3BHS1_RAT
ID 3BHS1_RAT Reviewed; 373 AA.
AC P22071; Q19P43;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1;
DE AltName: Full=3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type I {ECO:0000303|PubMed:1537836};
DE Short=3-beta-HSD I;
DE AltName: Full=3-beta-hydroxy-5-ene steroid dehydrogenase {ECO:0000250|UniProtKB:P14060};
DE AltName: Full=3-beta-hydroxy-Delta(5)-steroid dehydrogenase {ECO:0000305|PubMed:1537836, ECO:0000305|PubMed:1985917};
DE EC=1.1.1.145 {ECO:0000269|PubMed:1537836, ECO:0000269|PubMed:1985917};
DE AltName: Full=3-beta-hydroxysteroid 3-dehydrogenase {ECO:0000305|PubMed:1537836};
DE EC=1.1.1.270 {ECO:0000269|PubMed:1537836};
DE AltName: Full=Delta-5-3-ketosteroid isomerase;
DE AltName: Full=Dihydrotestosterone oxidoreductase {ECO:0000303|PubMed:1537836};
DE EC=1.1.1.210 {ECO:0000269|PubMed:1537836};
DE AltName: Full=Steroid Delta-isomerase {ECO:0000305|PubMed:1537836, ECO:0000305|PubMed:1985917};
DE EC=5.3.3.1 {ECO:0000269|PubMed:1537836, ECO:0000269|PubMed:1985917};
GN Name=Hsd3b1 {ECO:0000312|RGD:1308676};
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], FUNCTION, TISSUE SPECIFICITY, CATALYTIC
RP ACTIVITY, AND SUBSTRATE SPECIFICITY.
RX PubMed=1985917; DOI=10.1016/s0021-9258(18)52475-3;
RA Zhao H.-F., Labrie C., Simard J., de Launoit Y., Trudel C., Martel C.,
RA Rheaume E., Dupont E., Luu-The V., Pelletier G., Labrie F.;
RT "Characterization of rat 3 beta-hydroxysteroid dehydrogenase/delta 5-delta
RT 4 isomerase cDNAs and differential tissue-specific expression of the
RT corresponding mRNAs in steroidogenic and peripheral tissues.";
RL J. Biol. Chem. 266:583-593(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Testis;
RX PubMed=1955079; DOI=10.1016/0303-7207(91)90139-j;
RA Lorence M.C., Naville D., Graham-Lorence S.E., Mack S.O., Murry B.A.,
RA Trant J.M., Mason J.I.;
RT "3 beta-hydroxysteroid dehydrogenase/delta 5-->4-isomerase expression in
RT rat and characterization of the testis isoform.";
RL Mol. Cell. Endocrinol. 80:21-31(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 227-358.
RC STRAIN=Wistar;
RA Si J.L., Li J., Xu X.Q.;
RL Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE
RP SPECIFICITY, AND PATHWAY.
RX PubMed=1537836; DOI=10.1016/s0021-9258(18)42863-3;
RA de Launoit Y., Zhao H.F., Belanger A., Labrie F., Simard J.;
RT "Expression of liver-specific member of the 3 beta-hydroxysteroid
RT dehydrogenase family, an isoform possessing an almost exclusive 3-
RT ketosteroid reductase activity.";
RL J. Biol. Chem. 267:4513-4517(1992).
CC -!- FUNCTION: A bifunctional enzyme responsible for the oxidation and
CC isomerization of 3beta-hydroxy-Delta(5)-steroid precursors to 3-oxo-
CC Delta(4)-steroids, an essential step in steroid hormone biosynthesis.
CC Specifically catalyzes the conversion of pregnenolone to progesterone,
CC dehydroepiandrosterone (DHEA) to 4-androstenedione, and androstenediol
CC to testosterone (PubMed:1537836, PubMed:1985917). Additionally,
CC catalyzes the interconversion between 3beta-hydroxy and 3-oxo-5alpha-
CC androstane steroids controlling the bioavalability of the active forms.
