1.239 {ECO:0000269|PubMed:17978863};
GN Name=HSD17B8; Synonyms=FABGL, HKE6, RING2, SDR30C1;
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 [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-261.
RX PubMed=8812499; DOI=10.1006/geno.1996.0405;
RA Ando A., Kikuti Y.Y., Shigenari A., Kawata H., Okamoto N., Shiina T.,
RA Chen L., Ikemura T., Abe K., Kimura M., Inoko H.;
RT "cDNA cloning of the human homologues of the mouse Ke4 and Ke6 genes at the
RT centromeric end of the human MHC region.";
RL Genomics 35:600-602(1996).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND TISSUE SPECIFICITY.
RX PubMed=17978863; DOI=10.1007/s11010-007-9637-9;
RA Ohno S., Nishikawa K., Honda Y., Nakajin S.;
RT "Expression in E. coli and tissue distribution of the human homologue of
RT the mouse Ke 6 gene, 17beta-hydroxysteroid dehydrogenase type 8.";
RL Mol. Cell. Biochem. 309:209-215(2008).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP CBR4.
RX PubMed=19571038; DOI=10.1096/fj.09-133587;
RA Chen Z., Kastaniotis A.J., Miinalainen I.J., Rajaram V., Wierenga R.K.,
RA Hiltunen J.K.;
RT "17beta-Hydroxysteroid dehydrogenase type 8 and carbonyl reductase type 4
RT assemble as a ketoacyl reductase of human mitochondrial FAS.";
RL FASEB J. 23:3682-3691(2009).
RN [8]
RP INDUCTION BY ESTRADIOL.
RX PubMed=18852215; DOI=10.1677/joe-08-0134;
RA Rotinen M., Celay J., Alonso M.M., Arrazola A., Encio I., Villar J.;
RT "Estradiol induces type 8 17beta-hydroxysteroid dehydrogenase expression:
RT crosstalk between estrogen receptor alpha and C/EBPbeta.";
RL J. Endocrinol. 200:85-92(2009).
RN [9]
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 [10]
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 [11]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=30508570; DOI=10.1016/j.mce.2018.11.012;
RA Hiltunen J.K., Kastaniotis A.J., Autio K.J., Jiang G., Chen Z., Glumoff T.;
RT "17B-hydroxysteroid dehydrogenases as acyl thioester metabolizing
RT enzymes.";
RL Mol. Cell. Endocrinol. 489:107-118(2019).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 6-261 IN COMPLEX WITH NAD.
RG Structural genomics consortium (SGC);
RT "Structure of human hydroxysteroid dehydrogenase type 8, HSD17B8.";
RL Submitted (FEB-2009) to the PDB data bank.
RN [13] {ECO:0007744|PDB:4CQL, ECO:0007744|PDB:4CQM}
RP X-RAY CRYSTALLOGRAPHY (2.34 ANGSTROMS) IN COMPLEX WITH NAD AND CBR4,
RP SUBUNIT, FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND MUTAGENESIS OF ASP-42;
RP ARG-148; TYR-169; LYS-173 AND ARG-189.
RX PubMed=25203508; DOI=10.1038/ncomms5805;
RA Venkatesan R., Sah-Teli S.K., Awoniyi L.O., Jiang G., Prus P.,
RA Kastaniotis A.J., Hiltunen J.K., Wierenga R.K., Chen Z.;
RT "Insights into mitochondrial fatty acid synthesis from the structure of
RT heterotetrameric 3-ketoacyl-ACP reductase/3R-hydroxyacyl-CoA
RT dehydrogenase.";
RL Nat. Commun. 5:4805-4805(2014).
RN [14]
RP VARIANT [LARGE SCALE ANALYSIS] LEU-158.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Required for the solubility and assembly of the
CC heterotetramer 3-ketoacyl-[acyl carrier protein] (ACP) reductase
CC functional complex (KAR or KAR1) that forms part of the mitochondrial
CC fatty acid synthase (mtFAS). Alpha-subunit of the KAR complex that acts
CC as a scaffold protein required for the stability of carbonyl reductase
CC type-4 (CBR4, beta-subunit of the KAR complex) and for its 3-ketoacyl-
CC ACP reductase activity, thereby participating in mitochondrial fatty
CC acid biosynthesis. Catalyzes the NAD-dependent conversion of (3R)-3-
CC hydroxyacyl-CoA into 3-ketoacyl-CoA (3-oxoacyl-CoA) with no chain
CC length preference; this enzymatic activity is not needed for the KAR
CC function (PubMed:19571038, PubMed:25203508, PubMed:30508570). Prefers
CC (3R)-3-hydroxyacyl-CoA over (3S)-3-hydroxyacyl-CoA and displays
CC enzymatic activity only in the presence of NAD(+) (PubMed:19571038).
