ID   CP7A1_HUMAN             Reviewed;         504 AA.
AC   P22680; P78454; Q3MIL8; Q7KZ19;
DT   01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-1994, sequence version 2.
DT   02-SEP-2026, entry version 217.
DE   RecName: Full=Cytochrome P450 7A1 {ECO:0000303|PubMed:21813643};
DE   AltName: Full=24-hydroxycholesterol 7-alpha-hydroxylase {ECO:0000305|PubMed:11013305};
DE            EC=1.14.14.26 {ECO:0000269|PubMed:11013305};
DE   AltName: Full=CYPVII;
DE   AltName: Full=Cholesterol 7-alpha-hydroxylase {ECO:0000303|PubMed:11013305};
DE   AltName: Full=Cholesterol 7-alpha-monooxygenase;
DE            EC=1.14.14.23 {ECO:0000269|PubMed:2384150};
GN   Name=CYP7A1 {ECO:0000303|PubMed:12077124, ECO:0000312|HGNC:HGNC:2651};
GN   Synonyms=CYP7;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=8439551; DOI=10.1016/0167-4781(93)90281-h;
RA   Nishimoto M., Noshiro M., Okuda K.;
RT   "Structure of the gene encoding human liver cholesterol 7 alpha-
RT   hydroxylase.";
RL   Biochim. Biophys. Acta 1172:147-150(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, VARIANT ASN-347, FUNCTION,
RP   PATHWAY, AND SUBCELLULAR LOCATION.
RX   PubMed=2384150; DOI=10.1016/0014-5793(90)80992-r;
RA   Noshiro M., Okuda K.;
RT   "Molecular cloning and sequence analysis of cDNA encoding human cholesterol
RT   7 alpha-hydroxylase.";
RL   FEBS Lett. 268:137-140(1990).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-100.
RX   PubMed=1610352; DOI=10.1016/0006-291x(92)91665-d;
RA   Karam W.G., Chiang J.Y.;
RT   "Polymorphisms of human cholesterol 7 alpha-hydroxylase.";
RL   Biochem. Biophys. Res. Commun. 185:588-595(1992).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   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   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-140.
RC   TISSUE=Placenta;
RX   PubMed=8020987; DOI=10.1006/geno.1994.1177;
RA   Wang D.P., Chiang J.Y.;
RT   "Structure and nucleotide sequences of the human cholesterol 7 alpha-
RT   hydroxylase gene (CYP7).";
RL   Genomics 20:320-323(1994).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-25.
RX   PubMed=1312351; DOI=10.1021/bi00124a014;
RA   Molowa D.T., Chen W.S., Cimis G.M., Tan C.P.;
RT   "Transcriptional regulation of the human cholesterol 7 alpha-hydroxylase
RT   gene.";
RL   Biochemistry 31:2539-2544(1992).
RN   [7]
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, AND
RP   SUBCELLULAR LOCATION.
RX   PubMed=11013305; DOI=10.1016/s0022-2275(20)31996-9;
RA   Norlin M., Toll A., Bjoerkhem I., Wikvall K.;
RT   "24-hydroxycholesterol is a substrate for hepatic cholesterol 7alpha-
RT   hydroxylase (CYP7A).";
RL   J. Lipid Res. 41:1629-1639(2000).
RN   [8]
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RX   PubMed=12077124; DOI=10.1074/jbc.m201712200;
RA   Bodin K., Andersson U., Rystedt E., Ellis E., Norlin M., Pikuleva I.,
RA   Eggertsen G., Bjoerkhem I., Diczfalusy U.;
RT   "Metabolism of 4 beta -hydroxycholesterol in humans.";
RL   J. Biol. Chem. 277:31534-31540(2002).
RN   [9]
RP   INDUCTION BY CHENODEOXYCHOLIC ACID AND CHOLESTYRAMINE, AND TISSUE
RP   SPECIFICITY.
