Cytochrome P450 3A4

NameCytochrome P450 3A4
Synonyms1,8-cineole 2-exo-monooxygenase 1.14.13.- Albendazole monooxygenase Albendazole sulfoxidase Cholesterol 25-hydroxylase CYP3A3 CYPIIIA3 CYPIIIA4 Cytochrome P450 3A3 Cytochrome P450 HLp Cytochrome P450 NF-25 Cytochrome P450-PCN1 Nifedipine oxidase Quinine 3-monooxygenase Taurochenodeoxycholate 6-alpha-hydroxylase
Gene NameCYP3A4
OrganismHuman
Amino acid sequence
>lcl|BSEQ0021936|Cytochrome P450 3A4
MALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNILSYHKGFCMF
DMECHKKYGKVWGFYDGQQPVLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFMKSAISI
AEDEEWKRLRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREAETGKPVTLKDVFGAYS
MDVITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDPFFLSITVFPFLIPILEVLNICV
FPREVTNFLRKSVKRMKESRLEDTQKHRVDFLQLMIDSQNSKETESHKALSDLELVAQSI
IFIFAGYETTSSVLSFIMYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYLDMVV
NETLRLFPIAMRLERVCKKDVEINGMFIPKGVVVMIPSYALHRDPKYWTEPEKFLPERFS
KKNKDNIDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLSLG
GLLQPEKPVVLKVESRDGTVSGA
Number of residues503
Molecular Weight57342.67
Theoretical pI8.25
GO Classification
Functions
    enzyme binding
testosterone 6-beta-hydroxylase activity
oxidoreductase activity
vitamin D3 25-hydroxylase activity
aromatase activity
iron ion binding
albendazole monooxygenase activity
caffeine oxidase activity
heme binding
quinine 3-monooxygenase activity
monooxygenase activity
taurochenodeoxycholate 6alpha-hydroxylase activity
steroid binding
oxygen binding
steroid hydroxylase activity
vitamin D 24-hydroxylase activity
Processes
    vitamin D metabolic process
exogenous drug catabolic process
alkaloid catabolic process
small molecule metabolic process
steroid catabolic process
oxidation-reduction process
steroid metabolic process
drug catabolic process
lipid metabolic process
heterocycle metabolic process
xenobiotic metabolic process
monoterpenoid metabolic process
drug metabolic process
oxidative demethylation
androgen metabolic process
calcitriol biosynthetic process from calciol
Components
    integral component of membrane
intracellular membrane-bounded organelle
cytoplasm
endoplasmic reticulum membrane
General FunctionVitamin d3 25-hydroxylase activity
Specific FunctionCytochromes 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).
Transmembrane Regions2-22
GenBank Protein ID
UniProtKB IDP08684
UniProtKB Entry NameCP3A4_HUMAN
Cellular LocationEndoplasmic reticulum membrane
Gene sequence
>lcl|BSEQ0021937|Cytochrome P450 3A4 (CYP3A4)
ATGGCTCTCATCCCAGACTTGGCCATGGAAACCTGGCTTCTCCTGGCTGTCAGCCTGGTG
CTCCTCTATCTATATGGAACCCATTCACATGGACTTTTTAAGAAGCTTGGAATTCCAGGG
