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P33261

- CP2CJ_HUMAN

UniProt

P33261 - CP2CJ_HUMAN

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Protein

Cytochrome P450 2C19

Gene

CYP2C19

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

Functioni

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.

Catalytic activityi

+-(R)-limonene + NADPH + O2 = (+)-trans-carveol + NADP+ + H2O.
--(S)-limonene + NADPH + O2 = (-)-trans-carveol + NADP+ + H2O.
--(S)-limonene + NADPH + O2 = (-)-perillyl alcohol + NADP+ + H2O.

Cofactori

heme1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi435 – 4351Iron (heme axial ligand)

GO - Molecular functioni

  1. (R)-limonene 6-monooxygenase activity Source: UniProtKB-EC
  2. (S)-limonene 6-monooxygenase activity Source: UniProtKB-EC
  3. (S)-limonene 7-monooxygenase activity Source: UniProtKB-EC
  4. enzyme binding Source: BHF-UCL
  5. heme binding Source: UniProtKB
  6. iron ion binding Source: InterPro
  7. monooxygenase activity Source: BHF-UCL
  8. oxidoreductase activity Source: BHF-UCL
  9. oxygen binding Source: ProtInc
  10. steroid hydroxylase activity Source: BHF-UCL

GO - Biological processi

  1. arachidonic acid metabolic process Source: Reactome
  2. drug metabolic process Source: BHF-UCL
  3. epoxygenase P450 pathway Source: Reactome
  4. exogenous drug catabolic process Source: BHF-UCL
  5. heterocycle metabolic process Source: BHF-UCL
  6. monoterpenoid metabolic process Source: BHF-UCL
  7. omega-hydroxylase P450 pathway Source: Reactome
  8. oxidation-reduction process Source: BHF-UCL
  9. small molecule metabolic process Source: Reactome
  10. steroid metabolic process Source: BHF-UCL
  11. xenobiotic metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Monooxygenase, Oxidoreductase

Keywords - Ligandi

Heme, Iron, Metal-binding, NADP

Enzyme and pathway databases

BioCyciMetaCyc:HS09293-MONOMER.
ReactomeiREACT_13543. Xenobiotics.
REACT_13797. CYP2E1 reactions.
REACT_150134. Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE).
REACT_150417. Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET).
SABIO-RKP33261.

Names & Taxonomyi

Protein namesi
Recommended name:
Cytochrome P450 2C19 (EC:1.14.13.-)
Alternative name(s):
(R)-limonene 6-monooxygenase (EC:1.14.13.80)
(S)-limonene 6-monooxygenase (EC:1.14.13.48)
(S)-limonene 7-monooxygenase (EC:1.14.13.49)
CYPIIC17
CYPIIC19
Cytochrome P450-11A
Cytochrome P450-254C
Mephenytoin 4-hydroxylase
Gene namesi
Name:CYP2C19
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 10

Organism-specific databases

HGNCiHGNC:2621. CYP2C19.

Subcellular locationi

GO - Cellular componenti

  1. endoplasmic reticulum membrane Source: Reactome
  2. intracellular membrane-bounded organelle Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

Pathology & Biotechi

Organism-specific databases

MIMi609535. phenotype.
Orphaneti240847. Amitriptyline toxicity.
240865. Clomipramine toxicity.
240883. Imipramine toxicity.
240893. Nortriptyline toxicity.
240931. Resistance to amitriptyline in the treatment of depression.
240933. Resistance to clomipramine in the treatment of depression.
240935. Resistance to clopidogrel in myocardial infarction, cerebrovascular accident, oblitering arteriopathy of the lower limbs.
240939. Resistance to imipramine in the treatment of depression.
240941. Resistance to nortripilline in the treatment of depression.
240949. Resistance to trimipramine in the treatment of depression.
240951. Resistance to venlafaxine in the treatment of depression.
240957. Susceptibility to adverse reaction due to amitriptyline treatment.
240965. Susceptibility to adverse reaction due to clomipramine treatment.
240971. Susceptibility to adverse reaction due to imipramine treatment.
240979. Susceptibility to adverse reaction due to nortriptyline treatment.
240987. Susceptibility to adverse reaction due to trimipramine treatment.
240989. Susceptibility to adverse reaction due to venlafaxine treatment.
241003. Susceptibility to hepatitis due to voriconazole treatment.
240915. Trimipramine toxicity.
240919. Venlafaxine toxicity.
240921. Voriconazole toxicity.
PharmGKBiPA124.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 490490Cytochrome P450 2C19PRO_0000051708Add
BLAST

Proteomic databases

PaxDbiP33261.
PRIDEiP33261.

