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Protein

Cytochrome P450 3A4

Gene

CYP3A4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide (PubMed:11159812). Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro (PubMed:21576599).2 Publications

Miscellaneous

Chimeric transcripts, characterized by CYP3A43 exon 1 joined at canonical splice sites to distinct sets of CYP3A4 exons, have been detected. All are possibly produced by trans-splicing. The chimeric transcripts exist in 3 different combinations: CYP3A43 exon 1 joined in frame to CYP3A4 exons 2-13, CYP3A43 exon 1 joined in frame to CYP3A4 exons 4-13 and CYP3A43 exon 1 joined in frame to CYP3A4 exon 7-13. The longest chimeric isoform (CYP3A43 exon 1 joined to CYP3A4 exons 2-13) exhibits 6-beta-hydroxylase activity, while a shorter isoform (CYP3A43 exon 1 joined to CYP3A4 exons 4-13) does not. All chimeric transcripts are expressed at very low levels in the liver (PubMed:11726664).1 Publication

Catalytic activityi

Quinine + [reduced NADPH--hemoprotein reductase] + O2 = 3-hydroxyquinine + [oxidized NADPH--hemoprotein reductase] + H2O.1 Publication
Taurochenodeoxycholate + [reduced NADPH--hemoprotein reductase] + O2 = taurohyocholate + [oxidized NADPH--hemoprotein reductase] + H2O.1 Publication
Lithocholate + [reduced NADPH--hemoprotein reductase] + O2 = hyodeoxycholate + [oxidized NADPH--hemoprotein reductase] + H2O.1 Publication
Albendazole + [reduced NADPH--hemoprotein reductase] + O2 = albendazole S-oxide + [oxidized NADPH--hemoprotein reductase] + H2O.1 Publication
Fenbendazole + [reduced NADPH--hemoprotein reductase] + O2 = fenbendazole S-oxide + [oxidized NADPH--hemoprotein reductase] + H2O.1 Publication
1,8-cineole + [reduced NADPH--hemoprotein reductase] + O2 = 2-exo-hydroxy-1,8-cineole + [oxidized NADPH--hemoprotein reductase] + H2O.1 Publication
Cholesterol + [reduced NADPH--hemoprotein reductase] + O2 = 25-hydroxycholesterol + [oxidized NADPH--hemoprotein reductase] + H2O.1 Publication

Cofactori

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi442Iron (heme axial ligand)1

GO - Molecular functioni

  • caffeine oxidase activity Source: BHF-UCL
  • enzyme binding Source: BHF-UCL
  • estrogen 16-alpha-hydroxylase activity Source: BHF-UCL
  • heme binding Source: InterPro
  • iron ion binding Source: BHF-UCL
  • 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: InterPro
  • oxygen binding Source: ProtInc
  • steroid binding Source: BHF-UCL
  • steroid hydroxylase activity Source: BHF-UCL
  • testosterone 6-beta-hydroxylase activity Source: BHF-UCL
  • vitamin D 24-hydroxylase activity Source: BHF-UCL
  • vitamin D3 25-hydroxylase activity Source: BHF-UCL

GO - Biological processi

  • alkaloid catabolic process Source: BHF-UCL
  • androgen metabolic process Source: BHF-UCL
  • drug catabolic process Source: BHF-UCL
  • drug metabolic process Source: BHF-UCL
  • exogenous drug catabolic process Source: BHF-UCL
  • heterocycle metabolic process Source: BHF-UCL
  • lipid hydroxylation Source: BHF-UCL
  • lipid metabolic process Source: ProtInc
  • long-chain fatty acid biosynthetic process Source: Reactome
  • monoterpenoid metabolic process Source: BHF-UCL
  • oxidation-reduction process Source: BHF-UCL
  • oxidative demethylation Source: BHF-UCL
  • steroid catabolic process Source: BHF-UCL
  • steroid metabolic process Source: BHF-UCL
  • vitamin D metabolic process Source: BHF-UCL
  • xenobiotic metabolic process Source: Reactome

Keywordsi

Molecular functionMonooxygenase, Oxidoreductase
Biological processLipid metabolism, Steroid metabolism, Sterol metabolism
LigandHeme, Iron, Metal-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS08544-MONOMER
BRENDAi1.14.13.67 2681
1.14.99.38 2681
ReactomeiR-HSA-211981 Xenobiotics
R-HSA-5423646 Aflatoxin activation and detoxification
R-HSA-9027307 Biosynthesis of maresin-like SPMs
SABIO-RKiP08684
SIGNORiP08684