CCCACACCTCTGCCTTTTTTGGGAAATATTTTGTCCTACCATAAGGGCTTTTGTATGTTT
GACATGGAATGTCATAAAAAGTATGGAAAAGTGTGGGGCTTTTATGATGGTCAACAGCCT
GTGCTGGCTATCACAGATCCTGACATGATCAAAACAGTGCTAGTGAAAGAATGTTATTCT
GTCTTCACAAACCGGAGGCCTTTTGGTCCAGTGGGATTTATGAAAAGTGCCATCTCTATA
GCTGAGGATGAAGAATGGAAGAGATTACGATCATTGCTGTCTCCAACCTTCACCAGTGGA
AAACTCAAGGAGATGGTCCCTATCATTGCCCAGTATGGAGATGTGTTGGTGAGAAATCTG
AGGCGGGAAGCAGAGACAGGCAAGCCTGTCACCTTGAAAGACGTCTTTGGGGCCTACAGC
ATGGATGTGATCACTAGCACATCATTTGGAGTGAACATCGACTCTCTCAACAATCCACAA
GACCCCTTTGTGGAAAACACCAAGAAGCTTTTAAGATTTGATTTTTTGGATCCATTCTTT
CTCTCAATAATCTTTCCATTCCTCATCCCAATTCTTGAAGTATTAAATATCTGTGTGTTT
CCAAGAGAAGTTACAAATTTTTTAAGAAAATCTGTAAAAAGGATGAAAGAAAGTCGCCTC
GAAGATACACAAAAGCACCGAGTGGATTTCCTTCAGCTGATGATTGACTCTCAGAATTCA
AAAGAAACTGAGTCCCACAAAGCTCTGTCCGATCTGGAGCTCGTGGCCCAATCAATTATC
TTTATTTTTGCTGGCTATGAAACCACGAGCAGTGTTCTCTCCTTCATTATGTATGAACTG
GCCACTCACCCTGATGTCCAGCAGAAACTGCAGGAGGAAATTGATGCAGTTTTACCCAAT
AAGGCACCACCCACCTATGATACTGTGCTACAGATGGAGTATCTTGACATGGTGGTGAAT
GAAACGCTCAGATTATTCCCAATTGCTATGAGACTTGAGAGGGTCTGCAAAAAAGATGTT
GAGATCAATGGGATGTTCATTCCCAAAGGGGTGGTGGTGATGATTCCAAGCTATGCTCTT
CACCGTGACCCAAAGTACTGGACAGAGCCTGAGAAGTTCCTCCCTGAAAGATTCAGCAAG
AAGAACAAGGACAACATAGATCCTTACATATACACACCCTTTGGAAGTGGACCCAGAAAC
TGCATTGGCATGAGGTTTGCTCTCATGAACATGAAACTTGCTCTAATCAGAGTCCTTCAG
AACTTCTCCTTCAAACCTTGTAAAGAAACACAGATCCCCCTGAAATTAAGCTTAGGAGGA
CTTCTTCAACCAGAAAAACCCGTTGTTCTAAAGGTTGAGTCAAGGGATGGCACCGTAAGT
GGAGCCTGA
GenBank Gene IDM18907
GeneCard IDNone
GenAtlas IDCYP3A4
HGNC IDHGNC:2637
Chromosome Location7
Locus7q21.1
References
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  14. Zhang H, Coville PF, Walker RJ, Miners JO, Birkett DJ, Wanwimolruk S: Evidence for involvement of human CYP3A in the 3-hydroxylation of quinine. Br J Clin Pharmacol. 1997 Mar;43(3):245-52.[9088578 ]
  15. Zhao XJ, Kawashiro T, Ishizaki T: Mutual inhibition between quinine and etoposide by human liver microsomes. Evidence for cytochrome P4503A4 involvement in their major metabolic pathways. Drug Metab Dispos. 1998 Feb;26(2):188-91.[9456308 ]
  16. Miyazawa M, Shindo M, Shimada T: Oxidation of 1,8-cineole, the monoterpene cyclic ether originated from eucalyptus polybractea, by cytochrome P450 3A enzymes in rat and human liver microsomes. Drug Metab Dispos. 2001 Feb;29(2):200-5.[11159812 ]
  17. Finta C, Zaphiropoulos PG: Intergenic mRNA molecules resulting from trans-splicing. J Biol Chem. 2002 Feb 22;277(8):5882-90. Epub 2001 Nov 28.[11726664 ]
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  23. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22.[24275569 ]
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Related FRC