RX   PubMed=15796896; DOI=10.1016/j.bbrc.2005.02.170;
RA   Abrahamsson A., Gustafsson U., Ellis E., Nilsson L.M., Sahlin S.,
RA   Bjorkhem I., Einarsson C.;
RT   "Feedback regulation of bile acid synthesis in human liver: importance of
RT   HNF-4alpha for regulation of CYP7A1.";
RL   Biochem. Biophys. Res. Commun. 330:395-399(2005).
RN   [10]
RP   INDUCTION BY GLUCOSE, AND FUNCTION.
RX   PubMed=19965590; DOI=10.1194/jlr.m002782;
RA   Li T., Chanda D., Zhang Y., Choi H.S., Chiang J.Y.;
RT   "Glucose stimulates cholesterol 7alpha-hydroxylase gene transcription in
RT   human hepatocytes.";
RL   J. Lipid Res. 51:832-842(2010).
RN   [11]
RP   FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=21813643; DOI=10.1074/jbc.m111.282434;
RA   Shinkyo R., Xu L., Tallman K.A., Cheng Q., Porter N.A., Guengerich F.P.;
RT   "Conversion of 7-dehydrocholesterol to 7-ketocholesterol is catalyzed by
RT   human cytochrome P450 7A1 and occurs by direct oxidation without an epoxide
RT   intermediate.";
RL   J. Biol. Chem. 286:33021-33028(2011).
RN   [12]
RP   X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) IN COMPLEX WITH HEME, AND COFACTOR.
RG   Structural genomics consortium (SGC);
RT   "Crystal structure of human CYP7A1.";
RL   Submitted (FEB-2009) to the PDB data bank.
RN   [13]
RP   VARIANTS SER-233 AND ASN-347.
RX   PubMed=12721789; DOI=10.1007/s10038-003-0021-7;
RA   Saito S., Iida A., Sekine A., Kawauchi S., Higuchi S., Ogawa C.,
RA   Nakamura Y.;
RT   "Catalog of 680 variations among eight cytochrome p450 (CYP) genes, nine
RT   esterase genes, and two other genes in the Japanese population.";
RL   J. Hum. Genet. 48:249-270(2003).
CC   -!- FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of
CC       endogenous cholesterol and its oxygenated derivatives (oxysterols)
CC       (PubMed:11013305, PubMed:12077124, PubMed:19965590, PubMed:21813643,
CC       PubMed:2384150). 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) (PubMed:11013305,
CC       PubMed:12077124, PubMed:19965590, PubMed:21813643, PubMed:2384150).
CC       Functions as a critical regulatory enzyme of bile acid biosynthesis and
CC       cholesterol homeostasis. Catalyzes the hydroxylation of carbon hydrogen
CC       bond at 7-alpha position of cholesterol, a rate-limiting step in
CC       cholesterol catabolism and bile acid biosynthesis (PubMed:12077124,
CC       PubMed:19965590, PubMed:2384150). 7-alpha hydroxylates several
CC       oxysterols, including 4beta-hydroxycholesterol and 24-
CC       hydroxycholesterol (PubMed:11013305, PubMed:12077124). 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 (PubMed:21813643). {ECO:0000269|PubMed:11013305,
CC       ECO:0000269|PubMed:12077124, ECO:0000269|PubMed:19965590,
CC       ECO:0000269|PubMed:21813643, ECO:0000269|PubMed:2384150}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=cholesterol + reduced [NADPH--hemoprotein reductase] + O2 =
CC         7alpha-hydroxycholesterol + oxidized [NADPH--hemoprotein reductase] +
CC         H2O + H(+); 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:0000269|PubMed:11013305, ECO:0000269|PubMed:12077124,
CC         ECO:0000269|PubMed:2384150};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21813;
CC         Evidence={ECO:0000305|PubMed:11013305, ECO:0000305|PubMed:12077124,
CC         ECO:0000305|PubMed:2384150};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=4beta-hydroxycholesterol + reduced [NADPH--hemoprotein
CC         reductase] + O2 = 4beta,7alpha-dihydroxycholesterol + oxidized
CC         [NADPH--hemoprotein reductase] + H2O + H(+); 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:0000269|PubMed:12077124};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46121;
