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P08684 (CP3A4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 165. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cytochrome P450 3A4

EC=1.14.13.-
Alternative name(s):
1,8-cineole 2-exo-monooxygenase
EC=1.14.13.157
Albendazole monooxygenase
EC=1.14.13.32
Albendazole sulfoxidase
CYPIIIA3
CYPIIIA4
Cytochrome P450 3A3
Cytochrome P450 HLp
Cytochrome P450 NF-25
Cytochrome P450-PCN1
Nifedipine oxidase
Quinine 3-monooxygenase
EC=1.14.13.67
Taurochenodeoxycholate 6-alpha-hydroxylase
EC=1.14.13.97
Gene names
Name:CYP3A4
Synonyms:CYP3A3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length503 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.17

Catalytic activity

Quinine + NADPH + O2 = 3-hydroxyquinine + NADP+ + H2O. Ref.17

Taurochenodeoxycholate + NADPH + O2 = taurohyocholate + NADP+ + H2O. Ref.17

Lithocholate + NADPH + O2 = hyodeoxycholate + NADP+ + H2O. Ref.17

Albendazole + NADPH + O2 = albendazole S-oxide + NADP+ + H2O. Ref.17

1,8-cineole + NADPH + O2 = 2-exo-hydroxy-1,8-cineole + NADP+ + H2O. Ref.17

Cofactor

Heme group.

Subcellular location

Endoplasmic reticulum membrane; Single-pass membrane protein. Microsome membrane; Single-pass membrane protein.

Tissue specificity

Expressed in prostate and liver. According to some authors, it is not expressed in brain (Ref.19). According to others, weak levels of expression are measured in some brain locations (Ref.22 and Ref.20). 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). Ref.12 Ref.13 Ref.14 Ref.19 Ref.20 Ref.22

Induction

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

Post-translational modification

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

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 (CYP3A43exon 1 joined to CYP3A4 exons 2-13) exhibits 6-beta-hydroxylase activity, while a shorter isoform (CYP3A43exon 1 joined to CYP3A4 exons 4-13) does not. All chimeric transcripts are expressed at very low levels in the liver (Ref.18).

Sequence similarities

Belongs to the cytochrome P450 family.

Ontologies

Keywords
   Cellular componentEndoplasmic reticulum
Membrane
Microsome
   Coding sequence diversityPolymorphism
   DomainTransmembrane
Transmembrane helix
   LigandHeme
Iron
Metal-binding
NADP
   Molecular functionMonooxygenase
Oxidoreductase
   PTMUbl conjugation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processalkaloid catabolic process

Inferred from direct assay PubMed 15039299. Source: BHF-UCL

androgen metabolic process

Traceable author statement PubMed 19651758. Source: BHF-UCL

calcitriol biosynthetic process from calciol

Inferred from direct assay PubMed 15546903. Source: GOC

drug catabolic process

Inferred from direct assay PubMed 15039299. Source: BHF-UCL

drug metabolic process

Inferred from direct assay PubMed 15327587PubMed 19219744. Source: BHF-UCL

exogenous drug catabolic process

Inferred from direct assay PubMed 18619574. Source: BHF-UCL

heterocycle metabolic process

Inferred from direct assay PubMed 15327587. Source: BHF-UCL

lipid metabolic process

Traceable author statement PubMed 2492107. Source: ProtInc

monoterpenoid metabolic process

Inferred from direct assay PubMed 16401082. Source: BHF-UCL

oxidation-reduction process

Inferred from direct assay PubMed 16401082PubMed 19219744. Source: BHF-UCL

oxidative demethylation

Inferred from direct assay PubMed 15039299PubMed 18619574. Source: BHF-UCL

small molecule metabolic process

Traceable author statement. Source: Reactome

steroid catabolic process

Inferred from mutant phenotype PubMed 18356043. Source: BHF-UCL

steroid metabolic process

Inferred from mutant phenotype PubMed 3259858. Source: BHF-UCL

vitamin D metabolic process

Inferred by curator PubMed 15546903. Source: BHF-UCL

xenobiotic metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 18446064. Source: BHF-UCL

