3BHS7_MOUSE
ID 3BHS7_MOUSE Reviewed; 369 AA.
AC Q9EQC1; A2RTR5;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=3 beta-hydroxysteroid dehydrogenase type 7 {ECO:0000305};
DE AltName: Full=3 beta-hydroxysteroid dehydrogenase type VII;
DE Short=3-beta-HSD VII;
DE AltName: Full=3-beta-hydroxy-Delta(5)-C27 steroid oxidoreductase;
DE Short=C(27) 3-beta-HSD;
DE EC=1.1.1.-;
DE AltName: Full=Cholest-5-ene-3-beta,7-alpha-diol 3-beta-dehydrogenase;
DE EC=1.1.1.181 {ECO:0000269|PubMed:11067870};
GN Name=Hsd3b7 {ECO:0000312|MGI:MGI:2141879};
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], FUNCTION, TISSUE SPECIFICITY, AND CATALYTIC
RP ACTIVITY.
RC STRAIN=C57BL/6J X 129/SvEv;
RX PubMed=11067870; DOI=10.1172/jci10902;
RA Schwarz M., Wright A.C., Davis D.L., Nazer H., Bjorkhem I., Russell D.W.;
RT "The bile acid synthetic gene 3beta-hydroxy-delta(5)-C(27)-steroid
RT oxidoreductase is mutated in progressive intrahepatic cholestasis.";
RL J. Clin. Invest. 106:1175-1184(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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;
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).
RN [4]
RP FUNCTION.
RX PubMed=22999953; DOI=10.1016/j.immuni.2012.06.015;
RA Yi T., Wang X., Kelly L.M., An J., Xu Y., Sailer A.W., Gustafsson J.A.,
RA Russell D.W., Cyster J.G.;
RT "Oxysterol gradient generation by lymphoid stromal cells guides activated B
RT cell movement during humoral responses.";
RL Immunity 37:535-548(2012).
CC -!- FUNCTION: The 3-beta-HSD enzymatic system plays a crucial role in the
CC biosynthesis of all classes of hormonal steroids. HSD VII is active
CC against four 7-alpha-hydroxylated sterols. Does not metabolize several
CC different C(19/21) steroids as substrates. Involved in bile acid
CC synthesis (PubMed:11067870). Plays a key role in cell positioning and
CC movement in lymphoid tissues by mediating degradation of 7-alpha,25-
CC dihydroxycholesterol (7-alpha,25-OHC): 7-alpha,25-OHC acts as a ligand
CC for the G protein-coupled receptor GPR183/EBI2, a chemotactic receptor
CC for a number of lymphoid cells (PubMed:22999953).
CC {ECO:0000269|PubMed:11067870, ECO:0000269|PubMed:22999953}.
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;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=7alpha-hydroxycholesterol + NAD(+) = 7alpha-hydroxycholest-4-
CC en-3-one + H(+) + NADH; Xref=Rhea:RHEA:11896, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17500, ChEBI:CHEBI:17899, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; EC=1.1.1.181;
CC Evidence={ECO:0000269|PubMed:11067870};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11897;
CC Evidence={ECO:0000305|PubMed:11067870};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=7alpha,25-dihydroxycholesterol + NAD(+) = 7alpha,25-dihydroxy-
CC 4-cholesten-3-one + H(+) + NADH; Xref=Rhea:RHEA:47156,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:37623, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:81013;
CC Evidence={ECO:0000269|PubMed:11067870};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47157;
CC Evidence={ECO:0000305|PubMed:11067870};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(25R)-cholest-5-en-3beta,7alpha,26-triol + NAD(+) = (25R)-
CC 7alpha,26-dihydroxycholest-4-en-3-one + H(+) + NADH;
CC Xref=Rhea:RHEA:47180, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:76592, ChEBI:CHEBI:87476;
CC Evidence={ECO:0000269|PubMed:11067870};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47181;
CC Evidence={ECO:0000305|PubMed:11067870};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(24S)-7alpha-dihydroxycholesterol + NAD(+) = (24S)-7alpha,24-
CC dihydroxycholest-4-en-3-one + H(+) + NADH; Xref=Rhea:RHEA:47200,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:37640, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:63838;
CC Evidence={ECO:0000269|PubMed:11067870};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47201;
CC Evidence={ECO:0000305|PubMed:11067870};
CC -!- PATHWAY: Lipid metabolism; steroid biosynthesis.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass
CC membrane protein.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in liver.
CC {ECO:0000269|PubMed:11067870}.
CC -!- SIMILARITY: Belongs to the 3-beta-HSD family. {ECO:0000305}.
