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Protein

Cytochrome P450 1A2

Gene

CYP1A2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.1 Publication

Catalytic activityi

RH + [reduced NADPH--hemoprotein reductase] + O2 = ROH + [oxidized NADPH--hemoprotein reductase] + H2O.1 Publication

Cofactori

Kineticsi

  1. KM=4 µM for 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole1 Publication
  2. KM=21 µM for 2-amino-3-methylimidazo[4,5-f]quinoline1 Publication
  3. KM=26 µM for 2-amino-2,4-dimethylimidazo[4,5-f]quinoline1 Publication
  4. KM=27 µM for 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline1 Publication
  5. KM=71 µM for 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine1 Publication
  6. KM=25 µM for phenacetin1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei226SubstrateCurated1
    Metal bindingi458Iron (heme axial ligand)1

    GO - Molecular functioni

    • aromatase activity Source: UniProtKB-EC
    • caffeine oxidase activity Source: BHF-UCL
    • demethylase activity Source: UniProtKB
    • electron carrier activity Source: UniProtKB
    • enzyme binding Source: BHF-UCL
    • heme binding Source: UniProtKB
    • iron ion binding Source: InterPro
    • monooxygenase activity Source: BHF-UCL
    • oxidoreductase activity Source: BHF-UCL
    • 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 Source: UniProtKB
    • oxygen binding Source: Reactome

    GO - Biological processi

    • alkaloid metabolic process Source: BHF-UCL
    • cellular respiration Source: Ensembl
    • cellular response to cadmium ion Source: Ensembl
    • dibenzo-p-dioxin metabolic process Source: Ensembl
    • drug catabolic process Source: BHF-UCL
    • drug metabolic process Source: BHF-UCL
    • epoxygenase P450 pathway Source: Reactome
    • exogenous drug catabolic process Source: BHF-UCL
    • heterocycle metabolic process Source: BHF-UCL
    • hydrogen peroxide biosynthetic process Source: Ensembl
    • lung development Source: Ensembl
    • methylation Source: Reactome
    • monocarboxylic acid metabolic process Source: BHF-UCL
    • monoterpenoid metabolic process Source: BHF-UCL
    • omega-hydroxylase P450 pathway Source: Reactome
    • oxidation-reduction process Source: BHF-UCL
    • oxidative deethylation Source: BHF-UCL
    • oxidative demethylation Source: BHF-UCL
    • porphyrin-containing compound metabolic process Source: Ensembl
    • post-embryonic development Source: Ensembl
    • regulation of gene expression Source: Ensembl
    • response to estradiol Source: Ensembl
    • response to immobilization stress Source: Ensembl
    • response to lipopolysaccharide Source: Ensembl
    • steroid catabolic process Source: BHF-UCL
    • toxin biosynthetic process Source: BHF-UCL
    • xenobiotic metabolic process Source: Reactome
    Complete GO annotation...

    Keywords - Molecular functioni

    Monooxygenase, Oxidoreductase

    Keywords - Biological processi

    Lipid metabolism, Steroid metabolism, Sterol metabolism

    Keywords - Ligandi

    Heme, Iron, Metal-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:HS06728-MONOMER.
    ZFISH:HS06728-MONOMER.
    BRENDAi1.14.14.1. 2681.
    1.14.99.38. 2681.
    ReactomeiR-HSA-156581. Methylation.
    R-HSA-211957. Aromatic amines can be N-hydroxylated or N-dealkylated by CYP1A2.
    R-HSA-2142670. Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET).
    R-HSA-2142816. Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE).
    R-HSA-5423646. Aflatoxin activation and detoxification.
    SABIO-RKP05177.

    Chemistry databases

    SwissLipidsiSLP:000001202.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cytochrome P450 1A2 (EC:1.14.14.11 Publication)
    Alternative name(s):
    CYPIA2
    Cholesterol 25-hydroxylase1 Publication
    Cytochrome P(3)450
    Cytochrome P450 4
    Cytochrome P450-P3
    Gene namesi
    Name:CYP1A2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 15

    Organism-specific databases

    HGNCiHGNC:2596. CYP1A2.

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane, Microsome

    Pathology & Biotechi

    Organism-specific databases

    DisGeNETi1544.
    MalaCardsiCYP1A2.
    MIMi124060. gene+phenotype.
    OpenTargetsiENSG00000140505.
    Orphaneti284121. Toxixity or absent response to clozapine.
    PharmGKBiPA27093.

