ID CP1A2_HUMAN Reviewed; 515 AA. AC P05177; Q16754; Q6NWU5; Q9BXX7; Q9UK49; DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 16-SEP-2015, entry version 166. DE RecName: Full=Cytochrome P450 1A2; DE EC=1.14.14.1; DE AltName: Full=CYPIA2; DE AltName: Full=Cytochrome P(3)450; DE AltName: Full=Cytochrome P450 4; DE AltName: Full=Cytochrome P450-P3; GN Name=CYP1A2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=3755823; DOI=10.1093/nar/14.16.6773; RA Jaiswal A.K., Nebert D.W., Gonzalez F.J.; RT "Human P3(450): cDNA and complete amino acid sequence."; RL Nucleic Acids Res. 14:6773-6774(1986). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. RX PubMed=3462722; DOI=10.1073/pnas.83.18.6731; RA Quattrochi L.C., Pendurthi U.R., Okino S.T., Potenza C., Tukey R.H.; RT "Human cytochrome P-450 4 mRNA and gene: part of a multigene family RT that contains Alu sequences in its mRNA."; RL Proc. Natl. Acad. Sci. U.S.A. 83:6731-6735(1986). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2575218; DOI=10.1210/mend-3-9-1399; RA Ikeya K., Jaiswal A.K., Owens R.A., Jones J.E., Nebert D.W., RA Kimura S.; RT "Human CYP1A2: sequence, gene structure, comparison with the mouse and RT rat orthologous gene, and differences in liver 1A2 mRNA expression."; RL Mol. Endocrinol. 3:1399-1408(1989). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Liver; RX PubMed=3681487; RA Jaiswal A.K., Nebert D.W., McBride O.W., Gonzalez F.J.; RT "Human P(3)450: cDNA and complete protein sequence, repetitive Alu RT sequences in the 3' nontranslated region, and localization of gene to RT chromosome 15."; RL J. Exp. Pathol. 3:1-17(1987). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANT VAL-314. RC TISSUE=Liver; RA Zhuge J., Qian Y., Xie H., Yu Y.; RT "Sequence of a new human cytochrome P450-1A2 cDNA."; RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=11207026; DOI=10.1097/00008571-200102000-00001; RA Corchero J., Pimprale S., Kimura S., Gonzalez F.J.; RT "Organization of the CYP1A cluster on human chromosome 15: RT implications for gene regulation."; RL Pharmacogenetics 11:1-6(2001). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-73; ASN-104; RP PHE-111; VAL-205; TRP-281 AND ILE-438. RG NIEHS SNPs program; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP PROTEIN SEQUENCE OF 2-19. RX PubMed=3517618; RA Wrighton S.A., Campanile C., Thomas P.E., Maines S.L., Watkins P.B., RA Parker G., Mendez-Picon G., Haniu M., Shively J.E., Levin W., RA Guzelian P.S.; RT "Identification of a human liver cytochrome P-450 homologous to the RT major isosafrole-inducible cytochrome P-450 in the rat."; RL Mol. Pharmacol. 29:405-410(1986). RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 295-485. RC TISSUE=Liver; RX PubMed=3000715; DOI=10.1089/dna.1985.4.395; RA Quattrochi L.C., Okino S.T., Pendurthi U.R., Tukey R.H.; RT "Cloning and isolation of human cytochrome P-450 cDNAs homologous to RT dioxin-inducible rabbit mRNAs encoding P-450 4 and P-450 6."; RL DNA 4:395-400(1985). RN [11] RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND CHARACTERIZATION OF RP VARIANTS ASN-348; PHE-386; TYR-406 AND TRP-431. RX PubMed=14725854; DOI=10.1016/j.abb.2003.11.019; RA Zhou H., Josephy P.D., Kim D., Guengerich F.P.; RT "Functional characterization of four allelic variants of human RT cytochrome P450 1A2."; RL Arch. Biochem. Biophys. 422:23-30(2004). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [13] RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 27-515 IN COMPLEX WITH THE RP INHIBITOR ALPHA-NAPHTHOFLAVONE AND HEME. RX PubMed=17311915; DOI=10.1074/jbc.M611692200; RA Sansen S., Yano J.K., Reynald R.L., Schoch G.A., Griffin K.J., RA Stout C.D., Johnson E.F.; RT "Adaptations for the oxidation of polycyclic aromatic hydrocarbons RT exhibited by the structure of human P450 1A2."; RL J. Biol. Chem. 282:14348-14355(2007). RN [14] RP VARIANT LEU-21. RX PubMed=9884316; RA Huang J.D., Guo W.C., Lai M.D., Guo Y.L., Lambert G.H.; RT "Detection of a novel cytochrome P-450 1A2 polymorphism (F21L) in RT Chinese."; RL Drug Metab. Dispos. 