Chemistry databases

SwissLipidsiSLP:000001201

Names & Taxonomyi

Protein namesi
Recommended name:
Cytochrome P450 3A4 (EC:1.14.14.-)
Alternative name(s):
1,8-cineole 2-exo-monooxygenase (EC:1.14.14.561 Publication)
Albendazole monooxygenase (EC:1.14.14.-)
Albendazole sulfoxidase
CYPIIIA3
CYPIIIA4
Cholesterol 25-hydroxylase1 Publication (EC:1.14.14.-1 Publication)
Cytochrome P450 3A3
Cytochrome P450 HLp
Cytochrome P450 NF-25
Cytochrome P450-PCN1
Nifedipine oxidase
Quinine 3-monooxygenase (EC:1.14.14.551 Publication)
Taurochenodeoxycholate 6-alpha-hydroxylase (EC:1.14.14.-1 Publication)
Gene namesi
Name:CYP3A4
Synonyms:CYP3A3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000160868.14
HGNCiHGNC:2637 CYP3A4
MIMi124010 gene
neXtProtiNX_P08684

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

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei2 – 22HelicalSequence analysisAdd BLAST21

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

Pathology & Biotechi

Organism-specific databases

DisGeNETi1576
MalaCardsiCYP3A4
OpenTargetsiENSG00000160868
PharmGKBiPA130

Chemistry databases

ChEMBLiCHEMBL340
DrugBankiDB05812 Abiraterone
DB01418 Acenocoumarol
DB00316 Acetaminophen
DB00819 Acetazolamide
DB00546 Adinazolam
DB00518 Albendazole
DB00240 Alclometasone
DB00041 Aldesleukin
DB00802 Alfentanil
DB00346 Alfuzosin
DB01246 Alimemazine
DB09026 Aliskiren
DB01431 Allylestrenol
DB00918 Almotriptan
DB06203 Alogliptin
DB00969 Alosetron
DB00404 Alprazolam
DB06403 Ambrisentan
DB06742 Ambroxol
DB00357 Aminoglutethimide
DB01424 Aminophenazone
DB01223 Aminophylline
DB01118 Amiodarone
DB00321 Amitriptyline
DB00381 Amlodipine
DB00701 Amprenavir
DB01217 Anastrozole
DB01435 Antipyrine
DB06605 Apixaban
DB05676 Apremilast
DB00673 Aprepitant
DB00278 Argatroban
DB01238 Aripiprazole
DB06413 Armodafinil
DB01169 Arsenic trioxide
DB06697 Artemether
DB06216 Asenapine
DB00637 Astemizole
DB01072 Atazanavir
DB00289 Atomoxetine
DB01076 Atorvastatin
DB06237 Avanafil
DB06626 Axitinib
DB00719 Azatadine
DB00972 Azelastine
DB04957 Azimilide
DB00207 Azithromycin
DB04975 Banoxantrone
DB08903 Bedaquiline
DB00865 Benzphetamine
DB06770 Benzyl alcohol
DB00443 Betamethasone
DB00307 Bexarotene
DB01393 Bezafibrate
DB01128 Bicalutamide
DB04794 Bifonazole
DB00612 Bisoprolol
DB08873 Boceprevir
DB00188 Bortezomib
DB00559 Bosentan
DB06616 Bosutinib
DB08870 Brentuximab vedotin
DB09128 Brexpiprazole
DB01194 Brinzolamide
DB01558 Bromazepam
DB01200 Bromocriptine
DB00835 Brompheniramine
DB01222 Budesonide
DB00297 Bupivacaine
DB00921 Buprenorphine
DB01156 Bupropion
DB00490 Buspirone
DB01008 Busulfan
DB06772 Cabazitaxel
DB00248 Cabergoline
DB08875 Cabozantinib
DB00201 Caffeine
DB04886 Calanolide A
DB00136 Calcitriol
DB08907 Canagliflozin
DB06774 Capsaicin
DB00564 Carbamazepine
DB00748 Carbinoxamine
DB06016 Cariprazine
DB01136 Carvedilol
DB00520 Caspofungin
DB01333 Cefradine
DB00482 Celecoxib
DB04846 Celiprolol
DB00567 Cephalexin
DB09063 Ceritinib
DB00439 Cerivastatin
DB00185 Cevimeline
DB06777 Chenodeoxycholic acid
DB00446 Chloramphenicol
DB00475 Chlordiazepoxide
DB00608 Chloroquine
DB01114 Chlorphenamine
DB00856 Chlorphenesin
DB00477 Chlorpromazine
DB00356 Chlorzoxazone
DB00169 Cholecalciferol
DB01410 Ciclesonide
DB01166 Cilostazol
DB00501 Cimetidine
DB01012 Cinacalcet
DB00537 Ciprofloxacin
DB00604 Cisapride
DB00215 Citalopram
DB01211 Clarithromycin
