CYP2W1 (cytochrome P450, family 2, subfamily W, polypeptide 1)

2009-06-01   Maria Karlgren 

Department of Pharmacy, Uppsala University, Sweden

Identity

HGNC
LOCATION
7p22.3
LOCUSID
ALIAS
-

DNA/RNA

Description

The CYP2W1 gene has nine exons resulting in an open reading frame of 1473bp.

Transcription

At this point five different CYP2W1 transcripts have been described in different databases. In particular two transcripts have gained interest. The first variant, corresponding to the reference sequence, consists of nine exons and has a typical cytochrome P450 family 2 structure, containing conserved features etc. The second variant has only eight exons although the eight exon is longer in this transcript than in the nine-exon-transcript. The absence of a conserved cysteine indicates that this transcript can not result in a functional P450 enzyme (see figure below).

Pseudogene

No pseudogene is known to date for CYP2W1.

Proteins

Note

CYP2W1 is a cytochrome P450 enzyme belonging to family 2. Other family 2 members are important for the metabolism of drugs and other xenobiotics. In mammals the P450 enzymes are membrane bound and mainly localized to the endoplasmic reticulum (ER) but also to the mitochondria.
Atlas Image
Alignment of the deduced CYP2W1 amino acid sequences from human, chimpanzee, rat, mouse, dog and chicken. Human 9e corresponds to the CYP2W1 reference sequence consisting of nine exons, whereas human 8e corresponds to the eight-exon-transcript mentioned above. For chimpanzee three transcripts are know, here numbered 1-3. All animal sequences correspond to the CYP2W1 homologous genes listed below. The conserved cysteine serving as the fifth heme iron ligand (mentioned below) is indicated with a red box.

Description

All cytochrome P450 enzymes have a similar fold although their sequence identity can be very low. Structurally, P450 enzymes have a conserved core consisting of a four-helix bundle, including helices D, E, I and L, and the two helices J and K. In addition there are two sets of conserved beta-sheets containing five and two strands respectively. All P450 enzymes contain a heme group and one of the few conserved residues is a conserved cysteine serving as the fifth heme iron ligand. A structural similarity of mammalian P450 enzymes is the hydrophobic NH2-terminal part spanning the membrane and serving as membrane anchor.

Expression

CYP2W1 mRNA and/or protein are highly expressed in some cancer types including colon, adrenal gland, lung and gastric cancers. In addition high CYP2W1 expression has been detected in two human derived cell lines, Caco2-TC7 and HepG2. HepG2 is the cell line where CYP2W1 was first identified, however the expression levels in Caco2-TC7 exceeds the levels in HepG2 cells significantly. Some scientists have also reported CYP2W1 mRNA expression in various adult human tissues as well as in keratinocytes and MCF10A cells, however so far no protein has been identified in these tissues/cells, which might be an indication of low expression levels.
For non-human tissues high CYP2W1 mRNA expression levels are found in whole mouse embryo and in rat fetal colon. The expression in fetal rat colon increased by fetal age, whereas the opposite was seen in adult rat colon where the expression levels decreased again after birth.

Localisation

Cytochrome P450 family 2 members are usually located in the ER membrane, however CYP2W1 have been detected both in microsomes (i.e. ER) and in mitochondria.

Function

Cytochrome P450 enzymes are monooxidases and as mentioned other family 2 enzymes are involved in the metabolism of many drugs. The knowledge about CYP2W1 substrates are today limited. The substrates identified are arachidonic acid, benzfetamine and indole. In addition, CYP2W1 has been reported to activate a number of procarcinogens, e.g. PAHs, aflatoxin B1, sterigmatocystin etc. (for a more detailed list see Wu et al., 2006).
Based on the high CYP2W1 expression in fetal rat colon and mouse embryo it is possible that CYP2W1 has some yet unknown function during embryogenesis/differentiation.

Homology

- CYP2W1 (Pan troglodytes)
- Cyp2w1 (Mus musculus)
- Cyp2w1 (Rattus norvegicus)
Denoted as similar to CYP2W1:
- LOC416454 (Gallus gallus)
- LOC491601 (Canis lupus familiaris)

Mutations

Note

Several SNPs have been detected in the CYP2W1 gene, both synonymous and non-synonymous. For an updated overview of CYP2W1 polymorphisms and CYP2W1 alleles see http://www.cypalleles.ki.se/cyp2w1.htm.