endoplasmic reticulum membrane

Traceable author statement. Source: Reactome

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

intracellular membrane-bounded organelle

Traceable author statement Ref.1. Source: ProtInc

   Molecular_functionalbendazole monooxygenase activity

Inferred from electronic annotation. Source: UniProtKB-EC

caffeine oxidase activity

Inferred from direct assay PubMed 18619574. Source: BHF-UCL

enzyme binding

Inferred from physical interaction PubMed 15680923. Source: BHF-UCL

heme binding

Inferred from electronic annotation. Source: InterPro

iron ion binding

Inferred from direct assay Ref.24. Source: BHF-UCL

monooxygenase activity

Inferred from sequence or structural similarity. Source: UniProtKB

oxidoreductase activity

Inferred from direct assay PubMed 15039299PubMed 16401082PubMed 19219744. 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

Inferred from electronic annotation. Source: InterPro

oxygen binding

Traceable author statement PubMed 2492107Ref.1. Source: ProtInc

quinine 3-monooxygenase activity

Inferred from electronic annotation. Source: UniProtKB-EC

steroid binding

Inferred from direct assay Ref.24. Source: BHF-UCL

steroid hydroxylase activity

Inferred from mutant phenotype PubMed 18356043. Source: BHF-UCL

taurochenodeoxycholate 6alpha-hydroxylase activity

Inferred from electronic annotation. Source: UniProtKB-EC

testosterone 6-beta-hydroxylase activity

Inferred from mutant phenotype PubMed 3259858. Source: BHF-UCL

vitamin D 24-hydroxylase activity

Inferred from direct assay PubMed 15546903. Source: BHF-UCL

vitamin D3 25-hydroxylase activity

Inferred from direct assay PubMed 15546903. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.10 Ref.11
Chain2 – 503502Cytochrome P450 3A4
PRO_0000051786

Regions

Transmembrane2 – 2221Helical; Potential

Sites

Metal binding4421Iron (heme axial ligand)

Natural variations

Natural variant151L → P in allele CYP3A4*14. Ref.28
Corresponds to variant rs12721634 [ dbSNP | Ensembl ].
VAR_011597
Natural variant561G → D in allele CYP3A4*7. Ref.27
Corresponds to variant rs56324128 [ dbSNP | Ensembl ].
VAR_011598
Natural variant961K → E.
Corresponds to variant rs3091339 [ dbSNP | Ensembl ].
VAR_037547
Natural variant1181I → V in allele CYP3A4*4. Ref.8
Corresponds to variant rs55951658 [ dbSNP | Ensembl ].
VAR_011599
Natural variant1301R → Q in allele CYP3A4*8. Ref.27
VAR_011600
Natural variant1621R → Q in allele CYP3A4*15. Ref.26 Ref.28
Corresponds to variant rs4986907 [ dbSNP | Ensembl ].
VAR_011601
Natural variant1701V → I in allele CYP3A4*9. Ref.27
VAR_011602
Natural variant1741D → H in allele CYP3A4*10. Ref.27 Ref.28 Ref.29
Corresponds to variant rs4986908 [ dbSNP | Ensembl ].
VAR_011603
Natural variant1851T → S in allele CYP3A4*16. Ref.28 Ref.29
Corresponds to variant rs12721627 [ dbSNP | Ensembl ].
VAR_011604
Natural variant1891F → S in allele CYP3A4*17; exhibits lower turnover numbers for testosterone and chlorpyrifos. Ref.26
Corresponds to variant rs4987161 [ dbSNP | Ensembl ].
VAR_014322
Natural variant2181P → R in allele CYP3A4*5. Ref.8
Corresponds to variant rs55901263 [ dbSNP | Ensembl ].
VAR_011605
Natural variant2221S → P in allele CYP3A4*2; exhibits a lower intrinsic clearance toward nifedipine. Ref.25
Corresponds to variant rs55785340 [ dbSNP | Ensembl ].
VAR_008363
Natural variant2521S → A. Ref.1
Corresponds to variant rs3208363 [ dbSNP | Ensembl ].
VAR_037548
Natural variant2931L → P in allele CYP3A4*18; exhibits higher turnover numbers for testosterone and chlorpyrifos. Ref.26 Ref.29
Corresponds to variant rs28371759 [ dbSNP | Ensembl ].
VAR_014323
Natural variant3491T → N.
Corresponds to variant rs10250778 [ dbSNP | Ensembl ].
VAR_037549
Natural variant3631T → M in allele CYP3A4*11; unstable form. Ref.27
Corresponds to variant rs67784355 [ dbSNP | Ensembl ].
VAR_011606
Natural variant3731L → F in allele CYP3A4*12; has an altered testosterone hydroxylase activity. Ref.27 Ref.28
Corresponds to variant rs12721629 [ dbSNP | Ensembl ].
VAR_011607
Natural variant4161P → L in allele CYP3A4*13; lack of expression. Ref.27
Corresponds to variant rs4986909 [ dbSNP | Ensembl ].
VAR_011608
Natural variant4311I → T. Ref.3 Ref.5
Corresponds to variant rs1041988 [ dbSNP | Ensembl ].
VAR_037550
Natural variant4451M → T in allele CYP3A4*3. Ref.25 Ref.26
Corresponds to variant rs4986910 [ dbSNP | Ensembl ].
VAR_008364
Natural variant4671P → S in allele CYP3A4*19. Ref.26
Corresponds to variant rs4986913 [ dbSNP | Ensembl ].
VAR_014324