CC Specifically converts dihydrotestosterone to its inactive form 5alpha-
CC androstanediol, that does not bind androgen receptor/AR. Also converts
CC androstanedione, a precursor of testosterone and estrone, to
CC epiandrosterone (PubMed:1537836). Expected to use NAD(+) as preferred
CC electron donor for the 3beta-hydroxy-steroid dehydrogenase activity and
CC NADPH for the 3-ketosteroid reductase activity (Probable).
CC {ECO:0000269|PubMed:1537836, ECO:0000269|PubMed:1985917,
CC ECO:0000305|PubMed:1537836}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 3beta-hydroxy-Delta(5)-steroid + NAD(+) = a 3-oxo-Delta(5)-
CC steroid + H(+) + NADH; Xref=Rhea:RHEA:24076, ChEBI:CHEBI:1722,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:47907, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; EC=1.1.1.145;
CC Evidence={ECO:0000269|PubMed:1537836};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NAD(+) + pregnenolone = H(+) + NADH + pregn-5-ene-3,20-dione;
CC Xref=Rhea:RHEA:43924, ChEBI:CHEBI:15378, ChEBI:CHEBI:16581,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:63837;
CC Evidence={ECO:0000269|PubMed:1537836, ECO:0000269|PubMed:1985917};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3beta-hydroxyandrost-5-en-17-one + NAD(+) = androst-5-ene-
CC 3,17-dione + H(+) + NADH; Xref=Rhea:RHEA:43932, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:28689, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:83865; EC=1.1.1.145;
CC Evidence={ECO:0000269|PubMed:1537836};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=androst-5-en-3beta,17beta-diol + NAD(+) = 17beta-hydroxy-
CC androst-5-en-3-one + H(+) + NADH; Xref=Rhea:RHEA:56932,
CC ChEBI:CHEBI:2710, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:141179;
CC Evidence={ECO:0000269|PubMed:1537836, ECO:0000269|PubMed:1985917};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 3beta-hydroxysteroid + NADP(+) = a 3-oxosteroid + H(+) +
CC NADPH; Xref=Rhea:RHEA:34787, ChEBI:CHEBI:15378, ChEBI:CHEBI:36836,
CC ChEBI:CHEBI:47788, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC EC=1.1.1.270; Evidence={ECO:0000269|PubMed:1537836};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5alpha-androstane-3beta,17beta-diol + NADP(+) = 17beta-
CC hydroxy-5alpha-androstan-3-one + H(+) + NADPH; Xref=Rhea:RHEA:16297,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16330, ChEBI:CHEBI:18329,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.210;
CC Evidence={ECO:0000269|PubMed:1537836};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3beta-hydroxy-5alpha-androstan-17-one + NADP(+) = 5alpha-
CC androstan-3,17-dione + H(+) + NADPH; Xref=Rhea:RHEA:56916,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15994, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:541975;
CC Evidence={ECO:0000269|PubMed:1537836};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 3-oxo-Delta(5)-steroid = a 3-oxo-Delta(4)-steroid;
CC Xref=Rhea:RHEA:14709, ChEBI:CHEBI:47907, ChEBI:CHEBI:47909;
CC EC=5.3.3.1; Evidence={ECO:0000269|PubMed:1537836};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=pregn-5-ene-3,20-dione = progesterone; Xref=Rhea:RHEA:43928,
CC ChEBI:CHEBI:17026, ChEBI:CHEBI:63837;
CC Evidence={ECO:0000269|PubMed:1537836};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=androst-5-ene-3,17-dione = androst-4-ene-3,17-dione;
CC Xref=Rhea:RHEA:43936, ChEBI:CHEBI:16422, ChEBI:CHEBI:83865;
CC Evidence={ECO:0000269|PubMed:1537836};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-hydroxy-androst-5-en-3-one = testosterone;
CC Xref=Rhea:RHEA:56936, ChEBI:CHEBI:17347, ChEBI:CHEBI:141179;
CC Evidence={ECO:0000269|PubMed:1537836};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5alpha-androstane-3beta,17beta-diol + NAD(+) = 17beta-hydroxy-
CC 5alpha-androstan-3-one + H(+) + NADH; Xref=Rhea:RHEA:42184,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16330, ChEBI:CHEBI:18329,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC Evidence={ECO:0000250|UniProtKB:P14060};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.18 uM for dihydrotestosterone (in the presence of NADPH)
CC {ECO:0000269|PubMed:1537836};
CC KM=5.05 uM for dihydrotestosterone (in the presence of NADH)
CC {ECO:0000269|PubMed:1537836};
CC Note=Vmax for dihydrotestosterone reduction is 15-fold higher in the
CC presence of NADH than in the presence of NADPH.