    Chemistry databases

    ChEMBLiCHEMBL3356.
    DrugBankiDB05812. Abiraterone.
    DB01418. Acenocoumarol.
    DB00316. Acetaminophen.
    DB06594. Agomelatine.
    DB00518. Albendazole.
    DB00523. Alitretinoin.
    DB00918. Almotriptan.
    DB00969. Alosetron.
    DB00357. Aminoglutethimide.
    DB01424. Aminophenazone.
    DB01223. Aminophylline.
    DB01118. Amiodarone.
    DB00321. Amitriptyline.
    DB00381. Amlodipine.
    DB00261. Anagrelide.
    DB01217. Anastrozole.
    DB01435. Antipyrine.
    DB06605. Apixaban.
    DB00673. Aprepitant.
    DB06413. Armodafinil.
    DB06216. Asenapine.
    DB00572. Atropine.
    DB06626. Axitinib.
    DB00972. Azelastine.
    DB00207. Azithromycin.
    DB06770. Benzyl alcohol.
    DB00195. Betaxolol.
    DB00188. Bortezomib.
    DB01558. Bromazepam.
    DB01200. Bromocriptine.
    DB00297. Bupivacaine.
    DB00921. Buprenorphine.
    DB01156. Bupropion.
    DB00201. Caffeine.
    DB06774. Capsaicin.
    DB00564. Carbamazepine.
    DB00262. Carmustine.
    DB01136. Carvedilol.
    DB00477. Chlorpromazine.
    DB00356. Chlorzoxazone.
    DB01166. Cilostazol.
    DB00501. Cimetidine.
    DB01012. Cinacalcet.
    DB00568. Cinnarizine.
    DB00537. Ciprofloxacin.
    DB00604. Cisapride.
    DB00215. Citalopram.
    DB01211. Clarithromycin.
    DB01407. Clenbuterol.
    DB04920. Clevidipine.
    DB01013. Clobetasol propionate.
    DB00882. Clomifene.
    DB01242. Clomipramine.
    DB00575. Clonidine.
    DB00758. Clopidogrel.
    DB00257. Clotrimazole.
    DB00363. Clozapine.
    DB00286. Conjugated Estrogens.
    DB00924. Cyclobenzaprine.
    DB00851. Dacarbazine.
    DB06292. Dapagliflozin.
    DB01254. Dasatinib.
    DB00694. Daunorubicin.
    DB00705. Delavirdine.
    DB01151. Desipramine.
    DB00967. Desloratadine.
    DB01191. Dexfenfluramine.
    DB00633. Dexmedetomidine.
    DB00829. Diazepam.
    DB00586. Diclofenac.
    DB00917. Dinoprostone.
    DB01075. Diphenhydramine.
    DB01184. Domperidone.
    DB00988. Dopamine.
    DB01142. Doxepin.
    DB00476. Duloxetine.
    DB00974. Edetic Acid.
    DB00625. Efavirenz.
    DB06210. Eltrombopag.
    DB00467. Enoxacin.
    DB00668. Epinephrine.
    DB00696. Ergotamine.
    DB00530. Erlotinib.
    DB00199. Erythromycin.
    DB00783. Estradiol.
    DB00655. Estrone.
    DB04574. Estropipate.
    DB00898. Ethanol.
    DB00773. Etoposide.
    DB01628. Etoricoxib.
    DB04841. Flunarizine.
    DB01544. Flunitrazepam.
    DB00544. Fluorouracil.
    DB00472. Fluoxetine.
    DB00623. Fluphenazine.
    DB00499. Flutamide.
    DB01095. Fluvastatin.
    DB00176. Fluvoxamine.
    DB00998. Frovatriptan.
    DB01241. Gemfibrozil.
    DB00400. Griseofulvin.
    DB00629. Guanabenz.
    DB00502. Haloperidol.
    DB01094. Hesperetin.
    DB01355. Hexobarbital.
    DB04946. Iloperidone.
    DB00619. Imatinib.
    DB00458. Imipramine.
    DB00724. Imiquimod.
    DB05278. inhaled insulin.
    DB01306. Insulin Aspart.
    DB01307. Insulin Detemir.
    DB00047. Insulin Glargine.
    DB01309. Insulin Glulisine.
    DB00046. Insulin Lispro.
    DB00030. Insulin Regular.
    DB01029. Irbesartan.
    DB00951. Isoniazid.
    DB09570. Ixazomib.
    DB01026. Ketoconazole.
    DB00448. Lansoprazole.
    DB01097. Leflunomide.
    DB01002. Levobupivacaine.
    DB01137. Levofloxacin.
    DB00281. Lidocaine.
    DB00978. Lomefloxacin.
    DB01601. Lopinavir.
    DB04871. Lorcaserin.
    DB00678. Losartan.
    DB01283. Lumiracoxib.
    DB00772. Malathion.
    DB00934. Maprotiline.
    DB00737. Meclizine.
    DB01065. Melatonin.
    DB00170. Menadione.
    DB00333. Methadone.
    DB00763. Methimazole.
    DB01403. Methotrimeprazine.
    DB00553. Methoxsalen.
    DB01028. Methoxyflurane.
    DB00379. Mexiletine.
    DB06148. Mianserin.
    DB01110. Miconazole.
    DB00370. Mirtazapine.
    DB01171. Moclobemide.
    DB00745. Modafinil.
    DB00461. Nabumetone.
    DB00607. Nafcillin.
    DB00788. Naproxen.
    DB00220. Nelfinavir.
    DB00238. Nevirapine.
    DB06803. Niclosamide.
    DB00184. Nicotine.
    DB01115. Nifedipine.
    DB06712. Nilvadipine.
    DB00401. Nisoldipine.
    DB00435. Nitric Oxide.
    DB00325. Nitroprusside.
    DB00368. Norepinephrine.
    DB01059. Norfloxacin.
    DB00540. Nortriptyline.
    DB01165. Ofloxacin.
    DB00334. Olanzapine.
    DB00338. Omeprazole.
    DB00904. Ondansetron.
    DB09330. Osimertinib.
    DB00526. Oxaliplatin.
    DB01303. Oxtriphylline.
    DB06412. Oxymetholone.
    DB00377. Palonosetron.
    DB00213. Pantoprazole.
    DB06589. Pazopanib.
    DB00487. Pefloxacin.
    DB00738. Pentamidine.
    DB00806. Pentoxifylline.
    DB00850. Perphenazine.
    DB01174. Phenobarbital.
    DB00191. Phentermine.
    DB00388. Phenylephrine.
    DB00397. Phenylpropanolamine.
    DB01100. Pimozide.
    DB01621. Pipotiazine.
    DB08910. Pomalidomide.
    DB01058. Praziquantel.
    DB01087. Primaquine.
    DB00794. Primidone.
    DB00396. Progesterone.
    DB01131. Proguanil.
    DB00420. Promazine.
    DB01182. Propafenone.
    DB00818. Propofol.
    DB00571. Propranolol.
    DB00339. Pyrazinamide.
    DB00908. Quinidine.
    DB00468. Quinine.
    DB01129. Rabeprazole.
    DB00980. Ramelteon.
    DB00863. Ranitidine.
    DB01367. Rasagiline.
    DB00615. Rifabutin.
    DB01045. Rifampicin.
    DB08864. Rilpivirine.
    DB00740. Riluzole.
    DB00503. Ritonavir.
    DB00953. Rizatriptan.
    DB00268. Ropinirole.
    DB00296. Ropivacaine.
    DB00412. Rosiglitazone.
    DB05271. Rotigotine.
    DB00778. Roxithromycin.
    DB00418. Secobarbital.
    DB01037. Selegiline.
    DB01104. Sertraline.
    DB06290. Simeprevir.
    DB00398. Sorafenib.
    DB00428. Streptozocin.
    DB06820. Sulconazole.
    DB00605. Sulindac.
    DB00675. Tamoxifen.
    DB00976. Telithromycin.
    DB00300. Tenofovir.
    DB00857. Terbinafine.
    DB01041. Thalidomide.
    DB01412. Theobromine.
    DB00277. Theophylline.
    DB00730. Thiabendazole.
    DB00679. Thioridazine.
    DB01623. Thiothixene.
    DB00208. Ticlopidine.
    DB01007. Tioconazole.
    DB00697. Tizanidine.
    DB01056. Tocainide.
    DB00539. Toremifene.
    DB00752. Tranylcypromine.
    DB00384. Triamterene.
    DB00831. Trifluoperazine.
    DB08867. Ulipristal.
    DB00313. Valproic Acid.
    DB08881. Vemurafenib.
    DB00661. Verapamil.
    DB00682. Warfarin.
    DB00549. Zafirlukast.
    DB00744. Zileuton.
    DB00246. Ziprasidone.
    DB00315. Zolmitriptan.
    DB00425. Zolpidem.
    GuidetoPHARMACOLOGYi1319.