Experimental info

Sequence conflict31L → V in AAA35747. Ref.5
Sequence conflict121W → R in AAF13598. Ref.9
Sequence conflict721W → C in AAA35747. Ref.5
Sequence conflict921T → L in BAA00001. Ref.1
Sequence conflict921T → L in AAA35742. Ref.1
Sequence conflict1061R → E in BAA00001. Ref.1
Sequence conflict1061R → E in AAA35742. Ref.1
Sequence conflict1641A → R in BAA00001. Ref.1
Sequence conflict1641A → R in AAA35742. Ref.1
Sequence conflict1871T → S in BAA00001. Ref.1
Sequence conflict1871T → S in AAA35742. Ref.1
Sequence conflict1931I → V in BAA00001. Ref.1
Sequence conflict1931I → V in AAA35742. Ref.1
Sequence conflict2031F → L in BAA00001. Ref.1
Sequence conflict2031F → L in AAA35742. Ref.1
Sequence conflict224 – 2252TV → I in AAA35747. Ref.5
Sequence conflict2791Q → HK in BAA00001. Ref.1
Sequence conflict2791Q → HK in AAA35742. Ref.1
Sequence conflict3071Y → C in AAF13598. Ref.9
Sequence conflict3921V → W in BAA00001. Ref.1
Sequence conflict3921V → W in AAA35742. Ref.1
Sequence conflict3921V → W in AAA35744. Ref.3
Sequence conflict3921V → W in CAA30944. Ref.4
Sequence conflict3921V → W in AAA35747. Ref.5

Secondary structure

........................................................................................ 503
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P08684 [UniParc].

Last modified January 23, 2007. Version 4.
Checksum: 38ED122BF89F74F7

FASTA50357,343
        10         20         30         40         50         60 
MALIPDLAME TWLLLAVSLV LLYLYGTHSH GLFKKLGIPG PTPLPFLGNI LSYHKGFCMF 

        70         80         90        100        110        120 
DMECHKKYGK VWGFYDGQQP VLAITDPDMI KTVLVKECYS VFTNRRPFGP VGFMKSAISI 

       130        140        150        160        170        180 
AEDEEWKRLR SLLSPTFTSG KLKEMVPIIA QYGDVLVRNL RREAETGKPV TLKDVFGAYS 

       190        200        210        220        230        240 
MDVITSTSFG VNIDSLNNPQ DPFVENTKKL LRFDFLDPFF LSITVFPFLI PILEVLNICV 

       250        260        270        280        290        300 
FPREVTNFLR KSVKRMKESR LEDTQKHRVD FLQLMIDSQN SKETESHKAL SDLELVAQSI 

