H17B6_HUMAN
ID H17B6_HUMAN Reviewed; 317 AA.
AC O14756; O43275;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=17-beta-hydroxysteroid dehydrogenase type 6;
DE Short=17-beta-HSD 6;
DE Short=17-beta-HSD6;
DE EC=1.1.1.105 {ECO:0000269|PubMed:10896656, ECO:0000269|PubMed:11360992};
DE EC=1.1.1.209 {ECO:0000269|PubMed:10896656, ECO:0000269|PubMed:11360992};
DE EC=1.1.1.239 {ECO:0000250|UniProtKB:Q9R092};
DE EC=1.1.1.53 {ECO:0000269|PubMed:11360992};
DE EC=1.1.1.62 {ECO:0000250|UniProtKB:Q9R092};
DE AltName: Full=3-alpha->beta-hydroxysteroid epimerase;
DE Short=3-alpha->beta-HSE;
DE AltName: Full=Oxidative 3-alpha hydroxysteroid dehydrogenase;
DE AltName: Full=Short chain dehydrogenase/reductase family 9C member 6;
DE Flags: Precursor;
GN Name=HSD17B6; Synonyms=RODH, SDR9C6;
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], AND TISSUE SPECIFICITY.
RC TISSUE=Prostate;
RX PubMed=9188497; DOI=10.1074/jbc.272.25.15959;
RA Biswas M.G., Russell D.W.;
RT "Expression cloning and characterization of oxidative 17beta- and 3alpha-
RT hydroxysteroid dehydrogenases from rat and human prostate.";
RL J. Biol. Chem. 272:15959-15966(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=10896656; DOI=10.1074/jbc.m000562200;
RA Huang X.-F., Luu-The V.;
RT "Molecular characterization of a first human 3(alpha-->beta)-hydroxysteroid
RT epimerase.";
RL J. Biol. Chem. 275:29452-29457(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [4]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP SUBCELLULAR LOCATION.
RX PubMed=11360992; DOI=10.1006/abbi.2000.2203;
RA Chetyrkin S.V., Hu J., Gough W.H., Dumaual N., Kedishvili N.Y.;
RT "Further characterization of human microsomal 3alpha-hydroxysteroid
RT dehydrogenase.";
RL Arch. Biochem. Biophys. 386:1-10(2001).
RN [5]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=11513953; DOI=10.1016/s0167-4781(01)00247-0;
RA Huang X.-F., Luu-The V.;
RT "Gene structure, chromosomal localization and analysis of 3-ketosteroid
RT reductase activity of the human 3(alpha-->beta)-hydroxysteroid epimerase.";
RL Biochim. Biophys. Acta 1520:124-130(2001).
RN [6]
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).
CC -!- FUNCTION: NAD-dependent oxidoreductase with broad substrate specificity
CC that shows both oxidative and reductive activity (in vitro). Has 17-
CC beta-hydroxysteroid dehydrogenase activity towards various steroids (in
CC vitro). Converts 5-alpha-androstan-3-alpha,17-beta-diol to androsterone
CC and estradiol to estrone (in vitro). Has 3-alpha-hydroxysteroid
CC dehydrogenase activity towards androsterone (in vitro). Has retinol
CC dehydrogenase activity towards all-trans-retinol (in vitro). Can
CC convert androsterone to epi-androsterone. Androsterone is first
CC oxidized to 5-alpha-androstane-3,17-dione and then reduced to epi-
CC andosterone. Can act on both C-19 and C-21 3-alpha-hydroxysteroids.