27:98-101(1999). RN [15] RP VARIANTS ASN-348; PHE-386; TYR-406 AND TRP-431. RX PubMed=11295848; DOI=10.1002/humu.48; RA Chevalier D., Cauffiez C., Allorge D., Lo-Guidice J.-M., Lhermitte M., RA Lafitte J.-J., Broly F.; RT "Five novel natural allelic variants-951A->C, 1042G->A (D348N), RT 1156A->T (I386F), 1217G->A (C406Y) and 1291C->T (C431Y)-of the human RT CYP1A2 gene in a French Caucasian population."; RL Hum. Mutat. 17:355-356(2001). RN [16] RP VARIANTS MET-83; GLN-168; LEU-186; CYS-212; SER-299 AND ILE-438. RX PubMed=14563787; DOI=10.1124/jpet.103.055798; RA Murayama N., Soyama A., Saito Y., Nakajima Y., Komamura K., Ueno K., RA Kamakura S., Kitakaze M., Kimura H., Goto Y., Saitoh O., Katoh M., RA Ohnuma T., Kawai M., Sugai K., Ohtsuki T., Suzuki C., Minami N., RA Ozawa S., Sawada J.; RT "Six novel nonsynonymous CYP1A2 gene polymorphisms: catalytic RT activities of the naturally occurring variant enzymes."; RL J. Pharmacol. Exp. Ther. 308:300-306(2004). RN [17] RP VARIANTS CYS-18; ARG-298; VAL-314 AND TRP-431. RX PubMed=15469410; DOI=10.1517/14622416.5.7.895; RA Solus J.F., Arietta B.J., Harris J.R., Sexton D.P., Steward J.Q., RA McMunn C., Ihrie P., Mehall J.M., Edwards T.L., Dawson E.P.; RT "Genetic variation in eleven phase I drug metabolism genes in an RT ethnically diverse population."; RL Pharmacogenomics 5:895-931(2004). RN [18] RP VARIANTS ARG-42; GLN-377 AND HIS-456. RX PubMed=15770072; DOI=10.2133/dmpk.20.24; RA Soyama A., Saito Y., Hanioka N., Maekawa K., Komamura K., Kamakura S., RA Kitakaze M., Tomoike H., Ueno K., Goto Y., Kimura H., Katoh M., RA Sugai K., Saitoh O., Kawai M., Ohnuma T., Ohtsuki T., Suzuki C., RA Minami N., Kamatani N., Ozawa S., Sawada J.; RT "Single nucleotide polymorphisms and haplotypes of CYP1A2 in a RT Japanese population."; RL Drug Metab. Pharmacokinet. 20:24-33(2005). RN [19] RP VARIANT CYS-18. RX PubMed=15643613; DOI=10.1002/humu.20134; RA Jiang Z., Dalton T.P., Jin L., Wang B., Tsuneoka Y., Shertzer H.G., RA Deka R., Nebert D.W.; RT "Toward the evaluation of function in genetic variability: RT characterizing human SNP frequencies and establishing BAC-transgenic RT mice carrying the human CYP1A1_CYP1A2 locus."; RL Hum. Mutat. 25:196-206(2005). RN [20] RP EFFECT OF CAFFEINE METABOLISM ON RISKS OF MYOCARDIAL INFARCTION. RX PubMed=16522833; DOI=10.1001/jama.295.10.1135; RA Cornelis M.C., El-Sohemy A., Kabagambe E.K., Campos H.; RT "Coffee, CYP1A2 genotype, and risk of myocardial infarction."; RL JAMA 295:1135-1141(2006). CC -!- FUNCTION: Cytochromes P450 are a group of heme-thiolate CC monooxygenases. In liver microsomes, this enzyme is involved in an CC NADPH-dependent electron transport pathway. It oxidizes a variety CC of structurally unrelated compounds, including steroids, fatty CC acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. CC Caffeine is metabolized primarily by cytochrome CYP1A2 in the CC liver through an initial N3-demethylation. Also acts in the CC metabolism of aflatoxin B1 and acetaminophen. Participates in the CC bioactivation of carcinogenic aromatic and heterocyclic amines. CC Catalizes the N-hydroxylation of heterocyclic amines and the O- CC deethylation of phenacetin. {ECO:0000269|PubMed:14725854}. CC -!- CATALYTIC ACTIVITY: RH + reduced flavoprotein + O(2) = ROH + CC oxidized flavoprotein + H(2)O. CC -!