CC         Evidence={ECO:0000305|PubMed:12077124};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=lathosterol + reduced [NADPH--hemoprotein reductase] + O2 =
CC         7alpha,8alpha-epoxy-5alpha-cholestan-3beta-ol + oxidized
CC         [NADPH--hemoprotein reductase] + H2O + H(+); Xref=Rhea:RHEA:53256,
CC         Rhea:RHEA-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:0000269|PubMed:21813643};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53257;
CC         Evidence={ECO:0000305|PubMed:21813643};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=lathosterol + reduced [NADPH--hemoprotein reductase] + O2 =
CC         5alpha-cholestan-7-oxo-3beta-ol + oxidized [NADPH--hemoprotein
CC         reductase] + H2O + H(+); 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:0000269|PubMed:21813643};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53253;
CC         Evidence={ECO:0000305|PubMed:21813643};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=7-dehydrocholesterol + reduced [NADPH--hemoprotein reductase]
CC         + O2 = 7-oxocholesterol + oxidized [NADPH--hemoprotein reductase] +
CC         H2O + H(+); Xref=Rhea:RHEA:53248, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC         COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:17759, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC         ChEBI:CHEBI:64294; Evidence={ECO:0000269|PubMed:21813643};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53249;
CC         Evidence={ECO:0000305|PubMed:21813643};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(24S)-hydroxycholesterol + reduced [NADPH--hemoprotein
CC         reductase] + O2 = (24S)-7alpha-dihydroxycholesterol + oxidized
CC         [NADPH--hemoprotein reductase] + H2O + H(+); 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:0000269|PubMed:11013305};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46125;
CC         Evidence={ECO:0000305|PubMed:11013305};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(24R)-hydroxycholesterol + reduced [NADPH--hemoprotein
CC         reductase] + O2 = (24R)-7alpha-dihydroxycholesterol + oxidized
CC         [NADPH--hemoprotein reductase] + H2O + H(+); 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:0000269|PubMed:11013305};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16094;
CC         Evidence={ECO:0000305|PubMed:11013305};
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000269|Ref.12};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=3 uM for cholesterol {ECO:0000269|PubMed:11013305};
CC         KM=6 uM for 24-hydroxycholesterol {ECO:0000269|PubMed:11013305};
CC         KM=1.8 uM for 5alpha-cholest-7-en-3beta-ol (lathosterol)
CC         {ECO:0000269|PubMed:21813643};
CC         KM=1.1 uM for cholesta-5,7-dien-3beta-ol (7-dehydrocholesterol)
CC         {ECO:0000269|PubMed:21813643};
CC         Vmax=0.184 nmol/min/nmol enzyme toward cholesterol
CC         {ECO:0000269|PubMed:12077124};
CC         Vmax=0.087 nmol/min/nmol enzyme toward 4beta-hydroxycholesterol
CC         {ECO:0000269|PubMed:12077124};
CC         Note=kcat is 3.7 min(-1) with 5alpha-cholest-7-en-3beta-ol
CC         (lathosterol) as substrate. kcat is 2.2 min(-1) with
CC         cholesta-5,7-dien-3beta-ol (7-dehydrocholesterol) as substrate.
CC         {ECO:0000269|PubMed:21813643};
CC   -!- PATHWAY: Lipid metabolism; bile acid biosynthesis.
CC       {ECO:0000305|PubMed:11013305, ECO:0000305|PubMed:12077124,
CC       ECO:0000305|PubMed:2384150}.
CC   -!- PATHWAY: Steroid metabolism; cholesterol degradation.
