ID   DHB2_MOUSE              Reviewed;         381 AA.
AC   P51658; O08898;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1997, sequence version 2.
DT   24-JAN-2024, entry version 177.
DE   RecName: Full=Estradiol 17-beta-dehydrogenase 2;
DE            EC=1.1.1.62 {ECO:0000250|UniProtKB:P37059};
DE   AltName: Full=17-beta-hydroxysteroid dehydrogenase type 2;
DE            Short=17-beta-HSD 2;
DE   AltName: Full=Testosterone 17-beta-dehydrogenase;
DE            EC=1.1.1.239 {ECO:0000250|UniProtKB:P37059};
GN   Name=Hsd17b2; Synonyms=Edh17b2;
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].
RC   STRAIN=BALB/cJ; TISSUE=Liver;
RX   PubMed=9224647; DOI=10.1042/bj3250199;
RA   Mustonen M.;
RT   "Cloning of mouse 17beta-hydroxysteroid dehydrogenase type 2, and analysing
RT   expression of the mRNAs for types 1, 2, 3, 4 and 5 in mouse embryos and
RT   adult tissues.";
RL   Biochem. J. 325:199-205(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1-358.
RC   STRAIN=BALB/cJ;
RA   Stoffel W., Weiss B.;
RL   Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases.
RN   [3]
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: Catalyzes the NAD-dependent oxidation of highly active
CC       17beta-hydroxysteroids, such as estradiol (E2), testosterone (T), and
CC       dihydrotestosterone (DHT), to their less active forms and thus
CC       regulates the biological potency of these steroids. Oxidizes estradiol
CC       to estrone, testosterone to androstenedione, and dihydrotestosterone to
CC       5alpha-androstan-3,17-dione. Also has 20-alpha-HSD activity.
CC       {ECO:0000250|UniProtKB:P37059}.
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:0000250|UniProtKB:P37059};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24613;
CC         Evidence={ECO:0000250|UniProtKB:P37059};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:24614;
CC         Evidence={ECO:0000250|UniProtKB:P37059};
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:0000250|UniProtKB:P37059};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14930;
CC         Evidence={ECO:0000250|UniProtKB:P37059};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:14931;
CC         Evidence={ECO:0000250|UniProtKB:P37059};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=17beta-hydroxy-5alpha-androstan-3-one + NAD(+) = 5alpha-
CC         androstan-3,17-dione + H(+) + NADH; Xref=Rhea:RHEA:41992,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:15994, ChEBI:CHEBI:16330,
CC         ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC         Evidence={ECO:0000250|UniProtKB:P37059};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(20S)-hydroxypregn-4-en-3-one + NAD(+) = H(+) + NADH +
CC         progesterone; Xref=Rhea:RHEA:42108, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:17026, ChEBI:CHEBI:28453, ChEBI:CHEBI:57540,
CC         ChEBI:CHEBI:57945; Evidence={ECO:0000250|UniProtKB:P37059};
CC   -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P37059}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000250|UniProtKB:P37059}; Single-pass type II membrane protein
CC       {ECO:0000250|UniProtKB:P37059}.
CC   -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC       family. {ECO:0000305}.
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DR   EMBL; Y09517; CAA70706.1; -; mRNA.
DR   EMBL; X95685; CAA64982.1; -; mRNA.
DR   CCDS; CCDS40491.1; -.
DR   RefSeq; NP_032316.2; NM_008290.2.
DR   AlphaFoldDB; P51658; -.
DR   SMR; P51658; -.
DR   STRING; 10090.ENSMUSP00000034304; -.
DR   BindingDB; P51658; -.
DR   ChEMBL; CHEMBL1914270; -.
DR   GuidetoPHARMACOLOGY; 3094; -.
DR   iPTMnet; P51658; -.
DR   PhosphoSitePlus; P51658; -.
DR   SwissPalm; P51658; -.
DR   jPOST; P51658; -.
DR   MaxQB; P51658; -.
DR   PaxDb; 10090-ENSMUSP00000034304; -.
DR   PeptideAtlas; P51658; -.
DR   ProteomicsDB; 279353; -.
DR   Antibodypedia; 16980; 340 antibodies from 32 providers.
DR   DNASU; 15486; -.
DR   Ensembl; ENSMUST00000034304.9; ENSMUSP00000034304.8; ENSMUSG00000031844.9.
DR   GeneID; 15486; -.
DR   KEGG; mmu:15486; -.
DR   UCSC; uc009npf.1; mouse.
