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P08684

- CP3A4_HUMAN

UniProt

P08684 - CP3A4_HUMAN

Protein

Cytochrome P450 3A4

Gene

CYP3A4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 169 (01 Oct 2014)
      Sequence version 4 (23 Jan 2007)
      Previous versions | rss
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    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.1 Publication

    Catalytic activityi

    Quinine + NADPH + O2 = 3-hydroxyquinine + NADP+ + H2O.1 Publication
    Taurochenodeoxycholate + NADPH + O2 = taurohyocholate + NADP+ + H2O.1 Publication
    Lithocholate + NADPH + O2 = hyodeoxycholate + NADP+ + H2O.1 Publication
    Albendazole + NADPH + O2 = albendazole S-oxide + NADP+ + H2O.1 Publication
    1,8-cineole + NADPH + O2 = 2-exo-hydroxy-1,8-cineole + NADP+ + H2O.1 Publication

    Cofactori

    Heme group.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi442 – 4421Iron (heme axial ligand)

    GO - Molecular functioni

    1. albendazole monooxygenase activity Source: UniProtKB-EC
    2. caffeine oxidase activity Source: BHF-UCL
    3. enzyme binding Source: BHF-UCL
    4. heme binding Source: InterPro
    5. iron ion binding Source: BHF-UCL
    6. monooxygenase activity Source: UniProtKB
    7. oxidoreductase activity Source: BHF-UCL
    8. 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
    9. oxygen binding Source: ProtInc
    10. quinine 3-monooxygenase activity Source: UniProtKB-EC
    11. steroid binding Source: BHF-UCL
    12. steroid hydroxylase activity Source: BHF-UCL
    13. taurochenodeoxycholate 6alpha-hydroxylase activity Source: UniProtKB-EC
    14. testosterone 6-beta-hydroxylase activity Source: BHF-UCL
    15. vitamin D 24-hydroxylase activity Source: BHF-UCL
    16. vitamin D3 25-hydroxylase activity Source: BHF-UCL

    GO - Biological processi

    1. alkaloid catabolic process Source: BHF-UCL
    2. androgen metabolic process Source: BHF-UCL
    3. calcitriol biosynthetic process from calciol Source: GOC
    4. drug catabolic process Source: BHF-UCL
    5. drug metabolic process Source: BHF-UCL
    6. exogenous drug catabolic process Source: BHF-UCL
    7. heterocycle metabolic process Source: BHF-UCL
    8. lipid metabolic process Source: ProtInc
    9. monoterpenoid metabolic process Source: BHF-UCL
    10. oxidation-reduction process Source: BHF-UCL
    11. oxidative demethylation Source: BHF-UCL
    12. small molecule metabolic process Source: Reactome
    13. steroid catabolic process Source: BHF-UCL
    14. steroid metabolic process Source: BHF-UCL
    15. vitamin D metabolic process Source: BHF-UCL
    16. xenobiotic metabolic process Source: Reactome

    Keywords - Molecular functioni

    Monooxygenase, Oxidoreductase

    Keywords - Ligandi

    Heme, Iron, Metal-binding, NADP

    Enzyme and pathway databases

    BioCyciMetaCyc:HS08544-MONOMER.
    ReactomeiREACT_13543. Xenobiotics.
    SABIO-RKP08684.

    Names & Taxonomyi

    Protein namesi
    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 namesi
    Name:CYP3A4
    Synonyms:CYP3A3
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 7

    Organism-specific databases

    HGNCiHGNC:2637. CYP3A4.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: BHF-UCL
    2. endoplasmic reticulum membrane Source: Reactome
    3. integral component of membrane Source: UniProtKB-KW
    4. intracellular membrane-bounded organelle Source: ProtInc

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane, Microsome

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA130.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed2 Publications
    Chaini2 – 503502Cytochrome P450 3A4PRO_0000051786Add
    BLAST

    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.
    PRIDEiP08684.

    PTM databases

    PhosphoSiteiP08684.

    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

    ArrayExpressiP08684.
    BgeeiP08684.
    CleanExiHS_CYP3A4.
    GenevestigatoriP08684.

    Organism-specific databases

    HPAiCAB033671.

    Interactioni

    Protein-protein interaction databases

    BioGridi107948. 9 interactions.
    IntActiP08684. 2 interactions.
    STRINGi9606.ENSP00000337915.