CC       {ECO:0000305|PubMed:11013305, ECO:0000305|PubMed:12077124,
CC       ECO:0000305|PubMed:2384150}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000305|PubMed:11013305, ECO:0000305|PubMed:2384150}; Single-pass
CC       membrane protein {ECO:0000305}. Microsome membrane
CC       {ECO:0000305|PubMed:11013305, ECO:0000305|PubMed:2384150}; Single-pass
CC       membrane protein {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Detected in liver. {ECO:0000269|PubMed:15796896}.
CC   -!- INDUCTION: Up-regulated by glucose and by cholestyramine. Down-
CC       regulated by chenodeoxycholic acid. {ECO:0000269|PubMed:15796896,
CC       ECO:0000269|PubMed:19965590}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Cholesterol-7 alpha-hydroxylase
CC       entry;
CC       URL="https://en.wikipedia.org/wiki/Cholesterol_7_alpha-hydroxylase";
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC       Haematology;
CC       URL="https://atlasgeneticsoncology.org/gene/40254/CYP7A1";
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DR   EMBL; X56088; CAA39568.1; -; mRNA.
DR   EMBL; M93133; AAA58435.1; -; mRNA.
DR   EMBL; BC101777; AAI01778.1; -; mRNA.
DR   EMBL; BC112184; AAI12185.1; -; mRNA.
DR   EMBL; L13460; AAA61350.1; -; Genomic_DNA.
DR   EMBL; M89647; AAA58423.1; -; Genomic_DNA.
DR   CCDS; CCDS6171.1; -.
DR   PIR; S29818; JH0659.
DR   RefSeq; NP_000771.2; NM_000780.4.
DR   PDB; 3DAX; X-ray; 2.15 A; A/B=25-503.
DR   PDB; 3SN5; X-ray; 2.75 A; A/B=25-503.
DR   PDB; 3V8D; X-ray; 1.90 A; A/B=25-503.
DR   AlphaFoldDB; P22680; -.
DR   SMR; P22680; -.
DR   FunCoup; P22680; 254.
DR   NDEx; IQUERY-CP-CYP7A1; 18 NDEx IQuery Curated Pathways.
DR   STRING; 9606.ENSP00000301645; -.
DR   ChEMBL; CHEMBL1851; -.
DR   DrugBank; DB05667; Levoketoconazole.
DR   GuidetoPHARMACOLOGY; 1354; -.
DR   SwissLipids; SLP:000001200; -.
DR   GlyGen; P22680; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P22680; -.
DR   PhosphoSitePlus; P22680; -.
DR   BioMuta; CYP7A1; -.
DR   DMDM; 544084; -.
DR   jPOST; P22680; -.
DR   MassIVE; P22680; -.
DR   PaxDb; 9606-ENSP00000301645; -.
DR   PeptideAtlas; P22680; -.
DR   ProteomicsDB; 54016; -.
DR   Antibodypedia; 2602; 156 antibodies from 31 providers.
DR   DNASU; 1581; -.
DR   Ensembl; ENST00000301645.4; ENSP00000301645.3; ENSG00000167910.4.
DR   GeneID; 1581; -.
DR   KEGG; hsa:1581; -.
DR   MANE-Select; ENST00000301645.4; ENSP00000301645.3; NM_000780.4; NP_000771.2.
DR   UCSC; uc003xtm.5; human.
DR   AGR; HGNC:2651; -.
DR   ClinPGx; PA132; -.
DR   CTD; 1581; -.
DR   DisGeNET; 1581; -.
DR   GeneCards; CYP7A1; -.
DR   HGNC; HGNC:2651; CYP7A1.
DR   HPA; ENSG00000167910; Tissue enriched (liver).
DR   MalaCards; CYP7A1; -.
DR   MIM; 118455; gene.
DR   OpenTargets; ENSG00000167910; -.
DR   Orphanet; 209902; Hypercholesterolemia due to cholesterol 7alpha-hydroxylase deficiency.
DR   VEuPathDB; HostDB:ENSG00000167910; -.
