DHB2_RAT
ID DHB2_RAT Reviewed; 381 AA.
AC Q62730;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Estradiol 17-beta-dehydrogenase 2;
DE EC=1.1.1.62 {ECO:0000269|PubMed:8612487};
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:0000269|PubMed:8612487};
GN Name=Hsd17b2; Synonyms=Edh17b2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, CATALYTIC ACTIVITY, AND
RP FUNCTION.
RC STRAIN=Sprague-Dawley; TISSUE=Placenta;
RX PubMed=8612487; DOI=10.1210/endo.137.5.8612487;
RA Akinola L.A., Poutanen M., Vihko R.;
RT "Cloning of rat 17 beta-hydroxysteroid dehydrogenase type 2 and
RT characterization of tissue distribution and catalytic activity of rat type
RT 1 and type 2 enzymes.";
RL Endocrinology 137:1572-1579(1996).
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 (PubMed:8612487). Also has 20-alpha-HSD
CC activity (By similarity). {ECO:0000250|UniProtKB:P37059,
CC ECO:0000269|PubMed:8612487}.
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:8612487};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24613;
CC Evidence={ECO:0000305|PubMed:8612487};
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:8612487};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14930;
CC Evidence={ECO:0000305|PubMed:8612487};
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 -!- TISSUE SPECIFICITY: Highly expressed in the placenta, and in the small
CC intestine, and liver. {ECO:0000269|PubMed:8612487}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; X91234; CAA62617.1; -; mRNA.
DR RefSeq; NP_077367.1; NM_024391.1.
DR AlphaFoldDB; Q62730; -.
DR SMR; Q62730; -.
DR STRING; 10116.ENSRNOP00000018795; -.
DR BindingDB; Q62730; -.
DR ChEMBL; CHEMBL1914268; -.
DR PaxDb; Q62730; -.
DR PRIDE; Q62730; -.
DR GeneID; 79243; -.
DR KEGG; rno:79243; -.
DR UCSC; RGD:621803; rat.
DR CTD; 3294; -.
DR RGD; 621803; Hsd17b2.
DR eggNOG; KOG1610; Eukaryota.
DR InParanoid; Q62730; -.
DR OrthoDB; 1313182at2759; -.
DR PhylomeDB; Q62730; -.
DR Reactome; R-RNO-193144; Estrogen biosynthesis.
DR PRO; PR:Q62730; -.
DR Proteomes; UP000002494; Unplaced.
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; IDA:RGD.
DR GO; GO:0044594; F:17-beta-hydroxysteroid dehydrogenase (NAD+) activity; IEA:RHEA.
DR GO; GO:0004303; F:estradiol 17-beta-dehydrogenase activity; IDA:RGD.
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; IDA:RGD.
DR GO; GO:0006702; P:androgen biosynthetic process; IDA:RGD.
DR GO; GO:0008209; P:androgen metabolic process; ISO:RGD.
DR GO; GO:0060348; P:bone development; IEP:RGD.
DR GO; GO:0071248; P:cellular response to metal ion; IEP:RGD.
DR GO; GO:0006703; P:estrogen biosynthetic process; IDA:RGD.
DR GO; GO:0001701; P:in utero embryonic development; ISO:RGD.
DR GO; GO:0001890; P:placenta development; ISO:RGD.
DR GO; GO:0032526; P:response to retinoic acid; ISO:RGD.
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_0000054572"
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"
SQ SEQUENCE 381 AA; 41967 MW; 8E1D08DF345DE136 CRC64;
MNPFSSESAW LCLTATAVLG GMLLCKAWSS GQLRSQVVCL AGLWGGACLL SLSLLCSLFL
LSVSCFFLLY VSSSDQDLLP VDQKAVLVTG ADSGFGHALA KHLDKLGFTV FAGVLDKEGP
GAEELRKNCS ERLSVLQMDV TKPEQIKDVH SEVAEKIQDK GLWAVVNNAG VLHFPIDGEL
IPMTVYRKCM AVNFFGAVEV TKVFLPLLRK SKGRLVNVSS MGAMIPFQMV AAYASTKAAI
SMFSAVIRQE LAKWGVKVVT IHPGGFQTNI VGSQDSWDKM EKEILDHFSK EIQENYGQEY
VHTQKLALPV MREMSNPDIT PVLRDIQHAI CAKNPSSFYC SGRMTYLWIC FAAYSPISLL
DYILKNYFTP KLMPRALRTA S