    Structurei

    Secondary structure

    1
    503
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi29 – 313
    Helixi32 – 365
    Turni45 – 473
    Helixi50 – 556
    Helixi57 – 6812
    Beta strandi70 – 767
    Beta strandi79 – 846
    Helixi87 – 948
    Turni95 – 1017
    Helixi112 – 1165
    Turni118 – 1203
    Helixi123 – 13311
    Helixi134 – 1374
    Helixi139 – 16628
    Helixi172 – 18918
    Helixi195 – 1973
    Helixi202 – 2076
    Beta strandi209 – 2124
    Beta strandi215 – 2173
    Helixi218 – 2258
    Helixi229 – 2357
    Helixi243 – 26220
    Helixi271 – 2799
    Helixi292 – 32231
    Helixi325 – 33814
    Turni340 – 3423
    Helixi347 – 3526
    Helixi354 – 36613
    Beta strandi369 – 3713
    Beta strandi373 – 3764
    Beta strandi381 – 3833
    Beta strandi386 – 3883
    Beta strandi393 – 3964
    Helixi398 – 4025
    Turni405 – 4073
    Beta strandi408 – 4103
    Helixi416 – 4194
    Helixi421 – 4244
    Turni429 – 4313
    Helixi438 – 4403
    Helixi445 – 46016
    Beta strandi463 – 4664
    Beta strandi469 – 4713
    Beta strandi479 – 4824
    Beta strandi485 – 4873
    Beta strandi490 – 4956

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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-ray2.25A1-503[»]
    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[»]
    ProteinModelPortaliP08684.
    SMRiP08684. Positions 28-499.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP08684.

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei2 – 2221HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the cytochrome P450 family.Curated

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG2124.
    HOGENOMiHOG000039127.
    HOVERGENiHBG108567.
    InParanoidiP08684.
    KOiK17689.
    OMAiDMECHKK.
    OrthoDBiEOG744TBS.
    PhylomeDBiP08684.
    TreeFamiTF105087.

    Family and domain databases

    Gene3Di1.10.630.10. 1 hit.
    InterProiIPR001128. Cyt_P450.
    IPR017972. Cyt_P450_CS.
    IPR008072. Cyt_P450_E_CYP3A.
    IPR002402. Cyt_P450_E_grp-II.
    [Graphical view]
    PfamiPF00067. p450. 1 hit.
    [Graphical view]
    PRINTSiPR00464. EP450II.
    PR01689. EP450IICYP3A.
    PR00385. P450.
    SUPFAMiSSF48264. SSF48264. 1 hit.
    PROSITEiPS00086. CYTOCHROME_P450. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

