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UniProtKB/Swiss-Prot entry P05177


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name CP1A2_HUMAN
Primary accession number P05177
Secondary accession numbers Q16754 Q6NWU5 Q9BXX7 Q9UK49
Integrated into Swiss-Prot on August 13, 1987
Sequence was last modified on January 23, 2007 (Sequence version 3)
Annotations were last modified on    July 22, 2008 (Entry version 96)
Name and origin of the protein
Protein name Cytochrome P450 1A2
Synonyms EC 1.14.14.1
CYPIA2
P450-P3
P(3)450
P450 4
Gene name
Name: CYP1A2
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
DOI=10.1093/nar/14.16.6773; PubMed=3755823 [NCBI, ExPASy, EBI, Israel, Japan]
Jaiswal A.K., Nebert D.W., Gonzalez F.J.;
"Human P3(450): cDNA and complete amino acid sequence.";
Nucleic Acids Res. 14:6773-6774(1986).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
PubMed=3462722 [NCBI, ExPASy, EBI, Israel, Japan]
Quattrochi L.C., Pendurthi U.R., Okino S.T., Potenza C., Tukey R.H.;
"Human cytochrome P-450 4 mRNA and gene: part of a multigene family that contains Alu sequences in its mRNA.";
Proc. Natl. Acad. Sci. U.S.A. 83:6731-6735(1986).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=2575218 [NCBI, ExPASy, EBI, Israel, Japan]
Ikeya K., Jaiswal A.K., Owens R.A., Jones J.E., Nebert D.W., Kimura S.;
"Human CYP1A2: sequence, gene structure, comparison with the mouse and rat orthologous gene, and differences in liver 1A2 mRNA expression.";
Mol. Endocrinol. 3:1399-1408(1989).
[4]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
TISSUE=Liver;
PubMed=3681487 [NCBI, ExPASy, EBI, Israel, Japan]
Jaiswal A.K., Nebert D.W., McBride O.W., Gonzalez F.J.;
"Human P(3)450: cDNA and complete protein sequence, repetitive Alu sequences in the 3' nontranslated region, and localization of gene to chromosome 15.";
J. Exp. Pathol. 3:1-17(1987).
[5]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANT VAL-314.
TISSUE=Liver;
Zhuge J., Qian Y., Xie H., Yu Y.;
"Sequence of a new human cytochrome P450-1A2 cDNA.";
Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
[6]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
DOI=10.1097/00008571-200102000-00001; PubMed=11207026 [NCBI, ExPASy, EBI, Israel, Japan]
Corchero J., Pimprale S., Kimura S., Gonzalez F.J.;
"Organization of the CYP1A cluster on human chromosome 15: implications for gene regulation.";
Pharmacogenetics 11:1-6(2001).
[7]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-73; ASN-104; PHE-111; VAL-205; TRP-281 AND ILE-438.
Livingston R.J., Rieder M.J., Shaffer T., Bertucci C., Baier C.N., Rajkumar N., Willa H.T., Daniels M., Downing T.K., Stanaway I.B., Nguyen C.P., Gildersleeve H., Cassidy C.M., Johnson E.J., Swanson J.E., McFarland I., Yool B., Park C., Nickerson D.A.;
"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu).";
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
[8]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[9]
PROTEIN SEQUENCE OF 2-19.
PubMed=3517618 [NCBI, ExPASy, EBI, Israel, Japan]
Wrighton S.A., Campanile C., Thomas P.E., Maines S.L., Watkins P.B., Parker G., Mendez-Picon G., Haniu M., Shively J.E., Levin W., Guzelian P.S.;
"Identification of a human liver cytochrome P-450 homologous to the major isosafrole-inducible cytochrome P-450 in the rat.";
Mol. Pharmacol. 29:405-410(1986).
[10]
NUCLEOTIDE SEQUENCE [MRNA] OF 295-485.
