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 16-JUN-2009, entry version 55. DE RecName: Full=Hydroxysteroid 17-beta dehydrogenase 6; DE EC=1.1.1.62; DE EC=1.1.1.63; DE EC=1.1.1.105; DE AltName: Full=17-beta-HSD6; DE AltName: Full=Oxidative 3-alpha hydroxysteroid dehydrogenase; DE AltName: Full=3-alpha->beta-hydroxysteroid epimerase; DE Short=3-alpha->beta-HSE; DE Flags: Precursor; GN Name=Hsd17b6; Synonyms=Hsd17b9; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, RP ENZYME REGULATION, INDUCTION, AND TISSUE SPECIFICITY. RC TISSUE=Prostate; RX MEDLINE=97332686; 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 [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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). CC -!- FUNCTION: NAD-dependent oxidoreductase with broad substrate CC specificity that shows both oxidative and reductive activity (in CC vitro). Has retinol dehydrogenase activity towards all-trans- CC retinol (in vitro) (By similarity). Has 17-beta-hydroxysteroid CC dehydrogenase activity towards various steroids (in vitro). CC 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). CC -!- CATALYTIC ACTIVITY: Estradiol-17-beta + NAD(P)(+) = estrone + CC NAD(P)H. CC -!- CATALYTIC ACTIVITY: Testosterone + NAD(+) = androst-4-ene-3,17- CC dione + NADH. CC -!- CATALYTIC ACTIVITY: Retinol + NAD(+) = retinal + NADH. CC -!- ENZYME REGULATION: Competitively inhibited by 9-cis-retinoic ancid CC and 13-cis-retinoic acid. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.1 uM for 5-alpha-androstan-3-alpha,17-beta-diol; CC KM=0.2 uM for androsterone; CC KM=0.5 uM for dihydrotestosterone; CC KM=1.1 uM for testosterone; CC KM=0.8 uM for estradiol; CC KM=3 uM for NAD; CC KM=1 mM for NADP; CC Vmax=2.5 nmol/min/mg enzyme for 5-alpha-androstan-3-alpha,17- CC beta-diol; CC Vmax=0.1 nmol/min/mg enzyme for androsterone; CC Vmax=0.5 nmol/min/mg enzyme for dihydrotestosterone; CC Vmax=1.1 nmol/min/mg enzyme for testosterone; CC Vmax=2.1 nmol/min/mg enzyme for estradiol; CC Note=Vmax was measured using transfected cell lysates; CC -!- SUBCELLULAR LOCATION: Microsome membrane; Peripheral membrane CC protein; Lumenal side (By similarity). Endoplasmic reticulum CC membrane; Peripheral membrane protein; Lumenal side (By CC similarity). CC -!- TISSUE SPECIFICITY: Detected in prostate, liver and kidney. CC -!- INDUCTION: Up-regulated by testosterone. Levels are very low in CC castrated male rats. CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases CC (SDR) family. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- 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 IPI; IPI00197982; -. DR RefSeq; NP_775427.1; -. DR UniGene; Rn.10857; -. DR HSSP; P14061; 1FDS. DR PRIDE; O54753; -. DR Ensembl; ENSRNOG00000007758; Rattus norvegicus. DR GeneID; 286964; -. DR KEGG; rno:286964; -. DR RGD; 708343; Hsd17b6. DR HOVERGEN; O54753; -. DR BRENDA; 1.1.1.105; 248. DR BRENDA; 1.1.1.62; 248. DR BRENDA; 1.1.1.63; 248. DR NextBio; 625175; -. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005792; C:microsome; IEA:UniProtKB-SubCell. DR GO; GO:0047035; F:3-alpha(17-beta)-hydroxysteroid dehydrogena...; TAS:RGD. DR GO; GO:0005488; F:binding; IEA:InterPro. DR GO; GO:0004303; F:estradiol 17-beta-dehydrogenase activity; IEA:EC. DR GO; GO:0004745; F:retinol dehydrogenase activity; IEA:EC. DR GO; GO:0050327; F:testosterone 17-beta-dehydrogenase activity; IEA:EC. DR GO; GO:0008209; P:androgen metabolic process; TAS:RGD. DR GO; GO:0055114; P:oxidation reduction; IEA:UniProtKB-KW. DR InterPro; IPR002198; DH_sc/Rdtase_SDR. DR InterPro; IPR002347; Glc/ribitol_DH. DR InterPro; IPR016040; NAD(P)-bd_dom. DR Gene3D; G3DSA:3.40.50.720; NAD(P)-bd; 1. DR PANTHER; PTHR19410; ADH_short_C2; 1. DR Pfam; PF00106; adh_short; 1. DR PRINTS; PR00081; GDHRDH. DR PRINTS; PR00080; SDRFAMILY. DR PROSITE; PS00061; ADH_SHORT; 1. PE 1: Evidence at protein level; KW Endoplasmic reticulum; Glycoprotein; Lipid metabolism; Membrane; KW Microsome; NAD; Oxidoreductase; Signal; Steroid metabolism. FT SIGNAL 1 17 Potential. FT CHAIN 18 317 Hydroxysteroid 17-beta dehydrogenase 6. FT /FTId=PRO_0000303213. FT NP_BIND 33 57 NAD (By similarity). FT ACT_SITE 176 176 Proton acceptor (By similarity). FT BINDING 164 164 Substrate (Potential). FT CARBOHYD 161 161 N-linked (GlcNAc...) (Potential). FT CONFLICT 219 219 I -> S (in Ref. 1; AAB88253). 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 //