DHB3_RAT
ID DHB3_RAT Reviewed; 306 AA.
AC O54939;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=17-beta-hydroxysteroid dehydrogenase type 3;
DE Short=17-beta-HSD 3;
DE AltName: Full=Estradiol 17-beta-dehydrogenase 2;
DE EC=1.1.1.62 {ECO:0000250|UniProtKB:P37058};
DE AltName: Full=Testicular 17-beta-hydroxysteroid dehydrogenase;
DE AltName: Full=Testosterone 17-beta-dehydrogenase 3 {ECO:0000305};
DE EC=1.1.1.64 {ECO:0000250|UniProtKB:P37058};
GN Name=Hsd17b3 {ECO:0000312|RGD:621805}; Synonyms=Edh17b3;
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].
RA Khanum A., Tsai-Morris C.-H., Dufau M.L.;
RL Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Catalyzes the conversion of 17-oxosteroids to 17beta-
CC hydroxysteroids. Favors the reduction of androstenedione to
CC testosterone. Testosterone is the key androgen driving male development
CC and function (By similarity). Uses NADPH while the two other EDH17B
CC enzymes use NADH. Androgens such as epiandrosterone,
CC dehydroepiandrosterone, androsterone and androstanedione are accepted
CC as substrates and reduced at C-17. Can reduce 11-ketoandrostenedione as
CC well as 11beta-hydroxyandrostenedione at C-17 to the respective
CC testosterone forms (By similarity). Plays a role in the rate-limiting-
CC step for the maximum level of testosterone production by the testis but
CC does not affect basal testosterone production (By similarity).
CC {ECO:0000250|UniProtKB:P37058, ECO:0000250|UniProtKB:P70385}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 17beta-hydroxy steroid + NADP(+) = a 17-oxo steroid + H(+) +
CC NADPH; Xref=Rhea:RHEA:69284, ChEBI:CHEBI:15378, ChEBI:CHEBI:19168,
CC ChEBI:CHEBI:35343, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000250|UniProtKB:P37058};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:69286;
CC Evidence={ECO:0000250|UniProtKB:P37058};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NADP(+) + testosterone = androst-4-ene-3,17-dione + H(+) +
CC NADPH; Xref=Rhea:RHEA:14981, ChEBI:CHEBI:15378, ChEBI:CHEBI:16422,
CC ChEBI:CHEBI:17347, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.64;
CC Evidence={ECO:0000250|UniProtKB:P37058};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:14983;
CC Evidence={ECO:0000250|UniProtKB:P37058};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-estradiol + NADP(+) = estrone + H(+) + NADPH;
CC Xref=Rhea:RHEA:24616, ChEBI:CHEBI:15378, ChEBI:CHEBI:16469,
CC ChEBI:CHEBI:17263, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.62;
CC Evidence={ECO:0000250|UniProtKB:P37058};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:24618;
CC Evidence={ECO:0000250|UniProtKB:P37058};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3beta-hydroxyandrost-5-en-17-one + H(+) + NADPH = androst-5-
CC en-3beta,17beta-diol + NADP(+); Xref=Rhea:RHEA:46628,
CC ChEBI:CHEBI:2710, ChEBI:CHEBI:15378, ChEBI:CHEBI:28689,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000250|UniProtKB:P37058};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46629;
CC Evidence={ECO:0000250|UniProtKB:P37058};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-hydroxy-5alpha-androstan-3-one + NADP(+) = 5alpha-
CC androstan-3,17-dione + H(+) + NADPH; Xref=Rhea:RHEA:42120,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15994, ChEBI:CHEBI:16330,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000250|UniProtKB:P37058};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42122;
CC Evidence={ECO:0000250|UniProtKB:P37058};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3alpha-hydroxy-5alpha-androstan-17-one + H(+) + NADPH =
CC 5alpha-androstane-3alpha,17beta-diol + NADP(+); Xref=Rhea:RHEA:42156,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16032, ChEBI:CHEBI:36713,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000250|UniProtKB:P37058};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42157;
CC Evidence={ECO:0000250|UniProtKB:P37058};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3beta-hydroxy-5alpha-androstan-17-one + H(+) + NADPH = 5alpha-
CC androstane-3beta,17beta-diol + NADP(+); Xref=Rhea:RHEA:53480,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:18329, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:541975;
CC Evidence={ECO:0000250|UniProtKB:P37058};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53481;
CC Evidence={ECO:0000250|UniProtKB:P37058};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=androst-4-ene-3,11,17-trione + H(+) + NADPH = 17beta-
CC hydroxyandrost-4-ene-3,11-dione + NADP(+); Xref=Rhea:RHEA:53484,
CC ChEBI:CHEBI:2495, ChEBI:CHEBI:15378, ChEBI:CHEBI:34133,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000250|UniProtKB:P37058};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53485;
CC Evidence={ECO:0000250|UniProtKB:P37058};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=11beta-hydroxyandrost-4-ene-3,17-dione + H(+) + NADPH =
CC 11beta,17beta-dihydroxyandrost-4-ene-3-one + NADP(+);
CC Xref=Rhea:RHEA:53488, ChEBI:CHEBI:15378, ChEBI:CHEBI:27967,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:81481;
CC Evidence={ECO:0000250|UniProtKB:P37058};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53489;
CC Evidence={ECO:0000250|UniProtKB:P37058};
CC -!- PATHWAY: Hormone biosynthesis; testosterone biosynthesis.
CC {ECO:0000250|UniProtKB:P37058}.