- COFACTOR: CC Name=heme; Xref=ChEBI:CHEBI:30413; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=4 uM for 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole CC {ECO:0000269|PubMed:14725854}; CC KM=21 uM for 2-amino-3-methylimidazo[4,5-f]quinoline CC {ECO:0000269|PubMed:14725854}; CC KM=26 uM for 2-amino-2,4-dimethylimidazo[4,5-f]quinoline CC {ECO:0000269|PubMed:14725854}; CC KM=27 uM for 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline CC {ECO:0000269|PubMed:14725854}; CC KM=71 uM for 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine CC {ECO:0000269|PubMed:14725854}; CC KM=25 uM for phenacetin {ECO:0000269|PubMed:14725854}; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral CC membrane protein. Microsome membrane; Peripheral membrane protein. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P05177-1; Sequence=Displayed; CC Name=2; CC IsoId=P05177-2; Sequence=VSP_017123; CC -!- TISSUE SPECIFICITY: Liver. CC -!- INDUCTION: By nicotine, omeprazole, phenobarbital, primidone and CC rifampicin. CC -!- POLYMORPHISM: The CYP1A2*1F allele which is quite common (40 to CC 50%) is due to a substitution of a base in the non-coding region CC of the CYP1A2 gene and has the effect of decreasing the enzyme CC inducibility. Individuals who are homozygous for the CYP1A2*1F CC allele are 'slow' caffeine metabolizers. Thus for these individual CC increased intake of caffeine seems to be associated with a CC concomitant increase in the risk of non-fatal myocardial CC infraction (MI). CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Cytochrome P450 Allele Nomenclature Committee; CC Note=CYP1A2 alleles; CC URL="http://www.cypalleles.ki.se/cyp1a2.htm"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/cyp1a2/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Z00036; CAA77335.1; -; mRNA. DR EMBL; L00389; AAA35738.1; -; Genomic_DNA. DR EMBL; L00384; AAA35738.1; JOINED; Genomic_DNA. DR EMBL; L00385; AAA35738.1; JOINED; Genomic_DNA. DR EMBL; L00386; AAA35738.1; JOINED; Genomic_DNA. DR EMBL; L00388; AAA35738.1; JOINED; Genomic_DNA. DR EMBL; L00387; AAA35738.1; JOINED; Genomic_DNA. DR EMBL; M31667; AAA52163.1; -; Genomic_DNA. DR EMBL; M31664; AAA52163.1; JOINED; Genomic_DNA. DR EMBL; M31665; AAA52163.1; JOINED; Genomic_DNA. DR EMBL; M31666; AAA52163.1; JOINED; Genomic_DNA. DR EMBL; M12078; AAA52154.1; -; mRNA. DR EMBL; AF182274; AAF13599.1; -; mRNA. DR EMBL; AF253322; AAK25728.1; -; Genomic_DNA. DR EMBL; DQ022432; AAY26399.1; -; Genomic_DNA. DR EMBL; BC067424; AAH67424.1; -; mRNA. DR EMBL; BC067425; AAH67425.1; -; mRNA. DR EMBL; BC067426; AAH67426.1; -; mRNA. DR EMBL; BC067427; AAH67427.1; -; mRNA. DR EMBL; BC067428; AAH67428.1; -; mRNA. DR EMBL; M55053; AAA52146.1; -; mRNA. DR CCDS; CCDS32293.1; -. [P05177-2] DR PIR; S16718; O4HU4. DR RefSeq; NP_000752.2; NM_000761.4. [P05177-2] DR UniGene; Hs.1361; -. DR PDB; 2HI4; X-ray; 1.95 A; A=27-515. DR PDBsum; 2HI4; -. DR ProteinModelPortal; P05177; -. DR SMR; P05177; 34-513. DR BioGrid; 107924; 6. DR STRING; 9606.ENSP00000342007; -. DR BindingDB; P05177; -. DR ChEMBL; CHEMBL3356; -. DR DrugBank; DB01418; Acenocoumarol. DR DrugBank; DB00316; Acetaminophen. DR DrugBank; DB06594; Agomelatine. DR DrugBank; DB00518; Albendazole. DR DrugBank; DB00523; Alitretinoin. DR DrugBank; DB00918; Almotriptan. DR DrugBank; DB00969; Alosetron. DR DrugBank; DB00357; Aminoglutethimide. DR DrugBank; DB01424; Aminophenazone. DR DrugBank; DB01223; Aminophylline. DR DrugBank; DB01118; Amiodarone. DR DrugBank; DB00321; Amitriptyline. DR DrugBank; DB00381; Amlodipine. DR DrugBank; DB00261; Anagrelide. DR DrugBank; DB01217; Anastrozole. DR DrugBank; DB01435; Antipyrine. DR DrugBank; DB06605; Apixaban. DR DrugBank; DB00673; Aprepitant. DR DrugBank; DB06216; Asenapine. DR DrugBank; DB00572; Atropine. DR