CP7A1_RAT
ID CP7A1_RAT Reviewed; 503 AA.
AC P18125; P51543;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1990, sequence version 1.
DT 03-AUG-2022, entry version 168.
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:1694852};
DE AltName: Full=Cholesterol 7-alpha-monooxygenase;
DE EC=1.14.14.23 {ECO:0000269|PubMed:1694852, ECO:0000269|PubMed:2335522};
GN Name=Cyp7a1; Synonyms=Cyp7;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, FUNCTION, INDUCTION,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=1694852; DOI=10.1016/s0021-9258(19)38501-1;
RA Li Y.C., Wang D.P., Chiang J.Y.L.;
RT "Regulation of cholesterol 7 alpha-hydroxylase in the liver. Cloning,
RT sequencing, and regulation of cholesterol 7 alpha-hydroxylase mRNA.";
RL J. Biol. Chem. 265:12012-12019(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, CATALYTIC ACTIVITY,
RP FUNCTION, INDUCTION, AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley;
RX PubMed=2335522; DOI=10.1016/s0021-9258(19)39056-8;
RA Jelinek D.F., Andersson S., Slaughter C.A., Russell D.W.;
RT "Cloning and regulation of cholesterol 7 alpha-hydroxylase, the rate-
RT limiting enzyme in bile acid biosynthesis.";
RL J. Biol. Chem. 265:8190-8197(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2806567; DOI=10.1016/0014-5793(89)81795-8;
RA Noshiro M., Nishimoto M., Morohashi K., Okuda K.;
RT "Molecular cloning of cDNA for cholesterol 7 alpha-hydroxylase from rat
RT liver microsomes. Nucleotide sequence and expression.";
RL FEBS Lett. 257:97-100(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=1693613; DOI=10.1016/s0021-9258(19)38775-7;
RA Noshiro M., Nishimoto M., Okuda K.;
RT "Rat liver cholesterol 7 alpha-hydroxylase. Pretranslational regulation for
RT circadian rhythm.";
RL J. Biol. Chem. 265:10036-10041(1990).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2007596; DOI=10.1016/s0021-9258(18)38141-9;
RA Nishimoto M., Gotoh O., Okuda K., Noshiro M.;
RT "Structural analysis of the gene encoding rat cholesterol alpha-
RT hydroxylase, the key enzyme for bile acid biosynthesis.";
RL J. Biol. Chem. 266:6467-6471(1991).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-325.
RC STRAIN=Sprague-Dawley;
RX PubMed=8021257; DOI=10.1016/s0021-9258(17)32469-9;
RA Chiang J.Y., Stroup D.;
RT "Identification and characterization of a putative bile acid-responsive
RT element in cholesterol 7 alpha-hydroxylase gene promoter.";
RL J. Biol. Chem. 269:17502-17507(1994).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-27.
RC STRAIN=Sprague-Dawley;
RX PubMed=2261433; DOI=10.1021/bi00486a001;
RA Jelinek D.F., Russell D.W.;
RT "Structure of the rat gene encoding cholesterol 7 alpha-hydroxylase.";
RL Biochemistry 29:7781-7785(1990).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-26.
RX PubMed=1420318; DOI=10.1016/0167-4781(92)90175-y;
RA Chiang J.Y., Yang T.P., Wang D.P.;
RT "Cloning and 5'-flanking sequence of a rat cholesterol 7 alpha-hydroxylase
RT gene.";
RL Biochim. Biophys. Acta 1132:337-339(1992).
RN [9]
RP INDUCTION.
RX PubMed=11278771; DOI=10.1074/jbc.m010878200;
RA Gupta S., Stravitz R.T., Dent P., Hylemon P.B.;
RT "Down-regulation of cholesterol 7alpha-hydroxylase (CYP7A1) gene expression
RT by bile acids in primary rat hepatocytes is mediated by the c-Jun N-
RT terminal kinase pathway.";
RL J. Biol. Chem. 276:15816-15822(2001).
