P08684 (CP3A4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	503 AA.
Sequence status	Complete.
Protein existence	Evidence 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 CYP3A43 exon 1 joined to CYP3A4 exons 2-13) exhibits 6-beta-hydroxylase activity, while a shorter CYP3A43 exon 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 component	Endoplasmic reticulum Membrane Microsome
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	Heme Iron Metal-binding NADP
Molecular function	Monooxygenase Oxidoreductase
PTM	Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	alkaloid catabolic process Inferred from direct assay PubMed 15039299. Source: BHF-UCL androgen metabolic process Traceable author statement PubMed 19651758. 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 monoterpenoid metabolic process Inferred from direct assay PubMed 16401082. Source: BHF-UCL oxidative demethylation Inferred from direct assay PubMed 15039299PubMed 18619574. Source: BHF-UCL steroid catabolic process Inferred from mutant phenotype PubMed 18356043. Source: BHF-UCL vitamin D metabolic process Inferred by curator PubMed 15546903. Source: BHF-UCL xenobiotic metabolic process Traceable author statement. Source: Reactome
Cellular_component	cell surface Inferred from direct assay PubMed 12493773. Source: UniProtKB endoplasmic reticulum membrane Traceable author statement. Source: Reactome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	albendazole monooxygenase activity Inferred from electronic annotation. Source: EC caffeine oxidase activity Inferred from direct assay PubMed 18619574. Source: BHF-UCL electron carrier activity Inferred from electronic annotation. Source: InterPro heme binding Inferred from electronic annotation. Source: InterPro iron ion binding Inferred from direct assay Ref.24. 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: EC steroid binding Inferred from direct assay Ref.24. Source: BHF-UCL taurochenodeoxycholate 6alpha-hydroxylase activity Inferred from electronic annotation. Source: 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 503

503

Cytochrome P450 3A4

PRO_0000051786

Regions

Transmembrane

2 – 22

21

Helical; Potential

Sites

Metal binding

442

1

Iron (heme axial ligand)

Natural variations

Natural variant

15

1

L → P in allele CYP3A4*14. Ref.28
Corresponds to variant rs12721634 [ dbSNP | Ensembl ].

VAR_011597

Natural variant

56

1

G → D in allele CYP3A4*7. Ref.27
Corresponds to variant rs56324128 [ dbSNP | Ensembl ].

VAR_011598

Natural variant

96

1

K → E.
Corresponds to variant rs3091339 [ dbSNP | Ensembl ].

VAR_037547

Natural variant

118

1

I → V in allele CYP3A4*4. Ref.8
Corresponds to variant rs55951658 [ dbSNP | Ensembl ].

VAR_011599

Natural variant

130

1

R → Q in allele CYP3A4*8. Ref.27

VAR_011600

Natural variant

162

1

R → Q in allele CYP3A4*15. Ref.26 Ref.28
Corresponds to variant rs4986907 [ dbSNP | Ensembl ].

VAR_011601

Natural variant

170

1

V → I in allele CYP3A4*9. Ref.27

VAR_011602

Natural variant

174

1

D → H in allele CYP3A4*10. Ref.27 Ref.28 Ref.29

VAR_011603

Natural variant

185

1

T → S in allele CYP3A4*16. Ref.28 Ref.29
Corresponds to variant rs12721627 [ dbSNP | Ensembl ].

VAR_011604

Natural variant

189

1

F → S in allele CYP3A4*17; exhibits lower turnover numbers for testosterone and chlorpyrifos. Ref.26
Corresponds to variant rs4987161 [ dbSNP | Ensembl ].

VAR_014322

Natural variant

218

1

P → R in allele CYP3A4*5. Ref.8
Corresponds to variant rs55901263 [ dbSNP | Ensembl ].

VAR_011605

Natural variant

222

1

S → P in allele CYP3A4*2; exhibits a lower intrinsic clearance toward nifedipine. Ref.25
Corresponds to variant rs55785340 [ dbSNP | Ensembl ].

