CP8B1_RABIT
ID CP8B1_RABIT Reviewed; 500 AA.
AC O02766;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=7-alpha-hydroxycholest-4-en-3-one 12-alpha-hydroxylase;
DE EC=1.14.14.139 {ECO:0000269|PubMed:1400444, ECO:0000269|PubMed:8943286};
DE AltName: Full=7-alpha-hydroxy-4-cholesten-3-one 12-alpha-hydroxylase {ECO:0000303|PubMed:1400444};
DE AltName: Full=CYPVIIIB1;
DE AltName: Full=Cytochrome P450 8B1;
DE AltName: Full=Sterol 12-alpha-hydroxylase;
GN Name=CYP8B1; Synonyms=CYP12;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 109-120; 129-140; 215-223;
RP 231-242; 324-343; 367-376; 478-491 AND 496-500, FUNCTION, CATALYTIC
RP ACTIVITY, AND TISSUE SPECIFICITY.
RC STRAIN=New Zealand white; TISSUE=Liver;
RX PubMed=8943286; DOI=10.1074/jbc.271.50.32269;
RA Eggertsen G., Olin M., Andersson U., Ishida H., Kubota S., Hellman U.,
RA Okuda K., Bjoerkhem I.;
RT "Molecular cloning and expression of rabbit sterol 12alpha-hydroxylase.";
RL J. Biol. Chem. 271:32269-32275(1996).
RN [2]
RP PROTEIN SEQUENCE OF 2-16, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY
RP REGULATION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RC TISSUE=Liver;
RX PubMed=1400444; DOI=10.1016/s0021-9258(19)36611-6;
RA Ishida H., Noshiro M., Okuda K., Coon M.J.;
RT "Purification and characterization of 7 alpha-hydroxy-4-cholesten-3-one 12
RT alpha-hydroxylase.";
RL J. Biol. Chem. 267:21319-21323(1992).
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 (PubMed:1400444, PubMed:8943286). Controls biliary balance of cholic
CC acid and chenodeoxycholic acid, ultimately regulating the intestinal
CC absorption of dietary lipids (By similarity). Mechanistically, uses
CC 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) (PubMed:1400444, PubMed:8943286).
CC {ECO:0000250|UniProtKB:O88962, ECO:0000269|PubMed:1400444,
CC ECO:0000269|PubMed:8943286}.
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:0000269|PubMed:1400444, ECO:0000269|PubMed:8943286};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46753;
CC Evidence={ECO:0000305|PubMed:1400444, ECO:0000305|PubMed:8943286};
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:0000269|PubMed:1400444, ECO:0000269|PubMed:8943286};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15262;
CC Evidence={ECO:0000305|PubMed:1400444, ECO:0000305|PubMed:8943286};
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:0000269|PubMed:1400444, ECO:0000269|PubMed:8943286};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65701;
CC Evidence={ECO:0000305|PubMed:1400444, ECO:0000305|PubMed:8943286};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000269|PubMed:1400444};
CC -!- ACTIVITY REGULATION: Up-regulated upon treatment with streptozotocin.
CC {ECO:0000269|PubMed:1400444}.
CC -!- PATHWAY: Lipid metabolism; bile acid biosynthesis.
CC {ECO:0000250|UniProtKB:O88962}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:1400444}; Single-pass membrane protein
CC {ECO:0000255}. Microsome membrane {ECO:0000269|PubMed:1400444}; Single-
CC pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Liver (at protein level).
CC {ECO:0000269|PubMed:1400444, ECO:0000269|PubMed:8943286}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; Y08269; CAA69594.1; -; mRNA.
DR PIR; A45103; A45103.
DR RefSeq; NP_001076091.1; NM_001082622.1.
DR AlphaFoldDB; O02766; -.
DR SMR; O02766; -.
DR STRING; 9986.ENSOCUP00000023170; -.
DR SwissLipids; SLP:000001318; -.
DR GeneID; 100009301; -.
DR KEGG; ocu:100009301; -.
DR CTD; 1582; -.
DR eggNOG; KOG0684; Eukaryota.
DR InParanoid; O02766; -.
DR OrthoDB; 572303at2759; -.
DR BioCyc; MetaCyc:MON-14303; -.
DR SABIO-RK; O02766; -.
DR UniPathway; UPA00221; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA: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; IDA:UniProtKB.
DR GO; GO:0006699; P:bile acid biosynthetic process; IDA:UniProtKB.
DR GO; GO:0045797; P:positive regulation of intestinal cholesterol absorption; ISS: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 Direct protein sequencing; Endoplasmic reticulum; Heme; Iron;
KW Lipid biosynthesis; Lipid metabolism; Membrane; Metal-binding; Microsome;
KW Monooxygenase; Oxidoreductase; Phosphoprotein; Reference proteome;
KW Steroid biosynthesis; Stress response; Transmembrane; Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:1400444"
FT CHAIN 2..500
FT /note="7-alpha-hydroxycholest-4-en-3-one 12-alpha-
FT hydroxylase"
FT /id="PRO_0000051915"
FT TRANSMEM 2..21
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"
SQ SEQUENCE 500 AA; 57494 MW; 4FE56CBB724F751E CRC64;
MVLWGLLGAL LMVMVGWLCL PGLLRQRRPQ EPPLDKGSIP WLGHAMTFRK NMLEFLKHMR
SKHGDVFTVQ LGGQYFTFVM DPVSFGPILK DGQRKLDFVE YAKGLVLKVF GYQSIEGDHR
MIHLASTKHL MGHGLEELNK AMLDSLSLVM LGPEGRSPDA SRWHEDGLFH FCYGVMFKAG
YLSLFGHTSD KRQDLLQAEE IFIKFRRFDL LFPRFVYSLL GPREWREVGR LQQLFHELLS
VKHNPEKDGM SNWIGHMLQY LSEQGVAPAM QDKFNFMMLW ASQGNTGPAS FWALIYLLKH
PEAMRAVKEE ATRVLGEPRL EAKQSFTVQL SALQHIPVLD SVMEETLRLG AAPTLYRVVQ
KDILLKMASG QECLLRQGDI VTLFPYLSVH MDPDIHPEPT TFKYDRFLNP NGSRKVDFYK
AGQKIHHYTM PWGSGVSICP GRFFALSEMK LFVLLMVQYF DLELVDPNTP VPPIDPRRWG
FGTMQPTHDV RIRYRLKPLE