PTM databases

PhosphoSiteiP33261.

Expressioni

Inductioni

P450 can be induced to high levels in liver and other tissues by various foreign compounds, including drugs, pesticides, and carcinogens.

Gene expression databases

BgeeiP33261.
CleanExiHS_CYP2C19.
GenevestigatoriP33261.

Organism-specific databases

HPAiHPA015066.

Interactioni

Protein-protein interaction databases

BioGridi107935. 1 interaction.
STRINGi9606.ENSP00000360372.

Structurei

Secondary structure

1
490
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni37 – 393Combined sources
Helixi42 – 443Combined sources
Helixi47 – 493Combined sources
Helixi50 – 6112Combined sources
Beta strandi63 – 697Combined sources
Beta strandi72 – 776Combined sources
Helixi80 – 878Combined sources
Turni88 – 903Combined sources
Helixi91 – 944Combined sources
Helixi103 – 1064Combined sources
Turni107 – 1093Combined sources
Helixi117 – 13014Combined sources
Beta strandi135 – 1395Combined sources
Helixi141 – 15818Combined sources
Turni159 – 1613Combined sources
Turni166 – 1683Combined sources
Helixi169 – 18214Combined sources
Beta strandi183 – 1853Combined sources
Helixi192 – 20918Combined sources
Helixi211 – 2188Combined sources
Helixi222 – 2254Combined sources
Helixi228 – 25427Combined sources
Helixi263 – 27311Combined sources
Turni274 – 2763Combined sources
Helixi284 – 29714Combined sources
Helixi300 – 31516Combined sources
Helixi317 – 33014Combined sources
Beta strandi333 – 3353Combined sources
Helixi339 – 3446Combined sources
Helixi346 – 35914Combined sources
Beta strandi377 – 3793Combined sources
Beta strandi386 – 3894Combined sources
Helixi391 – 3955Combined sources
Turni398 – 4003Combined sources
Beta strandi401 – 4033Combined sources
Helixi409 – 4124Combined sources
Beta strandi415 – 4173Combined sources
Helixi438 – 45518Combined sources
Beta strandi456 – 4627Combined sources
Turni464 – 4663Combined sources
Beta strandi475 – 4773Combined sources
Beta strandi485 – 4895Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4GQSX-ray2.87A/B/C/D23-489[»]
ProteinModelPortaliP33261.
SMRiP33261. Positions 29-490.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the cytochrome P450 family.Curated

Phylogenomic databases

eggNOGiCOG2124.
GeneTreeiENSGT00760000118775.
HOGENOMiHOG000036992.
HOVERGENiHBG015789.
InParanoidiP33261.
KOiK17721.
OMAiRIVSTPW.
OrthoDBiEOG7RBZ85.
PhylomeDBiP33261.
TreeFamiTF352043.

Family and domain databases

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

Sequencei

Sequence statusi: Complete.

