Skip Header

 
Contribute Send feedback

Reviewed, UniProtKB/Swiss-Prot P08684 (CP3A4_HUMAN)

Last modified July 22, 2008. Version 104. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Hide | Top

Names and origin

Protein namesRecommended name:
    Cytochrome P450 3A4
    EC=1.14.13.67
Alternative name(s):
    Quinine 3-monooxygenase
    CYPIIIA4
    Nifedipine oxidase
    Cytochrome P450 3A3
    CYPIIIA3
    HLp
    Taurochenodeoxycholate 6-alpha-hydroxylase
    EC=1.14.13.97
    NF-25
    P450-PCN1
Gene names
Name: CYP3A4
Synonyms: CYP3A3
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Hide | Top

Protein attributes

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

Hide | Top

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. The enzyme also hydroxylates etoposide.

Catalytic activity

Quinine + NADPH + O(2) = 3-hydroxyquinine + NADP(+) + H(2)O.

Taurochenodeoxycholate + NADPH + O(2) = taurohyocholate + NADP(+) + H(2)O.

Lithocholate + NADPH + O(2) = hyodeoxycholate + NADP(+) + H(2)O.

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.

Induction

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

Sequence similarities

Belongs to the cytochrome P450 family.

Hide | Top

Ontologies

Keywords

   Cellular componentEndoplasmic reticulum
Membrane
Microsome
   Coding sequence diversityPolymorphism
   DomainTransmembrane
   LigandHeme
Iron
Metal-binding
NADP
   Molecular functionMonooxygenase
Oxidoreductase
   Technical term3D-structure
Direct protein sequencing

Gene Ontology (GO)

   Biological processlipid metabolic process

Traceable author statement. Source: ProtInc

   Cellular componentcell surface

Inferred from direct assay. Source: UniProtKB

microsome Ref.1

Traceable author statement. Source: ProtInc

   Molecular functionmonooxygenase activity

Inferred from sequence or structural similarity. Source: UniProtKB

oxygen binding Ref.1

Traceable author statement. Source: ProtInc

Complete GO annotation...

Hide | Top

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical view

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 503502Cytochrome P450 3A4

Regions

Transmembrane2 – 2221 Potential

Sites

Metal binding4421Iron (heme axial ligand)

Natural variations

Natural variant151L → P in allele CYP3A4*14. dbSNP rs12721634.
Natural variant561G → D in allele CYP3A4*7.
Natural variant961K → E: dbSNP rs3091339.
Natural variant1181I → V in allele CYP3A4*4.
Natural variant1301R → Q in allele CYP3A4*8.
Natural variant1621R → Q in allele CYP3A4*15. dbSNP rs4986907.
Natural variant1701V → I in allele CYP3A4*9.
Natural variant1741D → H in allele CYP3A4*10.
Natural variant1851T → S in allele CYP3A4*16. dbSNP rs12721627.
Natural variant1891F → S in allele CYP3A4*17; exhibits lower turnover numbers for testosterone and chlorpyrifos. dbSNP rs4987161.
Natural variant2181P → R in allele CYP3A4*5.
Natural variant2221S → P in allele CYP3A4*2; exhibits a lower intrinsic clearance toward nifedipine.
Natural variant2521S → A: dbSNP rs3208363.
Natural variant2931L → P in allele CYP3A4*18; exhibits higher turnover numbers for testosterone and chlorpyrifos. dbSNP rs28371759.
Natural variant3491T → N: dbSNP rs10250778.
Natural variant3631T → M in allele CYP3A4*11; unstable form.
Natural variant3731L → F in allele CYP3A4*12; has an altered testosterone hydroxylase activity. dbSNP rs45614732.
Natural variant4161P → L in allele CYP3A4*13; lack of expression. dbSNP rs4986909.
Natural variant4311I → T: dbSNP rs1041988.
Natural variant4451M → T in allele CYP3A4*3. dbSNP rs4986910.
Natural variant4671P → S in allele CYP3A4*19. dbSNP rs4986913.

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 and AAA35742. Ref.1
Sequence conflict1061R → E in BAA00001 and AAA35742. Ref.1
Sequence conflict1641A → R in BAA00001 and AAA35742. Ref.1
Sequence conflict1871T → S in BAA00001 and AAA35742. Ref.1
Sequence conflict1931I → V in BAA00001 and AAA35742. Ref.1
Sequence conflict2031F → L in BAA00001 and AAA35742. Ref.1
Sequence conflict224 – 2252TV → I in AAA35747. Ref.5
Sequence conflict2791Q → HK in BAA00001 and AAA35742. Ref.1
Sequence conflict3071Y → C in AAF13598. Ref.9
Sequence conflict3921V → W in BAA00001 and 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

1 .................................................................................... 503
Helix Strand Turn

Details...