       310        320        330        340        350        360 
IFIFAGYETT SSVLSFIMYE LATHPDVQQK LQEEIDAVLP NKAPPTYDTV LQMEYLDMVV 

       370        380        390        400        410        420 
NETLRLFPIA MRLERVCKKD VEINGMFIPK GVVVMIPSYA LHRDPKYWTE PEKFLPERFS 

       430        440        450        460        470        480 
KKNKDNIDPY IYTPFGSGPR NCIGMRFALM NMKLALIRVL QNFSFKPCKE TQIPLKLSLG 

       490        500 
GLLQPEKPVV LKVESRDGTV SGA 

« Hide

References

[1]"Complete cDNA sequence of a cytochrome P-450 inducible by glucocorticoids in human liver."
Molowa D.T., Schuetz E.G., Wrighton S.A., Watkins P.B., Kremers P., Mendez-Picon G., Parker G.A., Guzelian P.S.
Proc. Natl. Acad. Sci. U.S.A. 83:5311-5315(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ALA-252.
Tissue: Liver.
[2]"Human P450PCN1: sequence, chromosome localization, and direct evidence through cDNA expression that P450PCN1 is nifedipine oxidase."
Gonzalez F.J., Schmid B.J., Umeno M., McBride O.W., Hardwick J.P., Meyer U.A., Gelboin H.V., Idle J.R.
DNA 7:79-86(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Isolation and sequence determination of a cDNA clone related to human cytochrome P-450 nifedipine oxidase."
Beaune P.H., Umbenhauer D.R., Bork R.W., Lloyd R.S., Guengerich F.P.
Proc. Natl. Acad. Sci. U.S.A. 83:8064-8068(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT THR-431.
[4]"The human cytochrome P450 CYP3 locus: assignment to chromosome 7q22-qter."
Spurr N.K., Gough A.C., Stevenson K., Wolf C.R.
Hum. Genet. 81:171-174(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]"Characterization of mRNA species related to human liver cytochrome P-450 nifedipine oxidase and the regulation of catalytic activity."
Bork R.W., Muto T., Beaune P.H., Srivastava P.K., Lloyd R.S., Guengerich F.P.
J. Biol. Chem. 264:910-919(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT THR-431.
Tissue: Liver.
[6]"Establishment of transgenic cell line CHL-3A4 and its metabolic activation."
Chen Q., Wu J., Yu Y.
Zhonghua Yu Fang Yi Xue Za Zhi 32:281-284(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[7]"Genomic organization of the human CYP3A locus: identification of a new, inducible CYP3A gene."
Gellner K., Eiselt R., Hustert E., Arnold H., Koch I., Haberl M., Deglmann C.J., Burk O., Buntefuss D., Escher S., Bishop C., Koebe H.-G., Brinkmann U., Klenk H.-P., Kleine K., Meyer U.A., Wojnowski L.
Pharmacogenetics 11:111-121(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[8]"Novel mutations of CYP3A4 in Chinese."
Hsieh K.-P., Lin Y.-Y., Cheng C.-L., Lai M.-L., Lin M.-S., Siest J.-P., Huang J.-D.
Drug Metab. Dispos. 29:268-273(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS VAL-118 AND ARG-218.
[9]"Sequence of a new human cytochrome P450-3A4 cDNA."
Zhuge J., Qian Y., Xie H., Yu Y.
Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[10]"Cytochrome P-450 in human liver microsomes: high-performance liquid chromatographic isolation of three forms and their characterization."
Komori M., Hashizume T., Ohi H., Miura T., Kitada M., Nagashima K., Kamataki T.
J. Biochem. 104:912-916(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-25, CLEAVAGE OF INITIATOR METHIONINE.
[11]"Identification of an inducible form of cytochrome P-450 in human liver."
Watkins P.B., Wrighton S.A., Maurel P., Schuetz E.G., Mendez-Picon G., Parker G.A., Guzelian P.S.
Proc. Natl. Acad. Sci. U.S.A. 82:6310-6314(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-21, CLEAVAGE OF INITIATOR METHIONINE.
Tissue: Liver.
[12]"Cytochrome P-450 hPCN3, a novel cytochrome P-450 IIIA gene product that is differentially expressed in adult human liver. cDNA and deduced amino acid sequence and distinct specificities of cDNA-expressed hPCN1 and hPCN3 for the metabolism of steroid hormones and cyclosporine."
Aoyama T., Yamano S., Waxman D.J., Lapenson D.P., Meyer U.A., Fischer V., Tyndale R., Inaba T., Kalow W., Gelboin H.V., Gonzalez F.J.
J. Biol. Chem. 264:10388-10395(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[13]"Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians."
Shimada T., Yamazaki H., Mimura M., Inui Y., Guengerich F.P.
J. Pharmacol. Exp. Ther. 270:414-423(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[14]"CYP3A gene expression in human gut epithelium."
Kolars J.C., Lown K.S., Schmiedlin-Ren P., Ghosh M., Fang C., Wrighton S.A., Merion R.M., Watkins P.B.
Pharmacogenetics 4:247-259(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[15]"Evidence for involvement of human CYP3A in the 3-hydroxylation of quinine."
Zhang H., Coville P.F., Walker R.J., Miners J.O., Birkett D.J., Wanwimolruk S.
Br. J. Clin. Pharmacol. 43:245-252(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION.
[16]"Mutual inhibition between quinine and etoposide by human liver microsomes. Evidence for cytochrome P4503A4 involvement in their major metabolic pathways."
