3BHS1_MACMU
ID 3BHS1_MACMU Reviewed; 373 AA.
AC P27365;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 134.
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:0000250|UniProtKB:P14060};
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:0000250|UniProtKB:P14060};
DE EC=1.1.1.145 {ECO:0000250|UniProtKB:P22071};
DE AltName: Full=3-beta-hydroxysteroid 3-dehydrogenase {ECO:0000250|UniProtKB:P14060};
DE EC=1.1.1.270 {ECO:0000250|UniProtKB:P22071};
DE AltName: Full=Delta-5-3-ketosteroid isomerase;
DE AltName: Full=Dihydrotestosterone oxidoreductase {ECO:0000250|UniProtKB:P14060};
DE EC=1.1.1.210 {ECO:0000250|UniProtKB:P22071};
DE AltName: Full=Steroid Delta-isomerase {ECO:0000250|UniProtKB:P14060};
DE EC=5.3.3.1 {ECO:0000250|UniProtKB:P22071};
GN Name=HSD3B1;
OS Macaca mulatta (Rhesus macaque).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9544;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Ovary;
RX PubMed=2050270; DOI=10.1016/0303-7207(91)90224-g;
RA Simard J., Melner M.H., Breton N., Low K.G., Zhao H.-F., Periman L.M.,
RA Labrie F.;
RT "Characterization of macaque 3 beta-hydroxy-5-ene steroid
RT dehydrogenase/delta 5-delta 4 isomerase: structure and expression in
RT steroidogenic and peripheral tissues in primate.";
RL Mol. Cell. Endocrinol. 75:101-110(1991).
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 17alpha-hydroxypregnenolone to 17alpha-hydroxyprogesterone,
CC dehydroepiandrosterone (DHEA) to 4-androstenedione and androstenediol
CC to testosterone. Additionally, catalyzes the interconversion between
CC 3beta-hydroxy and 3-oxo-5alpha-androstane steroids controlling the
CC bioavalability of the active forms. Specifically converts
CC dihydrotestosterone to its inactive form 5alpha-androstanediol, that
CC does not bind androgen receptor/AR. Also converts androstanedione, a
CC precursor of testosterone and estrone, to epiandrosterone. Expected to
CC use NAD(+) as preferred electron donor for the 3beta-hydroxy-steroid
CC dehydrogenase activity and NADPH for the 3-ketosteroid reductase
CC activity. {ECO:0000250|UniProtKB:P14060, ECO:0000250|UniProtKB:P22071}.
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:0000250|UniProtKB:P22071};
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:0000250|UniProtKB:P22071};
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:0000250|UniProtKB:P22071};
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:0000250|UniProtKB:P22071};
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:0000250|UniProtKB:P22071};
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:0000250|UniProtKB:P22071};
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:0000250|UniProtKB:P22071};
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:0000250|UniProtKB:P22071};
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:0000250|UniProtKB:P22071};
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:0000250|UniProtKB:P22071};
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:0000250|UniProtKB:P22071};
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 -!- PATHWAY: Steroid hormone biosynthesis. {ECO:0000250|UniProtKB:P22071}.
CC -!- PATHWAY: Steroid metabolism. {ECO:0000250|UniProtKB:P22071}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass
CC membrane protein. Mitochondrion membrane; Single-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Adrenal glands, testes and ovaries.
CC -!- SIMILARITY: Belongs to the 3-beta-HSD family. {ECO:0000305}.
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DR EMBL; M67467; AAA36847.1; -; mRNA.
DR PIR; A54325; A54325.
DR AlphaFoldDB; P27365; -.
DR SMR; P27365; -.
DR STRING; 9544.ENSMMUP00000021766; -.
DR Ensembl; ENSMMUT00000023265; ENSMMUP00000021766; ENSMMUG00000016568.
DR VEuPathDB; HostDB:ENSMMUG00000016568; -.
DR VGNC; VGNC:99971; HSD3B2.
DR eggNOG; KOG1430; Eukaryota.
DR GeneTree; ENSGT00940000161374; -.
DR HOGENOM; CLU_007383_6_3_1; -.
DR InParanoid; P27365; -.
DR Proteomes; UP000006718; Chromosome 1.
DR Bgee; ENSMMUG00000016568; Expressed in ileum and 9 other tissues.
DR ExpressionAtlas; P27365; baseline.
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; IBA:GO_Central.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0003854; F:3-beta-hydroxy-delta5-steroid dehydrogenase activity; IEA:UniProtKB-EC.
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:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IBA:GO_Central.
DR GO; GO:0004769; F:steroid delta-isomerase activity; IEA:UniProtKB-EC.
DR GO; GO:0008207; P:C21-steroid hormone metabolic process; IBA:GO_Central.
DR GO; GO:0021766; P:hippocampus development; IBA:GO_Central.
DR GO; GO:0051412; P:response to corticosterone; IBA:GO_Central.
DR GO; GO:0006694; P:steroid biosynthetic process; IBA:GO_Central.
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 2: Evidence at transcript 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_0000087776"
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; 42005 MW; 9B6C172F319B5BB9 CRC64;
MTGWSCLVTG AGGFLGQRIV RLLVEEKELK EIRVLDKAFR PELREEFSKL QNKTKLTVLE
GDILDEPFLK RACQDVSVVI HTACIIDVFG VTHRESIMNV NVKGTQLLLE ACVQASVPVF
IYTSTLEVAG PNSYKEIIQN GHEEEPLENT WPAPYPYSKK LAEKAVLAAN GWTLKNGGTL
YTCALRPMYI YGEGGPFLSA SINEALNNNG ILSSVGKFST VNPVYVGNVA WAHILALRAL
RDPKKAPSVQ GQFYYISDDT PHQSYDNLNY ILSKEFGLCL DSRWSLPLAL MYWIGFLLEV
VSFLLSPVYS YQPPFNRHTV TLSNSVFTFS YKKAQRDLAY KPLYSWEEAK QKTVEWVGSL
VDRHKETLKS KTQ