DHB2_MOUSE
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 03-AUG-2022, entry version 169.
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 jPOST; P51658; -.
DR MaxQB; P51658; -.
DR PaxDb; P51658; -.
DR PeptideAtlas; P51658; -.
DR PRIDE; P51658; -.
DR ProteomicsDB; 279353; -.
DR Antibodypedia; 16980; 322 antibodies from 32 providers.
DR DNASU; 15486; -.
DR Ensembl; ENSMUST00000034304; ENSMUSP00000034304; ENSMUSG00000031844.
DR GeneID; 15486; -.
DR KEGG; mmu:15486; -.
DR UCSC; uc009npf.1; mouse.
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; 1313182at2759; -.
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 75 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 73 other tissues.
DR ExpressionAtlas; P51658; baseline and differential.
DR Genevisible; P51658; MM.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0044594; F:17-beta-hydroxysteroid dehydrogenase (NAD+) activity; IEA:RHEA.
DR GO; GO:0004303; F:estradiol 17-beta-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: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 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; 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