CC {ECO:0000269|PubMed:1537836};
CC -!- PATHWAY: Steroid hormone biosynthesis. {ECO:0000269|PubMed:1537836}.
CC -!- PATHWAY: Steroid metabolism. {ECO:0000269|PubMed:1537836}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass
CC membrane protein. Mitochondrion membrane; Single-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Adrenal glands, kidney, testes and ovaries.
CC {ECO:0000269|PubMed:1985917}.
CC -!- SIMILARITY: Belongs to the 3-beta-HSD family. {ECO:0000305}.
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DR EMBL; M38178; AAA63474.1; -; mRNA.
DR EMBL; BC086578; AAH86578.1; -; mRNA.
DR EMBL; DQ515797; ABF70960.1; -; mRNA.
DR PIR; A39051; DERTH1.
DR RefSeq; NP_001007720.3; NM_001007719.3.
DR AlphaFoldDB; P22071; -.
DR SMR; P22071; -.
DR Ensembl; ENSRNOT00000086835; ENSRNOP00000075324; ENSRNOG00000070622.
DR GeneID; 360348; -.
DR KEGG; rno:360348; -.
DR UCSC; RGD:1308676; rat.
DR CTD; 3283; -.
DR RGD; 1308676; Hsd3b1.
DR GeneTree; ENSGT00940000155444; -.
DR InParanoid; P22071; -.
DR PhylomeDB; P22071; -.
DR BRENDA; 1.1.1.145; 5301.
DR BRENDA; 5.3.3.1; 5301.
DR PRO; PR:P22071; -.
DR Proteomes; UP000002494; Chromosome 2.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
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:0030061; C:mitochondrial crista; IDA:RGD.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISO:RGD.
DR GO; GO:0005758; C:mitochondrial intermembrane space; ISO:RGD.
DR GO; GO:0003854; F:3-beta-hydroxy-delta5-steroid dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0000253; F:3-keto sterol reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0047024; F:5alpha-androstane-3beta,17beta-diol dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0102294; F:cholesterol dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0102176; F:cycloeucalenone reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0035410; F:dihydrotestosterone 17-beta-dehydrogenase activity; IDA:RGD.
DR GO; GO:0051287; F:NAD binding; IDA:RGD.
DR GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IBA:GO_Central.
DR GO; GO:0005496; F:steroid binding; IPI:RGD.
DR GO; GO:0004769; F:steroid delta-isomerase activity; IDA:UniProtKB.
DR GO; GO:0030325; P:adrenal gland development; IEP:RGD.
DR GO; GO:0018879; P:biphenyl metabolic process; IEP:RGD.
DR GO; GO:0008207; P:C21-steroid hormone metabolic process; IDA:RGD.
DR GO; GO:0071236; P:cellular response to antibiotic; IEP:RGD.
DR GO; GO:0071320; P:cellular response to cAMP; IEP:RGD.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEP:RGD.
DR GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; IEP:RGD.
DR GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; IEP:RGD.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IEP:RGD.