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

    P08684-1 [UniParc]FASTAAdd to Basket

    « Hide

    MALIPDLAME TWLLLAVSLV LLYLYGTHSH GLFKKLGIPG PTPLPFLGNI    50
    LSYHKGFCMF DMECHKKYGK VWGFYDGQQP VLAITDPDMI KTVLVKECYS 100
    VFTNRRPFGP VGFMKSAISI AEDEEWKRLR SLLSPTFTSG KLKEMVPIIA 150
    QYGDVLVRNL RREAETGKPV TLKDVFGAYS MDVITSTSFG VNIDSLNNPQ 200
    DPFVENTKKL LRFDFLDPFF LSITVFPFLI PILEVLNICV FPREVTNFLR 250
    KSVKRMKESR LEDTQKHRVD FLQLMIDSQN SKETESHKAL SDLELVAQSI 300
    IFIFAGYETT SSVLSFIMYE LATHPDVQQK LQEEIDAVLP NKAPPTYDTV 350
    LQMEYLDMVV NETLRLFPIA MRLERVCKKD VEINGMFIPK GVVVMIPSYA 400
    LHRDPKYWTE PEKFLPERFS KKNKDNIDPY IYTPFGSGPR NCIGMRFALM 450
    NMKLALIRVL QNFSFKPCKE TQIPLKLSLG GLLQPEKPVV LKVESRDGTV 500
    SGA 503
    Length:503
    Mass (Da):57,343
    Last modified:January 23, 2007 - v4
    Checksum:i38ED122BF89F74F7
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti3 – 31L → V in AAA35747. (PubMed:2463251)Curated
    Sequence conflicti12 – 121W → R in AAF13598. 1 PublicationCurated
    Sequence conflicti72 – 721W → C in AAA35747. (PubMed:2463251)Curated
    Sequence conflicti92 – 921T → L in BAA00001. (PubMed:3460094)Curated
    Sequence conflicti92 – 921T → L in AAA35742. (PubMed:3460094)Curated
    Sequence conflicti106 – 1061R → E in BAA00001. (PubMed:3460094)Curated
    Sequence conflicti106 – 1061R → E in AAA35742. (PubMed:3460094)Curated
    Sequence conflicti164 – 1641A → R in BAA00001. (PubMed:3460094)Curated
    Sequence conflicti164 – 1641A → R in AAA35742. (PubMed:3460094)Curated
    Sequence conflicti187 – 1871T → S in BAA00001. (PubMed:3460094)Curated
    Sequence conflicti187 – 1871T → S in AAA35742. (PubMed:3460094)Curated
    Sequence conflicti193 – 1931I → V in BAA00001. (PubMed:3460094)Curated
    Sequence conflicti193 – 1931I → V in AAA35742. (PubMed:3460094)Curated
    Sequence conflicti203 – 2031F → L in BAA00001. (PubMed:3460094)Curated
    Sequence conflicti203 – 2031F → L in AAA35742. (PubMed:3460094)Curated
    Sequence conflicti224 – 2252TV → I in AAA35747. (PubMed:2463251)Curated
    Sequence conflicti279 – 2791Q → HK in BAA00001. (PubMed:3460094)Curated
    Sequence conflicti279 – 2791Q → HK in AAA35742. (PubMed:3460094)Curated
    Sequence conflicti307 – 3071Y → C in AAF13598. 1 PublicationCurated
    Sequence conflicti392 – 3921V → W in BAA00001. (PubMed:3460094)Curated
    Sequence conflicti392 – 3921V → W in AAA35742. (PubMed:3460094)Curated
    Sequence conflicti392 – 3921V → W in AAA35744. (PubMed:3464943)Curated
    Sequence conflicti392 – 3921V → W in CAA30944. (PubMed:2563251)Curated
    Sequence conflicti392 – 3921V → W in AAA35747. (PubMed:2463251)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti15 – 151L → P in allele CYP3A4*14. 1 Publication
    Corresponds to variant rs12721634 [ dbSNP | Ensembl ].
    VAR_011597
    Natural varianti56 – 561G → D in allele CYP3A4*7. 1 Publication
    Corresponds to variant rs56324128 [ dbSNP | Ensembl ].
    VAR_011598
    Natural varianti96 – 961K → E.
    Corresponds to variant rs3091339 [ dbSNP | Ensembl ].
    VAR_037547
    Natural varianti118 – 1181I → V in allele CYP3A4*4. 1 Publication
    Corresponds to variant rs55951658 [ dbSNP | Ensembl ].
    VAR_011599
    Natural varianti130 – 1301R → Q in allele CYP3A4*8. 1 Publication
    VAR_011600
    Natural varianti162 – 1621R → Q in allele CYP3A4*15. 2 Publications
    Corresponds to variant rs4986907 [ dbSNP | Ensembl ].
    VAR_011601
    Natural varianti170 – 1701V → I in allele CYP3A4*9. 1 Publication
    VAR_011602
    Natural varianti174 – 1741D → H in allele CYP3A4*10. 3 Publications
    Corresponds to variant rs4986908 [ dbSNP | Ensembl ].
    VAR_011603
    Natural varianti185 – 1851T → S in allele CYP3A4*16. 2 Publications
    Corresponds to variant rs12721627 [ dbSNP | Ensembl ].
    VAR_011604
    Natural varianti189 – 1891F → S in allele CYP3A4*17; exhibits lower turnover numbers for testosterone and chlorpyrifos. 1 Publication
    Corresponds to variant rs4987161 [ dbSNP | Ensembl ].
    VAR_014322
    Natural varianti218 – 2181P → R in allele CYP3A4*5. 1 Publication
    Corresponds to variant rs55901263 [ dbSNP | Ensembl ].
    VAR_011605
    Natural varianti222 – 2221S → P in allele CYP3A4*2; exhibits a lower intrinsic clearance toward nifedipine. 1 Publication
    Corresponds to variant rs55785340 [ dbSNP | Ensembl ].
    VAR_008363
    Natural varianti252 – 2521S → A.1 Publication
    Corresponds to variant rs3208363 [ dbSNP | Ensembl ].
    VAR_037548
    Natural varianti293 – 2931L → P in allele CYP3A4*18; exhibits higher turnover numbers for testosterone and chlorpyrifos. 2 Publications
    Corresponds to variant rs28371759 [ dbSNP | Ensembl ].
    VAR_014323
    Natural varianti349 – 3491T → N.
    Corresponds to variant rs10250778 [ dbSNP | Ensembl ].
    VAR_037549
    Natural varianti363 – 3631T → M in allele CYP3A4*11; unstable form. 1 Publication
    Corresponds to variant rs67784355 [ dbSNP | Ensembl ].
    VAR_011606
    Natural varianti373 – 3731L → F in allele CYP3A4*12; has an altered testosterone hydroxylase activity. 2 Publications
    Corresponds to variant rs12721629 [ dbSNP | Ensembl ].
    VAR_011607
    Natural varianti416 – 4161P → L in allele CYP3A4*13; lack of expression. 1 Publication
    Corresponds to variant rs4986909 [ dbSNP | Ensembl ].
    VAR_011608
    Natural varianti431 – 4311I → T.2 Publications
    Corresponds to variant rs1041988 [ dbSNP | Ensembl ].
    VAR_037550
    Natural varianti445 – 4451M → T in allele CYP3A4*3. 2 Publications
    Corresponds to variant rs4986910 [ dbSNP | Ensembl ].
    VAR_008364
    Natural varianti467 – 4671P → S in allele CYP3A4*19. 1 Publication
    Corresponds to variant rs4986913 [ dbSNP | Ensembl ].
    VAR_014324