Zhao X.J., Kawashiro T., Ishizaki T.
Drug Metab. Dispos. 26:188-191(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION.
[17]"Oxidation of 1,8-cineole, the monoterpene cyclic ether originated from eucalyptus polybractea, by cytochrome P450 3A enzymes in rat and human liver microsomes."
Miyazawa M., Shindo M., Shimada T.
Drug Metab. Dispos. 29:200-205(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, FUNCTION AS 1,8-CINEOLE 2-EXO-MONOOXYGENASE.
[18]"Intergenic mRNA molecules resulting from trans-splicing."
Finta C., Zaphiropoulos P.G.
J. Biol. Chem. 277:5882-5890(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: TRANS-SPLICING.
[19]"ABC transporters, cytochromes P450 and their main transcription factors: expression at the human blood-brain barrier."
Dauchy S., Dutheil F., Weaver R.J., Chassoux F., Daumas-Duport C., Couraud P.O., Scherrmann J.M., De Waziers I., Decleves X.
J. Neurochem. 107:1518-1528(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[20]"Drug metabolism in human brain: high levels of cytochrome P4503A43 in brain and metabolism of anti-anxiety drug alprazolam to its active metabolite."
Agarwal V., Kommaddi R.P., Valli K., Ryder D., Hyde T.M., Kleinman J.E., Strobel H.W., Ravindranath V.
PLoS ONE 3:E2337-E2337(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[21]"CYP3A4 ubiquitination by gp78 (the tumor autocrine motility factor receptor, AMFR) and CHIP E3 ligases."
Pabarcus M.K., Hoe N., Sadeghi S., Patterson C., Wiertz E., Correia M.A.
Arch. Biochem. Biophys. 483:66-74(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION.
[22]"Xenobiotic-metabolizing enzymes and transporters in the normal human brain: regional and cellular mapping as a basis for putative roles in cerebral function."
Dutheil F., Dauchy S., Diry M., Sazdovitch V., Cloarec O., Mellottee L., Bieche I., Ingelman-Sundberg M., Flinois J.P., de Waziers I., Beaune P., Decleves X., Duyckaerts C., Loriot M.A.
Drug Metab. Dispos. 37:1528-1538(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[23]"The structure of human microsomal cytochrome P450 3A4 determined by X-ray crystallography to 2.05-A resolution."
Yano J.K., Wester M.R., Schoch G.A., Griffin K.J., Stout C.D., Johnson E.F.
J. Biol. Chem. 279:38091-38094(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 24-503.
[24]"Crystal structures of human cytochrome P450 3A4 bound to metyrapone and progesterone."
Williams P.A., Cosme J., Vinkovic D.M., Ward A., Angove H.C., Day P.J., Vonrhein C., Tickle I.J., Jhoti H.
Science 305:683-686(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 25-503.
[25]"CYP3A4 allelic variants with amino acid substitutions in exons 7 and 12: evidence for an allelic variant with altered catalytic activity."
Sata F., Sapone A., Elizondo G., Stocker P., Miller V.P., Zheng W., Raunio H., Crespi C.L., Gonzalez F.J.
Clin. Pharmacol. Ther. 67:48-56(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PRO-222 AND THR-445.
[26]"Identification of variants of CYP3A4 and characterization of their abilities to metabolize testosterone and chlorpyrifos."
Dai D., Tang J., Rose R., Hodgson E., Bienstock R.J., Mohrenweiser H.W., Goldstein J.A.
J. Pharmacol. Exp. Ther. 299:825-831(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GLN-162; SER-189; PRO-293; THR-445 AND SER-467, CHARACTERIZATION OF THE VARIANTS.
[27]"Identification and functional characterization of eight CYP3A4 protein variants."
Eiselt R., Domanski T.L., Zibat A., Mueller R., Presecan-Siedel E., Hustert E., Zanger U.M., Brockmoller J., Klenk H.-P., Meyer U.A., Khan K.K., He Y.-A., Halpert J.R., Wojnowski L.
Pharmacogenetics 11:447-458(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ASP-56; GLN-130; ILE-170; HIS-174; MET-363; PHE-373 AND LEU-416.
[28]"Common allelic variants of cytochrome P4503A4 and their prevalence in different populations."
Lamba J.K., Lin Y.S., Thummel K., Daly A., Watkins P.B., Strom S., Zhang J., Schuetz E.G.
Pharmacogenetics 12:121-132(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PRO-15; GLN-162; HIS-174; SER-185 AND PHE-373.
[29]"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 HIS-174; SER-185 AND PRO-293.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRA29410.
A29815.
RefSeqNP_001189784.1. NM_001202855.2.
NP_059488.2. NM_017460.5.
UniGeneHs.728751.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1TQNX-ray2.05A24-503[»]
1W0EX-ray2.80A25-503[»]
1W0FX-ray2.65A25-503[»]
1W0GX-ray2.74A25-503[»]
2J0DX-ray2.75A/B25-502[»]
2V0MX-ray2.80A/B/C/D25-503[»]
3NXUX-ray2.00A/B25-503[»]
3TJSX-ray2.25A23-503[»]
3UA1X-ray2.15A23-503[»]
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[»]
ProteinModelPortalP08684.
SMRP08684. Positions 28-499.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107948. 9 interactions.
IntActP08684. 2 interactions.
STRING9606.ENSP00000337915.

