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

Written2009-06Maria Karlgren
Department of Pharmacy, Uppsala University, Sweden

(Note : for Links provided by Atlas : click)

Identity

Alias_namescytochrome P450
Alias_symbol (synonym)FLJ20359
MGC34287
Other aliasCYPIIW1
HGNC (Hugo) CYP2W1
LocusID (NCBI) 54905
Atlas_Id 44337
Location 7p22.3  [Link to chromosome band 7p22]
Location_base_pair Starts at 983199 and ends at 989640 bp from pter ( according to hg19-Feb_2009)  [Mapping CYP2W1.png]
Local_order ADAP1 (960811 - 904066 on minus strand)
COX19 (981761 - 971012 on minus strand)
CYP2W1
C7orf50 (1144360 - 1003168 on minus strand)
LOC100130456 (1055992 - 1056381 on plus strand)
GPR146 (1063667 - 1065423 on plus strand)

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.

Protein

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.
 
  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

Note
  
Entity 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

Systematic 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, Oue N, Mitani Y, Nakayama H, Yoshida K, Noguchi T, Bosserhoff AK, Yasui W.
Oncogene. 2006 Apr 20;25(17):2546-57.
PMID 16331256
 
Expression patterns of mouse and human CYP orthologs (families 1-4) during development and in different adult tissues.
Choudhary D, Jansson I, Stoilov I, Sarfarazi M, Schenkman JB.
Arch Biochem Biophys. 2005 Apr 1;436(1):50-61.
PMID 15752708
 
Effects of the differentiated keratinocyte phenotype on expression levels of CYP1-4 family genes in human skin cells.
Du L, Neis MM, Ladd PA, Lanza DL, Yost GS, Keeney DS.
Toxicol Appl Pharmacol. 2006 Jun 1;213(2):135-44. Epub 2005 Nov 22.
PMID 16307767
 
The expression of the novel CYP2W1 enzyme is an independent prognostic factor in colorectal cancer - a pilot study.
Edler D, Stenstedt K, Ohrling K, Hallstrom M, Karlgren M, Ingelman-Sundberg M, Ragnhammar P.
Eur J Cancer. 2009 Mar;45(4):705-12. Epub 2008 Dec 30.
PMID 19118998
 
Expression of CYP2W1 in colon tumors: regulation by gene methylation.
Gomez A, Karlgren M, Edler D, Bernal ML, Mkrtchian S, Ingelman-Sundberg M.
Pharmacogenomics. 2007 Oct;8(10):1315-25.
PMID 17979506
 
Genetic polymorphisms and haplotype structures of the human CYP2W1 gene in a Japanese population.
Hanzawa Y, Sasaki T, Mizugaki M, Ishikawa M, Hiratsuka M.
Drug Metab Dispos. 2008 Feb;36(2):349-52. Epub 2007 Nov 12.
PMID 17998294
 
Tumour-specific expression of CYP2W1: its potential as a drug target in cancer therapy.
Karlgren M, Ingelman-Sundberg M.
Expert Opin Ther Targets. 2007 Jan;11(1):61-7.
PMID 17150034
 
Cytochrome 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, Green MR, Wilson C, Weckle AL, Duanmu Z, Kocarek TA, Runge-Morris M.
Chem Biol Interact. 2006 Apr 15;160(3):204-16. Epub 2006 Mar 9.
PMID 16527260
 
Recombinant enzymes overexpressed in bacteria show broad catalytic specificity of human cytochrome P450 2W1 and limited activity of human cytochrome P450 2S1.
Wu ZL, Sohl CD, Shimada T, Guengerich FP.
Mol Pharmacol. 2006 Jun;69(6):2007-14. Epub 2006 Mar 21.
PMID 16551781
 
Enzymatic properties of human CYP2W1 expressed in Escherichia coli.
Yoshioka H, Kasai N, Ikushiro S, Shinkyo R, Kamakura M, Ohta M, Inouye K, Sakaki T.
Biochem Biophys Res Commun. 2006 Jun 23;345(1):169-74. Epub 2006 Apr 27.
PMID 16677611
 

Citation

This paper should be referenced as such :
Karlgren, M
CYP2W1 (cytochrome P450, family 2, subfamily W, polypeptide 1)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(5):448-451.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/CYP2W1ID44337ch7p22.html


