CYP2A6

Protein identityUniProt · HPA

UniProt accession

P11509

Gene

CYP2A6

Ensembl

ENSG00000255974

Chromosome

19

Canonical length

494 aa

Protein class

Human disease related genes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins

OverviewNCBI Gene

This gene, CYP2A6, encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which 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 phenobarbital. The enzyme is known to hydroxylate coumarin, and also metabolizes nicotine, aflatoxin B1, nitrosamines, and some pharmaceuticals. Individuals with certain allelic variants are said to have a poor metabolizer phenotype, meaning they do not efficiently metabolize coumarin or nicotine. This gene is part of a large cluster of cytochrome P450 genes from the CYP2A, CYP2B and CYP2F subfamilies on chromosome 19q. The gene was formerly referred to as CYP2A3; however, it has been renamed CYP2A6. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

494 residues, UniProt reviewed canonical sequence.

>P11509|CYP2A6
     1  MLASGMLLVA LLVCLTVMVL MSVWQQRKSK GKLPPGPTPL PFIGNYLQLN TEQMYNSLMK
    61  ISERYGPVFT IHLGPRRVVV LCGHDAVREA LVDQAEEFSG RGEQATFDWV FKGYGVVFSN
   121  GERAKQLRRF SIATLRDFGV GKRGIEERIQ EEAGFLIDAL RGTGGANIDP TFFLSRTVSN
   181  VISSIVFGDR FDYKDKEFLS LLRMMLGIFQ FTSTSTGQLY EMFSSVMKHL PGPQQQAFQL
   241  LQGLEDFIAK KVEHNQRTLD PNSPRDFIDS FLIRMQEEEK NPNTEFYLKN LVMTTLNLFI
   301  GGTETVSTTL RYGFLLLMKH PEVEAKVHEE IDRVIGKNRQ PKFEDRAKMP YMEAVIHEIQ
   361  RFGDVIPMSL ARRVKKDTKF RDFFLPKGTE VYPMLGSVLR DPSFFSNPQD FNPQHFLNEK
   421  GQFKKSDAFV PFSIGKRNCF GEGLARMELF LFFTTVMQNF RLKSSQSPKD IDVSPKHVGF
   481  ATIPRNYTMS FLPR

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CYP2A6 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

0

Mean surface accessibility (rSASA)

0.22

Highest tissue expression

1,508 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CYP2A6.

Disease | ImmuneIEDB

Conditions an epitope on CYP2A6 was assayed in.

• hepatitis C T cell

ReferencesPubMed · IEDB

Publications for CYP2A6 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. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). 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)

1.2

gnomAD pLI

0

gnomAD missense Z

-1.53

DepMap mean gene effect

0.03

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

• coumarin metabolic process
• epoxygenase P450 pathway
• steroid metabolic process
• xenobiotic catabolic process
• xenobiotic metabolic process
• coumarin catabolic process

Molecular functions

• arachidonate epoxygenase activity
• coumarin 7-hydroxylase activity
• enzyme binding
• heme binding
• iron ion binding
• 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

Cellular components

• cytoplasm
• cytoplasmic microtubule
• endoplasmic reticulum membrane

Protein domainsUniProt · Pfam · InterPro

• Cytochrome P450
• Cytochrome P450, E-class, group I
• Cytochrome P450, E-class, group I, CYP2A-like
• Cytochrome P450, conserved site
• Cytochrome P450 superfamily
• Cytochrome P450 family 2
• Cytochrome P450

KeywordsUniProt

• Endoplasmic reticulum
• Heme
• Iron
• Lipid metabolism
• Membrane
• Metal-binding
• Microsome
• Monooxygenase
• NADP
• Oxidoreductase