TISSUE=Liver;
PubMed=3000715 [NCBI, ExPASy, EBI, Israel, Japan]
Quattrochi L.C., Okino S.T., Pendurthi U.R., Tukey R.H.;
"Cloning and isolation of human cytochrome P-450 cDNAs homologous to dioxin-inducible rabbit mRNAs encoding P-450 4 and P-450 6.";
DNA 4:395-400(1985).
[11]
VARIANT LEU-21.
PubMed=9884316 [NCBI, ExPASy, EBI, Israel, Japan]
Huang J.D., Guo W.C., Lai M.D., Guo Y.L., Lambert G.H.;
"Detection of a novel cytochrome P-450 1A2 polymorphism (F21L) in Chinese.";
Drug Metab. Dispos. 27:98-101(1999).
[12]
VARIANTS ASN-348; PHE-386; TYR-406 AND TRP-431.
DOI=10.1002/humu.48; PubMed=11295848 [NCBI, ExPASy, EBI, Israel, Japan]
Chevalier D., Cauffiez C., Allorge D., Lo-Guidice J.-M., Lhermitte M., Lafitte J.-J., Broly F.;
"Five novel natural allelic variants-951A->C, 1042G->A (D348N), 1156A->T (I386F), 1217G->A (C406Y) and 1291C->T (C431Y)-of the human CYP1A2 gene in a French Caucasian population.";
Hum. Mutat. 17:355-356(2001).
[13]
VARIANTS MET-83; GLN-168; LEU-186; CYS-212; SER-299 AND ILE-438.
DOI=10.1124/jpet.103.055798; PubMed=14563787 [NCBI, ExPASy, EBI, Israel, Japan]
Murayama N., Soyama A., Saito Y., Nakajima Y., Komamura K., Ueno K., Kamakura S., Kitakaze M., Kimura H., Goto Y., Saitoh O., Katoh M., Ohnuma T., Kawai M., Sugai K., Ohtsuki T., Suzuki C., Minami N., Ozawa S., Sawada J.;
"Six novel nonsynonymous CYP1A2 gene polymorphisms: catalytic activities of the naturally occurring variant enzymes.";
J. Pharmacol. Exp. Ther. 308:300-306(2004).
[14]
VARIANTS CYS-18; ARG-298; VAL-314 AND TRP-431.
DOI=10.1517/14622416.5.7.895; PubMed=15469410 [NCBI, ExPASy, EBI, Israel, Japan]
Solus J.F., Arietta B.J., Harris J.R., Sexton D.P., Steward J.Q., McMunn C., Ihrie P., Mehall J.M., Edwards T.L., Dawson E.P.;
"Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population.";
Pharmacogenomics 5:895-931(2004).
[15]
VARIANTS ARG-42; GLN-377 AND HIS-456.
DOI=10.2133/dmpk.20.24; PubMed=15770072 [NCBI, ExPASy, EBI, Israel, Japan]
Soyama A., Saito Y., Hanioka N., Maekawa K., Komamura K., Kamakura S., Kitakaze M., Tomoike H., Ueno K., Goto Y., Kimura H., Katoh M., Sugai K., Saitoh O., Kawai M., Ohnuma T., Ohtsuki T., Suzuki C., Minami N., Kamatani N., Ozawa S., Sawada J.;
"Single nucleotide polymorphisms and haplotypes of CYP1A2 in a Japanese population.";
Drug Metab. Pharmacokinet. 20:24-33(2005).
[16]
VARIANT CYS-18.
DOI=10.1002/humu.20134; PubMed=15643613 [NCBI, ExPASy, EBI, Israel, Japan]
Jiang Z., Dalton T.P., Jin L., Wang B., Tsuneoka Y., Shertzer H.G., Deka R., Nebert D.W.;
"Toward the evaluation of function in genetic variability: characterizing human SNP frequencies and establishing BAC-transgenic mice carrying the human CYP1A1_CYP1A2 locus.";
Hum. Mutat. 25:196-206(2005).
[17]
EFFECT OF CAFFEINE METABOLISM ON RISKS OF MYOCARDIAL INFARCTION.
