CP8B1_MOUSE
ID CP8B1_MOUSE Reviewed; 500 AA.
AC O88962; Q9R217;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=7-alpha-hydroxycholest-4-en-3-one 12-alpha-hydroxylase;
DE EC=1.14.14.139 {ECO:0000250|UniProtKB:O02766};
DE AltName: Full=7-alpha-hydroxy-4-cholesten-3-one 12-alpha-hydroxylase;
DE AltName: Full=CYPVIIIB1;
DE AltName: Full=Cytochrome P450 8B1;
DE AltName: Full=Sterol 12-alpha-hydroxylase;
GN Name=Cyp8b1; Synonyms=Cyp12;
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 [GENOMIC DNA / MRNA], VARIANT LYS-242, TISSUE
RP SPECIFICITY, AND INDUCTION.
RC STRAIN=129/SvJ, and BALB/cJ; TISSUE=Liver;
RX PubMed=10051404; DOI=10.1006/geno.1998.5606;
RA Gaafvels M., Olin M., Chowdhary B.P., Raudsepp T., Andersson U.,
RA Persson B., Jansson M., Bjoerkhem I., Eggertsen G.;
RT "Structure and chromosomal assignment of the sterol 12alpha-hydroxylase
RT gene (CYP8B1) in human and mouse: eukaryotic cytochrome P-450 gene devoid
RT of introns.";
RL Genomics 56:184-196(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=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 FUNCTION, PATHWAY, AND DISRUPTION PHENOTYPE.
RX PubMed=12393855; DOI=10.1172/jci16309;
RA Li-Hawkins J., Gaafvels M., Olin M., Lund E.G., Andersson U., Schuster G.,
RA Bjoerkhem I., Russell D.W., Eggertsen G.;
RT "Cholic acid mediates negative feedback regulation of bile acid synthesis
RT in mice.";
RL J. Clin. Invest. 110:1191-1200(2002).
RN [4]
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 [5]
RP FUNCTION, PATHWAY, AND DISRUPTION PHENOTYPE.
RX PubMed=28377401; DOI=10.1152/ajpendo.00409.2016;
RA Bertaggia E., Jensen K.K., Castro-Perez J., Xu Y., Di Paolo G., Chan R.B.,
RA Wang L., Haeusler R.A.;
RT "Cyp8b1 ablation prevents Western diet-induced weight gain and hepatic
RT steatosis because of impaired fat absorption.";
RL Am. J. Physiol. 313:E121-E133(2017).
CC -!- FUNCTION: A cytochrome P450 monooxygenase involved in primary bile acid
CC biosynthesis. Catalyzes the 12alpha-hydroxylation of 7alpha-hydroxy-4-
CC cholesten-3-one, an intermediate metabolite in cholic acid biosynthesis
CC (By similarity). Controls biliary balance of cholic acid and
CC chenodeoxycholic acid, ultimately regulating the intestinal absorption
CC of dietary lipids (PubMed:12393855, PubMed:28377401). Mechanistically,
CC uses molecular oxygen inserting one oxygen atom into a substrate, and
CC reducing the second into a water molecule, with two electrons provided
CC by NADPH via cytochrome P450 reductase (CPR; NADPH--hemoprotein
CC reductase) (By similarity). {ECO:0000250|UniProtKB:O02766,
CC ECO:0000250|UniProtKB:Q9UNU6, ECO:0000269|PubMed:12393855,
CC ECO:0000269|PubMed:28377401}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=7alpha-hydroxycholest-4-en-3-one + O2 + reduced [NADPH--
CC hemoprotein reductase] = 7alpha,12alpha-dihydroxycholest-4-en-3-one +
CC H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:46752, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:17899, ChEBI:CHEBI:28477, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; EC=1.14.14.139;
CC Evidence={ECO:0000250|UniProtKB:O02766};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46753;
CC Evidence={ECO:0000250|UniProtKB:O02766};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5beta-cholestane-3alpha,7alpha-diol + O2 + reduced [NADPH--
CC hemoprotein reductase] = 5beta-cholestane-3alpha,7alpha,12alpha-triol
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:15261, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16496, ChEBI:CHEBI:28047, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; EC=1.14.14.139;
CC Evidence={ECO:0000250|UniProtKB:O02766};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15262;
CC Evidence={ECO:0000250|UniProtKB:O02766};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chenodeoxycholate + O2 + reduced [NADPH--hemoprotein
CC reductase] = cholate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:65700, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:29747, ChEBI:CHEBI:36234, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; EC=1.14.14.139;
CC Evidence={ECO:0000250|UniProtKB:O02766};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65701;
CC Evidence={ECO:0000250|UniProtKB:O02766};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:O02766};
CC -!- PATHWAY: Lipid metabolism; bile acid biosynthesis.
CC {ECO:0000269|PubMed:12393855, ECO:0000269|PubMed:28377401}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:O02766}; Single-pass membrane protein
CC {ECO:0000255}. Microsome membrane {ECO:0000250|UniProtKB:O02766};
CC Single-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in liver. {ECO:0000269|PubMed:10051404}.