CC -!- PATHWAY: Steroid metabolism. {ECO:0000250|UniProtKB:P37058}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:P37058}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. 17-beta-HSD 3 subfamily. {ECO:0000305}.
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DR EMBL; AF035156; AAB99739.1; -; mRNA.
DR RefSeq; NP_446459.1; NM_054007.1.
DR AlphaFoldDB; O54939; -.
DR SMR; O54939; -.
DR STRING; 10116.ENSRNOP00000025850; -.
DR BindingDB; O54939; -.
DR ChEMBL; CHEMBL1075158; -.
DR DrugCentral; O54939; -.
DR iPTMnet; O54939; -.
DR PhosphoSitePlus; O54939; -.
DR PaxDb; O54939; -.
DR PRIDE; O54939; -.
DR GeneID; 117182; -.
DR KEGG; rno:117182; -.
DR UCSC; RGD:621805; rat.
DR CTD; 3293; -.
DR RGD; 621805; Hsd17b3.
DR eggNOG; KOG1014; Eukaryota.
DR InParanoid; O54939; -.
DR OrthoDB; 895581at2759; -.
DR PhylomeDB; O54939; -.
DR BRENDA; 1.1.1.51; 5301.
DR BRENDA; 1.1.1.64; 5301.
DR Reactome; R-RNO-193048; Androgen biosynthesis.
DR Reactome; R-RNO-75876; Synthesis of very long-chain fatty acyl-CoAs.
DR UniPathway; UPA00367; -.
DR PRO; PR:O54939; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:RGD.
DR GO; GO:0072582; F:17-beta-hydroxysteroid dehydrogenase (NADP+) 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:0047045; F:testosterone 17-beta-dehydrogenase (NADP+) activity; ISS:UniProtKB.
DR GO; GO:0047035; F:testosterone dehydrogenase (NAD+) activity; IDA:RGD.
DR GO; GO:0018879; P:biphenyl metabolic process; IEP:RGD.
DR GO; GO:0071236; P:cellular response to antibiotic; IEP:RGD.
DR GO; GO:0071371; P:cellular response to gonadotropin stimulus; IEP:RGD.
DR GO; GO:0032870; P:cellular response to hormone stimulus; IEP:RGD.
DR GO; GO:0021766; P:hippocampus development; IEP:RGD.
DR GO; GO:0017143; P:insecticide metabolic process; IEP:RGD.
DR GO; GO:0033327; P:Leydig cell differentiation; IEP:RGD.
DR GO; GO:0030539; P:male genitalia development; IEA:InterPro.
DR GO; GO:0006082; P:organic acid metabolic process; IEP:RGD.
DR GO; GO:0018958; P:phenol-containing compound metabolic process; IEP:RGD.
DR GO; GO:0014823; P:response to activity; IEP:RGD.
DR GO; GO:0046685; P:response to arsenic-containing substance; IEP:RGD.
DR GO; GO:0046686; P:response to cadmium ion; IEP:RGD.
DR GO; GO:0051412; P:response to corticosterone; IEP:RGD.
DR GO; GO:0043627; P:response to estrogen; IEP:RGD.
DR GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR GO; GO:0070542; P:response to fatty acid; IEP:RGD.
DR GO; GO:0060992; P:response to fungicide; IEP:RGD.
DR GO; GO:0009635; P:response to herbicide; IEP:RGD.
DR GO; GO:0017085; P:response to insecticide; IEP:RGD.
DR GO; GO:0033591; P:response to L-ascorbic acid; IEP:RGD.
DR GO; GO:0010288; P:response to lead ion; IEP:RGD.
DR GO; GO:0010038; P:response to metal ion; IEP:RGD.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0048545; P:response to steroid hormone; IEP:RGD.
DR GO; GO:0033197; P:response to vitamin E; IEP:RGD.
DR GO; GO:0006694; P:steroid biosynthetic process; IDA:RGD.
DR GO; GO:0061370; P:testosterone biosynthetic process; IEA:UniProtKB-UniPathway.
DR InterPro; IPR033281; HSD17B3.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR002347; SDR_fam.
DR PANTHER; PTHR43899:SF7; PTHR43899:SF7; 1.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 2: Evidence at transcript level;
KW Endoplasmic reticulum; Lipid biosynthesis; Lipid metabolism; NADP;
KW Oxidoreductase; Reference proteome; Steroid biosynthesis.
FT CHAIN 1..306
FT /note="17-beta-hydroxysteroid dehydrogenase type 3"
FT /id="PRO_0000054575"
FT ACT_SITE 194
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 44..73
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 181
FT /ligand="substrate"
FT /evidence="ECO:0000250"
SQ SEQUENCE 306 AA; 34223 MW; 8B88584047614B53 CRC64;
MEQFLLSVGL LVCLVCLVKC VRFSRYLFLS FCKALPGSFL RSMGQWAVIT GAGDGIGKAY
SFELARHGLN VVLISRTLEK LQVISEEIER TTGSRVKVVQ ADFTREDIYD HIEEQLKGLE
IGVLVNNVGM LPNLLPSHFL STSGESQSVI HCNITSVVKM TQLVLKHMES RRRGLILNIS
SGVGVRPWPL YSLYSASKAF VCTFSKALNV EYRDKGIIIQ VLTPYSVSTP MTKYLNTSRV
TKTADEFVKE SLKYVTIGAE TCGCLAHEIL AIILNLIPSR IFYSSTTQRF LLKQFSDYLK
SNISNR