DOI=10.1001/jama.295.10.1135; PubMed=16522833 [NCBI, ExPASy, EBI, Israel, Japan]
Cornelis M.C., El-Sohemy A., Kabagambe E.K., Campos H.;
"Coffee, CYP1A2 genotype, and risk of myocardial infarction.";
JAMA 295:1135-1141(2006).
Comments
  • FUNCTION: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen.
  • CATALYTIC ACTIVITY: RH + reduced flavoprotein + O2 = ROH + oxidized flavoprotein + H2O.
  • COFACTOR: Heme group (By similarity).
  • SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein.
  • ALTERNATIVE PRODUCTS: 2 named isoforms [FASTA] produced by alternative splicing.
    Name1
    Isoform IDP05177-1
    This is the isoform sequence displayed in this entry.
    Name2
    Isoform IDP05177-2
    Features which should be applied to build the isoform sequence: VSP_017123.
  • TISSUE SPECIFICITY: Liver.
  • INDUCTION: By nicotine, omeprazole, phenobarbital, primidone and rifampicin.
  • POLYMORPHISM: The CYP1A2*1F allele which is quite common (40 to 50%) is due to a substitution of a base in the non-coding region of the CYP1A2 gene and has the effect of decreasing the enzyme inducibility. Individuals who are homozygous for the CYP1A2*1F allele are 'slow' caffeine metabolizers. Thus for these individual increased intake of caffeine seems to be associated with a concommitant increase in the risk of non-fatal myocardial infraction (MI).
  • SIMILARITY: Belongs to the cytochrome P450 family.
  • WEB RESOURCE: Name=Cytochrome P450 Allele Nomenclature Committee; Note=CYP1A2 alleles; URL="http://www.cypalleles.ki.se/cyp1a2.htm";.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
Z00036; CAA77335.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M12078; AAA52154.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M31667; AAA52163.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M31664; AAA52163.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M31665; AAA52163.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M31666; AAA52163.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L00389; AAA35738.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L00384; AAA35738.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L00385; AAA35738.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L00386; AAA35738.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L00388; AAA35738.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L00387; AAA35738.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF182274; AAF13599.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF253322; AAK25728.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
DQ022432; AAY26399.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC067424; AAH67424.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC067425; AAH67425.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC067426; AAH67426.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC067427; AAH67427.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC067428; AAH67428.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M55053; AAA52146.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR S16718; O4HU4.
RefSeq NP_000752.2; -.
UniGene Hs.1361
3D structure databases
PDB
2HI4; X-ray; 1.95 A; A=27-515.[ExPASy / RCSB / EBI]
PDBsum 2HI4; -.
ModBase P05177.
Enzyme and pathway databases
Reactome REACT_2063; Metabolism of xenobiotics.
Polymorphism databases
NIEHS-SNPs CYP1A2.
Organism-specific databases
H-InvDB HIX0038087; -.
HGNC HGNC:2596; CYP1A2.
GenAtlas CYP1A2.
HPA CAB015446; -.
CAB016531; -.
MIM 108330; gene. [NCBI / EBI]
124060; gene+phenotype. [NCBI / EBI]
PharmGKB PA27093; -.
GeneCards P05177.
Gene expression databases
ArrayExpress P05177; -.
CleanEx HS_CYP1A2; -.
GermOnline ENSG00000140505; Homo sapiens.
Ontologies
GO
GO:0005789; Cellular component: endoplasmic reticulum membrane (inferred from experiment from Reactome).
GO:0005792; Cellular component: microsome (inferred from direct assay from UniProtKB).
GO:0032451; Molecular function: demethylase activity (inferred from direct assay from UniProtKB).
GO:0009055; Molecular function: electron carrier activity (traceable author statement from UniProtKB).
GO:0019825; Molecular function: oxygen binding (inferred from experiment from Reactome).
GO:0050381; Molecular function: unspecific monooxygenase activity (inferred from mutant phenotype from UniProtKB).
QuickGo view.
Family and domain databases
InterPro IPR001128; Cyt_P450.
IPR002401; Cyt_P450_E_grp-I.
IPR008066; Cyt_P450_E_grp-I_CYP1.
Graphical view of domain structure.