    Polymorphism and mutation databases

    BioMutaiCYP1A2.
    DMDMi117144.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Initiator methionineiRemoved1 Publication
    ChainiPRO_00000516512 – 515Cytochrome P450 1A2Add BLAST514

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Glycosylationi69O-linked (GlcNAc)By similarity1

    Keywords - PTMi

    Glycoprotein

    Proteomic databases

    MaxQBiP05177.
    PaxDbiP05177.
    PeptideAtlasiP05177.
    PRIDEiP05177.

    PTM databases

    iPTMnetiP05177.
    PhosphoSitePlusiP05177.

    Expressioni

    Tissue specificityi

    Liver.

    Inductioni

    By nicotine, omeprazole, phenobarbital, primidone and rifampicin.

    Gene expression databases

    BgeeiENSG00000140505.
    CleanExiHS_CYP1A2.
    GenevisibleiP05177. HS.

    Organism-specific databases

    HPAiCAB016531.

    Interactioni

    GO - Molecular functioni

    • enzyme binding Source: BHF-UCL

    Protein-protein interaction databases

    BioGridi107924. 6 interactors.
    STRINGi9606.ENSP00000342007.

    Chemistry databases

    BindingDBiP05177.

    Structurei

    Secondary structure

    1515
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Turni49 – 51Combined sources3
    Helixi54 – 57Combined sources4
    Helixi61 – 72Combined sources12
    Beta strandi74 – 80Combined sources7
    Beta strandi83 – 88Combined sources6
    Helixi91 – 98Combined sources8
    Turni99 – 101Combined sources3
    Helixi102 – 104Combined sources3
    Helixi112 – 115Combined sources4
    Turni123 – 125Combined sources3
    Helixi131 – 146Combined sources16
    Turni147 – 149Combined sources3
    Helixi160 – 181Combined sources22
    Helixi188 – 205Combined sources18
    Helixi206 – 208Combined sources3
    Helixi214 – 220Combined sources7
    Helixi221 – 223Combined sources3
    Helixi224 – 227Combined sources4
    Helixi235 – 237Combined sources3
    Helixi240 – 244Combined sources5
    Helixi248 – 273Combined sources26
    Helixi283 – 293Combined sources11
    Helixi305 – 308Combined sources4
    Helixi310 – 335Combined sources26
    Helixi337 – 350Combined sources14
    Turni351 – 353Combined sources3
    Helixi359 – 361Combined sources3
    Helixi366 – 379Combined sources14
    Beta strandi394 – 396Combined sources3
    Beta strandi399 – 401Combined sources3
    Beta strandi406 – 410Combined sources5
    Helixi411 – 416Combined sources6
    Turni418 – 420Combined sources3
    Helixi429 – 432Combined sources4
    Beta strandi437 – 440Combined sources4
    Helixi442 – 445Combined sources4
    Helixi454 – 456Combined sources3
    Helixi461 – 478Combined sources18
    Beta strandi480 – 482Combined sources3
    Beta strandi496 – 498Combined sources3
    Beta strandi507 – 510Combined sources4

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2HI4X-ray1.95A27-515[»]
    ProteinModelPortaliP05177.
    SMRiP05177.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP05177.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the cytochrome P450 family.Curated

    Phylogenomic databases

    eggNOGiKOG0156. Eukaryota.
    COG2124. LUCA.
    GeneTreeiENSGT00760000118992.
    HOVERGENiHBG106944.
    InParanoidiP05177.
    KOiK07409.
    OMAiKCCVFVN.
    OrthoDBiEOG091G0BT8.
    PhylomeDBiP05177.
    TreeFamiTF105095.

    Family and domain databases

    Gene3Di1.10.630.10. 1 hit.
    InterProiIPR001128. Cyt_P450.
    IPR017972. Cyt_P450_CS.
    IPR002401. Cyt_P450_E_grp-I.
    IPR008066. Cyt_P450_E_grp-I_CYP1.
    [Graphical view]
    PfamiPF00067. p450. 1 hit.
    [Graphical view]
    PRINTSiPR00463. EP450I.
    PR01683. EP450ICYP1A.
    PR00385. P450.
    SUPFAMiSSF48264. SSF48264. 1 hit.
    PROSITEiPS00086. CYTOCHROME_P450. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: P05177-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MALSQSVPFS ATELLLASAI FCLVFWVLKG LRPRVPKGLK SPPEPWGWPL
    60 70 80 90 100
    LGHVLTLGKN PHLALSRMSQ RYGDVLQIRI GSTPVLVLSR LDTIRQALVR
    110 120 130 140 150
    QGDDFKGRPD LYTSTLITDG QSLTFSTDSG PVWAARRRLA QNALNTFSIA
    160 170 180 190 200
    SDPASSSSCY LEEHVSKEAK ALISRLQELM AGPGHFDPYN QVVVSVANVI
    210 220 230 240 250
    GAMCFGQHFP ESSDEMLSLV KNTHEFVETA SSGNPLDFFP ILRYLPNPAL
    260 270 280 290 300
    QRFKAFNQRF LWFLQKTVQE HYQDFDKNSV RDITGALFKH SKKGPRASGN
    310 320 330 340 350
    LIPQEKIVNL VNDIFGAGFD TVTTAISWSL MYLVTKPEIQ RKIQKELDTV
    360 370 380 390 400
    IGRERRPRLS DRPQLPYLEA FILETFRHSS FLPFTIPHST TRDTTLNGFY
    410 420 430 440 450
    IPKKCCVFVN QWQVNHDPEL WEDPSEFRPE RFLTADGTAI NKPLSEKMML
    460 470 480 490 500
    FGMGKRRCIG EVLAKWEIFL FLAILLQQLE FSVPPGVKVD LTPIYGLTMK
    510
    HARCEHVQAR RFSIN
    Length:515
    Mass (Da):58,294
    Last modified:January 23, 2007 - v3
    Checksum:i23AEFEEBDF6806AB
    GO
    Isoform 2 (identifier: P05177-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         510-510: R → RL

