H17B6_RAT
ID H17B6_RAT Reviewed; 317 AA.
AC O54753; Q5M8C8;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-SEP-2007, sequence version 2.
DT 03-AUG-2022, entry version 122.
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:0000250|UniProtKB:O14756};
DE EC=1.1.1.209 {ECO:0000269|PubMed:9188497};
DE EC=1.1.1.239 {ECO:0000269|PubMed:9188497};
DE EC=1.1.1.53 {ECO:0000269|PubMed:9188497};
DE EC=1.1.1.62 {ECO:0000269|PubMed:9188497};
DE AltName: Full=3-alpha->beta-hydroxysteroid epimerase;
DE Short=3-alpha->beta-HSE;
DE AltName: Full=Oxidative 3-alpha hydroxysteroid dehydrogenase;
DE Flags: Precursor;
GN Name=Hsd17b6; Synonyms=Hsd17b9;
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], FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, INDUCTION, AND TISSUE
RP 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 [LARGE SCALE MRNA].
RC TISSUE=Liver;
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: NAD-dependent oxidoreductase with broad substrate specificity
CC that shows both oxidative and reductive activity (in vitro). Has
CC retinol dehydrogenase activity towards all-trans-retinol (in vitro) (By
CC similarity). Has 17-beta-hydroxysteroid dehydrogenase activity towards
CC various steroids (in vitro). Converts 5-alpha-androstan-3-alpha,17-
CC beta-diol to androsterone and estradiol to estrone (in vitro). Has 3-
CC alpha-hydroxysteroid dehydrogenase activity towards androsterone (in
CC vitro). {ECO:0000250|UniProtKB:O14756, ECO:0000269|PubMed:9188497}.
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:0000250|UniProtKB:O14756};
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:0000250|UniProtKB:O14756};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21285;
CC Evidence={ECO:0000250|UniProtKB:O14756};
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:9188497};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20382;
CC Evidence={ECO:0000305|PubMed:9188497};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:20383;
CC Evidence={ECO:0000305|PubMed:9188497};
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:9188497};
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:9188497};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42006;
CC Evidence={ECO:0000305|PubMed:9188497};
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:9188497};
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:9188497};
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:0000250|UniProtKB:O14756};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41981;
CC Evidence={ECO:0000250|UniProtKB:O14756};
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:0000250|UniProtKB:O14756};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42186;
CC Evidence={ECO:0000250|UniProtKB:O14756};
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:0000250|UniProtKB:O14756};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42190;
CC Evidence={ECO:0000250|UniProtKB:O14756};
CC -!- ACTIVITY REGULATION: Competitively inhibited by 9-cis-retinoic acid and
CC 13-cis-retinoic acid. {ECO:0000269|PubMed:9188497}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.1 uM for 5-alpha-androstan-3-alpha,17-beta-diol
CC {ECO:0000269|PubMed:9188497};
CC KM=0.2 uM for androsterone {ECO:0000269|PubMed:9188497};
CC KM=0.5 uM for dihydrotestosterone {ECO:0000269|PubMed:9188497};
CC KM=1.1 uM for testosterone {ECO:0000269|PubMed:9188497};
CC KM=0.8 uM for estradiol {ECO:0000269|PubMed:9188497};
CC KM=3 uM for NAD {ECO:0000269|PubMed:9188497};
CC KM=1 mM for NADP {ECO:0000269|PubMed:9188497};
CC Vmax=2.5 nmol/min/mg enzyme for 5-alpha-androstan-3-alpha,17-beta-
CC diol {ECO:0000269|PubMed:9188497};
CC Vmax=0.1 nmol/min/mg enzyme for androsterone
CC {ECO:0000269|PubMed:9188497};
CC Vmax=0.5 nmol/min/mg enzyme for dihydrotestosterone
CC {ECO:0000269|PubMed:9188497};
CC Vmax=1.1 nmol/min/mg enzyme for testosterone
CC {ECO:0000269|PubMed:9188497};
CC Vmax=2.1 nmol/min/mg enzyme for estradiol
CC {ECO:0000269|PubMed:9188497};
CC Note=Vmax was measured using transfected cell lysates.;
CC -!- SUBCELLULAR LOCATION: Microsome membrane
CC {ECO:0000250|UniProtKB:O14756}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:O14756}; Lumenal side
CC {ECO:0000250|UniProtKB:O14756}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:O14756}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:O14756}; Lumenal side
CC {ECO:0000250|UniProtKB:O14756}.
CC -!- TISSUE SPECIFICITY: Detected in prostate, liver and kidney.
CC {ECO:0000269|PubMed:9188497}.
CC -!- INDUCTION: Up-regulated by testosterone. Levels are very low in
CC castrated male rats. {ECO:0000269|PubMed:9188497}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB88253.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAH88104.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAH91114.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; U89280; AAB88253.1; ALT_INIT; mRNA.
DR EMBL; BC088104; AAH88104.1; ALT_INIT; mRNA.
DR EMBL; BC091114; AAH91114.1; ALT_INIT; mRNA.
DR RefSeq; NP_775427.1; NM_173305.1.
DR AlphaFoldDB; O54753; -.
DR SMR; O54753; -.
DR STRING; 10116.ENSRNOP00000003498; -.
DR GlyGen; O54753; 1 site.
DR PaxDb; O54753; -.
DR PeptideAtlas; O54753; -.
DR GeneID; 286964; -.
DR KEGG; rno:286964; -.
DR UCSC; RGD:708343; rat.
DR CTD; 8630; -.
DR RGD; 708343; Hsd17b6.
DR eggNOG; KOG1610; Eukaryota.
DR InParanoid; O54753; -.
DR OrthoDB; 1390068at2759; -.
DR PhylomeDB; O54753; -.
DR Reactome; R-RNO-2453902; The canonical retinoid cycle in rods (twilight vision).
DR PRO; PR:O54753; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
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; ISS: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:0004303; F:estradiol 17-beta-dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0004745; F:NAD-retinol dehydrogenase activity; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0047035; F:testosterone dehydrogenase (NAD+) activity; IDA:UniProtKB.
DR GO; GO:0008209; P:androgen metabolic process; TAS:RGD.
DR GO; GO:0062175; P:brexanolone catabolic process; ISS: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; Glycoprotein; Lipid metabolism; Membrane; Microsome;
KW NAD; Oxidoreductase; Reference proteome; Signal; 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_0000303213"
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 CONFLICT 219
FT /note="I -> S (in Ref. 1; AAB88253)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 317 AA; 36145 MW; 4AB3F3160C6675A9 CRC64;
MWFYLVTLVG LYYLLRWYRE RQVVSHLHDK YVFITGCDSG FGNLLARQLD RRGMRVLAAC
LTEKGAEELK SKTSDRLETV ILDVTNTDSI SAATQWVKEH VGDKGLWGLV NNAGVFQAFA
YIEWCRPEDC MSIFQVNLIG LAQVTLSMLF LVKKARGRIV NVSSVLGRVA LFGGFYSCSK
YGVEAFSDVL RREIRDFGVK VSIIEPGSFK TRMTDAELII EKTKKTWEAT PEHIRESYGQ
QFFDDFCNTT RRELKKCSTN LSLVTDCMEH ALTSKYPRTR YSAGWDARLF FIPLSYLPTS
LVDCLLAISR RKPAQAV