DrugBank; DB06626; Axitinib. DR DrugBank; DB00972; Azelastine. DR DrugBank; DB00207; Azithromycin. DR DrugBank; DB06770; Benzyl alcohol. DR DrugBank; DB00195; Betaxolol. DR DrugBank; DB00188; Bortezomib. DR DrugBank; DB01558; Bromazepam. DR DrugBank; DB01200; Bromocriptine. DR DrugBank; DB00297; Bupivacaine. DR DrugBank; DB00921; Buprenorphine. DR DrugBank; DB01156; Bupropion. DR DrugBank; DB00201; Caffeine. DR DrugBank; DB00564; Carbamazepine. DR DrugBank; DB00262; Carmustine. DR DrugBank; DB01136; Carvedilol. DR DrugBank; DB00477; Chlorpromazine. DR DrugBank; DB00356; Chlorzoxazone. DR DrugBank; DB01166; Cilostazol. DR DrugBank; DB00501; Cimetidine. DR DrugBank; DB01012; Cinacalcet. DR DrugBank; DB00568; Cinnarizine. DR DrugBank; DB00537; Ciprofloxacin. DR DrugBank; DB00604; Cisapride. DR DrugBank; DB00215; Citalopram. DR DrugBank; DB01211; Clarithromycin. DR DrugBank; DB01407; Clenbuterol. DR DrugBank; DB04920; Clevidipine. DR DrugBank; DB01013; Clobetasol propionate. DR DrugBank; DB00882; Clomifene. DR DrugBank; DB01242; Clomipramine. DR DrugBank; DB00575; Clonidine. DR DrugBank; DB00758; Clopidogrel. DR DrugBank; DB00257; Clotrimazole. DR DrugBank; DB00363; Clozapine. DR DrugBank; DB00286; Conjugated Estrogens. DR DrugBank; DB00924; Cyclobenzaprine. DR DrugBank; DB00851; Dacarbazine. DR DrugBank; DB06292; Dapagliflozin. DR DrugBank; DB01254; Dasatinib. DR DrugBank; DB00694; Daunorubicin. DR DrugBank; DB00705; Delavirdine. DR DrugBank; DB01151; Desipramine. DR DrugBank; DB00967; Desloratadine. DR DrugBank; DB01191; Dexfenfluramine. DR DrugBank; DB00633; Dexmedetomidine. DR DrugBank; DB00829; Diazepam. DR DrugBank; DB00586; Diclofenac. DR DrugBank; DB00917; Dinoprostone. DR DrugBank; DB01075; Diphenhydramine. DR DrugBank; DB01184; Domperidone. DR DrugBank; DB00988; Dopamine. DR DrugBank; DB01142; Doxepin. DR DrugBank; DB00476; Duloxetine. DR DrugBank; DB00974; Edetic Acid. DR DrugBank; DB00625; Efavirenz. DR DrugBank; DB06210; Eltrombopag. DR DrugBank; DB00467; Enoxacin. DR DrugBank; DB00668; Epinephrine. DR DrugBank; DB00696; Ergotamine. DR DrugBank; DB00530; Erlotinib. DR DrugBank; DB00199; Erythromycin. DR DrugBank; DB00783; Estradiol. DR DrugBank; DB00655; Estrone. DR DrugBank; DB04574; Estropipate. DR DrugBank; DB00898; Ethanol. DR DrugBank; DB00773; Etoposide. DR DrugBank; DB01628; Etoricoxib. DR DrugBank; DB04841; Flunarizine. DR DrugBank; DB01544; Flunitrazepam. DR DrugBank; DB00544; Fluorouracil. DR DrugBank; DB00472; Fluoxetine. DR DrugBank; DB00623; Fluphenazine. DR DrugBank; DB00499; Flutamide. DR DrugBank; DB01095; Fluvastatin. DR DrugBank; DB00176; Fluvoxamine. DR DrugBank; DB00998; Frovatriptan. DR DrugBank; DB01241; Gemfibrozil. DR DrugBank; DB00400; Griseofulvin. DR DrugBank; DB00629; Guanabenz. DR DrugBank; DB00502; Haloperidol. DR DrugBank; DB01094; Hesperetin. DR DrugBank; DB01355; Hexobarbital. DR DrugBank; DB04946; Iloperidone. DR DrugBank; DB00619; Imatinib. DR DrugBank; DB00458; Imipramine. DR DrugBank; DB00724; Imiquimod. DR DrugBank; DB05278; inhaled insulin. DR DrugBank; DB01306; Insulin Aspart. DR DrugBank; DB01307; Insulin Detemir. DR DrugBank; DB00047; Insulin Glargine. DR DrugBank; DB01309; Insulin Glulisine. DR DrugBank; DB00046; Insulin Lispro. DR DrugBank; DB00030; Insulin Regular. DR DrugBank; DB01029; Irbesartan. DR DrugBank; DB00951; Isoniazid. DR DrugBank; DB01026; Ketoconazole. DR DrugBank; DB00448; Lansoprazole. DR DrugBank; DB01097; Leflunomide. DR DrugBank; DB01002; Levobupivacaine. DR DrugBank; DB01137; Levofloxacin. DR DrugBank; DB00281; Lidocaine. DR DrugBank; DB00978; Lomefloxacin. DR DrugBank; DB01601; Lopinavir. DR DrugBank; DB04871; Lorcaserin. DR DrugBank; DB00678; Losartan. DR DrugBank; DB01283; Lumiracoxib. DR