DB00283 Clemastine
DB04920 Clevidipine
DB01190 Clindamycin
DB00349 Clobazam
DB00845 Clofazimine
DB00636 Clofibrate
DB00882 Clomifene
DB01242 Clomipramine
DB01068 Clonazepam
DB00575 Clonidine
DB00758 Clopidogrel
DB00628 Clorazepate
DB01559 Clotiazepam
DB00257 Clotrimazole
DB00363 Clozapine
DB09065 Cobicistat
DB05239 Cobimetinib
DB00907 Cocaine
DB00318 Codeine
DB01394 Colchicine
DB00872 Conivaptan
DB00286 Conjugated Equine Estrogens
DB01380 Cortisone acetate
DB08865 Crizotinib
DB00924 Cyclobenzaprine
DB00531 Cyclophosphamide
DB00091 Cyclosporine
DB00987 Cytarabine
DB08912 Dabrafenib
DB09102 Daclatasvir
DB01764 Dalfopristin
DB01406 Danazol
DB01219 Dantrolene
DB06292 Dapagliflozin
DB00250 Dapsone
DB00496 Darifenacin
DB01264 Darunavir
DB09183 Dasabuvir
DB01254 Dasatinib
DB00694 Daunorubicin
DB01609 Deferasirox
DB11921 Deflazacort
DB00705 Delavirdine
DB01151 Desipramine
DB06700 Desvenlafaxine
DB01234 Dexamethasone
DB04856 Dexloxiglumide
DB00514 Dextromethorphan
DB00647 Dextropropoxyphene
DB00829 Diazepam
DB00586 Diclofenac
DB00485 Dicloxacillin
DB00255 Diethylstilbestrol
DB01396 Digitoxin
DB00390 Digoxin
DB01551 Dihydrocodeine
DB00320 Dihydroergotamine
DB00343 Diltiazem
DB01093 Dimethyl sulfoxide
DB00280 Disopyramide
DB00822 Disulfiram
DB01248 Docetaxel
DB00204 Dofetilide
DB00757 Dolasetron
DB08930 Dolutegravir
DB01184 Domperidone
DB00843 Donepezil
DB00869 Dorzolamide
DB01142 Doxepin
DB00997 Doxorubicin
DB00254 Doxycycline
DB00470 Dronabinol
DB04855 Dronedarone
DB01395 Drospirenone
DB01126 Dutasteride
DB01127 Econazole
DB00625 Efavirenz
DB00216 Eletriptan
DB09039 Eliglustat
DB09101 Elvitegravir
DB00584 Enalapril
DB08899 Enzalutamide
DB00751 Epinastine
DB00668 Epinephrine
DB00700 Eplerenone
DB00153 Ergocalciferol
DB01049 Ergoloid mesylate
DB01253 Ergonovine
DB00696 Ergotamine
DB00530 Erlotinib
DB00199 Erythromycin
DB01175 Escitalopram
DB09119 Eslicarbazepine acetate
DB00736 Esomeprazole
DB01215 Estazolam
DB00783 Estradiol
DB01196 Estramustine
DB00655 Estrone
DB04574 Estrone sulfate
DB00402 Eszopiclone
DB00898 Ethanol
DB00977 Ethinyl Estradiol
DB00593 Ethosuximide
DB01466 Ethylmorphine
DB00294 Etonogestrel
DB00773 Etoposide
DB01628 Etoricoxib
DB06414 Etravirine
DB01590 Everolimus
DB00990 Exemestane
DB00973 Ezetimibe
DB00426 Famciclovir
DB00949 Felbamate
DB01023 Felodipine
DB01039 Fenofibrate
DB00813 Fentanyl
DB06702 Fesoterodine
DB01216 Finasteride
DB08868 Fingolimod
DB04908 Flibanserin
DB00301 Flucloxacillin
DB00196 Fluconazole
DB00180 Flunisolide
DB01544 Flunitrazepam
DB00324 Fluorometholone
DB00472 Fluoxetine
DB00690 Flurazepam
DB00499 Flutamide
DB08906 Fluticasone furoate
DB00588 Fluticasone Propionate
DB01095 Fluvastatin
DB00176 Fluvoxamine
DB01319 Fosamprenavir
DB06717 Fosaprepitant
DB01320 Fosphenytoin
DB00947 Fulvestrant
DB00674 Galantamine
DB00317 Gefitinib
DB01241 Gemfibrozil
DB01067 Glipizide
DB01016 Glyburide
DB08909 Glycerol Phenylbutyrate
DB00889 Granisetron
DB00365 Grepafloxacin
DB00400 Griseofulvin
DB01170 Guanethidine
DB01018 Guanfacine
DB01218 Halofantrine
DB00502 Haloperidol
DB01159 Halothane
DB01355 Hexobarbital
DB05381 Histamine
DB01275 Hydralazine
DB00956 Hydrocodone
DB00769 Hydrocortamate
DB00741 Hydrocortisone
DB00327 Hydromorphone
DB06789 Hydroxyprogesterone caproate
DB09053 Ibrutinib
DB11737 Icotinib
DB09054 Idelalisib
DB01181 Ifosfamide
DB04946 Iloperidone
DB00619 Imatinib
DB00458 Imipramine