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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.
    UCSCiuc003urv.2. human.

    Polymorphism databases

    DMDMi116241312.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    Cytochrome P450 Allele Nomenclature Committee

    CYP3A4 alleles

    Wikipedia

    CYP3A4 entry

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS5674.1.
    PIRi A29410.
    A29815.
    RefSeqi NP_001189784.1. NM_001202855.2.
    NP_059488.2. NM_017460.5.
    UniGenei Hs.728751.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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 25-503 [» ]
    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 1-503 [» ]
    3UA1 X-ray 2.15 A 23-503 [» ]
    4I3Q X-ray 2.60 A 23-503 [» ]
    4I4G X-ray 2.72 A 23-503 [» ]
    4I4H X-ray 2.90 A 23-503 [» ]
    4K9T X-ray 2.50 A 23-503 [» ]
    4K9U X-ray 2.85 A 23-503 [» ]
    4K9V X-ray 2.60 A 23-503 [» ]
    4K9W X-ray 2.40 A/B/C/D 23-503 [» ]
    4K9X X-ray 2.76 A 23-503 [» ]
    ProteinModelPortali P08684.
    SMRi P08684. Positions 28-499.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107948. 9 interactions.
    IntActi P08684. 2 interactions.
    STRINGi 9606.ENSP00000337915.

    Chemistry

    BindingDBi P08684.
    ChEMBLi CHEMBL2364675.
    DrugBanki 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.
    GuidetoPHARMACOLOGYi 1337.

    PTM databases

    PhosphoSitei P08684.

    Polymorphism databases

    DMDMi 116241312.

    Proteomic databases

    PaxDbi P08684.
    PRIDEi P08684.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000336411 ; ENSP00000337915 ; ENSG00000160868 .
    GeneIDi 1576.
    KEGGi hsa:1576.
    UCSCi uc003urv.2. human.

    Organism-specific databases

    CTDi 1576.
    GeneCardsi GC07M099355.
    HGNCi HGNC:2637. CYP3A4.
    HPAi CAB033671.
    MIMi 124010. gene.
    neXtProti NX_P08684.
    PharmGKBi PA130.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG2124.
    HOGENOMi HOG000039127.
    HOVERGENi HBG108567.
    InParanoidi P08684.
    KOi K17689.
    OMAi DMECHKK.
    OrthoDBi EOG744TBS.
    PhylomeDBi P08684.
    TreeFami TF105087.

    Enzyme and pathway databases

    BioCyci MetaCyc:HS08544-MONOMER.
    Reactomei REACT_13543. Xenobiotics.
    SABIO-RK P08684.

    Miscellaneous databases

    EvolutionaryTracei P08684.
    GeneWikii CYP3A4.
    GenomeRNAii 1576.
    NextBioi 6475.
    PROi P08684.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P08684.
    Bgeei P08684.
    CleanExi HS_CYP3A4.
    Genevestigatori P08684.

    Family and domain databases

    Gene3Di 1.10.630.10. 1 hit.
    InterProi IPR001128. Cyt_P450.
    IPR017972. Cyt_P450_CS.
    IPR008072. Cyt_P450_E_CYP3A.
    IPR002402. Cyt_P450_E_grp-II.
    [Graphical view ]
    Pfami PF00067. p450. 1 hit.
    [Graphical view ]
    PRINTSi PR00464. EP450II.
    PR01689. EP450IICYP3A.
    PR00385. P450.
    SUPFAMi SSF48264. SSF48264. 1 hit.
    PROSITEi PS00086. CYTOCHROME_P450. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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. 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. 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. 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.

    Entry informationi

    Entry nameiCP3A4_HUMAN
    AccessioniPrimary (citable) accession number: P08684
    Secondary accession number(s): P05184, Q16757, Q9UK50
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 1, 1988
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 169 of the entry and version 4 of the sequence. [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

    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

    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

    External Data

    Dasty 3