DrugBank; DB00772; Malathion. DR DrugBank; DB00934; Maprotiline. DR DrugBank; DB00737; Meclizine. DR DrugBank; DB01065; Melatonin. DR DrugBank; DB00170; Menadione. DR DrugBank; DB00333; Methadone. DR DrugBank; DB00763; Methimazole. DR DrugBank; DB01403; Methotrimeprazine. DR DrugBank; DB00553; Methoxsalen. DR DrugBank; DB01028; Methoxyflurane. DR DrugBank; DB00379; Mexiletine. DR DrugBank; DB06148; Mianserin. DR DrugBank; DB01110; Miconazole. DR DrugBank; DB00370; Mirtazapine. DR DrugBank; DB01171; Moclobemide. DR DrugBank; DB00745; Modafinil. DR DrugBank; DB00461; Nabumetone. DR DrugBank; DB00607; Nafcillin. DR DrugBank; DB00788; Naproxen. DR DrugBank; DB00220; Nelfinavir. DR DrugBank; DB00238; Nevirapine. DR DrugBank; DB06803; Niclosamide. DR DrugBank; DB00184; Nicotine. DR DrugBank; DB01115; Nifedipine. DR DrugBank; DB06712; Nilvadipine. DR DrugBank; DB00401; Nisoldipine. DR DrugBank; DB00435; Nitric Oxide. DR DrugBank; DB00325; Nitroprusside. DR DrugBank; DB00368; Norepinephrine. DR DrugBank; DB01059; Norfloxacin. DR DrugBank; DB00540; Nortriptyline. DR DrugBank; DB01165; Ofloxacin. DR DrugBank; DB00334; Olanzapine. DR DrugBank; DB00338; Omeprazole. DR DrugBank; DB00904; Ondansetron. DR DrugBank; DB00526; Oxaliplatin. DR DrugBank; DB01303; Oxtriphylline. DR DrugBank; DB00377; Palonosetron. DR DrugBank; DB00213; Pantoprazole. DR DrugBank; DB06589; Pazopanib. DR DrugBank; DB00487; Pefloxacin. DR DrugBank; DB00738; Pentamidine. DR DrugBank; DB00806; Pentoxifylline. DR DrugBank; DB00850; Perphenazine. DR DrugBank; DB01174; Phenobarbital. DR DrugBank; DB00191; Phentermine. DR DrugBank; DB00388; Phenylephrine. DR DrugBank; DB00397; Phenylpropanolamine. DR DrugBank; DB01100; Pimozide. DR DrugBank; DB01621; Pipotiazine. DR DrugBank; DB08910; Pomalidomide. DR DrugBank; DB01058; Praziquantel. DR DrugBank; DB01087; Primaquine. DR DrugBank; DB00794; Primidone. DR DrugBank; DB00396; Progesterone. DR DrugBank; DB01131; Proguanil. DR DrugBank; DB00420; Promazine. DR DrugBank; DB01182; Propafenone. DR DrugBank; DB00818; Propofol. DR DrugBank; DB00571; Propranolol. DR DrugBank; DB00339; Pyrazinamide. DR DrugBank; DB00908; Quinidine. DR DrugBank; DB00468; Quinine. DR DrugBank; DB01129; Rabeprazole. DR DrugBank; DB00980; Ramelteon. DR DrugBank; DB00863; Ranitidine. DR DrugBank; DB01367; Rasagiline. DR DrugBank; DB00615; Rifabutin. DR DrugBank; DB01045; Rifampicin. DR DrugBank; DB08864; Rilpivirine. DR DrugBank; DB00740; Riluzole. DR DrugBank; DB00503; Ritonavir. DR DrugBank; DB00953; Rizatriptan. DR DrugBank; DB00268; Ropinirole. DR DrugBank; DB00296; Ropivacaine. DR DrugBank; DB00412; Rosiglitazone. DR DrugBank; DB05271; Rotigotine. DR DrugBank; DB00778; Roxithromycin. DR DrugBank; DB00418; Secobarbital. DR DrugBank; DB01037; Selegiline. DR DrugBank; DB01104; Sertraline. DR DrugBank; DB06290; Simeprevir. DR DrugBank; DB00398; Sorafenib. DR DrugBank; DB00428; Streptozocin. DR DrugBank; DB00605; Sulindac. DR DrugBank; DB00675; Tamoxifen. DR DrugBank; DB00976; Telithromycin. DR DrugBank; DB00300; Tenofovir. DR DrugBank; DB00857; Terbinafine. DR DrugBank; DB01041; Thalidomide. DR DrugBank; DB01412; Theobromine. DR DrugBank; DB00277; Theophylline. DR DrugBank; DB00730; Thiabendazole. DR DrugBank; DB00679; Thioridazine. DR DrugBank; DB01623; Thiothixene. DR DrugBank; DB00208; Ticlopidine. DR DrugBank; DB01007; Tioconazole. DR DrugBank; DB00697; Tizanidine. DR DrugBank; DB01056; Tocainide. DR DrugBank; DB00539; Toremifene. DR DrugBank; DB00752; Tranylcypromine. DR DrugBank; DB00384; Triamterene. DR DrugBank; DB00831; Trifluoperazine. DR DrugBank; DB00313; Valproic Acid. DR DrugBank; DB08881; Vemurafenib. DR DrugBank; DB00661; Verapamil. DR DrugBank; DB00682; Warfarin. DR