DB00724 Imiquimod
DB05039 Indacaterol
DB00808 Indapamide
DB00224 Indinavir
DB00332 Ipratropium bromide
DB01029 Irbesartan
DB00762 Irinotecan
DB06636 Isavuconazonium
DB00951 Isoniazid
DB00883 Isosorbide Dinitrate
DB01020 Isosorbide Mononitrate
DB00270 Isradipine
DB01167 Itraconazole
DB09083 Ivabradine
DB08820 Ivacaftor
DB00602 Ivermectin
DB04845 Ixabepilone
DB09570 Ixazomib
DB01321 Josamycin
DB01221 Ketamine
DB01587 Ketazolam
DB06738 Ketobemidone
DB01026 Ketoconazole
DB00448 Lansoprazole
DB01259 Lapatinib
DB06685 Laquinimod
DB09078 Lenvatinib
DB00528 Lercanidipine
DB01006 Letrozole
DB01002 Levobupivacaine
DB06282 Levocetirizine
DB01137 Levofloxacin
DB01227 Levomethadyl Acetate
DB08918 Levomilnacipran
DB00367 Levonorgestrel
DB13139 Levosalbutamol
DB00451 Levothyroxine
DB00281 Lidocaine
DB08882 Linagliptin
DB00589 Lisuride
DB08827 Lomitapide
DB01206 Lomustine
DB00836 Loperamide
DB01601 Lopinavir
DB00455 Loratadine
DB04871 Lorcaserin
DB00678 Losartan
DB00227 Lovastatin
DB08933 Luliconazole
DB09280 Lumacaftor
DB06708 Lumefantrine
DB08815 Lurasidone
DB08932 Macitentan
DB04835 Maraviroc
DB00643 Mebendazole
DB00603 Medroxyprogesterone acetate
DB00358 Mefloquine
DB00814 Meloxicam
DB01071 Mequitazine
DB04817 Metamizole
DB00333 Methadone
DB04833 Methaqualone
DB00703 Methazolamide
DB00763 Methimazole
DB00553 Methoxsalen
DB01028 Methoxyflurane
DB09543 Methyl salicylate
DB00353 Methylergometrine
DB00959 Methylprednisolone
DB06710 Methyltestosterone
DB00916 Metronidazole
DB01011 Metyrapone
DB00379 Mexiletine
DB06148 Mianserin
DB01388 Mibefradil
DB01110 Miconazole
DB00683 Midazolam
DB00834 Mifepristone
DB08893 Mirabegron
DB00370 Mirtazapine
DB00648 Mitotane
DB01204 Mitoxantrone
DB00745 Modafinil
DB00471 Montelukast
DB00295 Morphine
DB00688 Mycophenolate mofetil
DB00607 Nafcillin
DB09049 Naloxegol
DB01183 Naloxone
DB00731 Nateglinide
DB01149 Nefazodone
DB00220 Nelfinavir
DB09048 Netupitant
DB00238 Nevirapine
DB00622 Nicardipine
DB02701 Nicotinamide
DB00184 Nicotine
DB01115 Nifedipine
DB04868 Nilotinib
DB06712 Nilvadipine
DB00393 Nimodipine
DB00401 Nisoldipine
DB01595 Nitrazepam
DB01054 Nitrendipine
DB00435 Nitric Oxide
DB00717 Norethisterone
DB01059 Norfloxacin
DB00957 Norgestimate
DB09389 Norgestrel
DB00540 Nortriptyline
DB00334 Olanzapine
DB09074 Olaparib
DB00768 Olopatadine
DB00338 Omeprazole
DB00904 Ondansetron
DB04911 Oritavancin
DB01083 Orlistat
DB01173 Orphenadrine
DB09330 Osimertinib
DB04938 Ospemifene
DB00842 Oxazepam
DB00776 Oxcarbazepine
DB00239 Oxiconazole
DB01062 Oxybutynin
DB00497 Oxycodone
DB01192 Oxymorphone
DB01229 Paclitaxel
DB09073 Palbociclib
DB01267 Paliperidone
DB00377 Palonosetron
DB06603 Panobinostat
DB00213 Pantoprazole
DB00617 Paramethadione
DB01384 Paramethasone
DB08439 Parecoxib
DB00910 Paricalcitol
DB09297 Paritaprevir
DB06589 Pazopanib
DB00082 Pegvisomant
DB00738 Pentamidine
DB00312 Pentobarbital
DB08883 Perampanel
DB01186 Pergolide
DB01074 Perhexiline
DB04930 Permethrin
DB00850 Perphenazine
DB00454 Pethidine
DB03783 Phenacetin
DB00780 Phenelzine
DB01174 Phenobarbital
DB00925 Phenoxybenzamine
DB00946 Phenprocoumon
DB00812 Phenylbutazone
DB00252 Phenytoin
DB01085 Pilocarpine
DB00337 Pimecrolimus
DB01100 Pimozide
DB01132 Pioglitazone
DB01621 Pipotiazine
DB04977 Plitidepsin
DB01179 Podofilox
DB08910 Pomalidomide
DB08901 Ponatinib
DB01263 Posaconazole
DB05478 Pradefovir Mesylate