CC -!- FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of
CC endogenous cholesterol and its oxygenated derivatives (oxysterols)
CC (PubMed:1694852, PubMed:2335522). 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-ferrihemoprotein reductase)
CC (PubMed:1694852, PubMed:2335522). Functions as a critical regulatory
CC enzyme of bile acid biosynthesis and cholesterol homeostasis. Catalyzes
CC the hydroxylation of carbon hydrogen bond at 7-alpha position of
CC cholesterol, a rate-limiting step in cholesterol catabolism and bile
CC acid biosynthesis (PubMed:1694852, PubMed:2335522). 7-alpha
CC hydroxylates several oxysterols, including 4beta-hydroxycholesterol and
CC 24-hydroxycholesterol. Catalyzes the oxidation of the 7,8 double bond
CC of 7-dehydrocholesterol and lathosterol with direct and predominant
CC formation of the 7-keto derivatives (By similarity).
CC {ECO:0000250|UniProtKB:P22680, ECO:0000269|PubMed:1694852,
CC ECO:0000269|PubMed:2335522}.
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:0000269|PubMed:1694852, ECO:0000269|PubMed:2335522};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21813;
CC Evidence={ECO:0000305|PubMed:1694852, ECO:0000305|PubMed:2335522};
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:1694852, ECO:0000305|PubMed:2335522}.
CC -!- PATHWAY: Steroid metabolism; cholesterol degradation.
CC {ECO:0000305|PubMed:1694852, ECO:0000305|PubMed:2335522}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000305|PubMed:1694852}; Single-pass membrane protein
CC {ECO:0000305}. Microsome membrane {ECO:0000305|PubMed:1694852}; Single-
CC pass membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Detected in liver (at protein level). Liver.
CC {ECO:0000269|PubMed:1694852, ECO:0000269|PubMed:2335522}.
CC -!- INDUCTION: Up-regulated by dietary cholesterol and cholestyramine.
CC Down-regulated by dietary bile acids, such as chenodeoxycholic acid and
CC cholic acid. {ECO:0000269|PubMed:11278771, ECO:0000269|PubMed:1694852,
CC ECO:0000269|PubMed:2335522}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; J05509; AAA40839.1; -; mRNA.
DR EMBL; J02926; AAA40923.1; -; Genomic_DNA.
DR EMBL; J05430; AAA41041.1; -; mRNA.
DR EMBL; J05460; AAA03649.1; -; mRNA.
DR EMBL; M59189; AAA41042.1; -; Genomic_DNA.
DR EMBL; M59184; AAA41042.1; JOINED; Genomic_DNA.
DR EMBL; M59185; AAA41042.1; JOINED; Genomic_DNA.
DR EMBL; M59186; AAA41042.1; JOINED; Genomic_DNA.
DR EMBL; M59187; AAA41042.1; JOINED; Genomic_DNA.
DR EMBL; M59188; AAA41042.1; JOINED; Genomic_DNA.
DR EMBL; U01962; AAA21144.2; -; Genomic_DNA.
DR EMBL; X17595; CAB57878.1; -; mRNA.
DR EMBL; Z14108; CAA78481.1; -; Genomic_DNA.
DR PIR; A35376; A35376.
DR RefSeq; NP_037074.1; NM_012942.2.
DR AlphaFoldDB; P18125; -.
DR SMR; P18125; -.
DR STRING; 10116.ENSRNOP00000012819; -.
DR BindingDB; P18125; -.
DR ChEMBL; CHEMBL2339; -.
DR DrugCentral; P18125; -.
DR SwissLipids; SLP:000001323; -.
DR PaxDb; P18125; -.
DR PRIDE; P18125; -.
DR Ensembl; ENSRNOT00000012819; ENSRNOP00000012819; ENSRNOG00000009488.
DR GeneID; 25428; -.
DR KEGG; rno:25428; -.
DR UCSC; RGD:2482; rat.
DR CTD; 1581; -.
DR RGD; 2482; Cyp7a1.
DR eggNOG; KOG0684; Eukaryota.
DR GeneTree; ENSGT00940000153141; -.
