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3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type I) (3-beta-HSD I) [Includes: 3-beta-hydroxy-Delta(5)-steroid dehydrogenase (EC 1.1.1.145) (3-beta-hydroxy-5-ene steroid dehydrogenase) (Progesterone reductase); Steroid Delta-isomerase (EC 5.3.3.1) (Delta-5-3-ketosteroid isomerase)]

 3BHS1_RAT               Reviewed;         373 AA.
P22071; Q19P43;
01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
23-JAN-2007, sequence version 3.
05-DEC-2018, entry version 144.
RecName: Full=3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1;
AltName: Full=3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type I {ECO:0000303|PubMed:1537836};
Short=3-beta-HSD I;
AltName: Full=3-beta-hydroxy-5-ene steroid dehydrogenase {ECO:0000250|UniProtKB:P14060};
AltName: Full=3-beta-hydroxy-Delta(5)-steroid dehydrogenase {ECO:0000305|PubMed:1537836, ECO:0000305|PubMed:1985917};
EC=1.1.1.145 {ECO:0000269|PubMed:1537836, ECO:0000269|PubMed:1985917};
AltName: Full=3-beta-hydroxysteroid 3-dehydrogenase {ECO:0000305|PubMed:1537836};
EC=1.1.1.270 {ECO:0000269|PubMed:1537836};
AltName: Full=Delta-5-3-ketosteroid isomerase;
AltName: Full=Dihydrotestosterone oxidoreductase {ECO:0000303|PubMed:1537836};
EC=1.1.1.210 {ECO:0000269|PubMed:1537836};
AltName: Full=Steroid Delta-isomerase {ECO:0000305|PubMed:1537836, ECO:0000305|PubMed:1985917};
EC=5.3.3.1 {ECO:0000269|PubMed:1537836, ECO:0000269|PubMed:1985917};
Name=Hsd3b1 {ECO:0000312|RGD:1308676};
Rattus norvegicus (Rat).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Rattus.
NCBI_TaxID=10116;
[1]
NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, CATALYTIC
ACTIVITY, AND SUBSTRATE SPECIFICITY.
PubMed=1985917;
Zhao H.-F., Labrie C., Simard J., de Launoit Y., Trudel C., Martel C.,
Rheaume E., Dupont E., Luu-The V., Pelletier G., Labrie F.;
"Characterization of rat 3 beta-hydroxysteroid dehydrogenase/delta 5-
delta 4 isomerase cDNAs and differential tissue-specific expression of
the corresponding mRNAs in steroidogenic and peripheral tissues.";
J. Biol. Chem. 266:583-593(1991).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Testis;
PubMed=1955079; DOI=10.1016/0303-7207(91)90139-J;
Lorence M.C., Naville D., Graham-Lorence S.E., Mack S.O., Murry B.A.,
Trant J.M., Mason J.I.;
"3 beta-hydroxysteroid dehydrogenase/delta 5-->4-isomerase expression
in rat and characterization of the testis isoform.";
Mol. Cell. Endocrinol. 80:21-31(1991).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Ovary;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[4]
NUCLEOTIDE SEQUENCE [MRNA] OF 227-358.
STRAIN=Wistar;
Si J.L., Li J., Xu X.Q.;
Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases.
[5]
FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE
SPECIFICITY, AND PATHWAY.
PubMed=1537836;
de Launoit Y., Zhao H.F., Belanger A., Labrie F., Simard J.;
"Expression of liver-specific member of the 3 beta-hydroxysteroid
dehydrogenase family, an isoform possessing an almost exclusive 3-
ketosteroid reductase activity.";
J. Biol. Chem. 267:4513-4517(1992).
-!- FUNCTION: A bifunctional enzyme responsible for the oxidation and
isomerization of 3beta-hydroxy-Delta(5)-steroid precursors to 3-
oxo-Delta(4)-steroids, an essential step in steroid hormone
biosynthesis. Specifically catalyzes the conversion of
pregnenolone to progesterone, dehydroepiandrosterone (DHEA) to 4-
androstenedione, and androstenediol to testosterone
(PubMed:1537836, PubMed:1985917). Additionally, catalyzes the
interconversion between 3beta-hydroxy and 3-oxo-5alpha-androstane
steroids controlling the bioavalability of the active forms.
Specifically converts dihydrotestosterone to its inactive form
5alpha-androstanediol, that does not bind androgen receptor/AR.