CC {ECO:0000269|PubMed:10896656, ECO:0000269|PubMed:11360992,
CC ECO:0000269|PubMed:11513953}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-retinol--[retinol-binding protein] + NAD(+) = all-
CC trans-retinal--[retinol-binding protein] + H(+) + NADH;
CC Xref=Rhea:RHEA:48488, Rhea:RHEA-COMP:14428, Rhea:RHEA-COMP:14430,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17336, ChEBI:CHEBI:17898,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:83228;
CC EC=1.1.1.105; Evidence={ECO:0000269|PubMed:10896656,
CC ECO:0000269|PubMed:11360992};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-retinol + NAD(+) = all-trans-retinal + H(+) + NADH;
CC Xref=Rhea:RHEA:21284, ChEBI:CHEBI:15378, ChEBI:CHEBI:17336,
CC ChEBI:CHEBI:17898, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC EC=1.1.1.105; Evidence={ECO:0000269|PubMed:10896656,
CC ECO:0000269|PubMed:11360992};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21285;
CC Evidence={ECO:0000305|PubMed:11360992};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3alpha-hydroxy-5alpha-androstan-17-one + NAD(+) = 5alpha-
CC androstan-3,17-dione + H(+) + NADH; Xref=Rhea:RHEA:20381,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15994, ChEBI:CHEBI:16032,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.209;
CC Evidence={ECO:0000269|PubMed:10896656, ECO:0000269|PubMed:11360992};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20382;
CC Evidence={ECO:0000269|PubMed:11360992};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:20383;
CC Evidence={ECO:0000269|PubMed:11360992};
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:0000250|UniProtKB:Q9R092};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5alpha-androstane-3alpha,17beta-diol + NAD(+) = 17beta-
CC hydroxy-5alpha-androstan-3-one + H(+) + NADH; Xref=Rhea:RHEA:42004,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16330, ChEBI:CHEBI:36713,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.53;
CC Evidence={ECO:0000269|PubMed:11360992};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42006;
CC Evidence={ECO:0000305|PubMed:11360992};
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:Q9R092};
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:Q9R092};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3alpha-hydroxy-5alpha-pregnan-20-one + NAD(+) = 5alpha-
CC pregnane-3,20-dione + H(+) + NADH; Xref=Rhea:RHEA:41980,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:28952, ChEBI:CHEBI:50169,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC Evidence={ECO:0000269|PubMed:10896656, ECO:0000269|PubMed:11360992};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41981;
CC Evidence={ECO:0000305|PubMed:11360992};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5alpha-androstane-3beta,17beta-diol + NAD(+) = 17beta-hydroxy-
CC 5alpha-androstan-3-one + H(+) + NADH; Xref=Rhea:RHEA:42184,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16330, ChEBI:CHEBI:18329,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC Evidence={ECO:0000269|PubMed:11360992};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42186;
CC Evidence={ECO:0000305|PubMed:11360992};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3beta-hydroxy-5alpha-androstan-17-one + NAD(+) = 5alpha-
CC androstan-3,17-dione + H(+) + NADH; Xref=Rhea:RHEA:42188,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15994, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:541975;
CC Evidence={ECO:0000269|PubMed:10896656, ECO:0000269|PubMed:11360992,
CC ECO:0000269|PubMed:11513953};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42190;
CC Evidence={ECO:0000305|PubMed:11360992};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.19 uM for NAD {ECO:0000269|PubMed:10896656,
CC ECO:0000269|PubMed:11360992};
CC KM=0.18 uM for NADH {ECO:0000269|PubMed:10896656,
CC ECO:0000269|PubMed:11360992};
CC KM=54 uM for NADPH {ECO:0000269|PubMed:10896656,
CC ECO:0000269|PubMed:11360992};
CC KM=940 uM for NADP {ECO:0000269|PubMed:10896656,
CC ECO:0000269|PubMed:11360992};
CC KM=3.2 uM for all-trans-retinol {ECO:0000269|PubMed:10896656,
CC ECO:0000269|PubMed:11360992};
CC KM=0.24 uM for allopregnanolone {ECO:0000269|PubMed:10896656,
CC ECO:0000269|PubMed:11360992};
CC KM=0.13 uM for 3-alpha-androstanediol {ECO:0000269|PubMed:10896656,
CC ECO:0000269|PubMed:11360992};
CC KM=0.23 uM for androsterone {ECO:0000269|PubMed:10896656,
CC ECO:0000269|PubMed:11360992};
CC KM=0.13 uM for dehydroepiandrosterone {ECO:0000269|PubMed:10896656,
CC ECO:0000269|PubMed:11360992};
CC Vmax=1.2 nmol/min/mg enzyme with all-trans-retinol
CC {ECO:0000269|PubMed:10896656, ECO:0000269|PubMed:11360992};
CC Vmax=14.7 nmol/min/mg enzyme with allopregnanolone
CC {ECO:0000269|PubMed:10896656, ECO:0000269|PubMed:11360992};
CC Vmax=16.5 nmol/min/mg enzyme with 3-alpha-androstanediol
CC {ECO:0000269|PubMed:10896656, ECO:0000269|PubMed:11360992};
CC Vmax=35 nmol/min/mg enzyme with androsterone
CC {ECO:0000269|PubMed:10896656, ECO:0000269|PubMed:11360992};
CC Vmax=0.90 nmol/min/mg enzyme with dehydroepiandrosterone
CC {ECO:0000269|PubMed:10896656, ECO:0000269|PubMed:11360992};
CC Note=The kinetic parameters were determined using microsomes from
CC transfected cells.;
CC -!- SUBCELLULAR LOCATION: Microsome membrane {ECO:0000269|PubMed:11360992};
CC Peripheral membrane protein {ECO:0000269|PubMed:11360992}; Lumenal side
CC {ECO:0000269|PubMed:11360992}. Early endosome membrane {ECO:0000305};
CC Peripheral membrane protein {ECO:0000305}; Lumenal side {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Detected in liver and prostate (at protein level).