FRCD ID Name Exact Mass Structure




F03283



Chlordane


409.758




F03370



Chlorpyrifos


350.575




F03378



Guthion


317.318




F03386



Dicofol


370.475




F03908



Pimpinellin


246.21




F03910



Isoimperatorin


270.28




F03912



Methoxsalen


216.19




F03890



Fipronil


437.141




F03892



Rotenone


394.423




F03981



Chlorpropham


213.661




F04025



Propoxur


209.245




F04032



Thiobencarb


257.776




F04040



Allethrin


302.414




F04050



Cypermethrin


416.298




F04044



Tetramethrin


331.412




F04085



(±)-Metalaxyl


279.336




F04086



Metolachlor


283.796




F04158



Hydroxytriphenylstannane


367.035




F04333



Chlorothalonil


265.902




F04334



2,6-Dichlorobenzonitrile


172.008




F04776



Ketoconazole


531.434




F04851



Omeprazole


345.417




F04924



Aflatoxin M2


330.292




F05026



Ametryn


227.33




F05034



Boscalid


343.207




F05040



Chloroneb


207.05




F05042



Chlorsulfuron


357.769




F05043



Cinmethylin


274.404




F05066



Fenamiphos


303.36




F05078



Flusilazole


315.399




F05083



Hexazinone


252.318




F05085



Enilconazole


297.179




F05089



Indoxacarb


527.837




F05092



Isoxaben


332.4




F05093



Isoxaflutole


359.319




F05095



Malathion


330.35




F05105



Metribuzin


214.287




F05103



Methidathion


302.318




F05111



Myclobutanil


288.779




F05112



Napropamide


271.36




F05121



Phosalone


367.799




F05130



Pyraclostrobin


387.82




F05132



Pyriproxyfen


321.376




F05137



Spiroxamine


297.483




F05138



Sulfentrazone


387.183




F05140



Tebufenpyrad


333.86




F05141



Tebupirimfos


318.372




F05143



Tetraconazole


372.145




F05146



Thiazopyr


396.376




F05320



Testosterone


288.4




F05349



Glutathione


307.321




F05392



Butylate


217.371




F05394



Carboxin


235.301




F05395



Chlorethoxyfos


335.985




F05398



Clomazone


239.699




F05403



Cyproconazole


291.779




F05411



Diuron


233.092




F05416



Fenarimol


331.196




F05419



Fluometuron


232.206




F05422



Hexaconazole


314.21




F05426



Linuron


249.091




F05433



Prallethrin


300.398




F05438



Quinoxyfen


308.133




F05440



Rimsulfuron


431.438




F05877



Thiacloprid


252.72




F05451



Triticonazole


317.817




F03312



Diazinon


304.35




F03315



Methoxychlor


345.644




F03387



Parathion


291.258




F03448



Ethoprop


242.332




F03774



Bisphenol A


228.291




F03879



Ethanol


46.07




F03900



Alachlor


269.769




F03901



Acetochlor


269.769




F03906



Sphondin


216.19




F03904



Angelicin


186.16




F03905



Isobergapten


216.19




F03907



Heratomin


270.284




F03909



Psoralen


186.16




F03911



Bergamottin


338.403




F03913



Imperatorin


270.28




F03914



Isopimpinellin


246.21




F03916



Phellopterin


300.31




F03957



Asulam


230.238




F03972



Carbaril


201.225




F04019



Pirimicarb


238.291




F04043



Resmethrin


338.447




F04084



Butachlor


311.85




F04380



Fenpropathrin


349.43




F04384



Permethrin


391.288




F04721



Acetaminophen


151.165




F04726



Digoxin


780.949




F04743



Clotrimazole


344.842




F04771



Ondansetron


293.37




F04783



Sertraline


306.2




F04846



Fenthion


278.321




F04874



Aflatoxin B1


312.277




F05025



Acifluorfen


361.657




F05030



Benfluralin


335.283




F05031



Bensulide


397.503




F05032



Bifenazate


300.358




F05035



Bromacil


261.119




F05036



Butafenacil


474.817




F05044



Clofentezine


303.146




F05048



Cyanazine


240.695




F05054



Dichloran


207.01




F05056



Diclosulam


406.213




F05060



Dimethenamid


275.791




F05062



Ethalfluralin


333.267




F05064



Etoxazole


359.417




F05068



Fenitrothion


277.24




F05071



Fluazinam


465.089




F05072



Flufenacet


363.331




F05076



Flumioxazin


354.337




F05081



Fosthiazate


283.341




F05091



Iprodione


330.165




F05094



Lactofen


461.774




F05104



Methoxyfenozide


368.477




F05114



Norflurazon


303.669




F05115



Oxadiazon


345.22




F05118



Penoxsulam


483.37




F05124



Prometryn


241.357




F05125



Propargite


350.473




F05126



Propazine


229.712




F05127



Propiconazole


342.22




F05807



Sethoxydim


327.483




F05139



Tebufenozide


352.478




F06000



Tralkoxydim


329.44




F05148



Triasulfuron


401.822




F05151



Triclosan


289.536




F05391



Butralin


295.339




F05400



Coumaphos


362.761




F05404



Cyromazine


166.188




F05405



Diazoxon


288.284




F05410



Dithiopyr


401.41




F05413



Ethofumesate


286.342




F05417



Fenbuconazole


336.823




F05418



Fludioxonil


248.189




F05424



Imazapyr


261.281




F05425



Isazofos


313.737




F05434



Profenofos


373.626




F05435



Propyzamide


256.126




F05437



Pyrimethanil


199.257




F05439



Quintozene


295.321




F05444



Thidiazuron


220.25




F05446



Triadimefon


293.751




F05447



Triadimenol


295.767




F06003



Triflumizole


345.75




F05450



Trifluralin


335.283




F05452



Zoxamide


336.637




F05589



5,7-Dihydroxyflavone


254.241




F05618



Flavone


222.243