CYP2C9

Protein identityUniProt · HPA

UniProt accession

P11712

Gene

CYP2C9

Ensembl

ENSG00000138109

Chromosome

10

Canonical length

490 aa

Protein class

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

Subcellular location

Vesicles,Plasma membrane

Secretome location

Intracellular and membrane

OverviewNCBI Gene

This gene 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 rifampin. The enzyme is known to metabolize many xenobiotics, including phenytoin, tolbutamide, ibuprofen and S-warfarin. Studies identifying individuals who are poor metabolizers of phenytoin and tolbutamide suggest that this gene is polymorphic. The gene is located within a cluster of cytochrome P450 genes on chromosome 10q24. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

490 residues, UniProt reviewed canonical sequence.

>P11712|CYP2C9
     1  MDSLVVLVLC LSCLLLLSLW RQSSGRGKLP PGPTPLPVIG NILQIGIKDI SKSLTNLSKV
    61  YGPVFTLYFG LKPIVVLHGY EAVKEALIDL GEEFSGRGIF PLAERANRGF GIVFSNGKKW
   121  KEIRRFSLMT LRNFGMGKRS IEDRVQEEAR CLVEELRKTK ASPCDPTFIL GCAPCNVICS
   181  IIFHKRFDYK DQQFLNLMEK LNENIKILSS PWIQICNNFS PIIDYFPGTH NKLLKNVAFM
   241  KSYILEKVKE HQESMDMNNP QDFIDCFLMK MEKEKHNQPS EFTIESLENT AVDLFGAGTE
   301  TTSTTLRYAL LLLLKHPEVT AKVQEEIERV IGRNRSPCMQ DRSHMPYTDA VVHEVQRYID
   361  LLPTSLPHAV TCDIKFRNYL IPKGTTILIS LTSVLHDNKE FPNPEMFDPH HFLDEGGNFK
   421  KSKYFMPFSA GKRICVGEAL AGMELFLFLT SILQNFNLKS LVDPKNLDTT PVVNGFASVP
   481  PFYQLCFIPV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CYP2C9 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)

0.23

Highest tissue expression

1,608 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CYP2C9.

Disease | GeneticClinVar

1 pathogenic / likely-pathogenic of 60 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Warfarin response

ReferencesPubMed · IEDB

Publications for CYP2C9 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)

1.4

gnomAD pLI

0

gnomAD missense Z

-2.94

DepMap mean gene effect

0.08

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

• cholesterol metabolic process
• epoxygenase P450 pathway
• estrogen metabolic process
• icosanoid biosynthetic process
• long-chain fatty acid biosynthetic process
• monocarboxylic acid metabolic process
• monoterpenoid metabolic process
• omega-hydroxylase P450 pathway
• organofluorine metabolic process
• oxidative demethylation
• steroid metabolic process
• xenobiotic catabolic process
• xenobiotic metabolic process
• urea metabolic process

Molecular functions

• (R)-limonene 6-monooxygenase activity
• (S)-limonene 6-monooxygenase activity
• (S)-limonene 7-monooxygenase activity
• arachidonate 11,12-epoxygenase activity
• arachidonate 14,15-epoxygenase activity
• arachidonate epoxygenase activity
• caffeine oxidase activity
• estrogen 2-hydroxylase activity
• heme binding
• iron ion binding
• monooxygenase activity
• oxidoreductase activity
• 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
• steroid hydroxylase activity

Cellular components

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

Protein domainsUniProt · Pfam · InterPro

• Cytochrome P450
• Cytochrome P450, E-class, group I
• 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
• Oxidoreductase
• Steroid metabolism
• Sterol metabolism