H17B6_MOUSE
ID H17B6_MOUSE Reviewed; 317 AA.
AC Q9R092;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 167.
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:10537158};
DE EC=1.1.1.209 {ECO:0000269|PubMed:10537158};
DE EC=1.1.1.239 {ECO:0000269|PubMed:10537158};
DE EC=1.1.1.53 {ECO:0000269|PubMed:10537158};
DE EC=1.1.1.62 {ECO:0000269|PubMed:10537158};
DE AltName: Full=17-beta-HSD9;
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=Gm182, Hsd17b9, Rdh8;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY
RP REGULATION.
RC TISSUE=Liver;
RX PubMed=10537158; DOI=10.1210/endo.140.11.7137;
RA Su J., Lin M., Napoli J.L.;
RT "Complementary deoxyribonucleic acid cloning and enzymatic characterization
RT of a novel 17beta/3alpha-hydroxysteroid/retinoid short chain
RT dehydrogenase/reductase.";
RL Endocrinology 140:5275-5284(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Small intestine;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; 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).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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).
CC {ECO:0000269|PubMed:10537158}.
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:10537158};
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:10537158};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21285;
CC Evidence={ECO:0000305|PubMed:10537158};
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:10537158};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20382;
CC Evidence={ECO:0000269|PubMed:10537158};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:20383;
CC Evidence={ECO:0000269|PubMed:10537158};
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:10537158};
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:10537158};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42006;
CC Evidence={ECO:0000305|PubMed:10537158};
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:10537158};
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:10537158};
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: Inhibited by carbenoxolone and phenyl arsenoxide.
CC {ECO:0000269|PubMed:10537158}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.4 uM for 5-alpha-androstan-3-alpha,17-beta-diol
CC {ECO:0000269|PubMed:10537158};
CC KM=1.3 uM for androsterone {ECO:0000269|PubMed:10537158};
CC KM=3.2 uM for all-trans-retinol {ECO:0000269|PubMed:10537158};
CC KM=1.5 uM for estradiol {ECO:0000269|PubMed:10537158};
CC Vmax=2.8 nmol/min/mg enzyme for 5-alpha-androstan-3-alpha,17-beta-
CC diol {ECO:0000269|PubMed:10537158};
CC Vmax=1.1 nmol/min/mg enzyme for androsterone
CC {ECO:0000269|PubMed:10537158};
CC Vmax=0.4 nmol/min/mg enzyme for all-trans-retinol
CC {ECO:0000269|PubMed:10537158};
CC Vmax=2.3 nmol/min/mg enzyme for estradiol
CC {ECO:0000269|PubMed:10537158};
CC pH dependence:
CC Optimum pH is 8.5-9.5. {ECO:0000269|PubMed:10537158};
CC -!- SUBCELLULAR LOCATION: Microsome membrane {ECO:0000269|PubMed:10537158};
CC Peripheral membrane protein {ECO:0000269|PubMed:10537158}; Lumenal side
CC {ECO:0000269|PubMed:10537158}. Early endosome membrane {ECO:0000305};
CC Peripheral membrane protein {ECO:0000305}; Lumenal side {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Detected in liver. {ECO:0000269|PubMed:10537158}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; AF103797; AAF04761.1; -; mRNA.
DR EMBL; AK008212; BAB25536.1; -; mRNA.
DR EMBL; BC021836; AAH21836.1; -; mRNA.
DR CCDS; CCDS24257.1; -.
DR RefSeq; NP_038814.1; NM_013786.2.
DR RefSeq; XP_011241765.1; XM_011243463.2.
DR RefSeq; XP_011241766.1; XM_011243464.2.
DR RefSeq; XP_011241767.1; XM_011243465.2.
DR RefSeq; XP_011241769.1; XM_011243467.2.
DR AlphaFoldDB; Q9R092; -.
DR SMR; Q9R092; -.
DR STRING; 10090.ENSMUSP00000026462; -.
DR GlyGen; Q9R092; 2 sites.
DR iPTMnet; Q9R092; -.
DR PhosphoSitePlus; Q9R092; -.
DR SwissPalm; Q9R092; -.
DR jPOST; Q9R092; -.
DR MaxQB; Q9R092; -.
DR PaxDb; Q9R092; -.
DR PeptideAtlas; Q9R092; -.
DR PRIDE; Q9R092; -.
DR ProteomicsDB; 270873; -.
DR Antibodypedia; 16013; 131 antibodies from 29 providers.
DR DNASU; 27400; -.
DR Ensembl; ENSMUST00000026462; ENSMUSP00000026462; ENSMUSG00000025396.
DR Ensembl; ENSMUST00000219183; ENSMUSP00000151661; ENSMUSG00000025396.
DR Ensembl; ENSMUST00000219447; ENSMUSP00000151556; ENSMUSG00000025396.
DR GeneID; 27400; -.
DR KEGG; mmu:27400; -.
DR UCSC; uc007hky.1; mouse.
DR CTD; 8630; -.
DR MGI; MGI:1351670; Hsd17b6.
DR VEuPathDB; HostDB:ENSMUSG00000025396; -.
DR eggNOG; KOG1610; Eukaryota.
DR GeneTree; ENSGT00940000162028; -.
DR HOGENOM; CLU_010194_2_0_1; -.
DR InParanoid; Q9R092; -.
DR OMA; FGGVYCS; -.
DR OrthoDB; 1390068at2759; -.
DR PhylomeDB; Q9R092; -.
DR TreeFam; TF325617; -.
DR Reactome; R-MMU-2453902; The canonical retinoid cycle in rods (twilight vision).
DR BioGRID-ORCS; 27400; 0 hits in 74 CRISPR screens.
DR ChiTaRS; Hsd17b6; mouse.
DR PRO; PR:Q9R092; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q9R092; protein.
DR Bgee; ENSMUSG00000025396; Expressed in left lobe of liver and 30 other tissues.
DR ExpressionAtlas; Q9R092; baseline and differential.
DR Genevisible; Q9R092; MM.
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:0004303; F:estradiol 17-beta-dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0004745; F:NAD-retinol dehydrogenase activity; ISO:MGI.
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; IDA:UniProtKB.
DR GO; GO:0047035; F:testosterone dehydrogenase (NAD+) activity; IDA:UniProtKB.
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; 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_0000303212"
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 71
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 161
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 317 AA; 36103 MW; 7B09D741424D3881 CRC64;
MWFYLVTLVG LYHLLRWYRE RQVVSHLQDK YVFITGCDSG FGNLLARQLD RRGMRVLAAC
LTEKGAEELR NKTSDRLETV ILDVTKTESI VAATQWVKER VGDRGLWGLV NNAGVLQPFA
YIEWYRPEDY MPIFQVNLIG LTQVTISMLF LVKKARGRIV NVSSALGRVA LFGGFYSCSK
YGVEAFSDVL RHEVQDFGVK VSIIEPGSFK TEMTDAELTI ERTKKVWEAA PEHIKESYGQ
QFFDDFCSTT KRELMKCSRN LSLVTDCMEH ALTSTHPRTR YSAGWDAKFF FIPLSYLPAS
LVDYLLAISR GKPAQAA
