Tchem CYP2C8 Cytochrome P450 2C8

Protein Summary

Description

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti-cancer drug paclitaxel (taxol). 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 phenobarbital. The enzyme is known to metabolize many xenobiotics, including the anticonvulsive drug mephenytoin, benzo(a)pyrene, 7-ethyoxycoumarin, and the anti-cancer drug taxol. This gene is located within a cluster of cytochrome P450 genes on chromosome 10q24. Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]

Uniprot Accession IDs

• P10632
• A8K9N8
• B0AZN2
• B7Z1F6
• Q5VX93
• Q8WWB1
• Q9UCZ9

Gene Name

• CYP2C8

Ensembl ID

• ENST00000371270
• ENSP00000360317
• ENSG00000138115
• ENST00000535898
• ENSP00000445062

Symbol

• CPC8
• CYPIIC8
• CYP2C8DM
• MP-12/MP-20

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
drug	1
chemical	0.97
disease	0.83
biological term	0.82
molecular function	0.81

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Target Illumination GWAS Analytics (TIGA)

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 523.82   (req: < 5)

Gene RIFs: 121   (req: <= 3)

Antibodies: 200   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 523.82   (req: >= 5)

Gene RIFs: 121   (req: > 3)

Antibodies: 200   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 20

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 5

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 1

Approved Drugs (1)

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1 – 1 of 1

phenelzine

CYP2C8Tchem

Ki : 5.13999987

Active Ligands (5)

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1 – 5 of 5

CHEMBL2036213

CYP2C8Tchem

IC50 : 7.36999989

CHEMBL3911035

CYP2C8Tchem

IC50 : 6.05

CHEMBL3910478

CYP2C8Tchem

IC50 : 6.3

CHEMBL3969750

CYP2C8Tchem

IC50 : 6.52

CHEMBL3925961

CYP2C8Tchem

IC50 : 6.52

GWAS Traits (3)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
testosterone measurement	EFO_0004908	2	2	2		89.3
appendicular lean mass	EFO_0004980	1	1	1		72.9
blood metabolite measurement	EFO_0005664	1	1	2		57.5

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
testosterone measurement	EFO_0004908	2		89.3
appendicular lean mass	EFO_0004980	1		72.9
blood metabolite measurement	EFO_0005664	2		57.5

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Orthologs (3)

1 – 3 of 3

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	cytochrome P450 family 2 subfamily C member 8	VGNC:6150	450909
Macaque	cytochrome P450, family 2, subfamily C, polypeptide 8		678683
Anole lizard	cytochrome P450 2C5		100561707

Species	Name	OMA	EggNOG	Inparanoid
Chimp	cytochrome P450 family 2 subfamily C member 8
Macaque	cytochrome P450, family 2, subfamily C, polypeptide 8
Anole lizard	cytochrome P450 2C5

Protein Data Bank (5)

1 – 5 of 5

PDB Structure Id	Ligand	Method	Resolution (Å)	M.W. (kDa)	Pub Year	Title

PDB Structure Id	M.W.	Resolution	Pub Year

Pathways (30)

Reactome (15)

KEGG (7)

PathwayCommons (1)

WikiPathways (7)

Arachidonic acid metabolism (R-HSA-2142753)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Arachidonic acid metabolism	59 targets	R-HSA-2142753
Reactome	Biological oxidations	221 targets	R-HSA-211859
Reactome	Biosynthesis of DHA-derived SPMs	17 targets	R-HSA-9018677
Reactome	Biosynthesis of maresin-like SPMs	6 targets	R-HSA-9027307
Reactome	Biosynthesis of maresins	8 targets	R-HSA-9018682

Name	Explore in Pharos	Explore in Source
Arachidonic acid metabolism	59 targets	R-HSA-2142753
Biological oxidations	221 targets	R-HSA-211859
Biosynthesis of DHA-derived SPMs	17 targets	R-HSA-9018677
Biosynthesis of maresin-like SPMs	6 targets	R-HSA-9027307
Biosynthesis of maresins	8 targets	R-HSA-9018682

Gene Ontology Terms (24)

Functions (9)

Components (4)

Processes (11)

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1 – 9 of 9

GO Term	Evidence	Assigned by
caffeine oxidase activity	Inferred from Direct Assay (IDA)	BHF-UCL
estrogen 16-alpha-hydroxylase activity	Inferred from Direct Assay (IDA)	BHF-UCL
monooxygenase activity	Inferred from Direct Assay (IDA)	BHF-UCL
arachidonic acid epoxygenase activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
heme binding	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
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	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
steroid hydroxylase activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
aromatase activity	Inferred from Electronic Annotation (IEA)	UniProtKB-EC
iron ion binding	Inferred from Electronic Annotation (IEA)	InterPro

Protein-Protein Interactions (132)

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1 – 10 of 132

• See Interactions on String-DB

EPHX1

Tchem

Family: Enzyme

Novelty: 0.00220169

Score: 0.949

Data Source: STRINGDB

EPHX2

Tchem

Family: Enzyme

Novelty: 0.00430741

Score: 0.949

Data Source: STRINGDB

CYP3A4

Tclin

Family: Enzyme

Novelty: 0.00015515

Score: 0.948

Data Source: STRINGDB

CYP4A11

Tbio

Novelty: 0.01121493

Score: 0.944

Data Source: STRINGDB

CYP4F2

Tchem

Family: Enzyme

Novelty: 0.0050361

Score: 0.937

Data Source: STRINGDB

CYP4F3

Tbio

Family: Enzyme

Novelty: 0.01392719

Score: 0.933

Data Source: STRINGDB

PTGS2

Tclin

Family: Enzyme

Novelty: 0.00007089

Score: 0.93

Data Source: STRINGDB

CYP1A2

Tchem

Novelty: 0.00034756

Score: 0.928

Data Source: STRINGDB

CYP4F8

Tbio

Novelty: 0.06814051

Score: 0.926

Data Source: STRINGDB

CYP1A1

Tchem

Novelty: 0.0002404

Score: 0.924

Data Source: STRINGDB

Publication Statistics

PubMed Score  523.82

PubMed score by year

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PubTator Score  435.9

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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3D-structure
Alternative splicing
Complete proteome
Direct protein sequencing
Endoplasmic reticulum
Heme
Iron
Membrane
Metal-binding
Microsome

GWAS Trait Find Similar Targets

appendicular lean mass
blood metabolite measurement
testosterone measurement