DR   eggNOG; KOG0684; Eukaryota.
DR   GeneTree; ENSGT00940000153141; -.
DR   HOGENOM; CLU_018012_1_3_1; -.
DR   InParanoid; P22680; -.
DR   OMA; MFRTAHN; -.
DR   OrthoDB; 6692864at2759; -.
DR   PAN-GO; P22680; 3 GO annotations based on evolutionary models.
DR   PhylomeDB; P22680; -.
DR   BioCyc; MetaCyc:HS09659-MONOMER; -.
DR   BRENDA; 1.14.14.23; 2681.
DR   PathwayCommons; P22680; -.
DR   Reactome; R-HSA-192105; Synthesis of bile acids and bile salts.
DR   Reactome; R-HSA-193368; Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
DR   Reactome; R-HSA-193807; Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
DR   Reactome; R-HSA-1989781; PPARA activates gene expression.
DR   Reactome; R-HSA-211976; Endogenous sterols.
DR   SABIO-RK; P22680; -.
DR   SignaLink; P22680; -.
DR   SIGNOR; P22680; -.
DR   UniPathway; UPA00221; -.
DR   UniPathway; UPA01058; -.
DR   Agora; ENSG00000167910; -.
DR   BioGRID-ORCS; 1581; 14 hits in 1146 CRISPR screens.
DR   EvolutionaryTrace; P22680; -.
DR   GeneWiki; Cholesterol_7_alpha-hydroxylase; -.
DR   GenomeRNAi; 1581; -.
DR   Pharos; P22680; Tchem.
DR   PRO; PR:P22680; -.
DR   Proteomes; UP000005640; Chromosome 8.
DR   RNAct; P22680; protein.
DR   Bgee; ENSG00000167910; Expressed in right lobe of liver and 24 other cell types or tissues.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; ISS:UniProtKB.
DR   GO; GO:0033782; F:24S-hydroxycholesterol 7-alpha-hydroxylase activity; EXP:UniProtKB.
DR   GO; GO:0008123; F:cholesterol 7-alpha-monooxygenase activity; IDA: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; IDA:UniProtKB.
DR   GO; GO:0071397; P:cellular response to cholesterol; ISS:UniProtKB.
DR   GO; GO:0071333; P:cellular response to glucose stimulus; IDA:UniProtKB.
DR   GO; GO:0006707; P:cholesterol catabolic process; ISS:UniProtKB.
DR   GO; GO:0042632; P:cholesterol homeostasis; ISS:UniProtKB.
DR   GO; GO:0032966; P:negative regulation of collagen biosynthetic process; IEA:Ensembl.
DR   GO; GO:0045717; P:negative regulation of fatty acid biosynthetic process; IEA:Ensembl.
DR   GO; GO:0045542; P:positive regulation of cholesterol biosynthetic process; IEA:Ensembl.
DR   GO; GO:0070857; P:regulation of bile acid biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR   GO; GO:0016125; P:sterol metabolic process; TAS:Reactome.
DR   CDD; cd20631; CYP7A1; 1.
DR   FunFam; 1.10.630.10:FF:000034; Cholesterol 7-alpha-monooxygenase; 1.
DR   Gene3D; 1.10.630.10; Cytochrome P450; 1.
DR   InterPro; IPR030681; Cholesterol_7a_monooxygenase.
DR   InterPro; IPR050529; CYP51A1-like.
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   3D-structure; Cholesterol metabolism; Endoplasmic reticulum; Heme; Iron;
KW   Lipid metabolism; Membrane; Metal-binding; Microsome; Monooxygenase;
KW   Oxidoreductase; Proteomics identification; Reference proteome;
KW   Steroid metabolism; Sterol metabolism; Transmembrane; Transmembrane helix.