CC Cooperates with enoyl-CoA hydratase 1 in mitochondria, together they
CC constitute an alternative route to the auxiliary enzyme pathways for
CC the breakdown of Z-PUFA (cis polyunsaturated fatty acid) enoyl-esters
CC (Probable) (PubMed:30508570). NAD-dependent 17-beta-hydroxysteroid
CC dehydrogenase with highest activity towards estradiol (17beta-estradiol
CC or E2). Has very low activity towards testosterone and
CC dihydrotestosterone (17beta-hydroxy-5alpha-androstan-3-one). Primarily
CC an oxidative enzyme, it can switch to a reductive mode determined in
CC the appropriate physiologic milieu and catalyze the reduction of
CC estrone (E1) to form biologically active 17beta-estradiol
CC (PubMed:17978863). {ECO:0000269|PubMed:17978863,
CC ECO:0000269|PubMed:19571038, ECO:0000269|PubMed:25203508,
CC ECO:0000303|PubMed:30508570, ECO:0000305|PubMed:25203508}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (3R)-3-hydroxyacyl-CoA + NAD(+) = a 3-oxoacyl-CoA + H(+) +
CC NADH; Xref=Rhea:RHEA:32711, ChEBI:CHEBI:15378, ChEBI:CHEBI:57319,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:90726;
CC EC=1.1.1.n12; Evidence={ECO:0000269|PubMed:19571038,
CC ECO:0000269|PubMed:25203508};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32712;
CC Evidence={ECO:0000269|PubMed:19571038, ECO:0000269|PubMed:25203508};
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:17978863};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24613;
CC Evidence={ECO:0000305|PubMed:17978863};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:24614;
CC Evidence={ECO:0000305|PubMed:17978863};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NAD(+) + testosterone = androst-4-ene-3,17-dione + H(+) +
CC NADH; Xref=Rhea:RHEA:14929, ChEBI:CHEBI:15378, ChEBI:CHEBI:16422,
CC ChEBI:CHEBI:17347, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC EC=1.1.1.239; Evidence={ECO:0000269|PubMed:17978863};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14930;
CC Evidence={ECO:0000305|PubMed:17978863};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-hydroxy-5alpha-androstan-3-one + NAD(+) = 5alpha-
CC androstan-3,17-dione + H(+) + NADH; Xref=Rhea:RHEA:41992,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15994, ChEBI:CHEBI:16330,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC Evidence={ECO:0000269|PubMed:17978863};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41993;
CC Evidence={ECO:0000305|PubMed:17978863};
CC -!- PATHWAY: Steroid biosynthesis; estrogen biosynthesis.
CC {ECO:0000269|PubMed:17978863}.
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis.
CC {ECO:0000269|PubMed:25203508}.
CC -!- PATHWAY: Lipid metabolism; mitochondrial fatty acid beta-oxidation.
CC {ECO:0000305|PubMed:25203508}.
CC -!- SUBUNIT: Heterotetramer with CBR4; contains two molecules of HSD17B8
CC and CBR4. {ECO:0000269|PubMed:25203508, ECO:0000269|Ref.12}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000269|PubMed:19571038}.
CC -!- TISSUE SPECIFICITY: Widely expressed, particularly abundant in
CC prostate, placenta and kidney (PubMed:17978863). Expressed at protein
CC level in various tissues like brain, cerebellum, heart, lung, kidney,
CC ovary, testis, adrenals and prostate (PubMed:30508570).
CC {ECO:0000269|PubMed:17978863, ECO:0000269|PubMed:30508570}.
CC -!- INDUCTION: Up-regulated by estradiol. {ECO:0000269|PubMed:18852215}.
CC -!- MISCELLANEOUS: The fatty acyl-CoA dehydrogenase activity is several
CC thousand times higher than the estradiol and testosterone 17beta-
CC hydroxysteroid dehydrogenase conversion. {ECO:0000269|PubMed:19571038}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; BT007239; AAP35903.1; -; mRNA.
