CYP3A4

Protein identityUniProt · HPA

UniProt accession

P08684

Gene

CYP3A4

Ensembl

ENSG00000160868

Chromosome

7

Canonical length

503 aa

Protein class

Cancer-related genes, Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Vesicles,Cytosol

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases that catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and its expression is induced by glucocorticoids and some pharmacological agents. This enzyme is involved in the metabolism of approximately half the drugs in use today, including acetaminophen, codeine, cyclosporin A, diazepam, erythromycin, and chloroquine. The enzyme also metabolizes some steroids and carcinogens. This gene is part of a cluster of cytochrome P450 genes on chromosome 7q21.1. Previously another CYP3A gene, CYP3A3, was thought to exist; however, it is now thought that this sequence represents a transcript variant of CYP3A4. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2020]

Canonical amino-acid sequenceUniProt

503 residues, UniProt reviewed canonical sequence.

>P08684|CYP3A4
     1  MALIPDLAME TWLLLAVSLV LLYLYGTHSH GLFKKLGIPG PTPLPFLGNI LSYHKGFCMF
    61  DMECHKKYGK VWGFYDGQQP VLAITDPDMI KTVLVKECYS VFTNRRPFGP VGFMKSAISI
   121  AEDEEWKRLR SLLSPTFTSG KLKEMVPIIA QYGDVLVRNL RREAETGKPV TLKDVFGAYS
   181  MDVITSTSFG VNIDSLNNPQ DPFVENTKKL LRFDFLDPFF LSITVFPFLI PILEVLNICV
   241  FPREVTNFLR KSVKRMKESR LEDTQKHRVD FLQLMIDSQN SKETESHKAL SDLELVAQSI
   301  IFIFAGYETT SSVLSFIMYE LATHPDVQQK LQEEIDAVLP NKAPPTYDTV LQMEYLDMVV
   361  NETLRLFPIA MRLERVCKKD VEINGMFIPK GVVVMIPSYA LHRDPKYWTE PEKFLPERFS
   421  KKNKDNIDPY IYTPFGSGPR NCIGMRFALM NMKLALIRVL QNFSFKPCKE TQIPLKLSLG
   481  GLLQPEKPVV LKVESRDGTV SGA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CYP3A4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.25

Highest tissue expression

3,367 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CYP3A4.

Disease | AllUniProt

Conditions CYP3A4 is implicated in, by any mechanism.

• Vitamin D-dependent rickets 3 (VDDR3) MIM:619073

Disease | GeneticClinVar

2 pathogenic / likely-pathogenic of 39 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Vitamin D-dependent rickets, type 3
• Familial hypercholesterolemia

ReferencesPubMed · IEDB

Publications for CYP3A4 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.12

gnomAD pLI

0

gnomAD missense Z

-0.35

DepMap mean gene effect

-0.01

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• aflatoxin metabolic process
• alkaloid catabolic process
• androgen metabolic process
• cholesterol metabolic process
• estrogen metabolic process
• lipid hydroxylation
• lipid metabolic process
• long-chain fatty acid biosynthetic process
• monoterpenoid metabolic process
• oxidative demethylation
• retinoic acid metabolic process
• retinol metabolic process
• steroid catabolic process
• steroid metabolic process
• vitamin D catabolic process
• vitamin D metabolic process
• xenobiotic catabolic process
• xenobiotic metabolic process

Molecular functions

• 1-alpha,25-dihydroxyvitamin D3 23-hydroxylase activity
• anandamide 11,12 epoxidase activity
• anandamide 14,15 epoxidase activity
• anandamide 8,9 epoxidase activity
• caffeine oxidase activity
• enzyme binding
• estrogen 16-alpha-hydroxylase activity
• estrogen 2-hydroxylase activity
• heme binding
• iron ion binding
• monooxygenase activity
• oxidoreductase activity
• oxygen binding
• retinoic acid 4-hydroxylase activity
• steroid binding
• steroid hydroxylase activity
• testosterone 6-beta-hydroxylase activity
• vitamin D 24-hydroxylase activity
• vitamin D3 25-hydroxylase activity
• 1,8-cineole 2-exo-monooxygenase activity
• quinine 3-monooxygenase activity

Cellular components

• cytoplasm
• endoplasmic reticulum membrane
• intracellular membrane-bounded organelle

Protein domainsUniProt · Pfam · InterPro

• Cytochrome P450
• Cytochrome P450, E-class, group II
• Cytochrome P450, E-class, CYP3A
• Cytochrome P450, conserved site
• Cytochrome P450 superfamily
• Cytochrome P450 3A
• Cytochrome P450

KeywordsUniProt

• Endoplasmic reticulum
• Fatty acid metabolism
• Heme
• Iron
• Lipid biosynthesis
• Lipid metabolism
• Membrane
• Metal-binding
• Microsome
• Monooxygenase
• Oxidoreductase
• Steroid biosynthesis
• Steroid metabolism
• Sterol metabolism
• Transmembrane
• Transmembrane helix
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of CYP3A4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• PGRMC1