Gene3D G3DSA:1.10.630.10; Cyt_P450; 1.
PANTHER PTHR19383; Cyt_P450; 1.
PTHR19383:SF63; Cyt_P450_E_grp-I_CYP1; 1.
Pfam PF00067; p450; 1.
Pfam graphical view of domain structure.
PRINTS PR00463; EP450I.
PR01683; EP450ICYP1A.
PR00385; P450.
PROSITE PS00086; CYTOCHROME_P450; 1.
BLOCKS P05177.
Genome annotation databases
Ensembl ENSG00000140505; Homo sapiens. [Contig view]
GeneID 1544; -.
KEGG hsa:1544; -.
Phylogenomic databases
HOVERGEN P05177; -.
Other
DrugBank DB01418; Acenocoumarol.
DB00316; Acetaminophen.
DB00787; Aciclovir.
DB00969; Alosetron.
DB01424; Aminophenazone.
DB00321; Amitriptyline.
DB00261; Anagrelide.
DB00972; Azelastine.
DB00188; Bortezomib.
DB00201; Caffeine.
DB00262; Carmustine.
DB00475; Chlordiazepoxide.
DB00477; Chlorpromazine.
DB00356; Chlorzoxazone.
DB00501; Cimetidine.
DB01012; Cinacalcet.
DB00537; Ciprofloxacin.
DB01242; Clomipramine.
DB00257; Clotrimazole.
DB00363; Clozapine.
DB00286; Conjugated Estrogens.
DB00924; Cyclobenzaprine.
DB00851; Dacarbazine.
DB00967; Desloratadine.
DB00829; Diazepam.
DB00527; Dibucaine.
DB00586; Diclofenac.
DB00476; Duloxetine.
DB00467; Enoxacin.
DB00736; Esomeprazole.
DB00783; Estradiol.
DB00655; Estrone.
DB00544; Fluorouracil.
DB00499; Flutamide.
DB00176; Fluvoxamine.
DB00998; Frovatriptan.
DB00365; Grepafloxacin.
DB00502; Haloperidol.
DB01094; Hesperetin.
DB00458; Imipramine.
DB01026; Ketoconazole.
DB01097; Leflunomide.
DB01002; Levobupivacaine.
DB01137; Levofloxacin.
DB00281; Lidocaine.
DB00978; Lomefloxacin.
DB01065; Melatonin.
DB00532; Mephenytoin.
DB00379; Mexiletine.
DB00370; Mirtazapine.
DB01059; Norfloxacin.
DB00540; Nortriptyline.
DB01165; Ofloxacin.
DB00334; Olanzapine.
DB00904; Ondansetron.
DB00377; Palonosetron.
DB00213; Pantoprazole.
DB00487; Pefloxacin.
DB01100; Pimozide.
DB01182; Propafenone.
DB00571; Propranolol.
DB00908; Quinidine.
DB00980; Ramelteon.
DB00863; Ranitidine.
DB01367; Rasagiline.
DB01045; Rifampin.
DB00740; Riluzole.
DB00533; Rofecoxib.
DB00268; Ropinirole.
DB00296; Ropivacaine.
DB00382; Tacrine.
DB00976; Telithromycin.
DB00342; Terfenadine.
DB00277; Theophylline.
DB00730; Thiabendazole.
DB00697; Tizanidine.
DB01124; Tolbutamide.
DB00661; Verapamil.
DB00682; Warfarin.
DB00744; Zileuton.
DB00315; Zolmitriptan.
SOURCE CYP1A2; Homo sapiens.
ProtoNet P05177.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Acetylation; Alternative splicing; Direct protein sequencing; Endoplasmic reticulum; Heme; Iron; Membrane; Metal-binding; Microsome; Monooxygenase; Oxidoreductase; Polymorphism.
Features
SEVIEWER logo Feature table viewer
KeyFrom   To Length Description FTId
INIT_MET   1     1        Removed. 
CHAIN   2   515  514     Cytochrome P450 1A2. PRO_0000051651
METAL   458   458        Iron (heme axial ligand) (By similarity). 