P33261-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MDPFVVLVLC LSCLLLLSIW RQSSGRGKLP PGPTPLPVIG NILQIDIKDV
60 70 80 90 100
SKSLTNLSKI YGPVFTLYFG LERMVVLHGY EVVKEALIDL GEEFSGRGHF
110 120 130 140 150
PLAERANRGF GIVFSNGKRW KEIRRFSLMT LRNFGMGKRS IEDRVQEEAR
160 170 180 190 200
CLVEELRKTK ASPCDPTFIL GCAPCNVICS IIFQKRFDYK DQQFLNLMEK
210 220 230 240 250
LNENIRIVST PWIQICNNFP TIIDYFPGTH NKLLKNLAFM ESDILEKVKE
260 270 280 290 300
HQESMDINNP RDFIDCFLIK MEKEKQNQQS EFTIENLVIT AADLLGAGTE
310 320 330 340 350
TTSTTLRYAL LLLLKHPEVT AKVQEEIERV VGRNRSPCMQ DRGHMPYTDA
360 370 380 390 400
VVHEVQRYID LIPTSLPHAV TCDVKFRNYL IPKGTTILTS LTSVLHDNKE
410 420 430 440 450
FPNPEMFDPR HFLDEGGNFK KSNYFMPFSA GKRICVGEGL ARMELFLFLT
460 470 480 490
FILQNFNLKS LIDPKDLDTT PVVNGFASVP PFYQLCFIPV
Length:490
Mass (Da):55,931
Last modified:March 1, 2005 - v3
Checksum:i17DB04C50A132C53
GO

Polymorphismi

Genetic variation in CYP2C19 is responsible for poor drug metabolism [MIMi:609535]. Individuals can be characterized as either extensive metabolizers (EM) or poor metabolizers (PM). The PM phenotype is inherited in an autosomal recessive manner, with the EM phenotype comprising both homozygous dominant and heteroyzgote genotypes. There are marked interracial differences in the frequency of this polymorphism. Poor metabolizers represent 2-5% of Caucasians, 13-23% of Asian populations, and as many as 38-79% of individuals of some of the islands of Polynesia and Micronesia. Different alleles of CYP2C19 are known: CYP2C19*1A CYP2C19*1B, CYP2C19*1C, CYP2C19*2A (CYP2C19m1 or CYP2C19m1A), CYP2C19*2B (CYP2C19m1B), CYP2C19*2C (CYP2C19*21), CYP2C19*3A (CYP2C19m2), CYP2C19*3B (CYP2C19*20), CYP2C19*4 (CYP2C19m3), CYP2C19*5A (CYP2C19m4), CYP2C19*5B, CYP2C19*6, CYP2C19*7, CYP2C19*8, CYP2C19*9, CYP2C19*10, CYP2C19*11 CYP2C19*12, CYP2C19*13, CYP2C19*14 CYP2C19*15, CYP2C19*16, CYP2C19*18, CYP2C19*19. Defective CYP2C19*2 and CYP2C19*3 alleles are characterized by a splice mutation and a stop codon, respectively, and account for most of the PM alleles. The sequence shown is that of allele CYP2C19*1B.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti17 – 171L → P in allele CYP2C19*14. 1 Publication
Corresponds to variant rs55752064 [ dbSNP | Ensembl ].
VAR_021268
Natural varianti19 – 191I → L in allele CYP2C19*15. 2 Publications
Corresponds to variant rs17882687 [ dbSNP | Ensembl ].
VAR_021269
Natural varianti51 – 511S → G in allele CYP2C19*19. 1 Publication
VAR_024083
Natural varianti74 – 741M → T.1 Publication
Corresponds to variant rs28399505 [ dbSNP | Ensembl ].
VAR_024718
Natural varianti92 – 921E → D.2 Publications
Corresponds to variant rs17878459 [ dbSNP | Ensembl ].
VAR_021270
Natural varianti120 – 1201W → R in allele CYP2C19*8; loss of activity. 1 Publication
Corresponds to variant rs41291556 [ dbSNP | Ensembl ].
VAR_008357
Natural varianti122 – 1221E → A.1 Publication
Corresponds to variant rs17885179 [ dbSNP | Ensembl ].
VAR_021271
Natural varianti132 – 1321R → Q in allele CYP2C19*6; loss of activity. 1 Publication
VAR_008358
Natural varianti144 – 1441R → H in allele CYP2C19*9. 3 Publications
Corresponds to variant rs17884712 [ dbSNP | Ensembl ].
VAR_021272
Natural varianti150 – 1501R → H in allele CYP2C19*11. 1 Publication
Corresponds to variant rs58973490 [ dbSNP | Ensembl ].
VAR_021273
Natural varianti161 – 1611A → P.1 Publication
Corresponds to variant rs181297724 [ dbSNP | Ensembl ].
VAR_024084
Natural varianti168 – 1681F → L.1 Publication
Corresponds to variant rs28399510 [ dbSNP | Ensembl ].
VAR_024719
Natural varianti227 – 2271P → L in allele CYP2C19*10. 1 Publication
Corresponds to variant rs6413438 [ dbSNP | Ensembl ].
VAR_020123
Natural varianti329 – 3291R → H in allele CYP2C19*18. 1 Publication
VAR_024085
Natural varianti331 – 3311V → I in allele CYP2C19*1A, allele CYP2C19*5A, allele CYP2C19*8 and allele CYP2C19*16. 4 Publications
Corresponds to variant rs3758581 [ dbSNP | Ensembl ].
VAR_001255
Natural varianti410 – 4101R → C in allele CYP2C19*13. 2 Publications
Corresponds to variant rs17879685 [ dbSNP | Ensembl ].
VAR_021274
Natural varianti433 – 4331R → W in allele CYP2C19*5A and allele CYP2C19*5B; loss of activity. 2 Publications
Corresponds to variant rs56337013 [ dbSNP | Ensembl ].
VAR_008359
Natural varianti442 – 4421R → C in allele CYP2C19*16; lowered catalytic activity. 1 Publication
Corresponds to variant rs192154563 [ dbSNP | Ensembl ].
VAR_021275

