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UniProtKB - P33261 (CP2CJ_HUMAN)

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Protein

Cytochrome P450 2C19

Gene

CYP2C19

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.

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

Catalytic activityi

+-(R)-limonene + [reduced NADPH--hemoprotein reductase] + O2 = (+)-trans-carveol + [oxidized NADPH--hemoprotein reductase] + H2O.1 Publication
(S)-limonene + [reduced NADPH--hemoprotein reductase] + O2 = (-)-trans-carveol + [oxidized NADPH--hemoprotein reductase] + H2O.1 Publication
(S)-limonene + [reduced NADPH--hemoprotein reductase] + O2 = (-)-perillyl alcohol + [oxidized NADPH--hemoprotein reductase] + H2O.1 Publication

Cofactori

heme1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi435Iron (heme axial ligand)Combined sources1 Publication1

GO - Molecular functioni

  • arachidonic acid epoxygenase activity Source: GO_Central
  • enzyme binding Source: BHF-UCL
  • heme binding Source: UniProtKB
  • iron ion binding Source: InterPro
  • monooxygenase activity Source: BHF-UCL
  • oxidoreductase activity Source: BHF-UCL
  • oxygen binding Source: ProtInc
  • steroid hydroxylase activity Source: BHF-UCL
View the complete GO annotation on QuickGO ...

GO - Biological processi

  • drug metabolic process Source: BHF-UCL
  • epoxygenase P450 pathway Source: GO_Central
  • exogenous drug catabolic process Source: BHF-UCL
  • heterocycle metabolic process Source: BHF-UCL
  • monoterpenoid metabolic process Source: BHF-UCL
  • omega-hydroxylase P450 pathway Source: Reactome
  • oxidation-reduction process Source: BHF-UCL
  • steroid metabolic process Source: BHF-UCL
  • xenobiotic metabolic process Source: Reactome
View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionMonooxygenase, Oxidoreductase
LigandHeme, Iron, Metal-binding, NADP

Enzyme and pathway databases

BioCyciMetaCyc:HS09293-MONOMER
ReactomeiR-HSA-211981 Xenobiotics
R-HSA-211999 CYP2E1 reactions
R-HSA-2142670 Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET)
R-HSA-2142816 Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE)
SABIO-RKiP33261

Chemistry databases

SwissLipidsiSLP:000001589

Names & Taxonomyi

Protein namesi
Recommended name:
Cytochrome P450 2C19 (EC:1.14.13.-)
Alternative name(s):
(R)-limonene 6-monooxygenase (EC:1.14.14.531 Publication)
(S)-limonene 6-monooxygenase (EC:1.14.14.511 Publication)
(S)-limonene 7-monooxygenase (EC:1.14.14.521 Publication)
CYPIIC17
CYPIIC19
Cytochrome P450-11A
Cytochrome P450-254C
Mephenytoin 4-hydroxylase
Gene namesi
Name:CYP2C19
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000165841.9
HGNCiHGNC:2621 CYP2C19
MIMi124020 gene
neXtProtiNX_P33261

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

Pathology & Biotechi

Organism-specific databases

DisGeNETi1557
MalaCardsiCYP2C19
MIMi609535 phenotype
Orphaneti413667 Antidepressant or antipsychotics toxicity or dose selection
240935 Resistance to clopidogrel
240921 Voriconazole toxicity
PharmGKBiPA124

