CP2A7_HUMAN
ID CP2A7_HUMAN Reviewed; 494 AA.
AC P20853; Q13121;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 2.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Cytochrome P450 2A7;
DE EC=1.14.14.1;
DE AltName: Full=CYPIIA7;
DE AltName: Full=Cytochrome P450 IIA4;
GN Name=CYP2A7;
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 [MRNA], AND VARIANT GLY-479.
RC TISSUE=Liver;
RX PubMed=2322567; DOI=10.1021/bi00457a031;
RA Yamano S., Tatsuno J., Gonzalez F.J.;
RT "The CYP2A3 gene product catalyzes coumarin 7-hydroxylation in human liver
RT microsomes.";
RL Biochemistry 29:1322-1329(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7668294;
RA Fernandez-Salguero P., Hoffman S.M., Cholerton S., Mohrenweiser H.,
RA Raunio H., Rautio A., Pelkonen O., Huang J.D., Evans W.E., Idle J.R.;
RT "A genetic polymorphism in coumarin 7-hydroxylation: sequence of the human
RT CYP2A genes and identification of variant CYP2A6 alleles.";
RL Am. J. Hum. Genet. 57:651-660(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
CC -!- FUNCTION: Cytochromes P450 are a group of heme-thiolate monooxygenases.
CC In liver microsomes, this enzyme is involved in an NADPH-dependent
CC electron transport pathway. It oxidizes a variety of structurally
CC unrelated compounds, including steroids, fatty acids, and xenobiotics.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an organic molecule + O2 + reduced [NADPH--hemoprotein
CC reductase] = an alcohol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:17149, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:30879, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:142491; EC=1.14.14.1;
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral
CC membrane protein. Microsome membrane; Peripheral membrane protein.
CC -!- INDUCTION: P450 can be induced to high levels in liver and other
CC tissues by various foreign compounds, including drugs, pesticides, and
CC carcinogens.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; M33317; AAA52138.1; -; mRNA.
DR EMBL; U22029; AAB40520.1; -; mRNA.
DR EMBL; AC008537; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS12569.1; -.
DR PIR; C34271; C34271.
DR PIR; I38967; I38967.
DR RefSeq; NP_000755.2; NM_000764.2.
DR RefSeq; NP_085079.2; NM_030589.2.
DR AlphaFoldDB; P20853; -.
DR SMR; P20853; -.
DR BioGRID; 107928; 16.
DR IntAct; P20853; 2.
DR STRING; 9606.ENSP00000301146; -.
DR BindingDB; P20853; -.
DR ChEMBL; CHEMBL4523986; -.
DR iPTMnet; P20853; -.
DR PhosphoSitePlus; P20853; -.
DR BioMuta; CYP2A7; -.
DR DMDM; 215273959; -.
DR MassIVE; P20853; -.
DR PaxDb; P20853; -.
DR PeptideAtlas; P20853; -.
DR PRIDE; P20853; -.
DR TopDownProteomics; P20853; -.
DR Antibodypedia; 30661; 202 antibodies from 23 providers.
DR DNASU; 1549; -.
DR Ensembl; ENST00000301146.9; ENSP00000301146.4; ENSG00000198077.11.
DR GeneID; 1549; -.
DR KEGG; hsa:1549; -.
DR MANE-Select; ENST00000301146.9; ENSP00000301146.4; NM_000764.3; NP_000755.2.
DR UCSC; uc002opm.3; human.
DR CTD; 1549; -.
DR DisGeNET; 1549; -.
DR GeneCards; CYP2A7; -.
DR HGNC; HGNC:2611; CYP2A7.
DR HPA; ENSG00000198077; Tissue enriched (liver).
DR MIM; 608054; gene.
DR neXtProt; NX_P20853; -.
DR OpenTargets; ENSG00000198077; -.
DR PharmGKB; PA27102; -.
DR VEuPathDB; HostDB:ENSG00000198077; -.
DR eggNOG; KOG0156; Eukaryota.
DR GeneTree; ENSGT00940000154117; -.
DR HOGENOM; CLU_001570_22_3_1; -.
DR InParanoid; P20853; -.
DR OMA; RRICKFE; -.
DR OrthoDB; 702827at2759; -.
DR PhylomeDB; P20853; -.
DR TreeFam; TF352043; -.
DR PathwayCommons; P20853; -.
DR Reactome; R-HSA-211935; Fatty acids.
DR Reactome; R-HSA-211981; Xenobiotics.
DR Reactome; R-HSA-211999; CYP2E1 reactions.
DR SignaLink; P20853; -.
DR BioGRID-ORCS; 1549; 16 hits in 1051 CRISPR screens.
DR ChiTaRS; CYP2A7; human.
DR GeneWiki; CYP2A7; -.
DR GenomeRNAi; 1549; -.
DR Pharos; P20853; Tbio.
DR PRO; PR:P20853; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P20853; protein.
DR Bgee; ENSG00000198077; Expressed in liver and 93 other tissues.
DR ExpressionAtlas; P20853; baseline and differential.