DR EMBL; AL031228; CAC38444.1; -; Genomic_DNA.
DR EMBL; AL662824; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL713971; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL645940; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL844527; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR759786; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR759733; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR847841; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471081; EAX03682.1; -; Genomic_DNA.
DR EMBL; BC008185; AAH08185.1; -; mRNA.
DR EMBL; D82061; BAA11529.1; -; mRNA.
DR CCDS; CCDS4769.1; -.
DR RefSeq; NP_055049.1; NM_014234.4.
DR PDB; 2PD6; X-ray; 2.00 A; A/B/C/D=6-261.
DR PDB; 4CQL; X-ray; 2.85 A; A/D/E/H/I/L/M/P=1-261.
DR PDB; 4CQM; X-ray; 2.34 A; A/D/E/H/I/L/M/P=1-261.
DR PDBsum; 2PD6; -.
DR PDBsum; 4CQL; -.
DR PDBsum; 4CQM; -.
DR AlphaFoldDB; Q92506; -.
DR SMR; Q92506; -.
DR BioGRID; 113653; 39.
DR IntAct; Q92506; 16.
DR MINT; Q92506; -.
DR STRING; 9606.ENSP00000363794; -.
DR DrugBank; DB00157; NADH.
DR DrugBank; DB03461; Nicotinamide adenine dinucleotide phosphate.
DR SwissLipids; SLP:000001271; -.
DR GlyGen; Q92506; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q92506; -.
DR PhosphoSitePlus; Q92506; -.
DR BioMuta; HSD17B8; -.
DR DMDM; 12643402; -.
DR EPD; Q92506; -.
DR jPOST; Q92506; -.
DR MassIVE; Q92506; -.
DR MaxQB; Q92506; -.
DR PaxDb; Q92506; -.
DR PeptideAtlas; Q92506; -.
DR PRIDE; Q92506; -.
DR ProteomicsDB; 75276; -.
DR TopDownProteomics; Q92506; -.
DR Antibodypedia; 28972; 228 antibodies from 28 providers.
DR DNASU; 7923; -.
DR Ensembl; ENST00000230236.4; ENSP00000230236.4; ENSG00000112474.4.
DR Ensembl; ENST00000374662.4; ENSP00000363794.3; ENSG00000204228.4.
DR Ensembl; ENST00000414463.2; ENSP00000387753.2; ENSG00000228357.2.
DR Ensembl; ENST00000422433.2; ENSP00000406488.2; ENSG00000232357.2.
DR Ensembl; ENST00000427295.2; ENSP00000403538.2; ENSG00000228712.2.
DR Ensembl; ENST00000454191.2; ENSP00000413950.2; ENSG00000225312.2.
DR GeneID; 7923; -.
DR KEGG; hsa:7923; -.
DR MANE-Select; ENST00000374662.4; ENSP00000363794.3; NM_014234.5; NP_055049.1.
DR UCSC; uc003odi.3; human.
DR CTD; 7923; -.
DR DisGeNET; 7923; -.
DR GeneCards; HSD17B8; -.
DR HGNC; HGNC:3554; HSD17B8.
DR HPA; ENSG00000204228; Low tissue specificity.
DR MIM; 601417; gene.
DR neXtProt; NX_Q92506; -.
DR OpenTargets; ENSG00000204228; -.
DR PharmGKB; PA29484; -.
DR VEuPathDB; HostDB:ENSG00000204228; -.
DR eggNOG; KOG1200; Eukaryota.
DR GeneTree; ENSGT00940000160668; -.
DR HOGENOM; CLU_010194_1_3_1; -.
DR InParanoid; Q92506; -.
DR OMA; KMPERDY; -.
DR OrthoDB; 1226147at2759; -.
DR PhylomeDB; Q92506; -.
DR TreeFam; TF313099; -.
DR BioCyc; MetaCyc:HS03575-MON; -.
DR BRENDA; 1.1.1.100; 2681.
DR PathwayCommons; Q92506; -.
DR Reactome; R-HSA-75105; Fatty acyl-CoA biosynthesis.
DR SABIO-RK; Q92506; -.
DR SignaLink; Q92506; -.
DR UniPathway; UPA00094; -.
DR UniPathway; UPA00660; -.
DR UniPathway; UPA00769; -.