DB01411 Pranlukast
DB01708 Prasterone
DB06209 Prasugrel
DB00175 Pravastatin
DB01588 Prazepam
DB01058 Praziquantel
DB00860 Prednisolone
DB00635 Prednisone
DB01087 Primaquine
DB00794 Primidone
DB01032 Probenecid
DB00433 Prochlorperazine
DB00396 Progesterone
DB01131 Proguanil
DB00420 Promazine
DB01182 Propafenone
DB00818 Propofol
DB09396 Propoxyphene napsylate
DB00571 Propranolol
DB00339 Pyrazinamide
DB00545 Pyridostigmine
DB01589 Quazepam
DB01224 Quetiapine
DB01103 Quinacrine
DB00908 Quinidine
DB00468 Quinine
DB01369 Quinupristin
DB01129 Rabeprazole
DB00481 Raloxifene
DB00980 Ramelteon
DB00863 Ranitidine
DB00243 Ranolazine
DB00234 Reboxetine
DB08896 Regorafenib
DB00912 Repaglinide
DB02709 Resveratrol
DB01256 Retapamulin
DB00615 Rifabutin
DB04934 Rifalazil
DB01045 Rifampicin
DB01201 Rifapentine
DB01220 Rifaximin
DB08864 Rilpivirine
DB06155 Rimonabant
DB08931 Riociguat
DB00734 Risperidone
DB00503 Ritonavir
DB06228 Rivaroxaban
DB00989 Rivastigmine
DB00533 Rofecoxib
DB09291 Rolapitant
DB01301 Rolitetracycline
DB06176 Romidepsin
DB00268 Ropinirole
DB00296 Ropivacaine
DB01098 Rosuvastatin
DB05271 Rotigotine
DB00778 Roxithromycin
DB12332 Rucaparib
DB06201 Rufinamide
DB01698 Rutin
DB08877 Ruxolitinib
DB06654 Safinamide
DB01001 Salbutamol
DB00938 Salmeterol
DB01232 Saquinavir
DB06335 Saxagliptin
DB01037 Selegiline
DB11362 Selexipag
DB06144 Sertindole
DB01104 Sertraline
DB01236 Sevoflurane
DB01105 Sibutramine
DB00203 Sildenafil
DB06207 Silodosin
DB06290 Simeprevir
DB00641 Simvastatin
DB00877 Sirolimus
DB01261 Sitagliptin
DB06268 Sitaxentan
DB01591 Solifenacin
DB09143 Sonidegib
DB00398 Sorafenib
DB06145 Spiramycin
DB01323 St. John's Wort
DB00708 Sufentanil
DB00359 Sulfadiazine
DB01015 Sulfamethoxazole
DB00259 Sulfanilamide
DB01138 Sulfinpyrazone
DB00263 Sulfisoxazole
DB01268 Sunitinib
DB00864 Tacrolimus
DB00820 Tadalafil
DB00675 Tamoxifen
DB00706 Tamsulosin
DB01349 Tasosartan
DB05521 Telaprevir
DB00976 Telithromycin
DB00231 Temazepam
DB00853 Temozolomide
DB06287 Temsirolimus
DB00444 Teniposide
DB00857 Terbinafine
DB00342 Terfenadine
DB04905 Tesmilifene
DB00624 Testosterone
DB00759 Tetracycline
DB00277 Theophylline
DB00599 Thiopental
DB04572 Thiotepa
DB00906 Tiagabine
DB08816 Ticagrelor
DB00208 Ticlopidine
DB00911 Tinidazole
DB01007 Tioconazole
DB01409 Tiotropium
DB00932 Tipranavir
DB08895 Tofacitinib
DB08811 Tofisopam
DB01036 Tolterodine
DB06212 Tolvaptan
DB00273 Topiramate
DB01030 Topotecan
DB00539 Toremifene
DB05109 Trabectedin
DB00193 Tramadol
DB08911 Trametinib
DB00752 Tranylcypromine
DB05773 Trastuzumab emtansine
DB00656 Trazodone
DB00755 Tretinoin
DB00620 Triamcinolone
DB00897 Triazolam
DB00347 Trimethadione
DB00440 Trimethoprim
DB00726 Trimipramine
DB00197 Troglitazone
DB01361 Troleandomycin
DB06267 Udenafil
DB08867 Ulipristal
DB00580 Valdecoxib
DB00313 Valproic Acid
DB05294 Vandetanib
DB03701 Vanoxerine
DB00862 Vardenafil
DB08881 Vemurafenib
DB11581 Venetoclax
DB00285 Venlafaxine
DB00661 Verapamil
DB09082 Vilanterol
DB06684 Vilazodone
DB00570 Vinblastine
DB00541 Vincristine
DB00309 Vindesine
DB00361 Vinorelbine
DB08828 Vismodegib
DB00582 Voriconazole
DB09068 Vortioxetine
DB00682 Warfarin
DB01392 Yohimbine
DB00549 Zafirlukast
DB00943 Zalcitabine
DB00962 Zaleplon
DB00495 Zidovudine
DB00744 Zileuton
DB00246 Ziprasidone
DB00425 Zolpidem
DB04828 Zomepirac
DB00909 Zonisamide
DB01198 Zopiclone
GuidetoPHARMACOLOGYi1337

