3BHS1_MOUSE
ID 3BHS1_MOUSE Reviewed; 373 AA.
AC P24815; Q7TQ00;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 173.
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 {ECO:0000312|MGI:MGI:96233}; Synonyms=Hsd3b;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=CD-1;
RX PubMed=1924345; DOI=10.1073/pnas.88.20.8870;
RA Bain P.A., Yoo M., Clarke T., Hammond S.H., Payne A.H.;
RT "Multiple forms of mouse 3 beta-hydroxysteroid dehydrogenase/delta 5-delta
RT 4 isomerase and differential expression in gonads, adrenal glands, liver,
RT and kidneys of both sexes.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:8870-8874(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Egg;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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: Steroidogenic tissues (includes testes, ovaries and
CC adrenal glands).
CC -!- SIMILARITY: Belongs to the 3-beta-HSD family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M58567; AAA37860.1; -; mRNA.
DR EMBL; BC052659; AAH52659.1; -; mRNA.
DR CCDS; CCDS17670.1; -.
DR PIR; I49762; I49762.
DR RefSeq; NP_001291729.1; NM_001304800.1.
DR RefSeq; NP_032319.1; NM_008293.4.
DR RefSeq; XP_006501099.1; XM_006501036.2.
DR AlphaFoldDB; P24815; -.
DR SMR; P24815; -.
DR BioGRID; 200437; 1.
DR STRING; 10090.ENSMUSP00000102630; -.
DR iPTMnet; P24815; -.
DR PhosphoSitePlus; P24815; -.
DR SwissPalm; P24815; -.
DR jPOST; P24815; -.
DR PaxDb; P24815; -.
DR PRIDE; P24815; -.
DR ProteomicsDB; 296444; -.
DR DNASU; 15492; -.
DR Ensembl; ENSMUST00000029465; ENSMUSP00000029465; ENSMUSG00000027871.
DR Ensembl; ENSMUST00000107016; ENSMUSP00000102630; ENSMUSG00000027871.
DR GeneID; 15492; -.
DR KEGG; mmu:15492; -.
DR UCSC; uc008qqh.2; mouse.
DR CTD; 3283; -.
DR MGI; MGI:96233; Hsd3b1.
DR VEuPathDB; HostDB:ENSMUSG00000027871; -.
DR eggNOG; KOG1430; Eukaryota.
DR GeneTree; ENSGT00940000155444; -.
DR HOGENOM; CLU_007383_6_3_1; -.
DR InParanoid; P24815; -.
DR OMA; SLEDCRG; -.
DR OrthoDB; 930591at2759; -.
DR PhylomeDB; P24815; -.
DR TreeFam; TF343138; -.
DR SABIO-RK; P24815; -.
DR BioGRID-ORCS; 15492; 2 hits in 59 CRISPR screens.
DR PRO; PR:P24815; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; P24815; protein.
DR Bgee; ENSMUSG00000027871; Expressed in adrenal gland and 51 other tissues.
DR ExpressionAtlas; P24815; baseline and differential.
DR Genevisible; P24815; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
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:0045171; C:intercellular bridge; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0030061; C:mitochondrial crista; ISO:MGI.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISO:MGI.
DR GO; GO:0005758; C:mitochondrial intermembrane space; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0003854; F:3-beta-hydroxy-delta5-steroid dehydrogenase activity; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0051287; F:NAD binding; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0004769; F:steroid delta-isomerase activity; ISO:MGI.
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 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_0000087780"
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"
FT CONFLICT 128
FT /note="V -> A (in Ref. 2; AAH52659)"
FT /evidence="ECO:0000305"
FT CONFLICT 319
FT /note="L -> S (in Ref. 2; AAH52659)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 373 AA; 42062 MW; 395F9D786C7BA010 CRC64;
MAGWSCLVTG AGGFVGQRII KMLVQEKELQ EVRALDKVFR PETKEEFSKL QTKTKVTVLE
GDILDAQCLR RACQGISVVI HTAAVIDVTG VIPRQTILDV NLKGTQNLLE ACVQASVPAF
IFCSSVDVAG PNSYKKIVLN GHEEQNHEST WSDPYPYSKK MAEKAVLAAN GSMLKNGGTL
NTCALRPMYI YGERSPFIFN AIIRALKNKG ILCVTGKFSI ANPVYVENVA WAHILAARGL
RDPKKSTSIQ GQFYYISDDT PHQSYDDLNY TLSKEWGLRP NASWSLPLPL LYWLAFLLET
VSFLLRPVYR YRPLFNRHLI TLSNSTFTFS YKKAQRDLGY EPLVNWEEAK QKTSEWIGTI
VEQHREILDT KCQ