FT   CHAIN           1..504
FT                   /note="Cytochrome P450 7A1"
FT                   /id="PRO_0000051901"
FT   TRANSMEM        4..24
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         444
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:0007744|PDB:3DAX"
FT   VARIANT         86
FT                   /note="H -> N (in dbSNP:rs62621283)"
FT                   /id="VAR_059152"
FT   VARIANT         100
FT                   /note="F -> S (in dbSNP:rs200836103)"
FT                   /evidence="ECO:0000269|PubMed:1610352"
FT                   /id="VAR_001259"
FT   VARIANT         233
FT                   /note="N -> S (in dbSNP:rs8192874)"
FT                   /evidence="ECO:0000269|PubMed:12721789"
FT                   /id="VAR_018376"
FT   VARIANT         347
FT                   /note="D -> N (in dbSNP:rs8192875)"
FT                   /evidence="ECO:0000269|PubMed:12721789,
FT                   ECO:0000269|PubMed:2384150"
FT                   /id="VAR_018377"
FT   CONFLICT        385
FT                   /note="D -> S (in Ref. 2; CAA39568)"
FT                   /evidence="ECO:0000305"
FT   HELIX           31..33
FT                   /evidence="ECO:0007829|PDB:3DAX"
FT   STRAND          34..41
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   TURN            42..45
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   HELIX           46..48
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   HELIX           52..63
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   STRAND          65..71
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   STRAND          74..79
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   HELIX           82..84
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   HELIX           85..89
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   STRAND          95..98
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   HELIX           99..105
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   HELIX           106..110
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   HELIX           116..118
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   STRAND          119..121
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   HELIX           125..133
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   HELIX           135..153
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   HELIX           160..163
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   STRAND          167..170
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   HELIX           171..188
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   HELIX           195..197
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   HELIX           198..220
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   HELIX           225..227
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   HELIX           229..241
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   HELIX           244..247
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   HELIX           255..267
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   HELIX           272..287
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   HELIX           290..303
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   HELIX           305..321
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   STRAND          328..331
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   HELIX           337..341
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   HELIX           344..357
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   STRAND          358..360
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   STRAND          362..373
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   STRAND          378..381
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   STRAND          386..389
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   HELIX           392..395
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   TURN            398..400
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   STRAND          401..403
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   TURN            409..412
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   STRAND          417..419
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   HELIX           447..464
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   STRAND          465..469
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   TURN            470..473
FT                   /evidence="ECO:0007829|PDB:3DAX"
FT   HELIX           475..478
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   HELIX           481..483
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   STRAND          485..488
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   STRAND          491..493
FT                   /evidence="ECO:0007829|PDB:3V8D"
FT   STRAND          496..501
FT                   /evidence="ECO:0007829|PDB:3V8D"
SQ   SEQUENCE   504 AA;  57661 MW;  D8067E0FF6342949 CRC64;
     MMTTSLIWGI AIAACCCLWL ILGIRRRQTG EPPLENGLIP YLGCALQFGA NPLEFLRANQ
     RKHGHVFTCK LMGKYVHFIT NPLSYHKVLC HGKYFDWKKF HFATSAKAFG HRSIDPMDGN
     TTENINDTFI KTLQGHALNS LTESMMENLQ RIMRPPVSSN SKTAAWVTEG MYSFCYRVMF
     EAGYLTIFGR DLTRRDTQKA HILNNLDNFK QFDKVFPALV AGLPIHMFRT AHNAREKLAE
     SLRHENLQKR ESISELISLR MFLNDTLSTF DDLEKAKTHL VVLWASQANT IPATFWSLFQ
     MIRNPEAMKA ATEEVKRTLE NAGQKVSLEG NPICLSQAEL NDLPVLDSII KESLRLSSAS
     LNIRTAKEDF TLHLEDGSYN IRKDDIIALY PQLMHLDPEI YPDPLTFKYD RYLDENGKTK
     TTFYCNGLKL KYYYMPFGSG ATICPGRLFA IHEIKQFLIL MLSYFELELI EGQAKCPPLD
     QSRAGLGILP PLNDIEFKYK FKHL
//