ID CP7A1_RABIT Reviewed; 501 AA.
AC P51542;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 08-NOV-2023, entry version 125.
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:0000303|PubMed:7751825};
DE AltName: Full=Cholesterol 7-alpha-monooxygenase;
DE EC=1.14.14.23 {ECO:0000269|PubMed:7751825};
GN Name=CYP7A1; Synonyms=CYP7;
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], CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY.
RC STRAIN=New Zealand white; TISSUE=Liver;
RX PubMed=7751825;
RA Kai M., Eto T., Kondo K., Setoguchi Y., Higashi S., Maeda Y., Setoguchi T.;
RT "Synchronous circadian rhythms of mRNA levels and activities of cholesterol
RT 7 alpha-hydroxylase in the rabbit and rat.";
RL J. Lipid Res. 36:367-374(1995).
CC -!- FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of
CC endogenous cholesterol and its oxygenated derivatives (oxysterols) (By
CC similarity). Mechanistically, uses molecular oxygen inserting one
CC oxygen atom into a substrate, and reducing the second into a water
CC molecule, with two electrons provided by NADPH via cytochrome P450
CC reductase (CPR; NADPH-ferrihemoprotein reductase) (By similarity).
CC Functions as a critical regulatory enzyme of bile acid biosynthesis and
CC cholesterol homeostasis (Probable). Catalyzes the hydroxylation of
CC carbon hydrogen bond at 7-alpha position of cholesterol, a rate-
CC limiting step in cholesterol catabolism and bile acid biosynthesis
CC (Probable). 7-alpha hydroxylates several oxysterols, including 4beta-
CC hydroxycholesterol and 24-hydroxycholesterol (By similarity). Catalyzes
CC the oxidation of the 7,8 double bond of 7-dehydrocholesterol and
CC lathosterol with direct and predominant formation of the 7-keto
CC derivatives (By similarity). {ECO:0000250|UniProtKB:P22680,
CC ECO:0000305|PubMed:7751825}.
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:0000305|PubMed:7751825};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21813;
CC Evidence={ECO:0000305|PubMed:7751825};
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:0000305|PubMed:7751825}.
CC -!- PATHWAY: Steroid metabolism; cholesterol degradation.
CC {ECO:0000305|PubMed:7751825}.
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 -!- TISSUE SPECIFICITY: Detected in liver. {ECO:0000269|PubMed:7751825}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; L10754; AAA74382.1; -; mRNA.
DR PIR; I46701; I46701.
DR RefSeq; NP_001164400.1; NM_001170929.1.
DR AlphaFoldDB; P51542; -.
DR SMR; P51542; -.
DR STRING; 9986.ENSOCUP00000010572; -.
DR PaxDb; 9986-ENSOCUP00000010572; -.
DR GeneID; 100328551; -.
DR KEGG; ocu:100328551; -.
DR CTD; 1581; -.
DR eggNOG; KOG0684; Eukaryota.
DR InParanoid; P51542; -.
DR OrthoDB; 1537669at2759; -.
DR UniPathway; UPA00221; -.
DR UniPathway; UPA01058; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
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: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 CDD; cd20631; CYP7A1; 1.
DR Gene3D; 1.10.630.10; Cytochrome P450; 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; CYTOCHROME P450 7A1; 1.
DR PANTHER; PTHR24304; CYTOCHROME P450 FAMILY 7; 1.
DR Pfam; PF00067; p450; 1.
DR PIRSF; PIRSF500625; Cytochrome_CYP7A1; 1.
DR PIRSF; PIRSF000047; Cytochrome_CYPVIIA1; 1.
DR PRINTS; PR00465; EP450IV.
DR SUPFAM; SSF48264; Cytochrome P450; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
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_0000051904"
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; 58090 MW; FEF1247B151AA6B1 CRC64;
MITIFWIWGI CLSVCCCLWL ILGLRRRRMG EPPLEKGWIP YLGCALQFGA NPLDFLRANQ
RKYGHVFTCK LMGKYVHFIT NSLSYHKVLC HGKYFDWKKF HFTTSAKAFG HRSIDPRDGN
TTENINNTFN KTLQGDALIS LTDAMMENLQ LTLRRPEPKS RAWVTEGMYS FCYRVMFEAG
YLTLFGRELT RQDAQRAFIL NSLEDFKQFD KVFPALVAGL PIHIFMTAHN AREKLAEGLK
HDNLRTRDHI SELIRLRMFL NDTLSTFDAM EKAKTHLAIL WASQANTIPA TFWSLFHMMR
SSEALKAATE EVNKALEDAD QQINFEGKPI HLNQTQLNDM PVLDSIIKES LRLSSASLNI
RTAKEDFTLH LEDGSYNIRK DDIIALYPQL MHLDPEIYPD PMTFKYDRYL DENRKTKTTF
YSKGLKLKYY YMPFGSGATI CPGRLFAIQE IKQFLILMLS YFELEFVDSH VKCPPLDQSR
AGLGILPPLN DIEFKYKFKH L
//
