Tchem CYP2A6 Cytochrome P450 2A6

Protein Summary

Description

Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase. Acts as a 1,4-cineole 2-exo-monooxygenase. Possesses low phenacetin O-deethylation activity. 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]

Uniprot Accession IDs

• P11509
• A7YAE5
• B2R7F6
• P00190
• P10890
• Q16803
• Q4VAT9
• Q4VAU0
• Q4VAU1
• Q9H1Z7
• Q9UCU0
• Q9UK48

Gene Name

• CYP2A6

Ensembl ID

• ENST00000301141
• ENSP00000301141
• ENSG00000255974

Symbol

• CYP2A3
• CPA6
• CYP2A
• CYP2A3
• P450PB
• CYPIIA6
• P450C2A

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
drug	1
chemical	0.99
biological term	0.91
co-expressed gene	0.82
molecular function	0.79

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: 733.85   (req: < 5)

Gene RIFs: 190   (req: <= 3)

Antibodies: 407   (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: 733.85   (req: >= 5)

Gene RIFs: 190   (req: > 3)

Antibodies: 407   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 16

Tchem

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

Active Ligands: 32

Tclin

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

Active Drug: 0

Active Ligands (32)

Explore Active Ligands

1 – 10 of 32

CHEMBL542118,CHEMBL313833

CYP2A6Tchem

IC50: 7.1

CHEMBL441367

CYP2A6Tchem

IC50: 6.8

CHEMBL178090

CYP2A6Tchem

Ki: 7.4000001

CHEMBL359657

CYP2A6Tchem

Ki: 7.69999981

CHEMBL179669

CYP2A6Tchem

IC50: 6.7

CHEMBL3358196

CYP2A6Tchem

Ki: 6.7

CHEMBL3358216

CYP2A6Tchem

Ki: 7

CHEMBL3358215

CYP2A6Tchem

Ki: 7.16

CHEMBL3640760

CYP2A6Tchem

IC50: 6

CHEMBL217125

CYP2A6Tchem

IC50: 6.1

Protein Data Bank (11)

1 – 5 of 11

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

PDB Structure Id	M.W.	Resolution	Pub Year

Pathways (59)

Reactome (6)

KEGG (7)

PathwayCommons (2)

WikiPathways (44)

Biological oxidations (R-HSA-211859)

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Items per page:

5

1 – 5 of 6

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Biological oxidations	221 targets	R-HSA-211859
Reactome	CYP2E1 reactions	11 targets	R-HSA-211999
Reactome	Cytochrome P450 - arranged by substrate type	65 targets	R-HSA-211897
Reactome	Metabolism	2112 targets	R-HSA-1430728
Reactome	Phase I - Functionalization of compounds	105 targets	R-HSA-211945

Name	Explore in Pharos	Explore in Source
Biological oxidations	221 targets	R-HSA-211859
CYP2E1 reactions	11 targets	R-HSA-211999
Cytochrome P450 - arranged by substrate type	65 targets	R-HSA-211897
Metabolism	2112 targets	R-HSA-1430728
Phase I - Functionalization of compounds	105 targets	R-HSA-211945

Gene Ontology Terms (21)

Functions (7)

Components (5)

Processes (9)

Items per page:

10

1 – 7 of 7

GO Term	Evidence	Assigned by
coumarin 7-hydroxylase activity	Inferred from Direct Assay (IDA)	UniProtKB
heme binding	Inferred from Direct Assay (IDA)	UniProtKB
enzyme binding	Inferred from Physical Interaction (IPI)	BHF-UCL
arachidonic acid epoxygenase activity	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
iron ion binding	Inferred from Electronic Annotation (IEA)	InterPro

Protein-Protein Interactions (114)