VAR_008363

Natural variant

252

1

S → A. Ref.1
Corresponds to variant rs3208363 [ dbSNP | Ensembl ].

VAR_037548

Natural variant

293

1

L → 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 variant

349

1

T → N.
Corresponds to variant rs10250778 [ dbSNP | Ensembl ].

VAR_037549

Natural variant

363

1

T → M in allele CYP3A4*11; unstable form. Ref.27

VAR_011606

Natural variant

373

1

L → F in allele CYP3A4*12; has an altered testosterone hydroxylase activity. Ref.27 Ref.28
Corresponds to variant rs12721629 [ dbSNP | Ensembl ].

VAR_011607

Natural variant

416

1

P → L in allele CYP3A4*13; lack of expression. Ref.27
Corresponds to variant rs4986909 [ dbSNP | Ensembl ].

VAR_011608

Natural variant

431

1

I → T. Ref.3 Ref.5
Corresponds to variant rs1041988 [ dbSNP | Ensembl ].

VAR_037550

Natural variant

445

1

M → T in allele CYP3A4*3. Ref.25 Ref.26
Corresponds to variant rs4986910 [ dbSNP | Ensembl ].

VAR_008364

Natural variant

467

1

P → S in allele CYP3A4*19. Ref.26
Corresponds to variant rs4986913 [ dbSNP | Ensembl ].

VAR_014324

Experimental info

Sequence conflict

3

1

L → V in AAA35747. Ref.5

Sequence conflict

12

1

W → R in AAF13598. Ref.9

Sequence conflict

72

1

W → C in AAA35747. Ref.5

Sequence conflict

92

1

T → L in BAA00001. Ref.1

Sequence conflict

92

1

T → L in AAA35742. Ref.1

Sequence conflict

106

1

R → E in BAA00001. Ref.1

Sequence conflict

106

1

R → E in AAA35742. Ref.1

Sequence conflict

164

1

A → R in BAA00001. Ref.1

Sequence conflict

164

1

A → R in AAA35742. Ref.1

Sequence conflict

187

1

T → S in BAA00001. Ref.1

Sequence conflict

187

1

T → S in AAA35742. Ref.1

Sequence conflict

193

1

I → V in BAA00001. Ref.1

Sequence conflict

193

1

I → V in AAA35742. Ref.1

Sequence conflict

203

1

F → L in BAA00001. Ref.1

Sequence conflict

203

1

F → L in AAA35742. Ref.1

Sequence conflict

224 – 225

2

TV → I in AAA35747. Ref.5

Sequence conflict

279

1

Q → HK in BAA00001. Ref.1

Sequence conflict

279

1

Q → HK in AAA35742. Ref.1

Sequence conflict

307

1

Y → C in AAF13598. Ref.9

Sequence conflict

392

1

V → W in BAA00001. Ref.1

Sequence conflict

392

1

V → W in AAA35742. Ref.1

Sequence conflict

392

1

V → W in AAA35744. Ref.3

Sequence conflict

392

1

V → W in CAA30944. Ref.4

Sequence conflict

392

1

V → W in AAA35747. Ref.5

Secondary structure

1

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503

Helix Strand Turn

Details...

