3BHS2_MOUSE
ID 3BHS2_MOUSE Reviewed; 373 AA.
AC P26149; B1ARN7; Q8R0J6;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 28-JUN-2011, sequence version 4.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2 {ECO:0000305};
DE AltName: Full=3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type II;
DE Short=3-beta-HSD II;
DE Includes:
DE RecName: Full=3-beta-hydroxy-Delta(5)-steroid dehydrogenase;
DE EC=1.1.1.145 {ECO:0000250|UniProtKB:P26439};
DE AltName: Full=3-beta-hydroxy-5-ene steroid dehydrogenase;
DE AltName: Full=Progesterone reductase;
DE Includes:
DE RecName: Full=Steroid Delta-isomerase;
DE EC=5.3.3.1 {ECO:0000250|UniProtKB:P26439};
DE AltName: Full=Delta-5-3-ketosteroid isomerase;
GN Name=Hsd3b2 {ECO:0000312|MGI:MGI:96234};
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Kidney, and Liver;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 109-373.
RC STRAIN=BALB/cJ;
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, and Liver;
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: 3-beta-HSD is a bifunctional enzyme, that catalyzes the
CC oxidative conversion of Delta(5)-ene-3-beta-hydroxy steroid, and the
CC oxidative conversion of ketosteroids. The 3-beta-HSD enzymatic system
CC plays a crucial role in the biosynthesis of all classes of hormonal
CC steroids. {ECO:0000250|UniProtKB:P26439}.
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:P26439};
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:P26439};
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:P26439};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43925;
CC Evidence={ECO:0000250|UniProtKB:P26439};
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:P26439};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43929;
CC Evidence={ECO:0000250|UniProtKB:P26439};
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:P26439};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43933;
CC Evidence={ECO:0000250|UniProtKB:P26439};
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:P26439};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43937;
CC Evidence={ECO:0000250|UniProtKB:P26439};
CC -!- PATHWAY: Lipid metabolism; steroid biosynthesis.
CC {ECO:0000250|UniProtKB:P26439}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P26439}; Single-pass membrane protein
CC {ECO:0000255}. Mitochondrion membrane {ECO:0000250|UniProtKB:P26439};
CC Single-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Liver and kidney.
CC -!- SIMILARITY: Belongs to the 3-beta-HSD family. {ECO:0000305}.
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DR EMBL; AL606755; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC026757; AAH26757.1; -; mRNA.
DR EMBL; BC040397; AAH40397.1; -; mRNA.
DR EMBL; M75886; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS17667.1; -.
DR RefSeq; NP_694873.2; NM_153193.3.
DR RefSeq; XP_006501101.1; XM_006501038.3.
DR AlphaFoldDB; P26149; -.
DR BioGRID; 200438; 1.
DR STRING; 10090.ENSMUSP00000102636; -.
DR iPTMnet; P26149; -.
DR PhosphoSitePlus; P26149; -.
DR jPOST; P26149; -.
DR MaxQB; P26149; -.
DR PaxDb; P26149; -.
DR PeptideAtlas; P26149; -.
DR PRIDE; P26149; -.
DR ProteomicsDB; 296417; -.
DR DNASU; 15493; -.
DR Ensembl; ENSMUST00000107021; ENSMUSP00000102635; ENSMUSG00000063730.
DR Ensembl; ENSMUST00000107022; ENSMUSP00000102636; ENSMUSG00000063730.
DR Ensembl; ENSMUST00000177651; ENSMUSP00000136533; ENSMUSG00000063730.
DR GeneID; 15493; -.
DR KEGG; mmu:15493; -.
DR UCSC; uc008qqc.2; mouse.
DR CTD; 3284; -.
DR MGI; MGI:96234; Hsd3b2.
DR VEuPathDB; HostDB:ENSMUSG00000063730; -.
DR eggNOG; KOG1430; Eukaryota.
DR GeneTree; ENSGT00940000155444; -.
DR HOGENOM; CLU_007383_6_3_1; -.
DR InParanoid; P26149; -.
DR OMA; ERDCLEN; -.
DR OrthoDB; 930591at2759; -.
DR PhylomeDB; P26149; -.
DR TreeFam; TF343138; -.
DR UniPathway; UPA00062; -.
DR BioGRID-ORCS; 15493; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Hsd3b2; mouse.
DR PRO; PR:P26149; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; P26149; protein.
DR Bgee; ENSMUSG00000063730; Expressed in right kidney and 22 other tissues.
DR Genevisible; P26149; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
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; IBA:GO_Central.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISO:MGI.
DR GO; GO:0005758; C:mitochondrial intermembrane space; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0003854; F:3-beta-hydroxy-delta5-steroid dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0102294; F:cholesterol dehydrogenase 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; ISS:UniProtKB.
DR GO; GO:0006702; P:androgen biosynthetic process; ISS:UniProtKB.
DR GO; GO:0006700; P:C21-steroid hormone biosynthetic process; 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:0034757; P:negative regulation of iron ion transport; ISO:MGI.
DR GO; GO:0051412; P:response to corticosterone; IBA:GO_Central.
DR GO; GO:0006694; P:steroid biosynthetic process; ISS:UniProtKB.
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; Oxidoreductase;
KW Reference proteome; Steroidogenesis; Transmembrane; Transmembrane helix.
FT CHAIN 1..373
FT /note="3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-
FT isomerase type 2"
FT /id="PRO_0000087781"
FT TRANSMEM 288..308
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ACT_SITE 155
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 159
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT CONFLICT 12
FT /note="G -> K (in Ref. 2; AAH26757/AAH40397)"
FT /evidence="ECO:0000305"
FT CONFLICT 54
FT /note="I -> N (in Ref. 2; AAH26757/AAH40397)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 373 AA; 41923 MW; 2500AF16F38C081B CRC64;
MPGWSCLVTG AGGFLGQRII QLLVQEEDLE EIRVLDKVFR PETRKEFFNL ETSIKVTVLE
GDILDTQYLR RACQGISVVI HTAAIIDVTG VIPRQTILDV NLKGTQNLLE ACIQASVPAF
IFSSSVDVAG PNSYKEIVLN GHEEECHEST WSDPYPYSKK MAEKAVLAAN GSMLKNGGTL
QTCALRPMCI YGERSPLISN IIIMALKHKG ILRSFGKFNT ANPVYVGNVA WAHILAARGL
RDPKKSPNIQ GEFYYISDDT PHQSFDDISY TLSKEWGFCL DSSWSLPVPL LYWLAFLLET
VSFLLSPIYR YIPPFNRHLV TLSGSTFTFS YKKAQRDLGY EPLVSWEEAK QKTSEWIGTL
VEQHRETLDT KSQ