CC -!- INDUCTION: By cholestyramine treatment (PubMed:10051404). Induced upon
CC starvation (PubMed:10051404). {ECO:0000269|PubMed:10051404}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice are resistant to Western diet-
CC induced hepatic steatosis due to impaired cholic acid synthesis and
CC deficient fat absorption. {ECO:0000269|PubMed:12393855,
CC ECO:0000269|PubMed:28377401}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; AF090317; AAC63036.1; -; mRNA.
DR EMBL; AF090319; AAD19876.1; -; Genomic_DNA.
DR EMBL; BC010973; AAH10973.1; -; mRNA.
DR EMBL; BC010974; AAH10974.1; -; mRNA.
DR EMBL; BC049969; AAH49969.1; -; mRNA.
DR CCDS; CCDS23641.1; -.
DR RefSeq; NP_034142.3; NM_010012.3.
DR AlphaFoldDB; O88962; -.
DR SMR; O88962; -.
DR STRING; 10090.ENSMUSP00000052989; -.
DR iPTMnet; O88962; -.
DR PhosphoSitePlus; O88962; -.
DR SwissPalm; O88962; -.
DR jPOST; O88962; -.
DR MaxQB; O88962; -.
DR PaxDb; O88962; -.
DR PeptideAtlas; O88962; -.
DR PRIDE; O88962; -.
DR ProteomicsDB; 285284; -.
DR GeneID; 13124; -.
DR KEGG; mmu:13124; -.
DR UCSC; uc009sef.2; mouse.
DR CTD; 1582; -.
DR MGI; MGI:1338044; Cyp8b1.
DR eggNOG; KOG0684; Eukaryota.
DR InParanoid; O88962; -.
DR OrthoDB; 572303at2759; -.
DR PhylomeDB; O88962; -.
DR TreeFam; TF105090; -.
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 Reactome; R-MMU-197264; Nicotinamide salvaging.
DR Reactome; R-MMU-211979; Eicosanoids.
DR Reactome; R-MMU-211994; Sterols are 12-hydroxylated by CYP8B1.
DR Reactome; R-MMU-2162123; Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
DR UniPathway; UPA00221; -.
DR BioGRID-ORCS; 13124; 1 hit in 75 CRISPR screens.
DR PRO; PR:O88962; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; O88962; protein.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0033779; F:5beta-cholestane-3alpha,7alpha-diol 12alpha-hydroxylase activity; IEA:UniProtKB-EC.
DR GO; GO:0033778; F:7alpha-hydroxycholest-4-en-3-one 12alpha-hydroxylase activity; IEA:UniProtKB-EC.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0008397; F:sterol 12-alpha-hydroxylase activity; ISS:UniProtKB.
DR GO; GO:0006699; P:bile acid biosynthetic process; IMP:UniProtKB.
DR GO; GO:0045797; P:positive regulation of intestinal cholesterol absorption; IDA:UniProtKB.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR024204; Cyt_P450_CYP7A1-type.
DR InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR InterPro; IPR036396; Cyt_P450_sf.
DR InterPro; IPR030686; Cytochrome_CYP8B1.
DR PANTHER; PTHR24306:SF0; PTHR24306:SF0; 1.
DR Pfam; PF00067; p450; 1.
DR PIRSF; PIRSF500627; Cytochrome_CYP8B1; 1.
DR PIRSF; PIRSF000047; Cytochrome_CYPVIIA1; 1.
DR PRINTS; PR00465; EP450IV.
DR SUPFAM; SSF48264; SSF48264; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Heme; Iron; Lipid biosynthesis; Lipid metabolism;
KW Membrane; Metal-binding; Microsome; Monooxygenase; Oxidoreductase;
KW Phosphoprotein; Reference proteome; Steroid biosynthesis; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..500
FT /note="7-alpha-hydroxycholest-4-en-3-one 12-alpha-
FT hydroxylase"
FT /id="PRO_0000051914"
FT TRANSMEM 4..24
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 439
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250"
FT MOD_RES 325
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UNU6"
FT VARIANT 242
FT /note="E -> K (in strain: 129/SvJ)"
FT /evidence="ECO:0000269|PubMed:10051404"
SQ SEQUENCE 500 AA; 57706 MW; D6902755B4AD141A CRC64;
MTLWCTVLGA LLTVVGCLCL SLLLRHRRPW EPPLDKGFVP WLGHSMAFRK NMFEFLKGMR
AKHGDVFTVQ LGGQYFTFVM DPLSFGPIIK NTEKALDFQS YAKELVLKVF GYQSVDGDHR
MIHLASTKHL MGQGLEELNQ AMLDSLSLVM LGPKGSSLGA SSWCEDGLFH FCYRILFKAG
FLSLFGYTKD KQQDLDEADE LFRKFRRFDF LFPRFVYSLL GPREWVEVSQ LQRLFHQRLS
VEQNLEKDGI SCWLGYMLQF LREQGIASSM QDKFNFMMLW ASQGNTGPTC FWVLLFLLKH
QDAMKAVREE ATRVMGKARL EAKKSFTFTP SALKHTPVLD SVMEESLRLC ATPTLLRVVQ
EDYVLKMASG QEYQIRRGDK VALFPYLSVH MDPDIHPEPT AFKYDRFLNP DGTRKVDFYK
SGKKIHHYSM PWGSGVSKCP GRFFALSEMK TFVLLMIMYF DFKLVDPDIP VPPIDPRRWG
FGTSQPSHEV RFLYRLKPVQ