DR BioGRID-ORCS; 7923; 10 hits in 1077 CRISPR screens.
DR ChiTaRS; HSD17B8; human.
DR EvolutionaryTrace; Q92506; -.
DR GeneWiki; HSD17B8; -.
DR GenomeRNAi; 7923; -.
DR Pharos; Q92506; Tbio.
DR PRO; PR:Q92506; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q92506; protein.
DR Bgee; ENSG00000112474; Expressed in prostate gland and 1 other tissue.
DR ExpressionAtlas; Q92506; baseline and differential.
DR Genevisible; Q92506; HS.
DR GO; GO:0005740; C:mitochondrial envelope; IEA:Ensembl.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB.
DR GO; GO:1990204; C:oxidoreductase complex; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0106386; F:(3R)-hydroxyacyl-CoA dehydrogenase (NAD) activity; IDA:UniProtKB.
DR GO; GO:0044594; F:17-beta-hydroxysteroid dehydrogenase (NAD+) activity; IEA:RHEA.
DR GO; GO:0004303; F:estradiol 17-beta-dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0070404; F:NADH binding; IDA:UniProtKB.
DR GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IBA:GO_Central.
DR GO; GO:0048038; F:quinone binding; IBA:GO_Central.
DR GO; GO:0047035; F:testosterone dehydrogenase (NAD+) activity; IEA:UniProtKB-EC.
DR GO; GO:0008209; P:androgen metabolic process; IEA:Ensembl.
DR GO; GO:0006703; P:estrogen biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IMP:UniProtKB.
DR GO; GO:0051290; P:protein heterotetramerization; IDA:UniProtKB.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
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 3D-structure; Fatty acid biosynthesis; Fatty acid metabolism;
KW Lipid biosynthesis; Lipid metabolism; Mitochondrion; NAD; Oxidoreductase;
KW Phosphoprotein; Reference proteome; Steroid biosynthesis.
FT CHAIN 1..261
FT /note="(3R)-3-hydroxyacyl-CoA dehydrogenase"
FT /id="PRO_0000054598"
FT ACT_SITE 169
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 15..23
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:25203508, ECO:0000269|Ref.12,
FT ECO:0007744|PDB:2PD6, ECO:0007744|PDB:4CQL"
FT BINDING 42..43
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:25203508, ECO:0000269|Ref.12,
FT ECO:0007744|PDB:2PD6, ECO:0007744|PDB:4CQL"
FT BINDING 74..76
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:25203508, ECO:0000269|Ref.12,
FT ECO:0007744|PDB:2PD6, ECO:0007744|PDB:4CQL"
FT BINDING 156
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 169..173
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:25203508, ECO:0000269|Ref.12,
FT ECO:0007744|PDB:2PD6, ECO:0007744|PDB:4CQL"
FT BINDING 202..204
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|Ref.12, ECO:0007744|PDB:2PD6,
FT ECO:0007744|PDB:4CQM"
FT MOD_RES 60
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P50171"
FT MOD_RES 160
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P50171"
FT MOD_RES 173
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P50171"
FT VARIANT 158
FT /note="V -> L (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035844"
FT VARIANT 190
FT /note="H -> R (in dbSNP:rs34491699)"
FT /id="VAR_052316"
FT MUTAGEN 42
FT /note="D->A: Reduced NADH-dependent reductase activity with
FT acetoacetyl-CoA. Reduced NADH-dependent reductase activity
FT with 9,10-phenanthrene quinone. Increases NADPH-dependent
FT reductase activities. No effect on the ability to restore
FT growth of an OAR1-deficient yeast mutant."
FT /evidence="ECO:0000269|PubMed:25203508"
FT MUTAGEN 148
FT /note="R->E: No effect on the ability to restore growth of
FT an OAR1-deficient yeast mutant."
FT /evidence="ECO:0000269|PubMed:25203508"
FT MUTAGEN 169
FT /note="Y->A: Strongly reduced NADH-dependent reductase
FT activity with acetoacetyl-CoA. Strongly reduced NADH-
FT dependent reductase activity with 9,10-phenanthrene
FT quinone. Decreases NADPH-dependent reductase activity with
FT acetoacetyl-CoA, but increases NADPH-dependent reductase
FT activity with 9,10-phenanthrene quinone. No effect on the
FT ability to restore growth of an OAR1-deficient yeast
FT mutant."