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M61854 mRNA. Translation: AAB59426.1.
M61858 mRNA. Translation: AAA52145.1. Sequence problems.
L07093 mRNA. Translation: AAA36660.1. Sequence problems.
AY796203 Genomic DNA. Translation: AAV41877.1.
AL583836, AL133513 Genomic DNA. Translation: CAH74068.1.
AL133513, AL583836 Genomic DNA. Translation: CAH73444.1.
L39098, L39097 Genomic DNA. Translation: AAL31347.1.
L39102
, L39099, L39100, L39101 Genomic DNA. Translation: AAL31348.1.
L31506 Genomic DNA. No translation available.
L31507 Genomic DNA. No translation available.
L32982 Genomic DNA. No translation available.
L32983 Genomic DNA. No translation available.
CCDSiCCDS7436.1.
PIRiF38462.
G38462.
I52418.
RefSeqiNP_000760.1. NM_000769.2.
UniGeneiHs.282409.

Genome annotation databases

EnsembliENST00000371321; ENSP00000360372; ENSG00000165841.
GeneIDi1557.
KEGGihsa:1557.
UCSCiuc010qny.2. human.

Polymorphism databases

DMDMi60416369.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Cytochrome P450 Allele Nomenclature Committee

CYP2C19 alleles

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M61854 mRNA. Translation: AAB59426.1 .
M61858 mRNA. Translation: AAA52145.1 . Sequence problems.
L07093 mRNA. Translation: AAA36660.1 . Sequence problems.
AY796203 Genomic DNA. Translation: AAV41877.1 .
AL583836 , AL133513 Genomic DNA. Translation: CAH74068.1 .
AL133513 , AL583836 Genomic DNA. Translation: CAH73444.1 .
L39098 , L39097 Genomic DNA. Translation: AAL31347.1 .
L39102
, L39099 , L39100 , L39101 Genomic DNA. Translation: AAL31348.1 .
L31506 Genomic DNA. No translation available.
L31507 Genomic DNA. No translation available.
L32982 Genomic DNA. No translation available.
L32983 Genomic DNA. No translation available.
CCDSi CCDS7436.1.
PIRi F38462.
G38462.
I52418.
RefSeqi NP_000760.1. NM_000769.2.
UniGenei Hs.282409.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
4GQS X-ray 2.87 A/B/C/D 23-489 [» ]
ProteinModelPortali P33261.
SMRi P33261. Positions 29-490.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 107935. 1 interaction.
STRINGi 9606.ENSP00000360372.