DR   AGR; MGI:1096386; -.
DR   CTD; 3294; -.
DR   MGI; MGI:1096386; Hsd17b2.
DR   VEuPathDB; HostDB:ENSMUSG00000031844; -.
DR   eggNOG; KOG1610; Eukaryota.
DR   GeneTree; ENSGT00940000160204; -.
DR   HOGENOM; CLU_010194_2_0_1; -.
DR   InParanoid; P51658; -.
DR   OMA; KKCMAVN; -.
DR   OrthoDB; 5403248at2759; -.
DR   PhylomeDB; P51658; -.
DR   TreeFam; TF325617; -.
DR   BRENDA; 1.1.1.62; 3474.
DR   Reactome; R-MMU-193144; Estrogen biosynthesis.
DR   BioGRID-ORCS; 15486; 7 hits in 80 CRISPR screens.
DR   ChiTaRS; Hsd17b2; mouse.
DR   PRO; PR:P51658; -.
DR   Proteomes; UP000000589; Chromosome 8.
DR   RNAct; P51658; Protein.
DR   Bgee; ENSMUSG00000031844; Expressed in placenta labyrinth and 74 other cell types or tissues.
DR   ExpressionAtlas; P51658; baseline and differential.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR   GO; GO:0004303; F:estradiol 17-beta-dehydrogenase [NAD(P)] activity; ISO:MGI.
DR   GO; GO:0047035; F:testosterone dehydrogenase (NAD+) activity; ISO:MGI.
DR   GO; GO:0006702; P:androgen biosynthetic process; ISO:MGI.
DR   GO; GO:0008209; P:androgen metabolic process; ISS:UniProtKB.
DR   GO; GO:0006703; P:estrogen biosynthetic process; ISS:UniProtKB.
DR   GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR   GO; GO:0001890; P:placenta development; IMP:MGI.
DR   GO; GO:0032526; P:response to retinoic acid; ISO:MGI.
DR   GO; GO:0008202; P:steroid metabolic process; IBA:GO_Central.
DR   CDD; cd09805; type2_17beta_HSD-like_SDR_c; 1.
DR   Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR   InterPro; IPR002347; SDR_fam.
DR   PANTHER; PTHR43313:SF3; 17-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 2; 1.
DR   PANTHER; PTHR43313; SHORT-CHAIN DEHYDROGENASE/REDUCTASE FAMILY 9C; 1.
DR   Pfam; PF00106; adh_short; 1.
DR   PRINTS; PR00081; GDHRDH.
DR   PRINTS; PR00080; SDRFAMILY.
DR   SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
DR   PROSITE; PS00061; ADH_SHORT; 1.
DR   Genevisible; P51658; MM.
PE   1: Evidence at protein level;
KW   Endoplasmic reticulum; Lipid biosynthesis; Lipid metabolism; Membrane; NAD;
KW   Oxidoreductase; Reference proteome; Signal-anchor; Steroid biosynthesis;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..381
FT                   /note="Estradiol 17-beta-dehydrogenase 2"
FT                   /id="PRO_0000054571"
FT   TRANSMEM        4..24
FT                   /note="Helical; Signal-anchor for type II membrane protein"
FT                   /evidence="ECO:0000255"
FT   ACT_SITE        233
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT   BINDING         83..112
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
FT   BINDING         220
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   CONFLICT        36..37
FT                   /note="QA -> RP (in Ref. 2; CAA64982)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   381 AA;  41836 MW;  74A62797947E6086 CRC64;
     MSPFASESAW LCLAAAAVLG GTLLCGCRSG RQLRSQAVCL AGLWGGACLL SLSLLCTLFL
     LSVACFLLLY MSSSDQDLLP VDQKAVLVTG ADSGFGHGLA KHLDKLGFTV FAGVLDKEGP
     GAEELRKHCS ERLSVLQMDV TKPEQIKDAH SKVTEKIQDK GLWAVVNNAG VFHLPIDGEL
     IPMSIYRKCM AVNFFGTVEV TKAFLPLLRK SKGRLVNVSS MGGTVPLQMT SAYAATKAAL
     TMFSTIIRQE LDKWGVKVVT IKPGGFKTNI TGSQDIWDKM EKEILDHFSK DIQENYGQDY
     VHTQKLIIPT LKERSNPDIT PVLRDIQHAI SARNPSSFYY PGRMAYLWVC LAAYCPTSLL
     DYVIKKGFYP QPTPRALRTV H
//