DrugBank; DB00549; Zafirlukast. DR DrugBank; DB00744; Zileuton. DR DrugBank; DB00246; Ziprasidone. DR DrugBank; DB00315; Zolmitriptan. DR DrugBank; DB00425; Zolpidem. DR PhosphoSite; P05177; -. DR BioMuta; CYP1A2; -. DR DMDM; 117144; -. DR MaxQB; P05177; -. DR PaxDb; P05177; -. DR PRIDE; P05177; -. DR Ensembl; ENST00000343932; ENSP00000342007; ENSG00000140505. [P05177-2] DR GeneID; 1544; -. DR KEGG; hsa:1544; -. DR UCSC; uc002ayr.1; human. [P05177-2] DR CTD; 1544; -. DR GeneCards; GC15P074748; -. DR HGNC; HGNC:2596; CYP1A2. DR HPA; CAB016531; -. DR MIM; 108330; gene. DR MIM; 124060; gene+phenotype. DR neXtProt; NX_P05177; -. DR Orphanet; 284121; Toxixity or absent response to clozapine. DR PharmGKB; PA27093; -. DR eggNOG; COG2124; -. DR GeneTree; ENSGT00760000118992; -. DR HOVERGEN; HBG106944; -. DR InParanoid; P05177; -. DR KO; K07409; -. DR OMA; KCCVFVN; -. DR OrthoDB; EOG7RBZ85; -. DR PhylomeDB; P05177; -. DR TreeFam; TF105095; -. DR BioCyc; MetaCyc:HS06728-MONOMER; -. DR BRENDA; 1.14.14.1; 2681. DR BRENDA; 1.14.99.38; 2681. DR Reactome; R-HSA-156581; Methylation. DR Reactome; R-HSA-211957; Aromatic amines can be N-hydroxylated or N-dealkylated by CYP1A2. DR Reactome; R-HSA-2142670; Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET). DR Reactome; R-HSA-2142816; Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE). DR Reactome; R-HSA-5423646; Aflatoxin activation and detoxification. DR SABIO-RK; P05177; -. DR EvolutionaryTrace; P05177; -. DR GeneWiki; CYP1A2; -. DR GenomeRNAi; 1544; -. DR NextBio; 6391; -. DR PRO; PR:P05177; -. DR Proteomes; UP000005640; Chromosome 15. DR Bgee; P05177; -. DR CleanEx; HS_CYP1A2; -. DR Genevisible; P05177; HS. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:UniProtKB. DR GO; GO:0070330; F:aromatase activity; IEA:UniProtKB-EC. DR GO; GO:0034875; F:caffeine oxidase activity; IDA:BHF-UCL. DR GO; GO:0032451; F:demethylase activity; IDA:UniProtKB. DR GO; GO:0009055; F:electron carrier activity; TAS:UniProtKB. DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL. DR GO; GO:0020037; F:heme binding; IDA:UniProtKB. DR GO; GO:0005506; F:iron ion binding; IEA:InterPro. DR GO; GO:0004497; F:monooxygenase activity; IDA:BHF-UCL. DR GO; GO:0016491; F:oxidoreductase activity; IDA:BHF-UCL. 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; IMP:UniProtKB. DR GO; GO:0009820; P:alkaloid metabolic process; IDA:BHF-UCL. DR GO; GO:0019369; P:arachidonic acid metabolic process; TAS:Reactome. DR GO; GO:0045333; P:cellular respiration; IEA:Ensembl. DR GO; GO:0071276; P:cellular response to cadmium ion; IEA:Ensembl. DR GO; GO:0018894; P:dibenzo-p-dioxin metabolic process; IEA:Ensembl. DR GO; GO:0042737; P:drug catabolic process; IMP:BHF-UCL. DR GO; GO:0017144; P:drug metabolic process; IDA:BHF-UCL. DR GO; GO:0019373; P:epoxygenase P450 pathway; TAS:Reactome. DR GO; GO:0042738; P:exogenous drug catabolic process; IDA:BHF-UCL. DR GO; GO:0046483; P:heterocycle metabolic process; IDA:BHF-UCL. DR GO; GO:0050665; P:hydrogen peroxide biosynthetic process; IEA:Ensembl. DR GO; GO:0030324; P:lung development; IEA:Ensembl. DR GO; GO:0032259; P:methylation; TAS:Reactome. DR GO; GO:0032787; P:monocarboxylic acid metabolic process; IDA:BHF-UCL. DR GO; GO:0016098; P:monoterpenoid metabolic process; IDA:BHF-UCL. DR GO; GO:0097267; P:omega-hydroxylase P450 pathway; TAS:Reactome. DR GO; GO:0055114; P:oxidation-reduction process; IDA:BHF-UCL. DR GO; GO:0071615; P:oxidative deethylation; IDA:BHF-UCL. DR GO; GO:0070989; P:oxidative demethylation; IDA:BHF-UCL. DR GO; GO:0006778; P:porphyrin-containing compound metabolic process; IEA:Ensembl. DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl. DR GO; GO:0010468; P:regulation of gene expression; IEA:Ensembl. DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl. DR GO; GO:0035902; P:response to immobilization stress; IEA:Ensembl. DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome. DR GO; GO:0006706; P:steroid catabolic process; IMP:BHF-UCL. DR GO; GO:0009403; P:toxin biosynthetic process; IDA:BHF-UCL. DR GO; GO:0006805; P:xenobiotic metabolic process; TAS:Reactome. 