Chemistry

BindingDBP08684.
ChEMBLCHEMBL2364675.
DrugBankDB00518. Albendazole.
DB00240. Alclometasone.
DB00802. Alfentanil.
DB00346. Alfuzosin.
DB01258. Aliskiren.
DB00918. Almotriptan.
DB00969. Alosetron.
DB00404. Alprazolam.
DB00381. Amlodipine.
DB00701. Amprenavir.
DB00673. Aprepitant.
DB01238. Aripiprazole.
DB00637. Astemizole.
DB01072. Atazanavir.
DB01076. Atorvastatin.
DB00542. Benazepril.
DB01244. Bepridil.
DB00443. Betamethasone.
DB00307. Bexarotene.
DB00188. Bortezomib.
DB00559. Bosentan.
DB01200. Bromocriptine.
DB01222. Budesonide.
DB00297. Bupivacaine.
DB00921. Buprenorphine.
DB00490. Buspirone.
DB01008. Busulfan.
DB00564. Carbamazepine.
DB00185. Cevimeline.
DB01114. Chlorpheniramine.
DB01410. Ciclesonide.
DB01166. Cilostazol.
DB01012. Cinacalcet.
DB00604. Cisapride.
DB01211. Clarithromycin.
DB01190. Clindamycin.
DB00636. Clofibrate.
DB01068. Clonazepam.
DB00758. Clopidogrel.
DB00907. Cocaine.
DB00872. Conivaptan.
DB00286. Conjugated Estrogens.
DB04839. Cyproterone.
DB00496. Darifenacin.
DB01264. Darunavir.
DB01254. Dasatinib.
DB00705. Delavirdine.
DB00304. Desogestrel.
DB01234. Dexamethasone.
DB00829. Diazepam.
DB00320. Dihydroergotamine.
DB00343. Diltiazem.
DB01075. Diphenhydramine.
DB00280. Disopyramide.
DB00204. Dofetilide.
DB00757. Dolasetron.
DB01184. Domperidone.
DB00843. Donepezil.
DB00997. Doxorubicin.
DB01395. Drospirenone.
DB01126. Dutasteride.
DB00625. Efavirenz.
DB00216. Eletriptan.
DB00584. Enalapril.
DB00445. Epirubicin.
DB00700. Eplerenone.
DB00696. Ergotamine.
DB00530. Erlotinib.
DB00199. Erythromycin.
DB01175. Escitalopram.
DB00736. Esomeprazole.
DB01215. Estazolam.
DB00402. Eszopiclone.
DB00977. Ethinyl Estradiol.
DB00593. Ethosuximide.
DB00294. Etonogestrel.
DB00773. Etoposide.
DB01628. Etoricoxib.
DB00990. Exemestane.
DB01023. Felodipine.
DB00813. Fentanyl.
DB00950. Fexofenadine.
DB01216. Finasteride.
DB00196. Fluconazole.
DB00663. Flumethasone Pivalate.
DB00180. Flunisolide.
DB00591. Fluocinolone Acetonide.
DB01047. Fluocinonide.
DB00324. Fluorometholone.
DB00846. Flurandrenolide.
DB00588. Fluticasone Propionate.
DB01319. Fosamprenavir.
DB00947. Fulvestrant.
DB00674. Galantamine.
DB00317. Gefitinib.
DB01241. Gemfibrozil.
DB00889. Granisetron.
DB00365. Grepafloxacin.
DB01218. Halofantrine.
DB00956. Hydrocodone.
DB00769. Hydrocortamate.
DB00741. Hydrocortisone.
DB00327. Hydromorphone.
DB00619. Imatinib.
DB00224. Indinavir.
DB00332. Ipratropium.
DB00762. Irinotecan.