DR Genevisible; P20853; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0008392; F:arachidonic acid epoxygenase activity; IBA:GO_Central.
DR GO; GO:0070330; F:aromatase activity; IEA:UniProtKB-EC.
DR GO; GO:0020037; F:heme binding; IBA:GO_Central.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0016712; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen; IBA:GO_Central.
DR GO; GO:0019825; F:oxygen binding; TAS:ProtInc.
DR GO; GO:0008395; F:steroid hydroxylase activity; IBA:GO_Central.
DR GO; GO:0009804; P:coumarin metabolic process; IBA:GO_Central.
DR GO; GO:0019373; P:epoxygenase P450 pathway; IBA:GO_Central.
DR GO; GO:0006082; P:organic acid metabolic process; IBA:GO_Central.
DR GO; GO:0006805; P:xenobiotic metabolic process; IBA:GO_Central.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR008067; Cyt_P450_E_grp-I_CYP2A-like.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR01684; EP450ICYP2A.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 2: Evidence at transcript level;
KW Endoplasmic reticulum; Heme; Iron; Membrane; Metal-binding; Microsome;
KW Monooxygenase; Oxidoreductase; Reference proteome.
FT CHAIN 1..494
FT /note="Cytochrome P450 2A7"
FT /id="PRO_0000051669"
FT BINDING 439
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 VARIANT 61
FT /note="F -> I (in dbSNP:rs10425176)"
FT /id="VAR_047815"
FT VARIANT 64
FT /note="C -> R (in dbSNP:rs10425169)"
FT /id="VAR_047816"
FT VARIANT 169
FT /note="D -> E (in dbSNP:rs4142867)"
FT /id="VAR_061043"
FT VARIANT 274
FT /note="H -> R (in dbSNP:rs4079366)"
FT /id="VAR_047817"
FT VARIANT 301
FT /note="A -> G (in dbSNP:rs2545754)"
FT /id="VAR_047818"
FT VARIANT 311
FT /note="R -> C (in dbSNP:rs3869579)"
FT /id="VAR_047819"
FT VARIANT 368
FT /note="M -> T (in dbSNP:rs2261144)"
FT /id="VAR_047820"
FT VARIANT 479
FT /note="V -> G (in dbSNP:rs12460590)"
FT /evidence="ECO:0000269|PubMed:2322567"
FT /id="VAR_061044"
FT CONFLICT 108
FT /note="D -> E (in Ref. 2; AAB40520)"
FT /evidence="ECO:0000305"
FT CONFLICT 163
FT /note="T -> S (in Ref. 1; AAA52138)"
FT /evidence="ECO:0000305"
FT CONFLICT 226
FT /note="V -> L (in Ref. 2; AAB40520)"
FT /evidence="ECO:0000305"
FT CONFLICT 242
FT /note="Q -> L (in Ref. 2; AAB40520)"
FT /evidence="ECO:0000305"
FT CONFLICT 402..403
FT /note="PS -> LR (in Ref. 2; AAB40520)"
FT /evidence="ECO:0000305"
FT CONFLICT 409
FT /note="Q -> R (in Ref. 2; AAB40520)"
FT /evidence="ECO:0000305"
FT CONFLICT 418..419
FT /note="DD -> GE (in Ref. 2; AAB40520)"
FT /evidence="ECO:0000305"
FT CONFLICT 426
FT /note="S -> R (in Ref. 2; AAB40520)"
FT /evidence="ECO:0000305"
FT CONFLICT 435
FT /note="G -> R (in Ref. 2; AAB40520)"
FT /evidence="ECO:0000305"
FT CONFLICT 438
FT /note="N -> Y (in Ref. 1; AAA52138)"
FT /evidence="ECO:0000305"
FT CONFLICT 475
FT /note="P -> S (in Ref. 1; AAA52138)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 494 AA; 56425 MW; 4DA10D0C2714E6AA CRC64;
MLASGLLLVA LLACLTVMVL MSVWQQRKSR GKLPPGPTPL PFIGNYLQLN TEHICDSIMK
FSECYGPVFT IHLGPRRVVV LCGHDAVREA LVDQAEEFSG RGEQATFDWV FKGYGVAFSN
GERAKQLLRF AIATLRDFGV GKRGIEERIQ EESGFLIEAI RSTHGANIDP TFFLSRTVSN
VISSIVFGDR FDYEDKEFLS LLSMMLGIFQ FTSTSTGQLY EMFSSVMKHL PGPQQQAFKL
LQGLEDFIAK KVEHNQRTLD PNSPQDFIDS FLIHMQEEEK NPNTEFYLKN LMMSTLNLFI
AGTETVSTTL RYGFLLLMKH PEVEAKVHEE IDRVIGKNRQ PKFEDRTKMP YMEAVIHEIQ
RFGDVIPMSL ARRVKKDTKF RDFFLPKGTE VFPMLGSVLR DPSFFSNPQD FNPQHFLDDK
GQFKKSDAFV PFSIGKRNCF GEGLARMELF LFFTTVMQNF RLKSSQSPKD IDVSPKHVVF
ATIPRNYTMS FLPR