MOD_RES   289   289        N6-acetyllysine (By similarity). 
VAR_SEQ   510   510        R -> RL (in isoform 2). VSP_017123
VARIANT   18    18  1     S -> C. VAR_023196 
VARIANT   21    21  1     F -> L (in allele CYP1A2*2). VAR_008349 
VARIANT   42    42  1     P -> R (in allele CYP1A2*15). VAR_025182 [3D]
VARIANT   73    73  1     G -> R. VAR_025183 [3D]
VARIANT   83    83  1     T -> M (in allele CYP1A2*9). VAR_020848 [3D]
VARIANT   104   104  1     D -> N. VAR_025184 [3D]
VARIANT   111   111  1     L -> F. VAR_025185 [3D]
VARIANT   168   168  1     E -> Q (in allele CYP1A2*10). VAR_020849 [3D]
VARIANT   186   186  1     F -> L (in allele CYP1A2*11; drastic reduction in O-deethylation of phenacetin and 7-ethoxyresorufin. Has a Vmax of approximately 5% of that of the wild-type and 5-fold lower Km value). VAR_020850 [3D]
VARIANT   205   205  1     F -> V. VAR_025186 [3D]
VARIANT   212   212  1     S -> C (in allele CYP1A2*12). VAR_020851 [3D]
VARIANT   281   281  1     R -> W. VAR_025187 [3D]
VARIANT   298   298  1     S -> R. VAR_024709 [3D]
VARIANT   299   299  1     G -> S (in allele CYP1A2*13). VAR_020852 [3D]
VARIANT   314   314  1     I -> V. VAR_024710 [3D]
VARIANT   348   348  1     D -> N (in allele CYP1A2*3). VAR_020793 [3D]
VARIANT   377   377  1     R -> Q (in allele CYP1A2*16). VAR_025188 [3D]
VARIANT   386   386  1     I -> F (in allele CYP1A2*4). VAR_020794 [3D]
VARIANT   406   406  1     C -> Y (in allele CYP1A2*5). VAR_020795 [3D]
VARIANT   431   431  1     R -> W (in allele CYP1A2*6). VAR_020796 [3D]
VARIANT   438   438  1     T -> I (in allele CYP1A2*14). VAR_020853 [3D]
VARIANT   456   456  1     R -> H (in allele CYP1A2*8). VAR_025189 [3D]
CONFLICT   79    79        R -> S (in Ref. 2; AAA35738). 
CONFLICT   81    81        G -> D (in Ref. 8; AAH67427). 
CONFLICT   170   170        K -> M (in Ref. 5; AAF13599). 
CONFLICT   311   311        V -> L (in Ref. 10; AAA52154). 
CONFLICT   450   451        LF -> MLV (in Ref. 10; AAA52154). 
CONFLICT   492   492        T -> I (in Ref. 5; AAF13599). 
CONFLICT   511   511        R -> LP (in Ref. 2). 
TURN   49    51  3      
HELIX   54    57  4      
HELIX   61    72  12      
STRAND   74    80  7      
STRAND   83    88  6      
HELIX   91    98  8      
TURN   99   101  3      
HELIX   102   104  3      
HELIX   112   115  4      
TURN   123   125  3      
HELIX   131   146  16      
TURN   147   149  3      
HELIX   160   181  22      
HELIX   188   205  18      
HELIX   206   208  3      
HELIX   214   220  7      
HELIX   221   223  3      
HELIX   224   227  4      
HELIX   235   237  3      
HELIX   240   244  5      
HELIX   248   273  26      
HELIX   283   293  11      
HELIX   305   308  4      
HELIX   310   335  26      
HELIX   337   350  14      
TURN   351   353  3      
HELIX   359   361  3      
HELIX   366   379  14      
STRAND   394   396  3      
STRAND   399   401  3      
STRAND   406   410  5      
HELIX   411   416  6      
TURN   418   420  3      
HELIX   429   432  4      
STRAND   437   440  4      
HELIX   442   445  4      
HELIX   454   456  3      
HELIX   461   478  18      
STRAND