ID   DHB8_MOUSE              Reviewed;         260 AA.
AC   P50171; Q60958; Q60959; Q9Z1W2;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   16-DEC-2008, entry version 76.
DE   RecName: Full=Estradiol 17-beta-dehydrogenase 8;
DE            EC=1.1.1.62;
DE   AltName: Full=Testosterone 17-beta-dehydrogenase 8;
DE            EC=1.1.1.63;
DE   AltName: Full=17-beta-hydroxysteroid dehydrogenase 8;
DE            Short=17-beta-HSD 8;
DE   AltName: Full=Protein Ke6;
DE            Short=Ke-6;
GN   Name=Hsd17b8; Synonyms=H2-Ke6, Hke6;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC   Muroidea; Muridae; Murinae; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=DBA/2J; TISSUE=Kidney;
RX   MEDLINE=93180832; PubMed=8441417;
RA   Aziz N., Maxwell M.M., St Jacques B., Brenner B.M.;
RT   "Downregulation of Ke 6, a novel gene encoded within the major
RT   histocompatibility complex, in murine polycystic kidney disease.";
RL   Mol. Cell. Biol. 13:1847-1853(1993).
RN   [2]
RP   ERRATUM.
RA   Aziz N., Maxwell M.M., St Jacques B., Brenner B.M.;
RL   Mol. Cell. Biol. 13:6614-6614(1993).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=C57BL/6;
RX   MEDLINE=96027630; PubMed=7559658; DOI=10.1074/jbc.270.42.25213;
RA   Maxwell M.M., Nearing J., Aziz N.;
RT   "Ke 6 gene. Sequence and organization and aberrant regulation in
RT   murine polycystic kidney disease.";
RL   J. Biol. Chem. 270:25213-25219(1995).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=129/SvJ;
RA   Rowen L., Qin S., Madan A., Loretz C., James R., Dors M., Mix L.,
RA   Hall J., Lasky S., Hood L.;
RT   "Sequence of the mouse major histocomaptibility locus class II
RT   region.";
RL   Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=9712896; DOI=10.1074/jbc.273.35.22664;
RA   Fomitcheva J., Baker M.E., Anderson E., Lee G.Y., Aziz N.;
RT   "Characterization of Ke 6, a new 17beta-hydroxysteroid dehydrogenase,
RT   and its expression in gonadal tissues.";
RL   J. Biol. Chem. 273:22664-22671(1998).
RN   [6]
RP   SUBCELLULAR LOCATION.
RX   PubMed=15923359; DOI=10.1369/jhc.5A6692.2005;
RA   Pelletier G., Luu-The V., Li S., Labrie F.;
RT   "Localization of type 8 17beta-hydroxysteroid dehydrogenase mRNA in
RT   mouse tissues as studied by in situ hybridization.";
RL   J. Histochem. Cytochem. 53:1257-1271(2005).
RN   [7]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-67, AND MASS SPECTROMETRY.
RC   TISSUE=Liver;
RX   PubMed=16916647; DOI=10.1016/j.molcel.2006.06.026;
RA   Kim S.C., Sprung R., Chen Y., Xu Y., Ball H., Pei J., Cheng T.,
RA   Kho Y., Xiao H., Xiao L., Grishin N.V., White M., Yang X.-J., Zhao Y.;
RT   "Substrate and functional diversity of lysine acetylation revealed by
RT   a proteomics survey.";
RL   Mol. Cell 23:607-618(2006).
CC   -!- FUNCTION: Uses estradiol as its preferred substrate.
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   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.110 uM for estradiol;
CC         KM=0.422 uM for testosterone;
CC         KM=0.368 uM for estrone;
CC         KM=0.360 uM for dihydrotestosterone;
CC         Vmax=0.405 nmol/min/mg enzyme for estradiol as substrate;
CC         Vmax=0.123 nmol/min/mg enzyme for testosterone as substrate;
CC         Vmax=0.186 nmol/min/mg enzyme for estrone as substrate;
CC         Vmax=0.081 nmol/min/mg enzyme for dihydrotestosterone as
CC         substrate;
CC   -!- PATHWAY: Steroid biosynthesis; estrogen biosynthesis.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=Short;
CC         IsoId=P50171-1; Sequence=Displayed;
CC       Name=Long;
CC         IsoId=P50171-2; Sequence=VSP_006030;
CC   -!- TISSUE SPECIFICITY: Kidney, liver, testis, ovary, oviduct, uterus,
CC       mammary gland, vagina, prostate, clitoral gland and moderately in
CC       spleen, heart, dorsal skin, brain and lung.