DB00883. Isosorbide Dinitrate.
DB01020. Isosorbide Mononitrate.
DB00270. Isradipine.
DB01167. Itraconazole.
DB01026. Ketoconazole.
DB01259. Lapatinib.
DB00528. Lercanidipine.
DB01006. Letrozole.
DB01002. Levobupivacaine.
DB01227. Levomethadyl Acetate.
DB00451. Levothyroxine.
DB01206. Lomustine.
DB00836. Loperamide.
DB01601. Lopinavir.
DB00455. Loratadine.
DB00678. Losartan.
DB00227. Lovastatin.
DB04835. Maraviroc.
DB00470. Marinol.
DB00643. Mebendazole.
DB00603. Medroxyprogesterone.
DB00333. Methadone.
DB00959. Methylprednisolone.
DB01011. Metyrapone.
DB01388. Mibefradil.
DB00683. Midazolam.
DB00834. Mifepristone.
DB00370. Mirtazapine.
DB00745. Modafinil.
DB00764. Mometasone.
DB00471. Montelukast.
DB00731. Nateglinide.
DB01149. Nefazodone.
DB00220. Nelfinavir.
DB00238. Nevirapine.
DB00622. Nicardipine.
DB01115. Nifedipine.
DB00393. Nimodipine.
DB00401. Nisoldipine.
DB01054. Nitrendipine.
DB00717. Norethindrone.
DB00506. Norgestrel.
DB00646. Nystatin.
DB00904. Ondansetron.
DB01062. Oxybutynin.
DB01229. Paclitaxel.
DB01267. Paliperidone.
DB00377. Palonosetron.
DB00213. Pantoprazole.
DB00910. Paricalcitol.
DB00830. Phenmetrazine.
DB00337. Pimecrolimus.
DB01100. Pimozide.
DB01132. Pioglitazone.
DB01263. Posaconazole.
DB01411. Pranlukast.
DB00860. Prednisolone.
DB00635. Prednisone.
DB00433. Prochlorperazine.
DB01224. Quetiapine.
DB00881. Quinapril.
DB00468. Quinine.
DB01129. Rabeprazole.
DB00243. Ranolazine.
DB00234. Reboxetine.
DB01256. Retapamulin.
DB00615. Rifabutin.
DB01045. Rifampin.
DB06155. Rimonabant.
DB00503. Ritonavir.
DB00533. Rofecoxib.
DB00778. Roxithromycin.
DB00938. Salmeterol.
DB01232. Saquinavir.
DB06144. Sertindole.
DB01105. Sibutramine.
DB00641. Simvastatin.
DB00877. Sirolimus.
DB01261. Sitagliptin.
DB01591. Solifenacin.
DB00398. Sorafenib.
DB01268. Sunitinib.
DB00864. Tacrolimus.
DB00820. Tadalafil.
DB00675. Tamoxifen.
DB00976. Telithromycin.
DB00251. Terconazole.
DB00342. Terfenadine.
DB00624. Testosterone.
DB00906. Tiagabine.
DB00208. Ticlopidine.
DB00911. Tinidazole.
DB01409. Tiotropium.
DB00932. Tipranavir.
DB00539. Toremifene.
DB00897. Triazolam.
DB01157. Trimetrexate.
DB00197. Troglitazone.
DB00580. Valdecoxib.
DB00862. Vardenafil.
DB00570. Vinblastine.
DB00541. Vincristine.
DB00309. Vindesine.
DB00361. Vinorelbine.
DB00582. Voriconazole.
DB00962. Zaleplon.
DB00744. Zileuton.
DB00246. Ziprasidone.
DB00425. Zolpidem.
DB00909. Zonisamide.
GuidetoPHARMACOLOGY1337.