    Show »
    Length:516
    Mass (Da):58,407
    Checksum:i8557AB02860C4806
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti79R → S in AAA35738 (PubMed:3462722).Curated1
    Sequence conflicti81G → D in AAH67427 (PubMed:15489334).Curated1
    Sequence conflicti170K → M in AAF13599 (Ref. 5) Curated1
    Sequence conflicti311V → L in AAA52154 (PubMed:3000715).Curated1
    Sequence conflicti450 – 451LF → MLV in AAA52154 (PubMed:3000715).Curated2
    Sequence conflicti492T → I in AAF13599 (Ref. 5) Curated1
    Sequence conflicti511R → LP in AAA35738 (PubMed:3462722).Curated1

    Polymorphismi

    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 concomitant increase in the risk of non-fatal myocardial infraction (MI).

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_02319618S → C.2 PublicationsCorresponds to variant rs17861152dbSNPEnsembl.1
    Natural variantiVAR_00834921F → L in allele CYP1A2*2. 1 PublicationCorresponds to variant rs56160784dbSNPEnsembl.1
    Natural variantiVAR_02518242P → R in allele CYP1A2*15. 1 Publication1
    Natural variantiVAR_02518373G → R.1 PublicationCorresponds to variant rs45565238dbSNPEnsembl.1
    Natural variantiVAR_02084883T → M in allele CYP1A2*9. 1 Publication1
    Natural variantiVAR_025184104D → N.1 PublicationCorresponds to variant rs34067076dbSNPEnsembl.1
    Natural variantiVAR_025185111L → F.1 PublicationCorresponds to variant rs45442197dbSNPEnsembl.1
    Natural variantiVAR_020849168E → Q in allele CYP1A2*10. 1 Publication1
    Natural variantiVAR_020850186F → 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. 1 Publication1
    Natural variantiVAR_025186205F → V.1 PublicationCorresponds to variant rs45540640dbSNPEnsembl.1
    Natural variantiVAR_020851212S → C in allele CYP1A2*12. 1 Publication1
    Natural variantiVAR_025187281R → W.1 PublicationCorresponds to variant rs45468096dbSNPEnsembl.1
    Natural variantiVAR_024709298S → R.1 PublicationCorresponds to variant rs17861157dbSNPEnsembl.1
    Natural variantiVAR_020852299G → S in allele CYP1A2*13. 1 PublicationCorresponds to variant rs35796837dbSNPEnsembl.1
    Natural variantiVAR_024710314I → V.2 PublicationsCorresponds to variant rs28399418dbSNPEnsembl.1
    Natural variantiVAR_020793348D → N in allele CYP1A2*3; increases N-hydroxylation activity of heterocyclic amines; reduces phenacetin O-deethylation activity. 2 PublicationsCorresponds to variant rs56276455dbSNPEnsembl.1
    Natural variantiVAR_025188377R → Q in allele CYP1A2*16. 1 Publication1
    Natural variantiVAR_020794386I → F in allele CYP1A2*4; increases catalytic efficiency of N-hydroxylation towards some heterocyclic amines and reduces towards others; reduces catalytic efficiency of phenacetin O-deethylation due to a high decrease in the affinity for phenacetin. 2 Publications1
    Natural variantiVAR_020795406C → Y in allele CYP1A2*5; increases N-hydroxylation activity of heterocyclic amines; reduces catalytic efficiency of phenacetin O-deethylation. 2 PublicationsCorresponds to variant rs55889066dbSNPEnsembl.1
    Natural variantiVAR_020796431R → W in allele CYP1A2*6; not detected when expressed in heterologous system as it may be critical for maintenance of protein tertiary structure. 3 PublicationsCorresponds to variant rs28399424dbSNPEnsembl.1
    Natural variantiVAR_020853438T → I in allele CYP1A2*14. 2 PublicationsCorresponds to variant rs45486893dbSNPEnsembl.1
    Natural variantiVAR_025189456R → H in allele CYP1A2*8. 1 Publication1
    Natural variantiVAR_055563457R → W.Corresponds to variant rs34151816dbSNPEnsembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_017123510R → RL in isoform 2. 2 Publications1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    Z00036 mRNA. Translation: CAA77335.1.
    L00389
    , L00384, L00385, L00386, L00388, L00387 Genomic DNA. Translation: AAA35738.1.
    M31667
    , M31664, M31665, M31666 Genomic DNA. Translation: AAA52163.1.
    M12078 mRNA. Translation: AAA52154.1.
    AF182274 mRNA. Translation: AAF13599.1.
    AF253322 Genomic DNA. Translation: AAK25728.1.
    DQ022432 Genomic DNA. Translation: AAY26399.1.
    BC067424 mRNA. Translation: AAH67424.1.
    BC067425 mRNA. Translation: AAH67425.1.
    BC067426 mRNA. Translation: AAH67426.1.
    BC067427 mRNA. Translation: AAH67427.1.
    BC067428 mRNA. Translation: AAH67428.1.
    M55053 mRNA. Translation: AAA52146.1.
    CCDSiCCDS32293.1. [P05177-2]
    PIRiS16718. O4HU4.
    RefSeqiNP_000752.2. NM_000761.4. [P05177-2]
    UniGeneiHs.1361.