FT /evidence="ECO:0000269|PubMed:25203508"
FT MUTAGEN 173
FT /note="K->A: Abolishes NADH-dependent reductase activity
FT with acetoacetyl-CoA. Strongly reduced NADH-dependent
FT reductase activity with 9,10-phenanthrene quinone. Slightly
FT decreases NADPH-dependent reductase activity with
FT acetoacetyl-CoA, but increases NADPH-dependent reductase
FT activity with 9,10-phenanthrene quinone. No effect on the
FT ability to restore growth of an OAR1-deficient yeast
FT mutant."
FT /evidence="ECO:0000269|PubMed:25203508"
FT MUTAGEN 189
FT /note="R->E: No effect on the ability to restore growth of
FT an OAR1-deficient yeast mutant."
FT /evidence="ECO:0000269|PubMed:25203508"
FT CONFLICT 117
FT /note="E -> R (in Ref. 5; BAA11529)"
FT /evidence="ECO:0000305"
FT CONFLICT 193
FT /note="R -> P (in Ref. 5; BAA11529)"
FT /evidence="ECO:0000305"
FT CONFLICT 208
FT /note="Q -> K (in Ref. 5; BAA11529)"
FT /evidence="ECO:0000305"
FT CONFLICT 212
FT /note="Q -> K (in Ref. 5; BAA11529)"
FT /evidence="ECO:0000305"
FT TURN 8..11
FT /evidence="ECO:0007829|PDB:4CQM"
FT STRAND 13..17
FT /evidence="ECO:0007829|PDB:2PD6"
FT TURN 18..20
FT /evidence="ECO:0007829|PDB:2PD6"
FT HELIX 22..33
FT /evidence="ECO:0007829|PDB:2PD6"
FT STRAND 37..44
FT /evidence="ECO:0007829|PDB:2PD6"
FT HELIX 45..53
FT /evidence="ECO:0007829|PDB:2PD6"
FT STRAND 70..73
FT /evidence="ECO:0007829|PDB:2PD6"
FT HELIX 79..93
FT /evidence="ECO:0007829|PDB:2PD6"
FT STRAND 98..102
FT /evidence="ECO:0007829|PDB:2PD6"
FT HELIX 112..114
FT /evidence="ECO:0007829|PDB:2PD6"
FT HELIX 117..127
FT /evidence="ECO:0007829|PDB:2PD6"
FT HELIX 129..145
FT /evidence="ECO:0007829|PDB:2PD6"
FT STRAND 149..154
FT /evidence="ECO:0007829|PDB:2PD6"
FT HELIX 158..161
FT /evidence="ECO:0007829|PDB:2PD6"
FT HELIX 167..187
FT /evidence="ECO:0007829|PDB:2PD6"
FT HELIX 188..190
FT /evidence="ECO:0007829|PDB:2PD6"
FT STRAND 192..199
FT /evidence="ECO:0007829|PDB:2PD6"
FT STRAND 201..204
FT /evidence="ECO:0007829|PDB:4CQM"
FT TURN 207..209
FT /evidence="ECO:0007829|PDB:2PD6"
FT HELIX 212..216
FT /evidence="ECO:0007829|PDB:2PD6"
FT HELIX 219..221
FT /evidence="ECO:0007829|PDB:2PD6"
FT HELIX 230..241
FT /evidence="ECO:0007829|PDB:2PD6"
FT HELIX 243..245
FT /evidence="ECO:0007829|PDB:2PD6"
FT STRAND 252..256
FT /evidence="ECO:0007829|PDB:2PD6"
FT TURN 257..260
FT /evidence="ECO:0007829|PDB:4CQM"
SQ SEQUENCE 261 AA; 26974 MW; 8B8B2D7131714D71 CRC64;
MASQLQNRLR SALALVTGAG SGIGRAVSVR LAGEGATVAA CDLDRAAAQE TVRLLGGPGS
KEGPPRGNHA AFQADVSEAR AARCLLEQVQ ACFSRPPSVV VSCAGITQDE FLLHMSEDDW
DKVIAVNLKG TFLVTQAAAQ ALVSNGCRGS IINISSIVGK VGNVGQTNYA ASKAGVIGLT
QTAARELGRH GIRCNSVLPG FIATPMTQKV PQKVVDKITE MIPMGHLGDP EDVADVVAFL
ASEDSGYITG TSVEVTGGLF M