Chemistry databases

ChEMBLiCHEMBL3622
DrugBankiDB05812 Abiraterone
DB01418 Acenocoumarol
DB00945 Acetylsalicylic acid
DB00546 Adinazolam
DB00918 Almotriptan
DB06403 Ambrisentan
DB00357 Aminoglutethimide
DB01424 Aminophenazone
DB01118 Amiodarone
DB00321 Amitriptyline
DB01060 Amoxicillin
DB00701 Amprenavir
DB01435 Antipyrine
DB06605 Apixaban
DB00673 Aprepitant
DB01274 Arformoterol
DB06413 Armodafinil
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
DB00439 Cerivastatin
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
DB09119 Eslicarbazepine acetate
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
DB06789 Hydroxyprogesterone caproate
DB01050 Ibuprofen
DB09054 Idelalisib
DB01181 Ifosfamide
DB00619 Imatinib
DB00458 Imipramine
DB00224 Indinavir
DB00328 Indomethacin
DB00951 Isoniazid
DB09570 Ixazomib
DB06738 Ketobemidone
DB01026 Ketoconazole
DB00448 Lansoprazole
DB01259 Lapatinib
DB08918 Levomilnacipran
DB01601 Lopinavir
DB00455 Loratadine
DB04871 Lorcaserin
DB00678 Losartan
DB00227 Lovastatin
DB08933 Luliconazole
DB09280 Lumacaftor
DB01283 Lumiracoxib
DB08932 Macitentan
DB01065 Melatonin
DB01043 Memantine
DB00532 Mephenytoin
DB00371 Meprobamate
DB00333 Methadone
DB00703 Methazolamide
DB00763 Methimazole
DB05246 Methsuximide
DB00849 Methylphenobarbital
DB00264 Metoprolol
DB01110 Miconazole
DB01171 Moclobemide
DB00745 Modafinil
DB09049 Naloxegol
DB00220 Nelfinavir
DB00622 Nicardipine
DB00184 Nicotine
DB00665 Nilutamide
DB06712 Nilvadipine
DB00717 Norethisterone
DB00540 Nortriptyline
DB00334 Olanzapine
DB00338 Omeprazole
DB04938 Ospemifene
DB00776 Oxcarbazepine
DB00239 Oxiconazole
DB06412 Oxymetholone
DB00213 Pantoprazole
DB00082 Pegvisomant
DB00738 Pentamidine
DB00312 Pentobarbital
DB00850 Perphenazine
DB00454 Pethidine
DB03783 Phenacetin
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
DB06176 Romidepsin
DB00412 Rosiglitazone
DB01098 Rosuvastatin
DB01232 Saquinavir
DB01037 Selegiline
DB01104 Sertraline
DB00203 Sildenafil
DB00641 Simvastatin
DB06268 Sitaxentan
DB00398 Sorafenib
DB09118 Stiripentol
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
DB00197 Troglitazone
DB01361 Troleandomycin
DB00580 Valdecoxib
DB00313 Valproic Acid
DB00285 Venlafaxine
DB00661 Verapamil
DB08828 Vismodegib
DB00582 Voriconazole
DB09068 Vortioxetine
DB00682 Warfarin
DB00549 Zafirlukast
DB00495 Zidovudine
DB00425 Zolpidem
DB00909 Zonisamide
GuidetoPHARMACOLOGYi1328

Polymorphism and mutation databases

BioMutaiCYP2C19
DMDMi60416369

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000517081 – 490Cytochrome P450 2C19Add BLAST490

Proteomic databases

PaxDbiP33261
PeptideAtlasiP33261
PRIDEiP33261
ProteomicsDBi54907

PTM databases

iPTMnetiP33261
PhosphoSitePlusiP33261

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

BgeeiENSG00000165841
CleanExiHS_CYP2C19
ExpressionAtlasiP33261 baseline and differential
GenevisibleiP33261 HS

Organism-specific databases

HPAiHPA015066

Interactioni

GO - Molecular functioni

  • enzyme binding Source: BHF-UCL
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi107935, 2 interactors
STRINGi9606.ENSP00000360372

Chemistry databases

BindingDBiP33261

Structurei

Secondary structure

1490
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni37 – 39Combined sources3
Helixi42 – 44Combined sources3
Helixi47 – 49Combined sources3
Helixi50 – 61Combined sources12
Beta strandi63 – 69Combined sources7
Beta strandi72 – 77Combined sources6
Helixi80 – 87Combined sources8
Turni88 – 90Combined sources3
Helixi91 – 94Combined sources4
Helixi103 – 106Combined sources4
Turni107 – 109Combined sources3
Helixi117 – 130Combined sources14
Beta strandi135 – 139Combined sources5
Helixi141 – 158Combined sources18
Turni159 – 161Combined sources3
Turni166 – 168Combined sources3
Helixi169 – 182Combined sources14
Beta strandi183 – 185Combined sources3
Helixi192 – 209Combined sources18
Helixi211 – 218Combined sources8
Helixi222 – 225Combined sources4
Helixi228 – 254Combined sources27
Helixi263 – 273Combined sources11
Turni274 – 276Combined sources3
Helixi284 – 297Combined sources14
Helixi300 – 315Combined sources16
Helixi317 – 330Combined sources14
Beta strandi333 – 335Combined sources3
Helixi339 – 344Combined sources6
Helixi346 – 359Combined sources14
Beta strandi377 – 379Combined sources3
Beta strandi386 – 389Combined sources4
Helixi391 – 395Combined sources5
Turni398 – 400Combined sources3
Beta strandi401 – 403Combined sources3
Helixi409 – 412Combined sources4
Beta strandi415 – 417Combined sources3
Helixi438 – 455Combined sources18
Beta strandi456 – 462Combined sources7
Turni464 – 466Combined sources3
Beta strandi475 – 477Combined sources3
Beta strandi485 – 489Combined sources5