    Genome annotation databases

    EnsembliENST00000343932; ENSP00000342007; ENSG00000140505. [P05177-2]
    GeneIDi1544.
    KEGGihsa:1544.
    UCSCiuc002ayr.2. human. [P05177-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Cytochrome P450 Allele Nomenclature Committee

    CYP1A2 alleles

    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    Z00036 mRNA. Translation: CAA77335.1.
    L00389
    , L00384, L00385, L00386, L00388, L00387 Genomic DNA. Translation: AAA35738.1.
    M31667
    , M31664, M31665, M31666 Genomic DNA. Translation: AAA52163.1.
    M12078 mRNA. Translation: AAA52154.1.
    AF182274 mRNA. Translation: AAF13599.1.
    AF253322 Genomic DNA. Translation: AAK25728.1.
    DQ022432 Genomic DNA. Translation: AAY26399.1.
    BC067424 mRNA. Translation: AAH67424.1.
    BC067425 mRNA. Translation: AAH67425.1.
    BC067426 mRNA. Translation: AAH67426.1.
    BC067427 mRNA. Translation: AAH67427.1.
    BC067428 mRNA. Translation: AAH67428.1.
    M55053 mRNA. Translation: AAA52146.1.
    CCDSiCCDS32293.1. [P05177-2]
    PIRiS16718. O4HU4.
    RefSeqiNP_000752.2. NM_000761.4. [P05177-2]
    UniGeneiHs.1361.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2HI4X-ray1.95A27-515[»]
    ProteinModelPortaliP05177.
    SMRiP05177.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi107924. 6 interactors.
    STRINGi9606.ENSP00000342007.

