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   27-MAR-2024, entry version 181.
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-
CC         ene-3,17-dione + H(+) + NADH; Xref=Rhea:RHEA:43932,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:28689, ChEBI:CHEBI:57540,
CC         ChEBI:CHEBI:57945, 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}.
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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; 10090-ENSMUSP00000102630; -.
DR   ProteomicsDB; 296444; -.
DR   DNASU; 15492; -.
DR   Ensembl; ENSMUST00000029465.10; ENSMUSP00000029465.8; ENSMUSG00000027871.17.
DR   Ensembl; ENSMUST00000107016.10; ENSMUSP00000102630.4; ENSMUSG00000027871.17.
DR   GeneID; 15492; -.
DR   KEGG; mmu:15492; -.
DR   UCSC; uc008qqh.2; mouse.
DR   AGR; MGI:96233; -.
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; PKYSWEE; -.
DR   OrthoDB; 3675908at2759; -.
DR   PhylomeDB; P24815; -.
DR   TreeFam; TF343138; -.
DR   Reactome; R-MMU-193048; Androgen biosynthesis.
DR   Reactome; R-MMU-193993; Mineralocorticoid biosynthesis.
DR   Reactome; R-MMU-194002; Glucocorticoid biosynthesis.
DR   SABIO-RK; P24815; -.
DR   BioGRID-ORCS; 15492; 2 hits in 62 CRISPR screens.
DR   PRO; PR:P24815; -.
DR   Proteomes; UP000000589; Chromosome 3.
DR   RNAct; P24815; Protein.
DR   Bgee; ENSMUSG00000027871; Expressed in adrenal gland and 52 other cell types or tissues.
DR   ExpressionAtlas; P24815; baseline and differential.
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:0045171; C:intercellular bridge; ISO:MGI.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
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: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   Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1.
DR   InterPro; IPR002225; 3Beta_OHSteriod_DH/Estase.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   PANTHER; PTHR43245; BIFUNCTIONAL POLYMYXIN RESISTANCE PROTEIN ARNA; 1.
DR   PANTHER; PTHR43245:SF51; SHORT CHAIN DEHYDROGENASE_REDUCTASE FAMILY 42E, MEMBER 2; 1.
DR   Pfam; PF01073; 3Beta_HSD; 1.
DR   SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
DR   Genevisible; P24815; MM.
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
//