Chemistry

BindingDBi P33261.
ChEMBLi CHEMBL3622.
DrugBanki DB01418. Acenocoumarol.
DB00945. Acetylsalicylic acid.
DB00546. Adinazolam.
DB00918. Almotriptan.
DB00357. Aminoglutethimide.
DB01424. Aminophenazone.
DB01118. Amiodarone.
DB00321. Amitriptyline.
DB01060. Amoxicillin.
DB00701. Amprenavir.
DB01435. Antipyrine.
DB06605. Apixaban.
DB00673. Aprepitant.
DB01274. Arformoterol.
DB06697. Artemether.
DB00289. Atomoxetine.
DB01076. Atorvastatin.
DB06626. Axitinib.
DB00972. Azelastine.
DB00245. Benzatropine.
DB01128. Bicalutamide.
DB04794. Bifonazole.
DB00188. Bortezomib.
DB01558. Bromazepam.
DB00835. Brompheniramine.
DB00297. Bupivacaine.
DB00921. Buprenorphine.
DB00564. Carbamazepine.
DB00748. Carbinoxamine.
DB00395. Carisoprodol.
DB00446. Chloramphenicol.
DB00672. Chlorpropamide.
DB00169. Cholecalciferol.
DB01166. Cilostazol.
DB00501. Cimetidine.
DB00604. Cisapride.
DB00215. Citalopram.
DB01211. Clarithromycin.
DB04920. Clevidipine.
DB00349. Clobazam.
DB01242. Clomipramine.
DB00758. Clopidogrel.
DB01559. Clotiazepam.
DB00257. Clotrimazole.
DB00363. Clozapine.
DB00531. Cyclophosphamide.
DB00091. Cyclosporine.
DB00250. Dapsone.
DB00705. Delavirdine.
DB01151. Desipramine.
DB00967. Desloratadine.
DB01234. Dexamethasone.
DB01191. Dexfenfluramine.
DB00514. Dextromethorphan.
DB00829. Diazepam.
DB00586. Diclofenac.
DB00343. Diltiazem.
DB01093. Dimethyl sulfoxide.
DB01075. Diphenhydramine.
DB00988. Dopamine.
DB00590. Doxazosin.
DB01142. Doxepin.
DB00470. Dronabinol.
DB00625. Efavirenz.
DB00216. Eletriptan.
DB00109. Enfuvirtide.
DB08899. Enzalutamide.
DB01175. Escitalopram.
DB00736. Esomeprazole.
DB00783. Estradiol.
DB00898. Ethanol.
DB00754. Ethotoin.
DB01628. Etoricoxib.
DB06414. Etravirine.
DB00927. Famotidine.
DB00949. Felbamate.
DB00196. Fluconazole.
DB01544. Flunitrazepam.
DB00472. Fluoxetine.
DB00499. Flutamide.
DB01095. Fluvastatin.
DB00176. Fluvoxamine.
DB00983. Formoterol.
DB01320. Fosphenytoin.
DB00317. Gefitinib.
DB01241. Gemfibrozil.
DB01120. Gliclazide.
DB01296. Glucosamine.
DB01016. Glyburide.
DB01018. Guanfacine.
DB00502. Haloperidol.
DB01355. Hexobarbital.
DB01050. Ibuprofen.
DB01181. Ifosfamide.
DB00619. Imatinib.
DB00458. Imipramine.
DB00224. Indinavir.
DB00328. Indomethacin.
DB00951. Isoniazid.
DB06738. Ketobemidone.
DB01026. Ketoconazole.
DB00448. Lansoprazole.
DB01259. Lapatinib.
DB08918. Levomilnacipran.