    Chemistry databases

    BindingDBiP05177.
    ChEMBLiCHEMBL3356.
    DrugBankiDB05812. Abiraterone.
    DB01418. Acenocoumarol.
    DB00316. Acetaminophen.
    DB06594. Agomelatine.
    DB00518. Albendazole.
    DB00523. Alitretinoin.
    DB00918. Almotriptan.
    DB00969. Alosetron.
    DB00357. Aminoglutethimide.
    DB01424. Aminophenazone.
    DB01223. Aminophylline.
    DB01118. Amiodarone.
    DB00321. Amitriptyline.
    DB00381. Amlodipine.
    DB00261. Anagrelide.
    DB01217. Anastrozole.
    DB01435. Antipyrine.
    DB06605. Apixaban.
    DB00673. Aprepitant.
    DB06413. Armodafinil.
    DB06216. Asenapine.
    DB00572. Atropine.
    DB06626. Axitinib.
    DB00972. Azelastine.
    DB00207. Azithromycin.
    DB06770. Benzyl alcohol.
    DB00195. Betaxolol.
    DB00188. Bortezomib.
    DB01558. Bromazepam.
    DB01200. Bromocriptine.
    DB00297. Bupivacaine.
    DB00921. Buprenorphine.
    DB01156. Bupropion.
    DB00201. Caffeine.
    DB06774. Capsaicin.
    DB00564. Carbamazepine.
    DB00262. Carmustine.
    DB01136. Carvedilol.
    DB00477. Chlorpromazine.
    DB00356. Chlorzoxazone.
    DB01166. Cilostazol.
    DB00501. Cimetidine.
    DB01012. Cinacalcet.
    DB00568. Cinnarizine.
    DB00537. Ciprofloxacin.
    DB00604. Cisapride.
    DB00215. Citalopram.
    DB01211. Clarithromycin.
    DB01407. Clenbuterol.
    DB04920. Clevidipine.
    DB01013. Clobetasol propionate.
    DB00882. Clomifene.
    DB01242. Clomipramine.
    DB00575. Clonidine.
    DB00758. Clopidogrel.
    DB00257. Clotrimazole.
    DB00363. Clozapine.
    DB00286. Conjugated Estrogens.
    DB00924. Cyclobenzaprine.
    DB00851. Dacarbazine.
    DB06292. Dapagliflozin.
    DB01254. Dasatinib.
    DB00694. Daunorubicin.
    DB00705. Delavirdine.
    DB01151. Desipramine.
    DB00967. Desloratadine.
    DB01191. Dexfenfluramine.
    DB00633. Dexmedetomidine.
    DB00829. Diazepam.
    DB00586. Diclofenac.
    DB00917. Dinoprostone.
    DB01075. Diphenhydramine.
    DB01184. Domperidone.
    DB00988. Dopamine.
    DB01142. Doxepin.
    DB00476. Duloxetine.
    DB00974. Edetic Acid.
    DB00625. Efavirenz.
    DB06210. Eltrombopag.
    DB00467. Enoxacin.
    DB00668. Epinephrine.
    DB00696. Ergotamine.
    DB00530. Erlotinib.
    DB00199. Erythromycin.
    DB00783. Estradiol.
    DB00655. Estrone.
    DB04574. Estropipate.
    DB00898. Ethanol.
    DB00773. Etoposide.
    DB01628. Etoricoxib.
    DB04841. Flunarizine.
    DB01544. Flunitrazepam.
    DB00544. Fluorouracil.
    DB00472. Fluoxetine.
    DB00623. Fluphenazine.
    DB00499. Flutamide.
    DB01095. Fluvastatin.
    DB00176. Fluvoxamine.
    DB00998. Frovatriptan.
    DB01241. Gemfibrozil.
    DB00400. Griseofulvin.
    DB00629. Guanabenz.
    DB00502. Haloperidol.
    DB01094. Hesperetin.
    DB01355. Hexobarbital.
    DB04946. Iloperidone.
    DB00619. Imatinib.
    DB00458. Imipramine.
    DB00724. Imiquimod.
    DB05278. inhaled insulin.
    DB01306. Insulin Aspart.
    DB01307. Insulin Detemir.
    DB00047. Insulin Glargine.
    DB01309. Insulin Glulisine.
    DB00046. Insulin Lispro.
    DB00030. Insulin Regular.
    DB01029. Irbesartan.
    DB00951. Isoniazid.
    DB09570. Ixazomib.
    DB01026. Ketoconazole.
    DB00448. Lansoprazole.
    DB01097. Leflunomide.