DR GO; GO:0071371; P:cellular response to gonadotropin stimulus; IEP:RGD.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEP:RGD.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEP:RGD.
DR GO; GO:0071373; P:cellular response to luteinizing hormone stimulus; IEP:RGD.
DR GO; GO:0071288; P:cellular response to mercury ion; IEP:RGD.
DR GO; GO:0071406; P:cellular response to methylmercury; IEP:RGD.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEP:RGD.
DR GO; GO:0018894; P:dibenzo-p-dioxin metabolic process; IEP:RGD.
DR GO; GO:0016101; P:diterpenoid metabolic process; IEP:RGD.
DR GO; GO:0008585; P:female gonad development; IEP:RGD.
DR GO; GO:0030851; P:granulocyte differentiation; 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:0008584; P:male gonad development; IEP:RGD.
DR GO; GO:0060135; P:maternal process involved in female pregnancy; IEP:RGD.
DR GO; GO:0006082; P:organic acid metabolic process; IEP:RGD.
DR GO; GO:0030728; P:ovulation; IEP:RGD.
DR GO; GO:0018958; P:phenol-containing compound metabolic process; IEP:RGD.
DR GO; GO:0046470; P:phosphatidylcholine metabolic process; IEP:RGD.
DR GO; GO:0006701; P:progesterone biosynthetic process; IDA:RGD.
DR GO; GO:0014823; P:response to activity; IEP:RGD.
DR GO; GO:0043279; P:response to alkaloid; 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:0051592; P:response to calcium ion; IEP:RGD.
DR GO; GO:0051412; P:response to corticosterone; IEP:RGD.
DR GO; GO:0032355; P:response to estradiol; 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:0033591; P:response to L-ascorbic acid; IEP:RGD.
DR GO; GO:0010288; P:response to lead ion; IEP:RGD.
DR GO; GO:0010226; P:response to lithium 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:0010033; P:response to organic substance; IEP:RGD.
DR GO; GO:0033197; P:response to vitamin E; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0006694; P:steroid biosynthetic process; IBA:GO_Central.
DR GO; GO:0008202; P:steroid metabolic process; IDA:RGD.
DR GO; GO:0061370; P:testosterone biosynthetic process; IEP:RGD.
DR GO; GO:0018970; P:toluene metabolic process; IEP:RGD.
DR InterPro; IPR002225; 3Beta_OHSteriod_DH/Estase.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF01073; 3Beta_HSD; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Isomerase; Lipid metabolism; Membrane;
KW Mitochondrion; Multifunctional enzyme; NAD; NADP; Oxidoreductase;
KW Reference proteome; Steroid metabolism; Steroidogenesis; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..373
FT /note="3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-
FT isomerase type 1"
FT /id="PRO_0000087787"
FT TRANSMEM 288..308
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ACT_SITE 159
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:Q12068"
FT BINDING 10..15
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q12068"
FT BINDING 155
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q12068"
FT BINDING 159
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q12068"
SQ SEQUENCE 373 AA; 42037 MW; 1BB058B5171C2F24 CRC64;
MPGWSCLVTG AGGFVGQRII RMLVQEKELQ EVRALDKVFR PETKEEFSKL QTKAKVTMLE
GDILDAQYLR RACQGISVVI HTAAVIDVSH VLPRQTILDV NLKGTQNILE ACVEASVPAF
IYCSTVDVAG PNSYKKIILN GHEEEHHEST WSDAYPYSKR MAEKAVLAAN GSILKNGGTL
HTCALRPMYI YGERSPFLSV MILAALKNKG ILNVTGKFSI ANPVYVGNVA WAHILAARGL
RDPKKSQNVQ GQFYYISDDT PHQSYDDLNC TLSKEWGLRL DSSWSLPLPL LYWLAFLLET
VSFLLRPFYN YRPPFNCHLV TLSNSKFTFS YKKAQRDLGY VPLVSWEEAK QKTSEWIGTL
VEQHRETLDT KSQ
