CP7A1_PIG
ID CP7A1_PIG Reviewed; 501 AA.
AC O46491;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Cytochrome P450 7A1 {ECO:0000250|UniProtKB:P22680};
DE AltName: Full=24-hydroxycholesterol 7-alpha-hydroxylase {ECO:0000250|UniProtKB:P22680};
DE EC=1.14.14.26 {ECO:0000250|UniProtKB:P22680};
DE AltName: Full=CYPVII;
DE AltName: Full=Cholesterol 7-alpha-hydroxylase {ECO:0000250|UniProtKB:P22680};
DE AltName: Full=Cholesterol 7-alpha-monooxygenase;
DE EC=1.14.14.23 {ECO:0000250|UniProtKB:P22680};
GN Name=CYP7A1; Synonyms=CYP7;
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].
RA Ishimura-Oka K., Li C.M., Chang B.H.J., Pond W.G., Oka K., Chan L.;
RT "Structure of the porcine cholesterol 7 alpha-hydroxylase gene.";
RL Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of
CC endogenous cholesterol and its oxygenated derivatives (oxysterols).
CC Mechanistically, uses molecular oxygen inserting one oxygen atom into a
CC substrate, and reducing the second into a water molecule, with two
CC electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-
CC ferrihemoprotein reductase). Functions as a critical regulatory enzyme
CC of bile acid biosynthesis and cholesterol homeostasis. Catalyzes the
CC hydroxylation of carbon hydrogen bond at 7-alpha position of
CC cholesterol, a rate-limiting step in cholesterol catabolism and bile
CC acid biosynthesis. 7-alpha hydroxylates several oxysterols, including
CC 4beta-hydroxycholesterol and 24-hydroxycholesterol. Catalyzes the
CC oxidation of the 7,8 double bond of 7-dehydrocholesterol and
CC lathosterol with direct and predominant formation of the 7-keto
CC derivatives. {ECO:0000250|UniProtKB:P22680}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholesterol + O2 + reduced [NADPH--hemoprotein reductase] =
CC 7alpha-hydroxycholesterol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:21812, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16113, ChEBI:CHEBI:17500, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; EC=1.14.14.23;
CC Evidence={ECO:0000250|UniProtKB:P22680};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21813;
CC Evidence={ECO:0000250|UniProtKB:P22680};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4beta-hydroxycholesterol + O2 + reduced [NADPH--hemoprotein
CC reductase] = 4beta,7alpha-dihydroxycholesterol + H(+) + H2O +
CC oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:46120,
CC Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:85778, ChEBI:CHEBI:85779;
CC Evidence={ECO:0000250|UniProtKB:P22680};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46121;
CC Evidence={ECO:0000250|UniProtKB:P22680};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=lathosterol + O2 + reduced [NADPH--hemoprotein reductase] =
CC 7alpha,8alpha-epoxy-5alpha-cholestan-3beta-ol + H(+) + H2O + oxidized
CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:53256, Rhea:RHEA-
CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17168,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:137063;
CC Evidence={ECO:0000250|UniProtKB:P22680};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53257;
CC Evidence={ECO:0000250|UniProtKB:P22680};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=lathosterol + O2 + reduced [NADPH--hemoprotein reductase] =
CC 5alpha-cholestan-7-oxo-3beta-ol + H(+) + H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:53252, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17168, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:137062;
CC Evidence={ECO:0000250|UniProtKB:P22680};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53253;
CC Evidence={ECO:0000250|UniProtKB:P22680};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=7-dehydrocholesterol + O2 + reduced [NADPH--hemoprotein
CC reductase] = 7-oxocholesterol + H(+) + H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:53248, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17759, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:64294;
CC Evidence={ECO:0000250|UniProtKB:P22680};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53249;
CC Evidence={ECO:0000250|UniProtKB:P22680};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(24S)-hydroxycholesterol + O2 + reduced [NADPH--hemoprotein
CC reductase] = (24S)-7alpha-dihydroxycholesterol + H(+) + H2O +
CC oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:46124,
CC Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:34310,
CC ChEBI:CHEBI:37640, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
CC EC=1.14.14.26; Evidence={ECO:0000250|UniProtKB:P22680};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46125;
CC Evidence={ECO:0000250|UniProtKB:P22680};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(24R)-hydroxycholesterol + O2 + reduced [NADPH--hemoprotein
CC reductase] = (24R)-7alpha-dihydroxycholesterol + H(+) + H2O +
CC oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:16093,
CC Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:50516,
CC ChEBI:CHEBI:50518, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
CC Evidence={ECO:0000250|UniProtKB:P22680};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16094;
CC Evidence={ECO:0000250|UniProtKB:P22680};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P22680};
CC -!- PATHWAY: Lipid metabolism; bile acid biosynthesis.
CC {ECO:0000250|UniProtKB:P22680}.
CC -!- PATHWAY: Steroid metabolism; cholesterol degradation.