CC   -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases
CC       (SDR) family.
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DR   EMBL; U34072; AAC53573.1; -; Genomic_DNA.
DR   EMBL; U34072; AAC53574.1; -; Genomic_DNA.
DR   EMBL; AF100956; AAC69902.1; -; Genomic_DNA.
DR   PIR; A48154; A48154.
DR   UniGene; Mm.275452; -.
DR   HSSP; P97852; 1GZ6.
DR   PhosphoSite; P50171; -.
DR   REPRODUCTION-2DPAGE; P50171; -.
DR   PRIDE; P50171; -.
DR   Ensembl; ENSMUSG00000073422; Mus musculus.
DR   MGI; MGI:95911; H2-Ke6.
DR   HOGENOM; P50171; -.
DR   HOVERGEN; P50171; -.
DR   CleanEx; MM_H2-KE6; -.
DR   GermOnline; ENSMUSG00000073422; Mus musculus.
DR   GO; GO:0005624; C:membrane fraction; IDA:MGI.
DR   GO; GO:0005740; C:mitochondrial envelope; IDA:MGI.
DR   GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR   GO; GO:0005488; F:binding; IEA:InterPro.
DR   GO; GO:0004303; F:estradiol 17-beta-dehydrogenase activity; IDA:MGI.
DR   GO; GO:0050327; F:testosterone 17-beta-dehydrogenase activity; IDA:MGI.
DR   GO; GO:0008209; P:androgen metabolic process; IDA:MGI.
DR   GO; GO:0008210; P:estrogen metabolic process; IDA:MGI.
DR   GO; GO:0055114; P:oxidation reduction; IEA:UniProtKB-KW.
DR   GO; GO:0006694; P:steroid biosynthetic process; IEA:UniProtKB-KW.
DR   InterPro; IPR002198; DHase_sc/Rdtase_SDR.
DR   InterPro; IPR002347; Glc/ribitol_DHase.
DR   InterPro; IPR016040; NAD(P)-bd.
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   Acetylation; Alternative splicing; Lipid synthesis; NAD;
KW   Oxidoreductase; Steroid biosynthesis.
FT   CHAIN         1    260       Estradiol 17-beta-dehydrogenase 8.
FT                                /FTId=PRO_0000054599.
FT   NP_BIND      13     38       NAD (By similarity).
FT   ACT_SITE    168    168       Proton acceptor (By similarity).
FT   BINDING     155    155       Substrate (By similarity).
FT   MOD_RES      67     67       N6-acetyllysine.
FT   VAR_SEQ     257    260       GLFM -> MRPSWGGGQENRTQVVMRK (in isoform
FT                                Long).
FT                                /FTId=VSP_006030.
FT   CONFLICT     16     16       G -> GSGVPSQ (in Ref. 3; AAC69902).
FT   CONFLICT     17     17       Missing (in Ref. 1; AAC53573/AAC53574).
FT   CONFLICT    230    230       E -> EG (in Ref. 1; AAC53573/AAC53574).
SQ   SEQUENCE   260 AA;  26645 MW;  19C712FCDD168B08 CRC64;
     MASQLRLRSA LALVTGGAGS GIGRAISVRL AAEGAAVAAC DLDGAAAQDT VRLLGSPGSE
     DGAPRGKHAA FQADVSQGPA ARRLLEEVQA CFSRPPSVVV SCAGITRDEF LLHMSEEDWD
     RVIAVNLKGT FLVTQAAAQA LVSSGGRGSI INISSIIGKV GNIGQTNYAS SKAGVIGLTQ
     TAARELGRHG IRCNSVLPGF IATPMTQKMP EKVKDKVTAM IPLGHMGDPE DVADVVAFLA
     SEDSGYITGA SVEVSGGLFM
//