Polymorphism and mutation databases

BioMutaiCYP3A4
DMDMi116241312

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved2 Publications
ChainiPRO_00000517862 – 503Cytochrome P450 3A4Add BLAST502

Post-translational modificationi

Polyubiquitinated in the presence of AMFR and UBE2G1 and also STUB1/CHIP and UBE2D1 (in vitro).1 Publication

Keywords - PTMi

Ubl conjugation

Proteomic databases

PaxDbiP08684
PeptideAtlasiP08684
PRIDEiP08684

PTM databases

iPTMnetiP08684
PhosphoSitePlusiP08684

Expressioni

Tissue specificityi

Expressed in prostate and liver. According to some authors, it is not expressed in brain (PubMed:19094056). According to others, weak levels of expression are measured in some brain locations (PubMed:19359404 and PubMed:18545703). Also expressed in epithelium of the small intestine and large intestine, bile duct, nasal mucosa, kidney, adrenal cortex, epithelium of the gastric mucosa with intestinal metaplasia, gallbladder, intercalated ducts of the pancreas, chief cells of the parathyroid and the corpus luteum of the ovary (at protein level).6 Publications

Inductioni

By glucocorticoids. Also induced to high levels in liver and other tissues by various foreign compounds, including drugs, pesticides, and carcinogens.

Gene expression databases

BgeeiENSG00000160868
CleanExiHS_CYP3A4
ExpressionAtlasiP08684 baseline and differential
GenevisibleiP08684 HS

Organism-specific databases

HPAiCAB033671
HPA072245

Interactioni

GO - Molecular functioni

  • enzyme binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi107948, 17 interactors
IntActiP08684, 2 interactors
STRINGi9606.ENSP00000337915

Chemistry databases

BindingDBiP08684

Structurei

Secondary structure

1503
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi23 – 26Combined sources4
Helixi28 – 31Combined sources4
Helixi32 – 36Combined sources5
Turni45 – 47Combined sources3
Helixi50 – 55Combined sources6
Helixi57 – 68Combined sources12
Beta strandi70 – 76Combined sources7
Beta strandi79 – 84Combined sources6
Helixi87 – 94Combined sources8
Turni95 – 101Combined sources7
Helixi112 – 116Combined sources5
Turni118 – 120Combined sources3
Helixi123 – 133Combined sources11
Helixi134 – 137Combined sources4
Helixi139 – 164Combined sources26
Turni165 – 167Combined sources3
Helixi172 – 189Combined sources18
Turni195 – 197Combined sources3
Helixi202 – 207Combined sources6
Beta strandi209 – 212Combined sources4
Beta strandi215 – 217Combined sources3
Helixi218 – 225Combined sources8
Helixi227 – 229Combined sources3
Helixi230 – 235Combined sources6
Helixi243 – 260Combined sources18
Helixi271 – 278Combined sources8
Beta strandi284 – 286Combined sources3
Helixi292 – 323Combined sources32
Helixi325 – 338Combined sources14
Helixi340 – 342Combined sources3
Helixi347 – 351Combined sources5
Helixi354 – 366Combined sources13
Beta strandi369 – 371Combined sources3
Beta strandi373 – 376Combined sources4
Beta strandi381 – 383Combined sources3
Beta strandi386 – 388Combined sources3
Beta strandi393 – 396Combined sources4
Helixi398 – 402Combined sources5
Turni405 – 407Combined sources3
Beta strandi408 – 410Combined sources3
Helixi416 – 419Combined sources4
Turni421 – 423Combined sources3
Helixi424 – 426Combined sources3
Turni429 – 431Combined sources3
Helixi438 – 440Combined sources3
Helixi445 – 462Combined sources18
Beta strandi463 – 467Combined sources5
Beta strandi469 – 471Combined sources3
Beta strandi479 – 482Combined sources4
Beta strandi485 – 487Combined sources3
Beta strandi490 – 495Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1TQNX-ray2.05A24-503[»]
1W0EX-ray2.80A25-503[»]
1W0FX-ray2.65A25-503[»]
1W0GX-ray2.74A25-503[»]
2J0DX-ray2.75A/B25-503[»]
2V0MX-ray2.80A/B/C/D25-503[»]
3NXUX-ray2.00A/B25-503[»]
3TJSX-ray2.25A23-503[»]
3UA1X-ray2.15A23-503[»]
4D6ZX-ray1.93A23-503[»]
4D75X-ray2.25A23-503[»]
4D78X-ray2.80A23-503[»]
4D7DX-ray2.76A23-503[»]
4I3QX-ray2.60A23-503[»]
4I4GX-ray2.72A23-503[»]
4I4HX-ray2.90A23-503[»]
4K9TX-ray2.50A23-503[»]
4K9UX-ray2.85A23-503[»]
4K9VX-ray2.60A23-503[»]
4K9WX-ray2.40A/B/C/D23-503[»]
4K9XX-ray2.76A23-503[»]
4NY4X-ray2.95A25-503[»]
5A1PX-ray2.50A23-503[»]
5A1RX-ray2.45A23-503[»]
5G5JX-ray2.60A21-503[»]
5TE8X-ray2.70A/B/C23-503[»]
5VC0X-ray2.70A21-503[»]
5VCCX-ray1.70A21-503[»]
5VCDX-ray1.95A21-503[»]
5VCEX-ray2.20A21-503[»]
5VCGX-ray2.20A21-503[»]
6BCZX-ray2.23A21-503[»]
6BD5X-ray2.50A21-503[»]
6BD6X-ray2.50A21-503[»]
6BD7X-ray2.42A21-503[»]
6BD8X-ray2.38A21-503[»]
6BDHX-ray2.25A21-503[»]
6BDIX-ray2.57A21-503[»]
6BDKX-ray2.67A21-503[»]
6BDMX-ray2.60A21-503[»]
ProteinModelPortaliP08684
SMRiP08684
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP08684