CC {ECO:0000250|UniProtKB:P22680}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P22680}; Single-pass membrane protein
CC {ECO:0000250|UniProtKB:P22680}. Microsome membrane
CC {ECO:0000250|UniProtKB:P22680}; Single-pass membrane protein
CC {ECO:0000250|UniProtKB:P22680}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; AF020322; AAC04676.1; -; Genomic_DNA.
DR EMBL; AF020317; AAC04676.1; JOINED; Genomic_DNA.
DR EMBL; AF020318; AAC04676.1; JOINED; Genomic_DNA.
DR EMBL; AF020319; AAC04676.1; JOINED; Genomic_DNA.
DR EMBL; AF020320; AAC04676.1; JOINED; Genomic_DNA.
DR EMBL; AF020321; AAC04676.1; JOINED; Genomic_DNA.
DR AlphaFoldDB; O46491; -.
DR SMR; O46491; -.
DR STRING; 9823.ENSSSCP00000006650; -.
DR PaxDb; O46491; -.
DR Ensembl; ENSSSCT00025061478; ENSSSCP00025026104; ENSSSCG00025045274.
DR Ensembl; ENSSSCT00035036823; ENSSSCP00035014675; ENSSSCG00035027837.
DR Ensembl; ENSSSCT00055009982; ENSSSCP00055007897; ENSSSCG00055005084.
DR Ensembl; ENSSSCT00070004802; ENSSSCP00070003923; ENSSSCG00070002514.
DR eggNOG; KOG0684; Eukaryota.
DR InParanoid; O46491; -.
DR Reactome; R-SSC-192105; Synthesis of bile acids and bile salts.
DR Reactome; R-SSC-193368; Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
DR Reactome; R-SSC-193807; Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
DR Reactome; R-SSC-211976; Endogenous sterols.
DR UniPathway; UPA00221; -.
DR UniPathway; UPA01058; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Chromosome 4.
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; ISS:UniProtKB.
DR GO; GO:0033782; F:24-hydroxycholesterol 7alpha-hydroxylase activity; IEA:UniProtKB-EC.
DR GO; GO:0008123; F:cholesterol 7-alpha-monooxygenase activity; ISS:UniProtKB.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0008395; F:steroid hydroxylase activity; IBA:GO_Central.
DR GO; GO:0006699; P:bile acid biosynthetic process; ISS:UniProtKB.
DR GO; GO:0071397; P:cellular response to cholesterol; ISS:UniProtKB.
DR GO; GO:0071333; P:cellular response to glucose stimulus; ISS:UniProtKB.
DR GO; GO:0006707; P:cholesterol catabolic process; ISS:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; ISS:UniProtKB.
DR GO; GO:0070857; P:regulation of bile acid biosynthetic process; ISS:UniProtKB.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR030681; Cholesterol_7a_monooxygenase.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR024204; Cyt_P450_CYP7A1-type.
DR InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR InterPro; IPR036396; Cyt_P450_sf.
DR PANTHER; PTHR24304:SF1; PTHR24304:SF1; 1.
DR Pfam; PF00067; p450; 1.
DR PIRSF; PIRSF500625; Cytochrome_CYP7A1; 1.
DR PIRSF; PIRSF000047; Cytochrome_CYPVIIA1; 1.
DR PRINTS; PR00465; EP450IV.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 3: Inferred from homology;
KW Cholesterol metabolism; Endoplasmic reticulum; Heme; Iron;
KW Lipid metabolism; Membrane; Metal-binding; Microsome; Monooxygenase;
KW Oxidoreductase; Reference proteome; Steroid metabolism; Sterol metabolism;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..501
FT /note="Cytochrome P450 7A1"
FT /id="PRO_0000051903"
FT TRANSMEM 4..24
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 441
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|UniProtKB:P22680"
SQ SEQUENCE 501 AA; 56846 MW; 7B56BEDC4371BFED CRC64;
MMSISLLGGI VTAVCCCLWL LLGMRRRQTG EPPLENGIIP YLGCALQFGA NPLEFLRANQ
RKHGHIFTCQ LMGNYVHFIT NPLSYHKVLC HGKYLDWKKF HFTASAKAFG HRSIDPSDGN
TTDNINKTII KTLQGDALNL LAAAMMENLQ LVLRPQVAPQ PEKPAWVTEG MYSFCYRVMF
EAGYVTLFGK DPIGHDAQKA LILNNLDNFK QFDKIFPALV AGFPIHVFKT GHYAREKLAE
GLRLQKLRKR DHISELVRFL NDTLSTLDDA EKAKSLLAVL WASQANTIPA TFWCLFQTIR
SPEAMKAASE EVNKTLEKAG QKISLDDKPI YLNQIELDSM PVLDSIIKES LRLSSASLNI
RTAKEDFTLH LQDGSYNIRK DDIIALYPQL MHLDPEIYPD PLTFKYDRYL DENGKTKTTF
YSHGLKLKYY YMPFGSGATI CPGRLFAVQE IKQFLILMLS YFDLELVESH VKCPPLDQSR
AGLGILPPSN DIEFRYKLKH L