Also converts androstanedione, a precursor of testosterone and
estrone, to epiandrosterone (PubMed:1537836). Expected to use
NAD(+) as preferred electron donor for the 3beta-hydroxy-steroid
dehydrogenase activity and NADPH for the 3-ketosteroid reductase
activity (Probable). {ECO:0000269|PubMed:1537836,
ECO:0000269|PubMed:1985917, ECO:0000305|PubMed:1537836}.
-!- CATALYTIC ACTIVITY:
Reaction=a 3beta-hydroxy-Delta(5)-steroid + NAD(+) = a 3-oxo-
Delta(5)-steroid + H(+) + NADH; Xref=Rhea:RHEA:24076,
ChEBI:CHEBI:1722, ChEBI:CHEBI:15378, ChEBI:CHEBI:47907,
ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.145;
Evidence={ECO:0000269|PubMed:1537836};
-!- CATALYTIC ACTIVITY:
Reaction=NAD(+) + pregnenolone = H(+) + NADH + pregn-5-ene-3,20-
dione; Xref=Rhea:RHEA:43924, ChEBI:CHEBI:15378,
ChEBI:CHEBI:16581, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
ChEBI:CHEBI:63837; Evidence={ECO:0000269|PubMed:1537836,
ECO:0000269|PubMed:1985917};
-!- CATALYTIC ACTIVITY:
Reaction=3beta-hydroxyandrost-5-en-17-one + NAD(+) = androst-5-
ene-3,17-dione + H(+) + NADH; Xref=Rhea:RHEA:43932,
ChEBI:CHEBI:15378, ChEBI:CHEBI:28689, ChEBI:CHEBI:57540,
ChEBI:CHEBI:57945, ChEBI:CHEBI:83865; EC=1.1.1.145;
Evidence={ECO:0000269|PubMed:1537836};
-!- CATALYTIC ACTIVITY:
Reaction=androst-5-en-3beta,17beta-diol + NAD(+) = 17beta-hydroxy-
androst-5-en-3-one + H(+) + NADH; Xref=Rhea:RHEA:56932,
ChEBI:CHEBI:2710, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
ChEBI:CHEBI:57945, ChEBI:CHEBI:141179;
Evidence={ECO:0000269|PubMed:1537836,
ECO:0000269|PubMed:1985917};
-!- CATALYTIC ACTIVITY:
Reaction=a 3beta-hydroxysteroid + NADP(+) = a 3-oxosteroid + H(+)
+ NADPH; Xref=Rhea:RHEA:34787, ChEBI:CHEBI:15378,
ChEBI:CHEBI:36836, ChEBI:CHEBI:47788, ChEBI:CHEBI:57783,
ChEBI:CHEBI:58349; EC=1.1.1.270;
Evidence={ECO:0000269|PubMed:1537836};
-!- CATALYTIC ACTIVITY:
Reaction=5alpha-androstane-3beta,17beta-diol + NADP(+) = 17beta-
hydroxy-5alpha-androstan-3-one + H(+) + NADPH;
Xref=Rhea:RHEA:16297, ChEBI:CHEBI:15378, ChEBI:CHEBI:16330,
ChEBI:CHEBI:18329, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
EC=1.1.1.210; Evidence={ECO:0000269|PubMed:1537836};
-!- CATALYTIC ACTIVITY:
Reaction=3beta-hydroxy-5alpha-androstan-17-one + NADP(+) = 5alpha-
androstan-3,17-dione + H(+) + NADPH; Xref=Rhea:RHEA:56916,
ChEBI:CHEBI:15378, ChEBI:CHEBI:15994, ChEBI:CHEBI:57783,
ChEBI:CHEBI:58349, ChEBI:CHEBI:541975;
Evidence={ECO:0000269|PubMed:1537836};
-!- CATALYTIC ACTIVITY:
Reaction=a 3-oxo-Delta(5)-steroid = a 3-oxo-Delta(4)-steroid;
Xref=Rhea:RHEA:14709, ChEBI:CHEBI:47907, ChEBI:CHEBI:47909;
EC=5.3.3.1; Evidence={ECO:0000269|PubMed:1537836};
-!- CATALYTIC ACTIVITY:
Reaction=pregn-5-ene-3,20-dione = progesterone;
Xref=Rhea:RHEA:43928, ChEBI:CHEBI:17026, ChEBI:CHEBI:63837;
Evidence={ECO:0000269|PubMed:1537836};
-!- CATALYTIC ACTIVITY:
Reaction=androst-5-ene-3,17-dione = androst-4-ene-3,17-dione;
Xref=Rhea:RHEA:43936, ChEBI:CHEBI:16422, ChEBI:CHEBI:83865;
Evidence={ECO:0000269|PubMed:1537836};
-!- CATALYTIC ACTIVITY:
Reaction=17beta-hydroxy-androst-5-en-3-one = testosterone;
Xref=Rhea:RHEA:56936, ChEBI:CHEBI:17347, ChEBI:CHEBI:141179;
Evidence={ECO:0000269|PubMed:1537836};
-!- BIOPHYSICOCHEMICAL PROPERTIES:
Kinetic parameters:
KM=1.18 uM for dihydrotestosterone (in the presence of NADPH)
{ECO:0000269|PubMed:1537836};
KM=5.05 uM for dihydrotestosterone (in the presence of NADH)
{ECO:0000269|PubMed:1537836};
Note=Vmax for dihydrotestosterone reduction is 15-fold higher in
the presence of NADH than in the presence of NADPH.
