CP8B1_PIG
ID CP8B1_PIG Reviewed; 501 AA.
AC Q7YRB2;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=5-beta-cholestane-3-alpha,7-alpha-diol 12-alpha-hydroxylase;
DE EC=1.14.14.139 {ECO:0000269|PubMed:14643796};
DE AltName: Full=CYPVIIIB1;
DE AltName: Full=Cytochrome P450 8B1;
DE AltName: Full=Sterol 12-alpha-hydroxylase;
GN Name=CYP8B1;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP DEVELOPMENTAL STAGE.
RC TISSUE=Liver;
RX PubMed=14643796; DOI=10.1016/j.bbalip.2003.09.002;
RA Lundell K., Wikvall K.;
RT "Gene structure of pig sterol 12alpha-hydroxylase (CYP8B1) and expression
RT in fetal liver: comparison with expression of taurochenodeoxycholic acid
RT 6alpha-hydroxylase (CYP4A21).";
RL Biochim. Biophys. Acta 1634:86-96(2003).
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:14643796). Controls biliary balance of cholic acid and
CC chenodeoxycholic acid, ultimately regulating the intestinal absorption
CC of dietary lipids (By similarity). Mechanistically, uses molecular
CC oxygen inserting one oxygen atom into a substrate, and reducing the
CC second into a water molecule, with two electrons provided by NADPH via
CC cytochrome P450 reductase (CPR; NADPH--hemoprotein reductase) (By
CC similarity). {ECO:0000250|UniProtKB:O02766,
CC ECO:0000250|UniProtKB:O88962, ECO:0000269|PubMed:14643796}.
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:14643796};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46753;
CC Evidence={ECO:0000305|PubMed:14643796};
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:14643796};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15262;
CC Evidence={ECO:0000305|PubMed:14643796};
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:14643796};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65701;
CC Evidence={ECO:0000305|PubMed:14643796};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:O02766};
CC -!- PATHWAY: Lipid metabolism; bile acid biosynthesis.
CC {ECO:0000250|UniProtKB:O88962}.
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 -!- DEVELOPMENTAL STAGE: Expressed in fetal liver, but absent in 4 days old
CC and 6 weeks old unweaned pigs. {ECO:0000269|PubMed:14643796}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; AJ488932; CAD32936.1; -; Genomic_DNA.
DR RefSeq; NP_999591.1; NM_214426.1.
DR AlphaFoldDB; Q7YRB2; -.
DR SMR; Q7YRB2; -.
DR PRIDE; Q7YRB2; -.
DR GeneID; 403328; -.
DR KEGG; ssc:403328; -.
DR CTD; 1582; -.
DR InParanoid; Q7YRB2; -.
DR OrthoDB; 1318335at2759; -.
DR UniPathway; UPA00221; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
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; 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 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..501
FT /note="5-beta-cholestane-3-alpha,7-alpha-diol 12-alpha-
FT hydroxylase"
FT /id="PRO_0000280745"
FT TRANSMEM 1..21
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 440
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 326
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UNU6"
SQ SEQUENCE 501 AA; 57772 MW; 68FFC6C70DA134ED CRC64;
MVLWGPVLGV LLVAIVGYLC LQGLLRQRRP EEPPLDKGSV PWLGHAMTFR KNMLEFLKHM
WARHGDIFTV QLGGQYFTFV MDPLSFGPIL KDAKRKLDFV EYAEKLVLKV FGYRSMQGDH
RMIHSASTKH LMGDGLEELN KAMLDNLSLV MLGPKGPSPD ASCWREDGLF HFCYDILFKA
GYLSLFGRTE DKEQDLLQAE ELFMQFRKFD RMFPRFVYSL LGPREWLEVG RLQCLFHKML
SVEHSLERHG ISSWITDMLQ VLREQGVAPA MQDKFNFMML WASQGNTGPT TFWALLFLLK
HPEAMRAVRE EATRVLGEAR LEDKQSFDVE VSALNHMPVL DSVMEETLRL GAAPTLLRVV
NSDQILKMAS GQEYRLRHGD ILALFPYLSV HMDPDIHPEP TTFKYDRFLT PSGSRKVNFY
KAGKKIHHYT MPWGSGISIC PGRFFALTEM KLFVLLMVTH FDLELVDPDT PVPPVDPQRW
GFGTMQPSYE VRFRYRLRPT E