Family & Domainsi

Sequence similaritiesi

Belongs to the cytochrome P450 family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0158 Eukaryota
COG2124 LUCA
GeneTreeiENSGT00900000140779
HOGENOMiHOG000039127
HOVERGENiHBG108567
InParanoidiP08684
KOiK17689
OMAiMAFEDIQ
OrthoDBiEOG091G0JNC
PhylomeDBiP08684
TreeFamiTF105087

Family and domain databases

Gene3Di1.10.630.10, 1 hit
InterProiView protein in InterPro
IPR001128 Cyt_P450
IPR017972 Cyt_P450_CS
IPR008072 Cyt_P450_E_CYP3A
IPR002402 Cyt_P450_E_grp-II
IPR036396 Cyt_P450_sf
PfamiView protein in Pfam
PF00067 p450, 1 hit
PRINTSiPR00464 EP450II
PR01689 EP450IICYP3A
PR00385 P450
SUPFAMiSSF48264 SSF48264, 1 hit
PROSITEiView protein in PROSITE
PS00086 CYTOCHROME_P450, 1 hit

Sequencei

Sequence statusi: Complete.

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

P08684-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MALIPDLAME TWLLLAVSLV LLYLYGTHSH GLFKKLGIPG PTPLPFLGNI
60 70 80 90 100
LSYHKGFCMF DMECHKKYGK VWGFYDGQQP VLAITDPDMI KTVLVKECYS
110 120 130 140 150
VFTNRRPFGP VGFMKSAISI AEDEEWKRLR SLLSPTFTSG KLKEMVPIIA
160 170 180 190 200
QYGDVLVRNL RREAETGKPV TLKDVFGAYS MDVITSTSFG VNIDSLNNPQ
210 220 230 240 250
DPFVENTKKL LRFDFLDPFF LSITVFPFLI PILEVLNICV FPREVTNFLR
260 270 280 290 300
KSVKRMKESR LEDTQKHRVD FLQLMIDSQN SKETESHKAL SDLELVAQSI
310 320 330 340 350
IFIFAGYETT SSVLSFIMYE LATHPDVQQK LQEEIDAVLP NKAPPTYDTV
360 370 380 390 400
LQMEYLDMVV NETLRLFPIA MRLERVCKKD VEINGMFIPK GVVVMIPSYA
410 420 430 440 450
LHRDPKYWTE PEKFLPERFS KKNKDNIDPY IYTPFGSGPR NCIGMRFALM
460 470 480 490 500
NMKLALIRVL QNFSFKPCKE TQIPLKLSLG GLLQPEKPVV LKVESRDGTV