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; IPR008066; Cyt_P450_E_grp-I_CYP1. DR Pfam; PF00067; p450; 1. DR PRINTS; PR00463; EP450I. DR PRINTS; PR01683; EP450ICYP1A. DR PRINTS; PR00385; P450. DR SUPFAM; SSF48264; SSF48264; 1. DR PROSITE; PS00086; CYTOCHROME_P450; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Complete proteome; KW Direct protein sequencing; Endoplasmic reticulum; Glycoprotein; Heme; KW Iron; Membrane; Metal-binding; Microsome; Monooxygenase; KW Oxidoreductase; Polymorphism; Reference proteome. FT INIT_MET 1 1 Removed. {ECO:0000269|PubMed:3517618}. FT CHAIN 2 515 Cytochrome P450 1A2. FT /FTId=PRO_0000051651. FT METAL 458 458 Iron (heme axial ligand). FT BINDING 226 226 Substrate. {ECO:0000305}. FT CARBOHYD 69 69 O-linked (GlcNAc). {ECO:0000250}. FT VAR_SEQ 510 510 R -> RL (in isoform 2). FT {ECO:0000303|PubMed:15489334, FT ECO:0000303|Ref.5}. FT /FTId=VSP_017123. FT VARIANT 18 18 S -> C (in dbSNP:rs17861152). FT {ECO:0000269|PubMed:15469410, FT ECO:0000269|PubMed:15643613}. FT /FTId=VAR_023196. FT VARIANT 21 21 F -> L (in allele CYP1A2*2; FT dbSNP:rs56160784). FT {ECO:0000269|PubMed:9884316}. FT /FTId=VAR_008349. FT VARIANT 42 42 P -> R (in allele CYP1A2*15). FT {ECO:0000269|PubMed:15770072}. FT /FTId=VAR_025182. FT VARIANT 73 73 G -> R (in dbSNP:rs45565238). FT {ECO:0000269|Ref.7}. FT /FTId=VAR_025183. FT VARIANT 83 83 T -> M (in allele CYP1A2*9). FT {ECO:0000269|PubMed:14563787}. FT /FTId=VAR_020848. FT VARIANT 104 104 D -> N (in dbSNP:rs34067076). FT {ECO:0000269|Ref.7}. FT /FTId=VAR_025184. FT VARIANT 111 111 L -> F (in dbSNP:rs45442197). FT {ECO:0000269|Ref.7}. FT /FTId=VAR_025185. FT VARIANT 168 168 E -> Q (in allele CYP1A2*10). FT {ECO:0000269|PubMed:14563787}. FT /FTId=VAR_020849. FT VARIANT 186 186 F -> L (in allele CYP1A2*11; drastic FT reduction in O-deethylation of phenacetin FT and 7-ethoxyresorufin; has a Vmax of FT approximately 5% of that of the wild-type FT and 5-fold lower Km value). FT {ECO:0000269|PubMed:14563787}. FT /FTId=VAR_020850. FT VARIANT 205 205 F -> V (in dbSNP:rs45540640). FT {ECO:0000269|Ref.7}. FT /FTId=VAR_025186. FT VARIANT 212 212 S -> C (in allele CYP1A2*12). FT {ECO:0000269|PubMed:14563787}. FT /FTId=VAR_020851. FT VARIANT 281 281 R -> W (in dbSNP:rs45468096). FT {ECO:0000269|Ref.7}. FT /FTId=VAR_025187. FT VARIANT 298 298 S -> R (in dbSNP:rs17861157). FT {ECO:0000269|PubMed:15469410}. FT /FTId=VAR_024709. FT VARIANT 299 299 G -> S (in allele CYP1A2*13; FT dbSNP:rs35796837). FT {ECO:0000269|PubMed:14563787}. FT /FTId=VAR_020852. FT VARIANT 314 314 I -> V (in dbSNP:rs28399418). FT {ECO:0000269|PubMed:15469410, FT ECO:0000269|Ref.5}. FT /FTId=VAR_024710. FT VARIANT 348 348 D -> N (in allele CYP1A2*3; increases N- FT hydroxylation activity of heterocyclic FT amines; reduces phenacetin O-deethylation FT activity; dbSNP:rs56276455). FT {ECO:0000269|PubMed:11295848, FT ECO:0000269|PubMed:14725854}. FT /FTId=VAR_020793. FT VARIANT 377 377 R -> Q (in allele CYP1A2*16). FT {ECO:0000269|PubMed:15770072}. FT /FTId=VAR_025188. FT VARIANT 386 386 I -> F (in allele CYP1A2*4; increases FT catalytic efficiency of N-hydroxylation FT towards some heterocyclic amines and FT reduces towards others; reduces catalytic FT efficiency of phenacetin O-deethylation FT due to a high decrease in the affinity FT for phenacetin). FT {ECO:0000269|PubMed:11295848, FT