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1 – 10 of 114

• See Interactions on String-DB

CYP2A7

Tbio

Novelty: 0.01122023

p_int: 1

Score: 0.943

Data Source: BioPlex,STRINGDB

RABAC1

Tbio

Novelty: 0.0162976

p_int: 0.761078473

p_ni: 0.00043792

p_wrong: 0.238483607

Score: 0.544

Data Source: BioPlex,STRINGDB

EPHX1

Tchem

Family: Enzyme

Novelty: 0.00210581

Score: 0.96

Data Source: STRINGDB

NAT2

Tbio

Family: Enzyme

Novelty: 0.00163877

Score: 0.955

Data Source: STRINGDB

AOX1

Tbio

Family: Enzyme

Novelty: 0.00323057

Score: 0.954

Data Source: STRINGDB

CYP3A4

Tclin

Family: Enzyme

Novelty: 0.00020884

Score: 0.949

Data Source: STRINGDB

DPYD

Tclin

Family: Enzyme

Novelty: 0.0022785

Score: 0.945

Data Source: STRINGDB

CYP4A11

Tbio

Novelty: 0.01325821

Score: 0.944

Data Source: STRINGDB

CYP3A5

Tclin

Family: Enzyme

Novelty: 0.00135473

Score: 0.942

Data Source: STRINGDB

CYP3A7

Tclin

Family: Enzyme

Novelty: 0.00963214

Score: 0.941

Data Source: STRINGDB

Publication Statistics

PubMed Score  733.85

PubMed score by year

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PubTator Score  660.53

PubTator score by year

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Amino Acid Sequence

Residue Counts

Sequence

MLASGMLLVALLVCLTVMVLMSVWQQRKSKGKLPPGPTPLPFIGNYLQLNTEQMYNSLMKISERYGPVFT

1-70

IHLGPRRVVVLCGHDAVREALVDQAEEFSGRGEQATFDWVFKGYGVVFSNGERAKQLRRFSIATLRDFGV

70-140

GKRGIEERIQEEAGFLIDALRGTGGANIDPTFFLSRTVSNVISSIVFGDRFDYKDKEFLSLLRMMLGIFQ

140-210

FTSTSTGQLYEMFSSVMKHLPGPQQQAFQLLQGLEDFIAKKVEHNQRTLDPNSPRDFIDSFLIRMQEEEK

210-280

NPNTEFYLKNLVMTTLNLFIGGTETVSTTLRYGFLLLMKHPEVEAKVHEEIDRVIGKNRQPKFEDRAKMP

280-350

YMEAVIHEIQRFGDVIPMSLARRVKKDTKFRDFFLPKGTEVFPMLGSVLRDPSFFSNPQDFNPQHFLNEK

350-420

GQFKKSDAFVPFSIGKRNCFGEGLARMELFLFFTTVMQNFRLKSSQSPKDIDVSPKHVGFATIPRNYTMS

420-490

FLPR

490-494

MLASGMLLVALLVCLTVMVLMSVWQQRKSKGKLPPGPTPLPFIGNYLQLNTEQMYNSLMKISERYGPVFTIHLGPRRVVVLCGHDAVREALVDQAEEFSGRGEQATFDWVFKGYGVVFSNGERAKQLRRFSIATLRDFGVGKRGIEERIQEEAGFLIDALRGTGGANIDPTFFLSRTVSNVISSIVFGDRFDYKDKEFLSLLRMMLGIFQFTSTSTGQLYEMFSSVMKHLPGPQQQAFQLLQGLEDFIAKKVEHNQRTLDPNSPRDFIDSFLIRMQEEEKNPNTEFYLKNLVMTTLNLFIGGTETVSTTLRYGFLLLMKHPEVEAKVHEEIDRVIGKNRQPKFEDRAKMPYMEAVIHEIQRFGDVIPMSLARRVKKDTKFRDFFLPKGTEVFPMLGSVLRDPSFFSNPQDFNPQHFLNEKGQFKKSDAFVPFSIGKRNCFGEGLARMELFLFFTTVMQNFRLKSSQSPKDIDVSPKHVGFATIPRNYTMSFLPR

Find similar targets by:

Uniprot Keyword

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