PTM databases

PhosphoSiteP08684.

Polymorphism databases

DMDM116241312.

Proteomic databases

PaxDbP08684.
PRIDEP08684.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000336411; ENSP00000337915; ENSG00000160868.
GeneID1576.
KEGGhsa:1576.
UCSCuc003urv.2. human.

Organism-specific databases

CTD1576.
GeneCardsGC07M099355.
HGNCHGNC:2637. CYP3A4.
HPACAB033671.
MIM124010. gene.
neXtProtNX_P08684.
PharmGKBPA130.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2124.
HOGENOMHOG000039127.
HOVERGENHBG108567.
InParanoidP08684.
KOK17689.
OMADMECHKK.
OrthoDBEOG744TBS.
PhylomeDBP08684.
TreeFamTF105087.

Enzyme and pathway databases

BioCycMetaCyc:HS08544-MONOMER.
ReactomeREACT_111217. Metabolism.
SABIO-RKP08684.

Gene expression databases

ArrayExpressP08684.
BgeeP08684.
CleanExHS_CYP3A4.
GenevestigatorP08684.

Family and domain databases

Gene3D1.10.630.10. 1 hit.
InterProIPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR008072. Cyt_P450_E_CYP3A.
IPR002402. Cyt_P450_E_grp-II.
[Graphical view]
PfamPF00067. p450. 1 hit.
[Graphical view]
PRINTSPR00464. EP450II.
PR01689. EP450IICYP3A.
PR00385. P450.
SUPFAMSSF48264. SSF48264. 1 hit.
PROSITEPS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP08684.
GeneWikiCYP3A4.
GenomeRNAi1576.
NextBio6475.
PROP08684.
SOURCESearch...

Entry information

Entry nameCP3A4_HUMAN
AccessionPrimary (citable) accession number: P08684
Secondary accession number(s): P05184, Q16757, Q9UK50
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 165 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM