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   13-FEB-2019, entry version 165.
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;
DE            EC=1.1.1.239;
DE            EC=1.1.1.62;
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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
RT   3alpha-hydroxysteroid dehydrogenases from rat and human prostate.";
RL   J. Biol. Chem. 272:15959-15966(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES,
RP   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)-
RT   hydroxysteroid 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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND 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.
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-
RT   ketosteroid reductase activity of the human 3(alpha-->beta)-
RT   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.,
RA   Wang L., Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT   liver phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
CC   -!- FUNCTION: NAD-dependent oxidoreductase with broad substrate
CC       specificity that shows both oxidative and reductive activity (in
CC       vitro). Has 17-beta-hydroxysteroid dehydrogenase activity towards
CC       various steroids (in vitro). Converts 5-alpha-androstan-3-
CC       alpha,17-beta-diol to androsterone and estradiol to estrone (in
CC       vitro). Has 3-alpha-hydroxysteroid dehydrogenase activity towards
CC       androsterone (in vitro). Has retinol dehydrogenase activity
CC       towards all-trans-retinol (in vitro). Can convert androsterone to
CC       epi-androsterone. Androsterone is first oxidized to 5-alpha-
CC       androstane-3,17-dione and then reduced to epi-andosterone. Can act
CC       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=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;
CC         EC=1.1.1.62;
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;
CC         EC=1.1.1.62;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=NAD(+) + testosterone = androst-4-ene-3,17-dione + H(+) +
CC         NADH; Xref=Rhea:RHEA:14929, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:16422, ChEBI:CHEBI:17347, ChEBI:CHEBI:57540,
CC         ChEBI:CHEBI:57945; EC=1.1.1.239;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=all-trans-retinol--[retinol-binding protein] + NAD(+) =
CC         all-trans-retinal--[retinol-binding protein] + H(+) + NADH;
CC         Xref=Rhea:RHEA:48488, Rhea:RHEA-COMP:14428, Rhea:RHEA-
CC         COMP:14430, ChEBI:CHEBI:15378, ChEBI:CHEBI:17336,
CC         ChEBI:CHEBI:17898, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC         ChEBI:CHEBI:83228; EC=1.1.1.105;
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
CC         {ECO:0000269|PubMed:10896656, 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
CC         {ECO:0000269|PubMed:10896656, 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
CC         from transfected cells.;
CC   -!- SUBCELLULAR LOCATION: Microsome membrane
CC       {ECO:0000269|PubMed:11360992}; Peripheral membrane protein
CC       {ECO:0000269|PubMed:11360992}; Lumenal side
CC       {ECO:0000269|PubMed:11360992}. Early endosome membrane
CC       {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Lumenal
CC       side {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Detected in liver and prostate (at protein
CC       level). Detected in adult liver, lung, brain, placenta, prostate,
CC       adrenal gland, testis, mammary gland, spleen, spinal cord and
CC       uterus. Detected in caudate nucleus, and at lower levels in
CC       amygdala, corpus callosum, hippocampus, substantia nigra and
CC       thalamus. Detected in fetal lung, liver and brain.
CC       {ECO:0000269|PubMed:10896656, ECO:0000269|PubMed:9188497}.
CC   -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases
CC       (SDR) family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAB88252.1; Type=Frameshift; Positions=158, 174; 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   UniGene; Hs.524513; -.
DR   ProteinModelPortal; O14756; -.
DR   BioGrid; 114183; 13.
DR   STRING; 9606.ENSP00000318631; -.
DR   DrugBank; DB00139; Succinic acid.
DR   SwissLipids; SLP:000000807; -.
DR   iPTMnet; O14756; -.
DR   PhosphoSitePlus; O14756; -.
DR   BioMuta; HSD17B6; -.
DR   jPOST; O14756; -.
DR   PaxDb; O14756; -.
DR   PeptideAtlas; O14756; -.
DR   PRIDE; O14756; -.
DR   ProteomicsDB; 48207; -.
DR   DNASU; 8630; -.
DR   Ensembl; ENST00000322165; ENSP00000318631; ENSG00000025423.
DR   Ensembl; ENST00000554150; ENSP00000452273; ENSG00000025423.
DR   Ensembl; ENST00000554643; ENSP00000451406; ENSG00000025423.
DR   Ensembl; ENST00000555159; ENSP00000450698; ENSG00000025423.
DR   Ensembl; ENST00000555805; ENSP00000451753; ENSG00000025423.
DR   GeneID; 8630; -.
DR   KEGG; hsa:8630; -.
DR   UCSC; uc001smg.3; human.
DR   CTD; 8630; -.
DR   DisGeNET; 8630; -.
DR   EuPathDB; HostDB:ENSG00000025423.11; -.
DR   GeneCards; HSD17B6; -.
DR   HGNC; HGNC:23316; HSD17B6.
DR   HPA; HPA059141; -.
DR   MIM; 606623; gene.
DR   neXtProt; NX_O14756; -.
DR   OpenTargets; ENSG00000025423; -.
DR   PharmGKB; PA142671671; -.
DR   eggNOG; KOG1610; Eukaryota.
DR   eggNOG; ENOG410Y7FK; LUCA.
DR   GeneTree; ENSGT00940000162028; -.
DR   HOVERGEN; HBG005482; -.
DR   InParanoid; O14756; -.
DR   KO; K13369; -.
DR   OMA; DVTKMES; -.
DR   OrthoDB; 1390068at2759; -.
DR   PhylomeDB; O14756; -.
DR   TreeFam; TF325617; -.
DR   BRENDA; 1.1.1.62; 2681.
DR   Reactome; R-HSA-2453902; The canonical retinoid cycle in rods (twilight vision).
DR   SABIO-RK; O14756; -.
DR   ChiTaRS; HSD17B6; human.
DR   GeneWiki; HSD17B6; -.
DR   GenomeRNAi; 8630; -.
DR   PRO; PR:O14756; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   Bgee; ENSG00000025423; Expressed in 164 organ(s), highest expression level in liver.
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:0005622; C:intracellular; NAS:UniProtKB.
DR   GO; GO:0003824; F:catalytic activity; TAS:ProtInc.
DR   GO; GO:0009055; F:electron transfer activity; TAS:UniProtKB.
DR   GO; GO:0004303; F:estradiol 17-beta-dehydrogenase activity; IEA:UniProtKB-EC.
DR   GO; GO:0016491; F:oxidoreductase activity; NAS:UniProtKB.
DR   GO; GO:0004745; F:retinol dehydrogenase activity; IEA:UniProtKB-EC.
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   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   Complete proteome; Endoplasmic reticulum; Endosome; Glycoprotein;
KW   Lipid metabolism; Membrane; Microsome; NAD; Oxidoreductase;
KW   Reference proteome; Signal; Steroid metabolism.
FT   SIGNAL        1     17       {ECO:0000255}.
FT   CHAIN        18    317       17-beta-hydroxysteroid dehydrogenase type
FT                                6.
FT                                /FTId=PRO_0000303211.
FT   NP_BIND      33     57       NAD. {ECO:0000250}.
FT   ACT_SITE    176    176       Proton acceptor. {ECO:0000255|PROSITE-
FT                                ProRule:PRU10001}.
FT   BINDING     164    164       Substrate. {ECO:0000255}.
FT   CARBOHYD    161    161       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    215    215       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    256    256       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CONFLICT     63     63       E -> D (in Ref. 1; AAB88252).
FT                                {ECO:0000305}.
FT   CONFLICT    105    105       G -> R (in Ref. 1; AAB88252).
FT                                {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
//