ECO:0000269|PubMed:14725854}. FT /FTId=VAR_020794. FT VARIANT 406 406 C -> Y (in allele CYP1A2*5; increases N- FT hydroxylation activity of heterocyclic FT amines; reduces catalytic efficiency of FT phenacetin O-deethylation; FT dbSNP:rs55889066). FT {ECO:0000269|PubMed:11295848, FT ECO:0000269|PubMed:14725854}. FT /FTId=VAR_020795. FT VARIANT 431 431 R -> W (in allele CYP1A2*6; not detected FT when expressed in heterologous system as FT it may be critical for maintenance of FT protein tertiary structure; FT dbSNP:rs28399424). FT {ECO:0000269|PubMed:11295848, FT ECO:0000269|PubMed:14725854, FT ECO:0000269|PubMed:15469410}. FT /FTId=VAR_020796. FT VARIANT 438 438 T -> I (in allele CYP1A2*14; FT dbSNP:rs45486893). FT {ECO:0000269|PubMed:14563787, FT ECO:0000269|Ref.7}. FT /FTId=VAR_020853. FT VARIANT 456 456 R -> H (in allele CYP1A2*8). FT {ECO:0000269|PubMed:15770072}. FT /FTId=VAR_025189. FT VARIANT 457 457 R -> W (in dbSNP:rs34151816). FT /FTId=VAR_055563. FT CONFLICT 79 79 R -> S (in Ref. 2; AAA35738). FT {ECO:0000305}. FT CONFLICT 81 81 G -> D (in Ref. 8; AAH67427). FT {ECO:0000305}. FT CONFLICT 170 170 K -> M (in Ref. 5; AAF13599). FT {ECO:0000305}. FT CONFLICT 311 311 V -> L (in Ref. 10; AAA52154). FT {ECO:0000305}. FT CONFLICT 450 451 LF -> MLV (in Ref. 10; AAA52154). FT {ECO:0000305}. FT CONFLICT 492 492 T -> I (in Ref. 5; AAF13599). FT {ECO:0000305}. FT CONFLICT 511 511 R -> LP (in Ref. 2; AAA35738). FT {ECO:0000305}. FT TURN 49 51 {ECO:0000244|PDB:2HI4}. FT HELIX 54 57 {ECO:0000244|PDB:2HI4}. FT HELIX 61 72 {ECO:0000244|PDB:2HI4}. FT STRAND 74 80 {ECO:0000244|PDB:2HI4}. FT STRAND 83 88 {ECO:0000244|PDB:2HI4}. FT HELIX 91 98 {ECO:0000244|PDB:2HI4}. FT TURN 99 101 {ECO:0000244|PDB:2HI4}. FT HELIX 102 104 {ECO:0000244|PDB:2HI4}. FT HELIX 112 115 {ECO:0000244|PDB:2HI4}. FT TURN 123 125 {ECO:0000244|PDB:2HI4}. FT HELIX 131 146 {ECO:0000244|PDB:2HI4}. FT TURN 147 149 {ECO:0000244|PDB:2HI4}. FT HELIX 160 181 {ECO:0000244|PDB:2HI4}. FT HELIX 188 205 {ECO:0000244|PDB:2HI4}. FT HELIX 206 208 {ECO:0000244|PDB:2HI4}. FT HELIX 214 220 {ECO:0000244|PDB:2HI4}. FT HELIX 221 223 {ECO:0000244|PDB:2HI4}. FT HELIX 224 227 {ECO:0000244|PDB:2HI4}. FT HELIX 235 237 {ECO:0000244|PDB:2HI4}. FT HELIX 240 244 {ECO:0000244|PDB:2HI4}. FT HELIX 248 273 {ECO:0000244|PDB:2HI4}. FT HELIX 283 293 {ECO:0000244|PDB:2HI4}. FT HELIX 305 308 {ECO:0000244|PDB:2HI4}. FT HELIX 310 335 {ECO:0000244|PDB:2HI4}. FT HELIX 337 350 {ECO:0000244|PDB:2HI4}. FT TURN 351 353 {ECO:0000244|PDB:2HI4}. FT HELIX 359 361 {ECO:0000244|PDB:2HI4}. FT HELIX 366 379 {ECO:0000244|PDB:2HI4}. FT STRAND 394 396 {ECO:0000244|PDB:2HI4}. FT STRAND 399 401 {ECO:0000244|PDB:2HI4}. FT STRAND 406 410 {ECO:0000244|PDB:2HI4}. FT HELIX 411 416 {ECO:0000244|PDB:2HI4}. FT TURN 418 420 {ECO:0000244|PDB:2HI4}. FT HELIX 429 432 {ECO:0000244|PDB:2HI4}. FT STRAND 437 440 {ECO:0000244|PDB:2HI4}. FT HELIX 442 445 {ECO:0000244|PDB:2HI4}. FT HELIX 454 456 {ECO:0000244|PDB:2HI4}. FT HELIX 461 478 {ECO:0000244|PDB:2HI4}. FT STRAND 480 482 {ECO:0000244|PDB:2HI4}. FT STRAND 496 498 {ECO:0000244|PDB:2HI4}. FT STRAND 507 510 {ECO:0000244|PDB:2HI4}. SQ SEQUENCE 515 AA; 58294 MW; 23AEFEEBDF6806AB CRC64; MALSQSVPFS ATELLLASAI FCLVFWVLKG LRPRVPKGLK SPPEPWGWPL LGHVLTLGKN PHLALSRMSQ RYGDVLQIRI GSTPVLVLSR LDTIRQALVR QGDDFKGRPD LYTSTLITDG QSLTFSTDSG PVWAARRRLA QNALNTFSIA SDPASSSSCY LEEHVSKEAK ALISRLQELM AGPGHFDPYN QVVVSVANVI GAMCFGQHFP ESSDEMLSLV KNTHEFVETA SSGNPLDFFP ILRYLPNPAL QRFKAFNQRF LWFLQKTVQE HYQDFDKNSV RDITGALFKH SKKGPRASGN LIPQEKIVNL VNDIFGAGFD TVTTAISWSL MYLVTKPEIQ RKIQKELDTV IGRERRPRLS DRPQLPYLEA FILETFRHSS FLPFTIPHST TRDTTLNGFY IPKKCCVFVN QWQVNHDPEL WEDPSEFRPE RFLTADGTAI NKPLSEKMML FGMGKRRCIG EVLAKWEIFL FLAILLQQLE FSVPPGVKVD LTPIYGLTMK HARCEHVQAR RFSIN //