DB01601. Lopinavir.
DB00455. Loratadine.
DB04871. Lorcaserin.
DB00678. Losartan.
DB00227. Lovastatin.
DB08933. LULICONAZOLE.
DB01283. Lumiracoxib.
DB08932. MACITENTAN.
DB01065. Melatonin.
DB01043. Memantine.
DB00371. Meprobamate.
DB00333. Methadone.
DB00703. Methazolamide.
DB00763. Methimazole.
DB05246. Methsuximide.
DB00849. Methylphenobarbital.
DB00264. Metoprolol.
DB01110. Miconazole.
DB01171. Moclobemide.
DB00745. Modafinil.
DB00220. Nelfinavir.
DB00622. Nicardipine.
DB00184. Nicotine.
DB00665. Nilutamide.
DB06712. Nilvadipine.
DB00717. Norethindrone.
DB00540. Nortriptyline.
DB00334. Olanzapine.
DB00338. Omeprazole.
DB04938. Ospemifene.
DB00776. Oxcarbazepine.
DB00239. Oxiconazole.
DB00213. Pantoprazole.
DB00082. Pegvisomant.
DB00738. Pentamidine.
DB00312. Pentobarbital.
DB00850. Perphenazine.
DB00454. Pethidine.
DB00780. Phenelzine.
DB01174. Phenobarbital.
DB00832. Phensuximide.
DB00252. Phenytoin.
DB01100. Pimozide.
DB01132. Pioglitazone.
DB01621. Pipotiazine.
DB01179. Podofilox.
DB06209. Prasugrel.
DB01058. Praziquantel.
DB00635. Prednisone.
DB00794. Primidone.
DB01032. Probenecid.
DB00396. Progesterone.
DB01131. Proguanil.
DB00420. Promazine.
DB00818. Propofol.
DB00571. Propranolol.
DB01589. Quazepam.
DB01224. Quetiapine.
DB00468. Quinine.
DB01129. Rabeprazole.
DB00980. Ramelteon.
DB00863. Ranitidine.
DB08896. Regorafenib.
DB01045. Rifampicin.
DB08864. Rilpivirine.
DB00503. Ritonavir.
DB00412. Rosiglitazone.
DB01098. Rosuvastatin.
DB01232. Saquinavir.
DB01037. Selegiline.
DB01104. Sertraline.
DB00203. Sildenafil.
DB00641. Simvastatin.
DB06268. Sitaxentan.
DB00398. Sorafenib.
DB00259. Sulfanilamide.
DB00675. Tamoxifen.
DB06204. Tapentadol.
DB00966. Telmisartan.
DB00231. Temazepam.
DB00444. Teniposide.
DB00857. Terbinafine.
DB00624. Testosterone.
DB01041. Thalidomide.
DB00679. Thioridazine.
DB00208. Ticlopidine.
DB00373. Timolol.
DB01007. Tioconazole.
DB00932. Tipranavir.
DB08895. Tofacitinib.
DB01124. Tolbutamide.
DB01036. Tolterodine.
DB00273. Topiramate.
DB00214. Torasemide.
DB05109. Trabectedin.
DB00752. Tranylcypromine.
DB00347. Trimethadione.
DB00726. Trimipramine.
DB01361. Troleandomycin.
DB00313. Valproic Acid.
DB00285. Venlafaxine.
DB00661. Verapamil.
DB08828. Vismodegib.
DB00582. Voriconazole.
DB00682. Warfarin.
DB00549. Zafirlukast.
DB00495. Zidovudine.
DB00425. Zolpidem.
DB00909. Zonisamide.