Helix

29 – 31

3

Helix

32 – 36

5

Turn

45 – 47

3

Helix

50 – 55

6

Helix

57 – 68

12

Beta strand

70 – 76

7

Beta strand

79 – 84

6

Helix

87 – 94

8

Turn

95 – 101

7

Helix

112 – 116

5

Turn

118 – 120

3

Helix

123 – 133

11

Helix

134 – 137

4

Helix

139 – 166

28

Helix

172 – 189

18

Helix

195 – 197

3

Helix

202 – 207

6

Helix

218 – 225

8

Helix

229 – 235

7

Helix

243 – 262

20

Helix

271 – 279

9

Helix

292 – 322

31

Helix

325 – 338

14

Turn

340 – 342

3

Helix

347 – 352

6

Helix

354 – 366

13

Beta strand

369 – 371

3

Beta strand

373 – 376

4

Beta strand

381 – 383

3

Beta strand

386 – 388

3

Beta strand

393 – 396

4

Helix

398 – 402

5

Turn

405 – 407

3

Beta strand

408 – 410

3

Helix

416 – 419

4

Helix

421 – 424

4

Turn

429 – 431

3

Helix

438 – 440

3

Helix

445 – 460

16

Beta strand

463 – 466

4

Beta strand

479 – 482

4

Beta strand

485 – 487

3

Beta strand

490 – 495

6

Sequences

	Sequence		Length	Mass (Da)
	P08684 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: 38ED122BF89F74F7	FASTA	503	57,343
	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

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.
[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. 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

Cytochrome P450 Allele Nomenclature Committee

CYP3A4 alleles

Wikipedia

CYP3A4 entry

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.

IPI

IPI00465138.

PIR

A29410.
A29815.

RefSeq

NP_001189784.1. NM_001202855.2.
NP_059488.2. NM_017460.5.

UniGene

Hs.728751.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1TQN	X-ray	2.05	A	24-503	[»]
1W0E	X-ray	2.80	A	25-503	[»]
1W0F	X-ray	2.65	A	25-503	[»]
1W0G	X-ray	2.74	A	25-503	[»]
2J0D	X-ray	2.75	A/B	25-502	[»]
2V0M	X-ray	2.80	A/B/C/D	25-503	[»]
3NXU	X-ray	2.00	A/B	25-503	[»]
3TJS	X-ray	2.25	A	23-503	[»]
3UA1	X-ray	2.15	A	23-503	[»]

ProteinModelPortal

P08684.

ModBase

Search...

Protein-protein interaction databases

IntAct

P08684. 2 interactions.

STRING

9606.ENSP00000337915.

PTM databases

PhosphoSite

P08684.

Polymorphism databases

DMDM

116241312.

Proteomic databases

PaxDb

P08684.

PRIDE

P08684.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000336411; ENSP00000337915; ENSG00000160868.

GeneID

1576.

KEGG

hsa:1576.

UCSC

uc003urv.2. human.

Organism-specific databases

CTD

1576.

GeneCards

GC07M099355.

HGNC

HGNC:2637. CYP3A4.

HPA

CAB033671.

MIM

124010. gene.

neXtProt

NX_P08684.

PharmGKB

PA130.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG2124.

HOGENOM

HOG000039127.

HOVERGEN

HBG108567.

InParanoid

P08684.

KO

K07424.

OMA

DMECHKK.

OrthoDB

EOG4ZW59X.

PhylomeDB

P08684.

Enzyme and pathway databases

BioCyc

MetaCyc:HS08544-MONOMER.

Reactome

REACT_111217. Metabolism.

SABIO-RK

P08684.

Gene expression databases

ArrayExpress

P08684.

Bgee

P08684.

CleanEx

HS_CYP3A4.

Genevestigator

P08684.

GermOnline

ENSG00000160868. Homo sapiens.

Family and domain databases

Gene3D

1.10.630.10. 1 hit.

InterPro

IPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR008072. Cyt_P450_E_CYP3A.
IPR002402. Cyt_P450_E_grp-II.
[Graphical view]

Pfam

PF00067. p450. 1 hit.
[Graphical view]

PRINTS

PR00464. EP450II.
PR01689. EP450IICYP3A.
PR00385. P450.

SUPFAM

SSF48264. Cytochrome_P450. 1 hit.

PROSITE

PS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P08684.

ChEMBL

CHEMBL340.

DrugBank

DB00518. 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.

EvolutionaryTrace

P08684.

GenomeRNAi

1576.

NextBio

6475.

SOURCE

Search...

Entry information

Entry name

CP3A4_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 157 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.