    DB01002. Levobupivacaine.
    DB01137. Levofloxacin.
    DB00281. Lidocaine.
    DB00978. Lomefloxacin.
    DB01601. Lopinavir.
    DB04871. Lorcaserin.
    DB00678. Losartan.
    DB01283. Lumiracoxib.
    DB00772. Malathion.
    DB00934. Maprotiline.
    DB00737. Meclizine.
    DB01065. Melatonin.
    DB00170. Menadione.
    DB00333. Methadone.
    DB00763. Methimazole.
    DB01403. Methotrimeprazine.
    DB00553. Methoxsalen.
    DB01028. Methoxyflurane.
    DB00379. Mexiletine.
    DB06148. Mianserin.
    DB01110. Miconazole.
    DB00370. Mirtazapine.
    DB01171. Moclobemide.
    DB00745. Modafinil.
    DB00461. Nabumetone.
    DB00607. Nafcillin.
    DB00788. Naproxen.
    DB00220. Nelfinavir.
    DB00238. Nevirapine.
    DB06803. Niclosamide.
    DB00184. Nicotine.
    DB01115. Nifedipine.
    DB06712. Nilvadipine.
    DB00401. Nisoldipine.
    DB00435. Nitric Oxide.
    DB00325. Nitroprusside.
    DB00368. Norepinephrine.
    DB01059. Norfloxacin.
    DB00540. Nortriptyline.
    DB01165. Ofloxacin.
    DB00334. Olanzapine.
    DB00338. Omeprazole.
    DB00904. Ondansetron.
    DB09330. Osimertinib.
    DB00526. Oxaliplatin.
    DB01303. Oxtriphylline.
    DB06412. Oxymetholone.
    DB00377. Palonosetron.
    DB00213. Pantoprazole.
    DB06589. Pazopanib.
    DB00487. Pefloxacin.
    DB00738. Pentamidine.
    DB00806. Pentoxifylline.
    DB00850. Perphenazine.
    DB01174. Phenobarbital.
    DB00191. Phentermine.
    DB00388. Phenylephrine.
    DB00397. Phenylpropanolamine.
    DB01100. Pimozide.
    DB01621. Pipotiazine.
    DB08910. Pomalidomide.
    DB01058. Praziquantel.
    DB01087. Primaquine.
    DB00794. Primidone.
    DB00396. Progesterone.
    DB01131. Proguanil.
    DB00420. Promazine.
    DB01182. Propafenone.
    DB00818. Propofol.
    DB00571. Propranolol.
    DB00339. Pyrazinamide.
    DB00908. Quinidine.
    DB00468. Quinine.
    DB01129. Rabeprazole.
    DB00980. Ramelteon.
    DB00863. Ranitidine.
    DB01367. Rasagiline.
    DB00615. Rifabutin.
    DB01045. Rifampicin.
    DB08864. Rilpivirine.
    DB00740. Riluzole.
    DB00503. Ritonavir.
    DB00953. Rizatriptan.
    DB00268. Ropinirole.
    DB00296. Ropivacaine.
    DB00412. Rosiglitazone.
    DB05271. Rotigotine.
    DB00778. Roxithromycin.
    DB00418. Secobarbital.
    DB01037. Selegiline.
    DB01104. Sertraline.
    DB06290. Simeprevir.
    DB00398. Sorafenib.
    DB00428. Streptozocin.
    DB06820. Sulconazole.
    DB00605. Sulindac.
    DB00675. Tamoxifen.
    DB00976. Telithromycin.
    DB00300. Tenofovir.
    DB00857. Terbinafine.
    DB01041. Thalidomide.
    DB01412. Theobromine.
    DB00277. Theophylline.
    DB00730. Thiabendazole.
    DB00679. Thioridazine.
    DB01623. Thiothixene.
    DB00208. Ticlopidine.
    DB01007. Tioconazole.
    DB00697. Tizanidine.
    DB01056. Tocainide.
    DB00539. Toremifene.
    DB00752. Tranylcypromine.
    DB00384. Triamterene.
    DB00831. Trifluoperazine.
    DB08867. Ulipristal.
    DB00313. Valproic Acid.
    DB08881. Vemurafenib.
    DB00661. Verapamil.
    DB00682. Warfarin.
    DB00549. Zafirlukast.
    DB00744. Zileuton.
    DB00246. Ziprasidone.
    DB00315. Zolmitriptan.
    DB00425. Zolpidem.
    GuidetoPHARMACOLOGYi1319.
    SwissLipidsiSLP:000001202.