SGA
Length:503
Mass (Da):57,343
Last modified:January 23, 2007 - v4
Checksum:i38ED122BF89F74F7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti3L → V in AAA35747 (PubMed:2463251).Curated1
Sequence conflicti12W → R in AAF13598 (Ref. 9) Curated1
Sequence conflicti72W → C in AAA35747 (PubMed:2463251).Curated1
Sequence conflicti92T → L in BAA00001 (PubMed:3460094).Curated1
Sequence conflicti92T → L in AAA35742 (PubMed:3460094).Curated1
Sequence conflicti106R → E in BAA00001 (PubMed:3460094).Curated1
Sequence conflicti106R → E in AAA35742 (PubMed:3460094).Curated1
Sequence conflicti164A → R in BAA00001 (PubMed:3460094).Curated1
Sequence conflicti164A → R in AAA35742 (PubMed:3460094).Curated1
Sequence conflicti187T → S in BAA00001 (PubMed:3460094).Curated1
Sequence conflicti187T → S in AAA35742 (PubMed:3460094).Curated1
Sequence conflicti193I → V in BAA00001 (PubMed:3460094).Curated1
Sequence conflicti193I → V in AAA35742 (PubMed:3460094).Curated1
Sequence conflicti203F → L in BAA00001 (PubMed:3460094).Curated1
Sequence conflicti203F → L in AAA35742 (PubMed:3460094).Curated1
Sequence conflicti224 – 225TV → I in AAA35747 (PubMed:2463251).Curated2
Sequence conflicti279Q → HK in BAA00001 (PubMed:3460094).Curated1
Sequence conflicti279Q → HK in AAA35742 (PubMed:3460094).Curated1
Sequence conflicti307Y → C in AAF13598 (Ref. 9) Curated1
Sequence conflicti392V → W in BAA00001 (PubMed:3460094).Curated1
Sequence conflicti392V → W in AAA35742 (PubMed:3460094).Curated1
Sequence conflicti392V → W in AAA35744 (PubMed:3464943).Curated1
Sequence conflicti392V → W in CAA30944 (PubMed:2563251).Curated1
Sequence conflicti392V → W in AAA35747 (PubMed:2463251).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01159715L → P in allele CYP3A4*14. 1 PublicationCorresponds to variant dbSNP:rs12721634Ensembl.1
Natural variantiVAR_01159856G → D in allele CYP3A4*7. 1 PublicationCorresponds to variant dbSNP:rs56324128Ensembl.1
Natural variantiVAR_03754796K → E. Corresponds to variant dbSNP:rs3091339Ensembl.1
Natural variantiVAR_011599118I → V in allele CYP3A4*4. 1 PublicationCorresponds to variant dbSNP:rs55951658Ensembl.1
Natural variantiVAR_011600130R → Q in allele CYP3A4*8. 1 PublicationCorresponds to variant dbSNP:rs72552799Ensembl.1
Natural variantiVAR_011601162R → Q in allele CYP3A4*15. 2 PublicationsCorresponds to variant dbSNP:rs4986907Ensembl.1
Natural variantiVAR_011602170V → I in allele CYP3A4*9. 1 PublicationCorresponds to variant dbSNP:rs72552798Ensembl.1
Natural variantiVAR_011603174D → H in allele CYP3A4*10. 3 PublicationsCorresponds to variant dbSNP:rs4986908Ensembl.1
Natural variantiVAR_011604185T → S in allele CYP3A4*16. 2 PublicationsCorresponds to variant dbSNP:rs12721627Ensembl.1
Natural variantiVAR_014322189F → S in allele CYP3A4*17; exhibits lower turnover numbers for testosterone and chlorpyrifos. 1 PublicationCorresponds to variant dbSNP:rs4987161Ensembl.1
Natural variantiVAR_011605218P → R in allele CYP3A4*5. 1 PublicationCorresponds to variant dbSNP:rs55901263Ensembl.1
Natural variantiVAR_008363222S → P in allele CYP3A4*2; exhibits a lower intrinsic clearance toward nifedipine. 1 PublicationCorresponds to variant dbSNP:rs55785340Ensembl.1
Natural variantiVAR_037548252S → A1 PublicationCorresponds to variant dbSNP:rs3208363Ensembl.1
Natural variantiVAR_014323293L → P in allele CYP3A4*18; exhibits higher turnover numbers for testosterone and chlorpyrifos. 2 PublicationsCorresponds to variant dbSNP:rs28371759Ensembl.1
Natural variantiVAR_037549349T → N. Corresponds to variant dbSNP:rs10250778Ensembl.1
Natural variantiVAR_011606363T → M in allele CYP3A4*11; unstable form. 1 PublicationCorresponds to variant dbSNP:rs67784355Ensembl.1
Natural variantiVAR_011607373L → F in allele CYP3A4*12; has an altered testosterone hydroxylase activity. 2 PublicationsCorresponds to variant dbSNP:rs12721629Ensembl.1
Natural variantiVAR_011608416P → L in allele CYP3A4*13; lack of expression. 1 PublicationCorresponds to variant dbSNP:rs4986909Ensembl.1
Natural variantiVAR_037550431I → T2 PublicationsCorresponds to variant dbSNP:rs1041988Ensembl.1
Natural variantiVAR_008364445M → T in allele CYP3A4*3. 2 PublicationsCorresponds to variant dbSNP:rs4986910Ensembl.1
Natural variantiVAR_014324467P → S in allele CYP3A4*19. 1 PublicationCorresponds to variant dbSNP:rs4986913Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D00003 mRNA Translation: BAA00001.1
M13785 mRNA Translation: AAA35742.1
M18907 mRNA Translation: AAA35745.1
M14096 mRNA Translation: AAA35744.1
X12387 mRNA Translation: CAA30944.1
J04449 mRNA Translation: AAA35747.1
AF182273 mRNA Translation: AAF13598.1
AF280107 Genomic DNA Translation: AAG32290.1
AF209389 Genomic DNA Translation: AAF21034.1
CCDSiCCDS5674.1
PIRiA29410
A29815
RefSeqiNP_001189784.1, NM_001202855.2
NP_059488.2, NM_017460.5
UniGeneiHs.728751

Genome annotation databases

EnsembliENST00000336411; ENSP00000337915; ENSG00000160868
GeneIDi1576
KEGGihsa:1576

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCP3A4_HUMAN
AccessioniPrimary (citable) accession number: P08684
Secondary accession number(s): P05184, Q16757, Q9UK50
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: January 23, 2007
Last modified: May 23, 2018
This is version 208 of the entry and version 4 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 7
    Human chromosome 7: 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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