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DR EMBL; AF277718; AAG37823.1; -; mRNA.
DR EMBL; BC132605; AAI32606.1; -; mRNA.
DR EMBL; BC138589; AAI38590.1; -; mRNA.
DR CCDS; CCDS40145.1; -.
DR RefSeq; NP_598704.2; NM_133943.2.
DR AlphaFoldDB; Q9EQC1; -.
DR SMR; Q9EQC1; -.
DR STRING; 10090.ENSMUSP00000036245; -.
DR SwissLipids; SLP:000001322; -.
DR iPTMnet; Q9EQC1; -.
DR PhosphoSitePlus; Q9EQC1; -.
DR SwissPalm; Q9EQC1; -.
DR jPOST; Q9EQC1; -.
DR MaxQB; Q9EQC1; -.
DR PaxDb; Q9EQC1; -.
DR PRIDE; Q9EQC1; -.
DR ProteomicsDB; 285535; -.
DR Antibodypedia; 27526; 198 antibodies from 27 providers.
DR DNASU; 101502; -.
DR Ensembl; ENSMUST00000046863; ENSMUSP00000036245; ENSMUSG00000042289.
DR GeneID; 101502; -.
DR KEGG; mmu:101502; -.
DR UCSC; uc009jwu.1; mouse.
DR CTD; 80270; -.
DR MGI; MGI:2141879; Hsd3b7.
DR VEuPathDB; HostDB:ENSMUSG00000042289; -.
DR eggNOG; KOG1430; Eukaryota.
DR GeneTree; ENSGT00940000160236; -.
DR HOGENOM; CLU_007383_6_3_1; -.
DR InParanoid; Q9EQC1; -.
DR OMA; GDHFKRG; -.
DR OrthoDB; 930591at2759; -.
DR PhylomeDB; Q9EQC1; -.
DR TreeFam; TF354279; -.
DR Reactome; R-MMU-193368; Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
DR Reactome; R-MMU-193775; Synthesis of bile acids and bile salts via 24-hydroxycholesterol.
DR Reactome; R-MMU-193807; Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
DR UniPathway; UPA00062; -.
DR BioGRID-ORCS; 101502; 2 hits in 76 CRISPR screens.
DR ChiTaRS; Hsd3b7; mouse.
DR PRO; PR:Q9EQC1; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q9EQC1; protein.
DR Bgee; ENSMUSG00000042289; Expressed in hepatobiliary system and 68 other tissues.
DR ExpressionAtlas; Q9EQC1; baseline.
DR Genevisible; Q9EQC1; MM.
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:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005811; C:lipid droplet; ISO:MGI.
DR GO; GO:0003854; F:3-beta-hydroxy-delta5-steroid dehydrogenase activity; IEA:InterPro.
DR GO; GO:0047016; F:cholest-5-ene-3-beta,7-alpha-diol 3-beta-dehydrogenase activity; IMP:UniProtKB.
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:0035754; P:B cell chemotaxis; IMP:UniProtKB.
DR GO; GO:0006707; P:cholesterol catabolic process; ISO:MGI.
DR GO; GO:0001558; P:regulation of cell growth; ISO:MGI.
DR GO; GO:0006694; P:steroid biosynthetic process; IEA:UniProtKB-UniPathway.
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; Lipid metabolism; Membrane; NAD; Oxidoreductase;
KW Reference proteome; Steroidogenesis; Transmembrane; Transmembrane helix.
FT CHAIN 1..369
FT /note="3 beta-hydroxysteroid dehydrogenase type 7"
FT /id="PRO_0000087792"
FT TRANSMEM 289..309
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 312..334
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ACT_SITE 159
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 163
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
SQ SEQUENCE 369 AA; 41135 MW; 5857A690E0600F13 CRC64;
MADSAQVPTL VYLVTGGCGF LGEHIVRMLL EREPRLRELR VFDLHLSSWL EELKAGPVQV
TAIQGDVTQA HEVAAAMSGS HVVIHTAGLV DVFGKASPKT IHKVNVQGTQ NVIDACVQTG
TQYLVYTSSM EVVGPNIKGH PFYRGNEDTP YEAVHSHPYP CSKALAEQLV LEANGRKVNG
GLPLVTCALR PTGIYGEGHQ VMRDFYYQGL RFGGRLFRAV PASVEHGRVY VGNVAWMHIL
VARELEQRAA LMGGQVYFCY DKSPYKSYED FNMEFLSPCG LRLIGAHPLL PYWLLVLLAT
LNALLQWLLR PLVLYTPLLN PYTLAMANTT FTVSTNKAQR HFGYKPLFSW EESRTRTIQW
VQAMEGSAR