DR HOGENOM; CLU_018012_1_3_1; -.
DR InParanoid; P18125; -.
DR OMA; VCCCLWL; -.
DR OrthoDB; 864748at2759; -.
DR PhylomeDB; P18125; -.
DR TreeFam; TF105090; -.
DR BioCyc; MetaCyc:MON-14293; -.
DR BRENDA; 1.14.14.23; 5301.
DR Reactome; R-RNO-192105; Synthesis of bile acids and bile salts.
DR Reactome; R-RNO-193368; Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
DR Reactome; R-RNO-193807; Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
DR Reactome; R-RNO-211976; Endogenous sterols.
DR SABIO-RK; P18125; -.
DR UniPathway; UPA00221; -.
DR UniPathway; UPA01058; -.
DR PRO; PR:P18125; -.
DR Proteomes; UP000002494; Chromosome 5.
DR Bgee; ENSRNOG00000009488; Expressed in liver.
DR Genevisible; P18125; RN.
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; IDA:UniProtKB.
DR GO; GO:0033782; F:24-hydroxycholesterol 7alpha-hydroxylase activity; IEA:UniProtKB-EC.
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:0008395; F:steroid hydroxylase activity; IBA:GO_Central.
DR GO; GO:0015721; P:bile acid and bile salt transport; IEP:RGD.
DR GO; GO:0006699; P:bile acid biosynthetic process; IDA:UniProtKB.
DR GO; GO:0038183; P:bile acid signaling pathway; IEP:RGD.
DR GO; GO:0071397; P:cellular response to cholesterol; IDA:UniProtKB.
DR GO; GO:0071333; P:cellular response to glucose stimulus; ISS:UniProtKB.
DR GO; GO:0006707; P:cholesterol catabolic process; IDA:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; IDA:UniProtKB.
DR GO; GO:0032966; P:negative regulation of collagen biosynthetic process; IMP:RGD.
DR GO; GO:0045717; P:negative regulation of fatty acid biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0045542; P:positive regulation of cholesterol biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0070857; P:regulation of bile acid biosynthetic process; IDA:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IMP:RGD.
DR GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
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 SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Cholesterol metabolism; Direct protein sequencing; Endoplasmic reticulum;
KW Heme; Iron; Lipid metabolism; Membrane; Metal-binding; Microsome;
KW Monooxygenase; Oxidoreductase; Reference proteome; Steroid metabolism;
KW Sterol metabolism; Transmembrane; Transmembrane helix.
FT CHAIN 1..503
FT /note="Cytochrome P450 7A1"
FT /id="PRO_0000051905"
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:0000250|UniProtKB:P22680"
FT CONFLICT 371
FT /note="T -> S (in Ref. 5; AAA41042)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 503 AA; 56883 MW; EA825AA6E74BF5F6 CRC64;
MMTISLIWGI AVLVSCCIWF IVGIRRRKAG EPPLENGLIP YLGCALKFGS NPLEFLRANQ
RKHGHVFTCK LMGKYVHFIT NSLSYHKVLC HGKYFDWKKF HYTTSAKAFG HRSIDPNDGN
TTENINNTFT KTLQGDALCS LSEAMMQNLQ SVMRPPGLPK SKSNAWVTEG MYAFCYRVMF
EAGYLTLFGR DISKTDTQKA LILNNLDNFK QFDQVFPALV AGLPIHLFKT AHKAREKLAE
GLKHKNLCVR DQVSELIRLR MFLNDTLSTF DDMEKAKTHL AILWASQANT IPATFWSLFQ
MIRSPEAMKA ASEEVSGALQ SAGQELSSGG SAIYLDQVQL NDLPVLDSII KEALRLSSAS
LNIRTAKEDF TLHLEDGSYN IRKDDMIALY PQLMHLDPEI YPDPLTFKYD RYLDESGKAK
TTFYSNGNKL KCFYMPFGSG ATICPGRLFA VQEIKQFLIL MLSCFELEFV ESQVKCPPLD
QSRAGLGILP PLHDIEFKYK LKH