3D structure databases

ProteinModelPortaliP33261
SMRiP33261
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the cytochrome P450 family.Curated

Phylogenomic databases

eggNOGiKOG0156 Eukaryota
COG2124 LUCA
HOGENOMiHOG000036992
HOVERGENiHBG015789
InParanoidiP33261
KOiK17721
OrthoDBiEOG091G0BT8
PhylomeDBiP33261
TreeFamiTF352043

Family and domain databases

Gene3Di1.10.630.10, 1 hit
InterProiView protein in InterPro
IPR001128 Cyt_P450
IPR017972 Cyt_P450_CS
IPR002401 Cyt_P450_E_grp-I
IPR036396 Cyt_P450_sf
PfamiView protein in Pfam
PF00067 p450, 1 hit
PRINTSiPR00463 EP450I
PR00385 P450
SUPFAMiSSF48264 SSF48264, 1 hit
PROSITEiView protein in PROSITE
PS00086 CYTOCHROME_P450, 1 hit

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 heterozygote 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)DescriptionActionsGraphical viewLength
Natural variantiVAR_02126817L → P in allele CYP2C19*14. 1 PublicationCorresponds to variant dbSNP:rs55752064Ensembl.1
Natural variantiVAR_02126919I → L in allele CYP2C19*15. 2 PublicationsCorresponds to variant dbSNP:rs17882687Ensembl.1
Natural variantiVAR_02408351S → G in allele CYP2C19*19. 1 Publication1
Natural variantiVAR_02471874M → T1 PublicationCorresponds to variant dbSNP:rs28399505Ensembl.1
Natural variantiVAR_02127092E → D2 PublicationsCorresponds to variant dbSNP:rs17878459Ensembl.1
Natural variantiVAR_008357120W → R in allele CYP2C19*8; loss of activity. 1 PublicationCorresponds to variant dbSNP:rs41291556EnsemblClinVar.1
Natural variantiVAR_021271122E → A1 PublicationCorresponds to variant dbSNP:rs17885179Ensembl.1
Natural variantiVAR_008358132R → Q in allele CYP2C19*6; loss of activity. 1 Publication1
Natural variantiVAR_021272144R → H in allele CYP2C19*9. 3 PublicationsCorresponds to variant dbSNP:rs17884712Ensembl.1
Natural variantiVAR_021273150R → H in allele CYP2C19*11. 1 PublicationCorresponds to variant dbSNP:rs58973490Ensembl.1
Natural variantiVAR_024084161A → P1 PublicationCorresponds to variant dbSNP:rs181297724Ensembl.1
Natural variantiVAR_024719168F → L1 PublicationCorresponds to variant dbSNP:rs28399510Ensembl.1
Natural variantiVAR_020123227P → L in allele CYP2C19*10. 1 PublicationCorresponds to variant dbSNP:rs6413438Ensembl.1
Natural variantiVAR_024085329R → H in allele CYP2C19*18. 1 Publication1
Natural variantiVAR_001255331V → I in allele CYP2C19*1A, allele CYP2C19*5A, allele CYP2C19*8 and allele CYP2C19*16. 4 PublicationsCorresponds to variant dbSNP:rs3758581Ensembl.1
Natural variantiVAR_021274410R → C in allele CYP2C19*13. 2 PublicationsCorresponds to variant dbSNP:rs17879685Ensembl.1
Natural variantiVAR_008359433R → W in allele CYP2C19*5A and allele CYP2C19*5B; loss of activity. 2 PublicationsCorresponds to variant dbSNP:rs56337013EnsemblClinVar.1
Natural variantiVAR_021275442R → C in allele CYP2C19*16; lowered catalytic activity. 1 PublicationCorresponds to variant dbSNP:rs192154563Ensembl.1

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 Genomic DNA No translation available.
AL133513 Genomic DNA No translation available.
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
UCSCiuc010qnz.3 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCP2CJ_HUMAN
AccessioniPrimary (citable) accession number: P33261
Secondary accession number(s): P33259
, Q8WZB1, Q8WZB2, Q9UCD4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: March 1, 2005
Last modified: June 20, 2018
This is version 176 of the entry and version 3 of the sequence. See 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 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

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