CC Detected in adult liver, lung, brain, placenta, prostate, adrenal
CC gland, testis, mammary gland, spleen, spinal cord and uterus. Detected
CC in caudate nucleus, and at lower levels in amygdala, corpus callosum,
CC hippocampus, substantia nigra and thalamus. Detected in fetal lung,
CC liver and brain. {ECO:0000269|PubMed:10896656,
CC ECO:0000269|PubMed:9188497}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB88252.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; U89281; AAB88252.1; ALT_FRAME; mRNA.
DR EMBL; AF016509; AAB67236.1; -; mRNA.
DR EMBL; AF223225; AAF81017.1; -; mRNA.
DR EMBL; BC020710; AAH20710.1; -; mRNA.
DR CCDS; CCDS8925.1; -.
DR RefSeq; NP_003716.2; NM_003725.3.
DR RefSeq; XP_005269264.1; XM_005269207.1.
DR RefSeq; XP_005269265.1; XM_005269208.1.
DR RefSeq; XP_005269266.1; XM_005269209.1.
DR RefSeq; XP_006719735.1; XM_006719672.1.
DR RefSeq; XP_011537227.1; XM_011538925.1.
DR RefSeq; XP_011537228.1; XM_011538926.1.
DR RefSeq; XP_011537229.1; XM_011538927.1.
DR AlphaFoldDB; O14756; -.
DR SMR; O14756; -.
DR BioGRID; 114183; 45.
DR IntAct; O14756; 12.
DR STRING; 9606.ENSP00000451406; -.
DR DrugCentral; O14756; -.
DR SwissLipids; SLP:000000807; -.
DR GlyGen; O14756; 3 sites.
DR iPTMnet; O14756; -.
DR PhosphoSitePlus; O14756; -.
DR BioMuta; HSD17B6; -.
DR jPOST; O14756; -.
DR MassIVE; O14756; -.
DR PaxDb; O14756; -.
DR PeptideAtlas; O14756; -.
DR PRIDE; O14756; -.
DR ProteomicsDB; 48207; -.
DR Antibodypedia; 16013; 131 antibodies from 29 providers.
DR DNASU; 8630; -.
DR Ensembl; ENST00000322165.1; ENSP00000318631.1; ENSG00000025423.11.
DR Ensembl; ENST00000554150.5; ENSP00000452273.1; ENSG00000025423.11.
DR Ensembl; ENST00000554643.5; ENSP00000451406.1; ENSG00000025423.11.
DR Ensembl; ENST00000555159.5; ENSP00000450698.1; ENSG00000025423.11.
DR Ensembl; ENST00000555805.5; ENSP00000451753.1; ENSG00000025423.11.
DR GeneID; 8630; -.
DR KEGG; hsa:8630; -.
DR MANE-Select; ENST00000322165.1; ENSP00000318631.1; NM_003725.4; NP_003716.2.
DR UCSC; uc001smg.3; human.
DR CTD; 8630; -.
DR DisGeNET; 8630; -.
DR GeneCards; HSD17B6; -.
DR HGNC; HGNC:23316; HSD17B6.