{ECO:0000269|PubMed:1537836};
-!- PATHWAY: Steroid hormone biosynthesis.
{ECO:0000269|PubMed:1537836}.
-!- PATHWAY: Steroid metabolism. {ECO:0000269|PubMed:1537836}.
-!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass
membrane protein. Mitochondrion membrane; Single-pass membrane
protein.
-!- TISSUE SPECIFICITY: Adrenal glands, kidney, testes and ovaries.
{ECO:0000269|PubMed:1985917}.
-!- SIMILARITY: Belongs to the 3-beta-HSD family. {ECO:0000305}.
-----------------------------------------------------------------------
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Distributed under the Creative Commons Attribution (CC BY 4.0) License
-----------------------------------------------------------------------
EMBL; M38178; AAA63474.1; -; mRNA.
EMBL; BC086578; AAH86578.1; -; mRNA.
EMBL; DQ515797; ABF70960.1; -; mRNA.
PIR; A39051; DERTH1.
RefSeq; NP_001007720.3; NM_001007719.3.
UniGene; Rn.128814; -.
ProteinModelPortal; P22071; -.
PRIDE; P22071; -.
GeneID; 360348; -.
KEGG; rno:360348; -.
UCSC; RGD:1308676; rat.
CTD; 3283; -.
RGD; 1308676; Hsd3b1.
HOGENOM; HOG000167989; -.
HOVERGEN; HBG000014; -.
InParanoid; P22071; -.
KO; K00070; -.
PhylomeDB; P22071; -.
BRENDA; 1.1.1.145; 5301.
BRENDA; 5.3.3.1; 5301.
PRO; PR:P22071; -.
Proteomes; UP000002494; Unplaced.
GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:RGD.
GO; GO:0030061; C:mitochondrial crista; IDA:RGD.
GO; GO:0003854; F:3-beta-hydroxy-delta5-steroid dehydrogenase activity; IDA:RGD.
GO; GO:0102294; F:cholesterol dehydrogenase activity; IEA:UniProtKB-EC.
GO; GO:0035410; F:dihydrotestosterone 17-beta-dehydrogenase activity; IDA:RGD.
GO; GO:0051287; F:NAD binding; IDA:RGD.
GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IBA:GO_Central.
GO; GO:0005496; F:steroid binding; IPI:RGD.
GO; GO:0004769; F:steroid delta-isomerase activity; IDA:RGD.
GO; GO:0030325; P:adrenal gland development; IEP:RGD.
GO; GO:0018879; P:biphenyl metabolic process; IEP:RGD.
GO; GO:0008207; P:C21-steroid hormone metabolic process; IDA:RGD.
GO; GO:0071236; P:cellular response to antibiotic; IEP:RGD.
GO; GO:0071320; P:cellular response to cAMP; IEP:RGD.
GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEP:RGD.
GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; IEP:RGD.
GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; IEP:RGD.
GO; GO:0071333; P:cellular response to glucose stimulus; IEP:RGD.
GO; GO:0071371; P:cellular response to gonadotropin stimulus; IEP:RGD.
GO; GO:0070301; P:cellular response to hydrogen peroxide; IEP:RGD.