Implicated in

Entity name
Various cancer
Note
CYP2W1 mRNA and/or protein are highly expressed in some cancer types, in particular colorectal cancer, but also adrenal gland, lung and gastric cancers. In addition CYP2W1 mRNA and protein expression has been detected in two human derived cancer cell lines, Caco2-TC7 (colorectal adenocarcinoma) and HepG2 (hepatocellular carcinoma).
Disease
A recent pilot study shows that CYP2W1 is a prognostic marker for overall survival in colon cancer. In addition high tumoral CYP2W1 protein expression was associated with a worse clinical outcome. Previously is has been shown that the overexpression of CYP2W1 in cancer tissue could be associated with a decreased CpG methylation within the CYP2W1 gene. At this point there is no further data regarding CYP2W1 and its role in carcinogenesis and/or cancer treatment.

Bibliography

Pubmed IDLast YearTitleAuthors
163312562006Systematic search for gastric cancer-specific genes based on SAGE data: melanoma inhibitory activity and matrix metalloproteinase-10 are novel prognostic factors in patients with gastric cancer.Aung PP et al
157527082005Expression patterns of mouse and human CYP orthologs (families 1-4) during development and in different adult tissues.Choudhary D et al
163077672006Effects of the differentiated keratinocyte phenotype on expression levels of CYP1-4 family genes in human skin cells.Du L et al
191189982009The expression of the novel CYP2W1 enzyme is an independent prognostic factor in colorectal cancer - a pilot study.Edler D et al
179795062007Expression of CYP2W1 in colon tumors: regulation by gene methylation.Gomez A et al
179982942008Genetic polymorphisms and haplotype structures of the human CYP2W1 gene in a Japanese population.Hanzawa Y et al
171500342007Tumour-specific expression of CYP2W1: its potential as a drug target in cancer therapy.Karlgren M et al
165272602006Cytochrome P450 expression and metabolic activation of cooked food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in MCF10A breast epithelial cells.Thomas RD et al
165517812006Recombinant enzymes overexpressed in bacteria show broad catalytic specificity of human cytochrome P450 2W1 and limited activity of human cytochrome P450 2S1.Wu ZL et al
166776112006Enzymatic properties of human CYP2W1 expressed in Escherichia coli.Yoshioka H et al

Other Information

Locus ID:

NCBI: 54905
MIM: 615967
HGNC: 20243
Ensembl: ENSG00000073067

Variants:

dbSNP: 54905
ClinVar: 54905
TCGA: ENSG00000073067
COSMIC: CYP2W1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000073067ENST00000308919Q8TAV3
ENSG00000073067ENST00000340150A6NJ10
ENSG00000073067ENST00000415893H7C015

Expression (GTEx)

0
5
10
15
20
25
30

Pathways

PathwaySourceExternal ID
MetabolismREACTOMER-HSA-1430728
Biological oxidationsREACTOMER-HSA-211859
Phase 1 - Functionalization of compoundsREACTOMER-HSA-211945
Cytochrome P450 - arranged by substrate typeREACTOMER-HSA-211897
XenobioticsREACTOMER-HSA-211981
Miscellaneous substratesREACTOMER-HSA-211958

Protein levels (Protein atlas)

Not detected
Low
Medium
High

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA443756Colonic NeoplasmsDiseaseMultilinkAnnotationassociated23589180

References

Pubmed IDYearTitleCitations
164265682006Tumor-specific expression of the novel cytochrome P450 enzyme, CYP2W1.25
208053012010Colorectal cancer-specific cytochrome P450 2W1: intracellular localization, glycosylation, and catalytic activity.13
179795062007Expression of CYP2W1 in colon tumors: regulation by gene methylation.12
229933312012The expression of CYP2W1: a prognostic marker in colon cancer.10
225917432012Metabolomic analysis and identification of a role for the orphan human cytochrome P450 2W1 in selective oxidation of lysophospholipids.9
251444582014CYP2W1 is highly expressed in adrenal glands and is positively associated with the response to mitotane in adrenocortical carcinoma.8
272577362016The CYP2W1 enzyme: regulation, properties and activation of prodrugs.6
248019062014Prognostic value of CYP2W1 expression in patients with human hepatocellular carcinoma.5
246252282014The expression of CYP2W1 in colorectal primary tumors, corresponding lymph node metastases and liver metastases.4
258449262015Developmental regulation and induction of cytochrome P450 2W1, an enzyme expressed in colon tumors.4

Citation

Maria Karlgren

CYP2W1 (cytochrome P450, family 2, subfamily W, polypeptide 1)

Atlas Genet Cytogenet Oncol Haematol. 2009-06-01

Online version: http://atlasgeneticsoncology.org/gene/44337/cyp2w1-(cytochrome-p450-family-2-subfamily-w-polypeptide-1)