    PTM databases

    iPTMnetiP05177.
    PhosphoSitePlusiP05177.

    Polymorphism and mutation databases

    BioMutaiCYP1A2.
    DMDMi117144.

    Proteomic databases

    MaxQBiP05177.
    PaxDbiP05177.
    PeptideAtlasiP05177.
    PRIDEiP05177.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000343932; ENSP00000342007; ENSG00000140505. [P05177-2]
    GeneIDi1544.
    KEGGihsa:1544.
    UCSCiuc002ayr.2. human. [P05177-1]

    Organism-specific databases

    CTDi1544.
    DisGeNETi1544.
    GeneCardsiCYP1A2.
    HGNCiHGNC:2596. CYP1A2.
    HPAiCAB016531.
    MalaCardsiCYP1A2.
    MIMi108330. gene.
    124060. gene+phenotype.
    neXtProtiNX_P05177.
    OpenTargetsiENSG00000140505.
    Orphaneti284121. Toxixity or absent response to clozapine.
    PharmGKBiPA27093.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG0156. Eukaryota.
    COG2124. LUCA.
    GeneTreeiENSGT00760000118992.
    HOVERGENiHBG106944.
    InParanoidiP05177.
    KOiK07409.
    OMAiKCCVFVN.
    OrthoDBiEOG091G0BT8.
    PhylomeDBiP05177.
    TreeFamiTF105095.

    Enzyme and pathway databases

    BioCyciMetaCyc:HS06728-MONOMER.
    ZFISH:HS06728-MONOMER.
    BRENDAi1.14.14.1. 2681.
    1.14.99.38. 2681.
    ReactomeiR-HSA-156581. Methylation.
    R-HSA-211957. Aromatic amines can be N-hydroxylated or N-dealkylated by CYP1A2.
    R-HSA-2142670. Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET).
    R-HSA-2142816. Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE).
    R-HSA-5423646. Aflatoxin activation and detoxification.
    SABIO-RKP05177.

    Miscellaneous databases

    EvolutionaryTraceiP05177.
    GeneWikiiCYP1A2.
    GenomeRNAii1544.
    PROiP05177.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000140505.
    CleanExiHS_CYP1A2.
    GenevisibleiP05177. HS.

    Family and domain databases

    Gene3Di1.10.630.10. 1 hit.
    InterProiIPR001128. Cyt_P450.
    IPR017972. Cyt_P450_CS.
    IPR002401. Cyt_P450_E_grp-I.
    IPR008066. Cyt_P450_E_grp-I_CYP1.
    [Graphical view]
    PfamiPF00067. p450. 1 hit.
    [Graphical view]
    PRINTSiPR00463. EP450I.
    PR01683. EP450ICYP1A.
    PR00385. P450.
    SUPFAMiSSF48264. SSF48264. 1 hit.
    PROSITEiPS00086. CYTOCHROME_P450. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiCP1A2_HUMAN
    AccessioniPrimary (citable) accession number: P05177
    Secondary accession number(s): Q16754
    , Q6NWU5, Q9BXX7, Q9UK49
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 13, 1987
    Last sequence update: January 23, 2007
    Last modified: November 2, 2016
    This is version 179 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 15
      Human chromosome 15: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.