PTM databases

PhosphoSitei P33261.

Polymorphism databases

DMDMi 60416369.

Proteomic databases

PaxDbi P33261.
PRIDEi P33261.

Protocols and materials databases

DNASUi 1557.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000371321 ; ENSP00000360372 ; ENSG00000165841 .
GeneIDi 1557.
KEGGi hsa:1557.
UCSCi uc010qny.2. human.

Organism-specific databases

CTDi 1557.
GeneCardsi GC10P096447.
HGNCi HGNC:2621. CYP2C19.
HPAi HPA015066.
MIMi 124020. gene.
609535. phenotype.
neXtProti NX_P33261.
Orphaneti 240847. Amitriptyline toxicity.
240865. Clomipramine toxicity.
240883. Imipramine toxicity.
240893. Nortriptyline toxicity.
240931. Resistance to amitriptyline in the treatment of depression.
240933. Resistance to clomipramine in the treatment of depression.
240935. Resistance to clopidogrel in myocardial infarction, cerebrovascular accident, oblitering arteriopathy of the lower limbs.
240939. Resistance to imipramine in the treatment of depression.
240941. Resistance to nortripilline in the treatment of depression.
240949. Resistance to trimipramine in the treatment of depression.
240951. Resistance to venlafaxine in the treatment of depression.
240957. Susceptibility to adverse reaction due to amitriptyline treatment.
240965. Susceptibility to adverse reaction due to clomipramine treatment.
240971. Susceptibility to adverse reaction due to imipramine treatment.
240979. Susceptibility to adverse reaction due to nortriptyline treatment.
240987. Susceptibility to adverse reaction due to trimipramine treatment.
240989. Susceptibility to adverse reaction due to venlafaxine treatment.
241003. Susceptibility to hepatitis due to voriconazole treatment.
240915. Trimipramine toxicity.
240919. Venlafaxine toxicity.
240921. Voriconazole toxicity.
PharmGKBi PA124.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG2124.
GeneTreei ENSGT00760000118775.
HOGENOMi HOG000036992.
HOVERGENi HBG015789.
InParanoidi P33261.
KOi K17721.
OMAi RIVSTPW.
OrthoDBi EOG7RBZ85.
PhylomeDBi P33261.
TreeFami TF352043.

Enzyme and pathway databases

BioCyci MetaCyc:HS09293-MONOMER.
Reactomei REACT_13543. Xenobiotics.
REACT_13797. CYP2E1 reactions.
REACT_150134. Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE).
REACT_150417. Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET).
SABIO-RK P33261.

Miscellaneous databases

GeneWikii CYP2C19.
GenomeRNAii 1557.
NextBioi 6430.
PROi P33261.
SOURCEi Search...

Gene expression databases

Bgeei P33261.
CleanExi HS_CYP2C19.
Genevestigatori P33261.

