3BHS1_MESAU
ID 3BHS1_MESAU Reviewed; 373 AA.
AC Q60555; Q60556;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 111.
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 Mesocricetus auratus (Golden hamster).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Mesocricetus.
OX NCBI_TaxID=10036;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Adrenal gland;
RX PubMed=8547173; DOI=10.1016/0960-0760(95)00197-2;
RA Rogerson F.M., Lehoux J.-G., Mason J.I.;
RT "Expression and characterization of isoforms of 3 beta-hydroxysteroid
RT dehydrogenase/delta 5-->4-isomerase in the hamster.";
RL J. Steroid Biochem. Mol. Biol. 55:481-487(1995).
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 3-beta-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: High levels in adrenal gland, kidney and male
CC liver. Low levels in female liver.
CC -!- SIMILARITY: Belongs to the 3-beta-HSD family. {ECO:0000305}.
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DR EMBL; L38709; AAB52546.1; -; mRNA.
DR RefSeq; NP_001297496.1; NM_001310567.1.
DR AlphaFoldDB; Q60555; -.
DR GeneID; 101842851; -.
DR OrthoDB; 930591at2759; -.
DR Proteomes; UP000189706; Unplaced.
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: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:0004769; F:steroid delta-isomerase activity; IEA:UniProtKB-EC.
DR GO; GO:0006694; P:steroid biosynthetic process; IEA:UniProtKB-KW.
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_0000087777"
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; 41754 MW; 4975BC9F2D93D159 CRC64;
MPGWSCLVTG AGGFLGQRII RMLVQEKELQ EVRALDKVFR PETREEFCKL QTKTKVTVLE
GDILDAQCLR RACQGISVVI HTAAAIDVFG AIPRQTIIDI NLKGTLNLLE ACVQASVPAF
IYTSSIDVAG PNSYKEIVLN GHEEQQHEST WSDPYPYSKK MAEKAVLAAN GSSLKNGGTL
HTCALRPMYI YGEKSPLISV TIIRAVKNSG ILDVTGKFST VNPVYVNNAA WAHILAARGL
QDPRKSPNIQ GQFYYISDDT PHQSYDDLNY VLSKDWGLRP DSSWRPPVAL LYWLGFLLEL
VSFLLRPVYN YQPPFNRHLV TLSNTVFTFS YKKAQRDLGY EPLVGWEEAR ENTSEWIGSL
VEQHKGTLNT KAQ
