3BHS4_MOUSE
ID 3BHS4_MOUSE Reviewed; 373 AA.
AC Q61767;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=NADPH-dependent 3-keto-steroid reductase Hsd3b4 {ECO:0000305|PubMed:8145763};
DE AltName: Full=3 beta-hydroxysteroid dehydrogenase type 4;
DE AltName: Full=3 beta-hydroxysteroid dehydrogenase type IV {ECO:0000303|PubMed:8145763};
DE Short=3 beta-HSD IV;
DE EC=1.1.1.270 {ECO:0000269|PubMed:8145763};
DE AltName: Full=Dihydrotestosterone 3-ketoreductase {ECO:0000305|PubMed:8145763};
DE EC=1.1.1.210 {ECO:0000269|PubMed:8145763};
GN Name=Hsd3b4 {ECO:0000312|MGI:MGI:96236};
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], TISSUE SPECIFICITY, CATALYTIC ACTIVITY,
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, AND DEVELOPMENTAL STAGE.
RC STRAIN=ICR (CD-1); TISSUE=Kidney;
RX PubMed=8145763; DOI=10.1210/mend.7.12.8145763;
RA Clarke T.R., Bain P.A., Greco T.L., Payne A.H.;
RT "A novel mouse kidney 3 beta-hydroxysteroid dehydrogenase complementary DNA
RT encodes a 3-ketosteroid reductase instead of a 3 beta-hydroxysteroid
RT dehydrogenase/delta 5-delta 4-isomerase.";
RL Mol. Endocrinol. 7:1569-1578(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Kidney;
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).
CC -!- FUNCTION: Responsible for the reduction of the oxo group on the C-3 of
CC 5alpha-androstane steroids. Catalyzes the conversion of
CC dihydrotestosterone to its inactive form 5alpha-androstanediol, that
CC does not bind androgen receptor/AR. Does not function as an isomerase.
CC {ECO:0000269|PubMed:8145763}.
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:0000269|PubMed:8145763};
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:0000269|PubMed:8145763};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.2 uM for dihydrotestosterone {ECO:0000269|PubMed:8145763};
CC -!- PATHWAY: Steroid metabolism. {ECO:0000269|PubMed:8145763}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass
CC membrane protein. Mitochondrion membrane; Single-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Kidney (at protein level); found only in the
CC cortex, appears to be associated with the proximal tubules; and a minor
CC expression in testis. {ECO:0000269|PubMed:8145763}.
CC -!- DEVELOPMENTAL STAGE: Expression between 15-20 days post-implantation
CC occurs only in the kidney of the male fetus and not in the female,
CC whereas a similar expression is found in adult male and female kidneys.
CC {ECO:0000269|PubMed:8145763}.
CC -!- SIMILARITY: Belongs to the 3-beta-HSD family. {ECO:0000305}.
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DR EMBL; L16919; AAA39374.1; -; mRNA.
DR EMBL; BC013449; AAH13449.1; -; mRNA.
DR CCDS; CCDS17665.1; -.
DR PIR; A49573; A49573.
DR RefSeq; NP_001104806.1; NM_001111336.1.
DR RefSeq; NP_001257358.1; NM_001270429.1.
DR RefSeq; NP_032320.1; NM_008294.2.
DR RefSeq; XP_017174900.1; XM_017319411.1.
DR RefSeq; XP_017174957.1; XM_017319468.1.
DR AlphaFoldDB; Q61767; -.
DR STRING; 10090.ENSMUSP00000055886; -.
DR iPTMnet; Q61767; -.
DR PhosphoSitePlus; Q61767; -.
DR jPOST; Q61767; -.
DR MaxQB; Q61767; -.
DR PaxDb; Q61767; -.
DR PRIDE; Q61767; -.
DR DNASU; 15495; -.
DR Ensembl; ENSMUST00000058728; ENSMUSP00000055886; ENSMUSG00000095388.
DR Ensembl; ENSMUST00000178221; ENSMUSP00000136749; ENSMUSG00000095388.
DR Ensembl; ENSMUST00000179429; ENSMUSP00000136588; ENSMUSG00000095143.
DR Ensembl; ENSMUST00000186215; ENSMUSP00000140584; ENSMUSG00000095388.
DR Ensembl; ENSMUST00000196861; ENSMUSP00000142522; ENSMUSG00000095143.
DR GeneID; 100043456; -.
DR GeneID; 15495; -.
DR KEGG; mmu:100043456; -.
DR KEGG; mmu:15495; -.
DR UCSC; uc008qpw.3; mouse.
DR CTD; 100043456; -.
DR CTD; 15495; -.
DR MGI; MGI:96236; Hsd3b4.
DR VEuPathDB; HostDB:ENSMUSG00000095143; -.
DR VEuPathDB; HostDB:ENSMUSG00000095388; -.
DR eggNOG; KOG1430; Eukaryota.
DR GeneTree; ENSGT00940000155444; -.
DR HOGENOM; CLU_007383_6_3_1; -.
DR InParanoid; Q61767; -.
DR OMA; PVYVGWA; -.
DR OrthoDB; 930591at2759; -.
DR PhylomeDB; Q61767; -.
DR TreeFam; TF343138; -.
DR BioGRID-ORCS; 100043456; 2 hits in 12 CRISPR screens.
DR BioGRID-ORCS; 15495; 4 hits in 20 CRISPR screens.
DR ChiTaRS; Hsd3b4; mouse.
DR PRO; PR:Q61767; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q61767; protein.
DR Bgee; ENSMUSG00000095143; Expressed in proximal tubule and 47 other tissues.
DR ExpressionAtlas; Q61767; baseline.
DR Genevisible; Q61767; 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:0005743; C:mitochondrial inner membrane; HDA: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: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: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:0042448; P:progesterone metabolic process; ISO:MGI.
DR GO; GO:0050810; P:regulation of steroid biosynthetic process; ISO:MGI.
DR GO; GO:0051412; P:response to corticosterone; IBA:GO_Central.
DR GO; GO:0035634; P:response to stilbenoid; IEP:UniProtKB.
DR GO; GO:0006694; P:steroid biosynthetic process; ISO:MGI.
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 Acetylation; Endoplasmic reticulum; Lipid metabolism; Membrane;
KW Mitochondrion; NADP; Oxidoreductase; Reference proteome;
KW Steroid metabolism; Transmembrane; Transmembrane helix.
FT CHAIN 1..373
FT /note="NADPH-dependent 3-keto-steroid reductase Hsd3b4"
FT /id="PRO_0000087783"
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 MOD_RES 350
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q61694"
SQ SEQUENCE 373 AA; 41766 MW; 303E56BF9A8FAF1A CRC64;
MPGWSCLVTG AGGFLGQRIV RMLVQEEELQ EIRALFRTFG RKQEEELSKL QTKTKVTVLK
GDILDAQCLK RACQGMSAVI HTAAAIDPLG AASRQTILDV NLKGTQLLLD ACVEANVPTF
IYSSSVLVAG PNSYKEIILN AHEEEHHEST WSNPYPYSKK MAEKAVLAAN GSILKNGGTL
HTCALRLSFI YGEECQVTST TVKTALKNNS IIKKNATFSI ANPVYVGNAA WAHILAARSL
QDPKKSPSIQ GQFYYITDDT PHQSYDDLKC TLSKEWGLRL DTSWSLPLPL LYWLAFLLET
VSFLLRPVYN YRPPFNRLLI TVLNSVFTFS YKKAQRDLGY EPLVSWEEAK QKTSEWIGTL
VMQHREIGNK KSQ