Family and domain databases

Gene3Di 1.10.630.10. 1 hit.
InterProi IPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
[Graphical view ]
Pfami PF00067. p450. 1 hit.
[Graphical view ]
PRINTSi PR00463. EP450I.
PR00385. P450.
SUPFAMi SSF48264. SSF48264. 1 hit.
PROSITEi PS00086. CYTOCHROME_P450. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and expression of complementary DNAs for multiple members of the human cytochrome P450IIC subfamily."
    Romkes M., Faletto M.B., Blaisdell J.A., Raucy J.L., Goldstein J.A.
    Biochemistry 30:3247-3255(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ALLELE CYP2C19*1A).
    Tissue: Liver.
  2. Cited for: SEQUENCE REVISION.
  3. NIEHS SNPs program
    Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LEU-19; ASP-92; ALA-122; HIS-144; ILE-331 AND CYS-410.
  4. "The DNA sequence and comparative analysis of human chromosome 10."
    Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J.
    , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
    Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "Gene structure, upstream region and allelic variants of cyp2c19, the s-mephenytoin hydroxylase."
    de Morais S.M.F., Blaisdell J.A.
    Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-160 AND 274-490, VARIANT ILE-331.
  6. "Isolation and characterization of human liver cytochrome P450 2C19: correlation between 2C19 and S-mephenytoin 4'-hydroxylation."
    Wrighton S.A., Stevens J.C., Becker G.W., VandenBranden M.
    Arch. Biochem. Biophys. 306:240-245(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 1-16.
    Tissue: Liver.
  7. "Metabolism of (+)- and (-)-limonenes to respective carveols and perillyl alcohols by CYP2C9 and CYP2C19 in human liver microsomes."
    Miyazawa M., Shindo M., Shimada T.
    Drug Metab. Dispos. 30:602-607(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION.
  8. "Structural characterization of human cytochrome P450 2C19: active site differences between P450s 2C8, 2C9, and 2C19."
    Reynald R.L., Sansen S., Stout C.D., Johnson E.F.
    J. Biol. Chem. 287:44581-44591(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.87 ANGSTROMS) OF 23-489 IN COMPLEX WITH HEME AND SYNTHETIC INHIBITOR, COFACTOR.
  9. "The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans."
    de Morais S.M.F., Wilkinson G.R., Blaisdell J., Nakamura K., Meyer U.A., Goldstein J.A.
    J. Biol. Chem. 269:15419-15422(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN POOR DRUG METABOLISM, IDENTIFICATION OF ALLELE CYP2C19*2A.
  10. "Identification of a new genetic defect responsible for the polymorphism of (S)-mephenytoin metabolism in Japanese."
    De Morais S.M.F., Wilkinson G.R., Blaisdell J., Meyer U.A., Nakamura K., Goldstein J.A.
    Mol. Pharmacol. 46:594-598(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN POOR DRUG METABOLISM, IDENTIFICATION OF ALLELE CYP2C19*3A.
  11. "Differences in the incidence of the CYP2C19 polymorphism affecting the S-mephenytoin phenotype in Chinese Han and Bai populations and identification of a new rare CYP2C19 mutant allele."
    Xiao Z.S., Goldstein J.A., Xie H.G., Blaisdell J., Wang W., Jiang C.H., Yan F.X., He N., Huang S.L., Xu Z.H., Zhou H.H.
    J. Pharmacol. Exp. Ther. 281:604-609(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT TRP-433.
  12. "Identification of new human CYP2C19 alleles (CYP2C19*6 and CYP2C19*2B) in a Caucasian poor metabolizer of mephenytoin."
    Ibeanu G.C., Goldstein J.A., Meyer U.A., Benhamou S., Bouchardy C., Dayer P., Ghanayem B.I., Blaisdell J.
    J. Pharmacol. Exp. Ther. 286:1490-1495(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS ASP-92 AND GLN-132.
  13. "An additional defective allele, CYP2C19*5, contributes to the S-mephenytoin poor metabolizer phenotype in Caucasians."
    Ibeanu G.C., Blaisdell J., Ghanayem B.I., Beyeler C., Benhamou S., Bouchardy C., Wilkinson G.R., Dayer P., Daly A.K., Goldstein J.A.
    Pharmacogenetics 8:129-135(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT TRP-433.
  14. "A novel transversion in the intron 5 donor splice junction of CYP2C19 and a sequence polymorphism in exon 3 contribute to the poor metabolizer phenotype for the anticonvulsant drug S-mephenytoin."
    Ibeanu G.C., Blaisdell J., Ferguson R.J., Ghanayem B.I., Brosen K., Benhamou S., Bouchardy C., Wilkinson G.R., Dayer P., Goldstein J.A.
    J. Pharmacol. Exp. Ther. 290:635-640(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT ARG-120.
  15. "Identification and functional characterization of new potentially defective alleles of human CYP2C19."
    Blaisdell J., Mohrenweiser H., Jackson J., Ferguson S., Coulter S., Chanas B., Xi T., Ghanayem B., Goldstein J.A.
    Pharmacogenetics 12:703-711(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS PRO-17; LEU-19; HIS-144; HIS-150; LEU-227 AND CYS-410.
  16. "A novel single nucleotide polymorphism (SNP) of the CYP2C19 gene in a Japanese subject with lowered capacity of mephobarbital 4'-hydroxylation."
    Morita J., Kobayashi K., Wanibuchi A., Kimura M., Irie S., Ishizaki T., Chiba K.
    Drug Metab. Pharmacokinet. 19:236-238(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT CYS-442.
  17. "Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population."
    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.
    Pharmacogenomics 5:895-931(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS THR-74; HIS-144; LEU-168 AND ILE-331.
  18. Cited for: VARIANTS GLY-51; PRO-161; HIS-329 AND ILE-331.

Entry informationi

Entry nameiCP2CJ_HUMAN
AccessioniPrimary (citable) accession number: P33261
Secondary accession number(s): P33259
, Q8WZB1, Q8WZB2, Q9UCD4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: March 1, 2005
Last modified: November 26, 2014
This is version 142 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

Caution

P450-254C was originally listed as a separate gene (CYP2C17). Resequencing demonstrated that it is not a separate gene, but a chimera. The 5'-portion corresponds to a partial 2C18 clone, and the 3'-portion corresponds to a partial 2C19 clone.Curated

Keywords - Technical termi

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

Documents

  1. Human chromosome 10
    Human chromosome 10: 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

External Data

Dasty 3