DR HPA; ENSG00000025423; Tissue enriched (liver).
DR MIM; 606623; gene.
DR neXtProt; NX_O14756; -.
DR OpenTargets; ENSG00000025423; -.
DR PharmGKB; PA142671671; -.
DR VEuPathDB; HostDB:ENSG00000025423; -.
DR eggNOG; KOG1610; Eukaryota.
DR GeneTree; ENSGT00940000162028; -.
DR HOGENOM; CLU_010194_2_0_1; -.
DR InParanoid; O14756; -.
DR OMA; FGGVYCS; -.
DR OrthoDB; 1390068at2759; -.
DR PhylomeDB; O14756; -.
DR TreeFam; TF325617; -.
DR BRENDA; 1.1.1.62; 2681.
DR PathwayCommons; O14756; -.
DR Reactome; R-HSA-2453902; The canonical retinoid cycle in rods (twilight vision).
DR SABIO-RK; O14756; -.
DR SignaLink; O14756; -.
DR BioGRID-ORCS; 8630; 8 hits in 1069 CRISPR screens.
DR ChiTaRS; HSD17B6; human.
DR GeneWiki; HSD17B6; -.
DR GenomeRNAi; 8630; -.
DR Pharos; O14756; Tbio.
DR PRO; PR:O14756; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; O14756; protein.
DR Bgee; ENSG00000025423; Expressed in right lobe of liver and 155 other tissues.
DR ExpressionAtlas; O14756; baseline and differential.
DR Genevisible; O14756; HS.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0044594; F:17-beta-hydroxysteroid dehydrogenase (NAD+) activity; IEA:RHEA.
DR GO; GO:0047024; F:5alpha-androstane-3beta,17beta-diol dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0047044; F:androstan-3-alpha,17-beta-diol dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0047023; F:androsterone dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0003824; F:catalytic activity; TAS:ProtInc.
DR GO; GO:0009055; F:electron transfer activity; TAS:UniProtKB.
DR GO; GO:0004745; F:NAD-retinol dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0016229; F:steroid dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0047045; F:testosterone 17-beta-dehydrogenase (NADP+) activity; IEA:Ensembl.
DR GO; GO:0047035; F:testosterone dehydrogenase (NAD+) activity; IEA:UniProtKB-EC.
DR GO; GO:0006702; P:androgen biosynthetic process; NAS:UniProtKB.
DR GO; GO:0006710; P:androgen catabolic process; TAS:UniProtKB.
DR GO; GO:0062175; P:brexanolone catabolic process; IDA:UniProtKB.
DR GO; GO:0042572; P:retinol metabolic process; IBA:GO_Central.
DR GO; GO:0008202; P:steroid metabolic process; IBA:GO_Central.
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 Endoplasmic reticulum; Endosome; Glycoprotein; Lipid metabolism; Membrane;
KW Microsome; NAD; Oxidoreductase; Reference proteome; Signal;
KW Steroid metabolism.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..317
FT /note="17-beta-hydroxysteroid dehydrogenase type 6"
FT /id="PRO_0000303211"
FT ACT_SITE 176
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 33..57
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 164
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT CARBOHYD 161
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 215
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 256
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 63
FT /note="E -> D (in Ref. 1; AAB88252)"
FT /evidence="ECO:0000305"
FT CONFLICT 105
FT /note="G -> R (in Ref. 1; AAB88252)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 317 AA; 35966 MW; 46F1E940605CBEE9 CRC64;
MWLYLAAFVG LYYLLHWYRE RQVVSHLQDK YVFITGCDSG FGNLLARQLD ARGLRVLAAC
LTEKGAEQLR GQTSDRLETV TLDVTKMESI AAATQWVKEH VGDRGLWGLV NNAGILTPIT
LCEWLNTEDS MNMLKVNLIG VIQVTLSMLP LVRRARGRIV NVSSILGRVA FFVGGYCVSK
YGVEAFSDIL RREIQHFGVK ISIVEPGYFR TGMTNMTQSL ERMKQSWKEA PKHIKETYGQ
QYFDALYNIM KEGLLNCSTN LNLVTDCMEH ALTSVHPRTR YSAGWDAKFF FIPLSYLPTS
LADYILTRSW PKPAQAV