GO; GO:0032869; P:cellular response to insulin stimulus; IEP:RGD.
GO; GO:0071373; P:cellular response to luteinizing hormone stimulus; IEP:RGD.
GO; GO:0071288; P:cellular response to mercury ion; IEP:RGD.
GO; GO:0071406; P:cellular response to methylmercury; IEP:RGD.
GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEP:RGD.
GO; GO:0018894; P:dibenzo-p-dioxin metabolic process; IEP:RGD.
GO; GO:0016101; P:diterpenoid metabolic process; IEP:RGD.
GO; GO:0008585; P:female gonad development; IEP:RGD.
GO; GO:0030851; P:granulocyte differentiation; IEP:RGD.
GO; GO:0021766; P:hippocampus development; IEP:RGD.
GO; GO:0017143; P:insecticide metabolic process; IEP:RGD.
GO; GO:0033327; P:Leydig cell differentiation; IEP:RGD.
GO; GO:0008584; P:male gonad development; IEP:RGD.
GO; GO:0060135; P:maternal process involved in female pregnancy; IEP:RGD.
GO; GO:0006082; P:organic acid metabolic process; IEP:RGD.
GO; GO:0030728; P:ovulation; IEP:RGD.
GO; GO:0018958; P:phenol-containing compound metabolic process; IEP:RGD.
GO; GO:0046470; P:phosphatidylcholine metabolic process; IEP:RGD.
GO; GO:0006701; P:progesterone biosynthetic process; IDA:RGD.
GO; GO:0014823; P:response to activity; IEP:RGD.
GO; GO:0043279; P:response to alkaloid; IEP:RGD.
GO; GO:0046685; P:response to arsenic-containing substance; IEP:RGD.
GO; GO:0046686; P:response to cadmium ion; IEP:RGD.
GO; GO:0051592; P:response to calcium ion; IEP:RGD.
GO; GO:0051412; P:response to corticosterone; IEP:RGD.
GO; GO:0042493; P:response to drug; IEP:RGD.
GO; GO:0032355; P:response to estradiol; IEP:RGD.
GO; GO:0045471; P:response to ethanol; IEP:RGD.
GO; GO:0070542; P:response to fatty acid; IEP:RGD.
GO; GO:0060992; P:response to fungicide; IEP:RGD.
GO; GO:0009635; P:response to herbicide; IEP:RGD.
GO; GO:0033591; P:response to L-ascorbic acid; IEP:RGD.
GO; GO:0010288; P:response to lead ion; IEP:RGD.
GO; GO:0010226; P:response to lithium ion; IEP:RGD.
GO; GO:0010038; P:response to metal ion; IEP:RGD.
GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
GO; GO:0010033; P:response to organic substance; IEP:RGD.
GO; GO:0033197; P:response to vitamin E; IEP:RGD.
GO; GO:0006694; P:steroid biosynthetic process; IBA:GO_Central.
GO; GO:0008202; P:steroid metabolic process; IDA:RGD.
GO; GO:0061370; P:testosterone biosynthetic process; IEP:RGD.
GO; GO:0018970; P:toluene metabolic process; IEP:RGD.
InterPro; IPR002225; 3Beta_OHSteriod_DH/Estase.
InterPro; IPR036291; NAD(P)-bd_dom_sf.
Pfam; PF01073; 3Beta_HSD; 1.
SUPFAM; SSF51735; SSF51735; 1.
1: Evidence at protein level;
Complete proteome; Endoplasmic reticulum; Isomerase; Lipid metabolism;
Membrane; Mitochondrion; Multifunctional enzyme; NAD; NADP;
Oxidoreductase; Reference proteome; Steroid metabolism;
Steroidogenesis; Transmembrane; Transmembrane helix.
CHAIN 1 373 3 beta-hydroxysteroid dehydrogenase/Delta
5-->4-isomerase type 1.
/FTId=PRO_0000087787.
TRANSMEM 288 308 Helical. {ECO:0000255}.
NP_BIND 10 15 NAD or NADP.
{ECO:0000250|UniProtKB:Q12068}.
ACT_SITE 159 159 Proton donor.
{ECO:0000250|UniProtKB:Q12068}.
BINDING 155 155 NAD or NADP.
{ECO:0000250|UniProtKB:Q12068}.
BINDING 159 159 NAD or NADP.
{ECO:0000250|UniProtKB:Q12068}.
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


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