External links

Nomenclature
HGNC (Hugo)CYP2W1   20243
Cards
AtlasCYP2W1ID44337ch7p22
Entrez_Gene (NCBI)CYP2W1  54905  cytochrome P450 family 2 subfamily W member 1
Aliases
GeneCards (Weizmann)CYP2W1
Ensembl hg19 (Hinxton)ENSG00000073067 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000073067 [Gene_View]  chr7:983199-989640 [Contig_View]  CYP2W1 [Vega]
ICGC DataPortalENSG00000073067
TCGA cBioPortalCYP2W1
AceView (NCBI)CYP2W1
Genatlas (Paris)CYP2W1
WikiGenes54905
SOURCE (Princeton)CYP2W1
Genetics Home Reference (NIH)CYP2W1
Genomic and cartography
GoldenPath hg38 (UCSC)CYP2W1  -     chr7:983199-989640 +  7p22.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)CYP2W1  -     7p22.3   [Description]    (hg19-Feb_2009)
EnsemblCYP2W1 - 7p22.3 [CytoView hg19]  CYP2W1 - 7p22.3 [CytoView hg38]
Mapping of homologs : NCBICYP2W1 [Mapview hg19]  CYP2W1 [Mapview hg38]
OMIM615967   
Gene and transcription
Genbank (Entrez)AK000366 BC025761
RefSeq transcript (Entrez)NM_017781
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)CYP2W1
Cluster EST : UnigeneHs.272795 [ NCBI ]
CGAP (NCI)Hs.272795
Alternative Splicing GalleryENSG00000073067
Gene ExpressionCYP2W1 [ NCBI-GEO ]   CYP2W1 [ EBI - ARRAY_EXPRESS ]   CYP2W1 [ SEEK ]   CYP2W1 [ MEM ]
Gene Expression Viewer (FireBrowse)CYP2W1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)54905
GTEX Portal (Tissue expression)CYP2W1
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ8TAV3   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ8TAV3  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ8TAV3
Splice isoforms : SwissVarQ8TAV3
Catalytic activity : Enzyme1.14.14.- [ Enzyme-Expasy ]   1.14.14.-1.14.14.- [ IntEnz-EBI ]   1.14.14.- [ BRENDA ]   1.14.14.- [ KEGG ]   
PhosPhoSitePlusQ8TAV3
Domaine pattern : Prosite (Expaxy)CYTOCHROME_P450 (PS00086)   
Domains : Interpro (EBI)Cyt_P450    Cyt_P450_CS    Cyt_P450_E_grp-I   
Domain families : Pfam (Sanger)p450 (PF00067)   
Domain families : Pfam (NCBI)pfam00067   
Conserved Domain (NCBI)CYP2W1
DMDM Disease mutations54905
Blocks (Seattle)CYP2W1
SuperfamilyQ8TAV3
Human Protein AtlasENSG00000073067
Peptide AtlasQ8TAV3
HPRD07901
IPIIPI00183606   IPI00414180   IPI00894301   
Protein Interaction databases
DIP (DOE-UCLA)Q8TAV3
IntAct (EBI)Q8TAV3
FunCoupENSG00000073067
BioGRIDCYP2W1
STRING (EMBL)CYP2W1
ZODIACCYP2W1
Ontologies - Pathways
QuickGOQ8TAV3
Ontology : AmiGOmonooxygenase activity  iron ion binding  endoplasmic reticulum lumen  endoplasmic reticulum membrane  plasma membrane  xenobiotic metabolic process  arachidonic acid epoxygenase activity  cell surface  epoxygenase P450 pathway  heme binding  aflatoxin B1 metabolic process  oxidation-reduction process  
Ontology : EGO-EBImonooxygenase activity  iron ion binding  endoplasmic reticulum lumen  endoplasmic reticulum membrane  plasma membrane  xenobiotic metabolic process  arachidonic acid epoxygenase activity  cell surface  epoxygenase P450 pathway  heme binding  aflatoxin B1 metabolic process  oxidation-reduction process  
REACTOMEQ8TAV3 [protein]
REACTOME PathwaysR-HSA-211981 [pathway]   
NDEx NetworkCYP2W1
Atlas of Cancer Signalling NetworkCYP2W1
Wikipedia pathwaysCYP2W1
Orthology - Evolution
OrthoDB54905
GeneTree (enSembl)ENSG00000073067
Phylogenetic Trees/Animal Genes : TreeFamCYP2W1
HOVERGENQ8TAV3
HOGENOMQ8TAV3
Homologs : HomoloGeneCYP2W1
Homology/Alignments : Family Browser (UCSC)CYP2W1
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerCYP2W1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)CYP2W1
dbVarCYP2W1
ClinVarCYP2W1
1000_GenomesCYP2W1 
Exome Variant ServerCYP2W1
ExAC (Exome Aggregation Consortium)CYP2W1 (select the gene name)
Genetic variants : HAPMAP54905
Genomic Variants (DGV)CYP2W1 [DGVbeta]
DECIPHERCYP2W1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisCYP2W1 
Mutations
ICGC Data PortalCYP2W1 
TCGA Data PortalCYP2W1 
Broad Tumor PortalCYP2W1
OASIS PortalCYP2W1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICCYP2W1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDCYP2W1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch CYP2W1
DgiDB (Drug Gene Interaction Database)CYP2W1
DoCM (Curated mutations)CYP2W1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)CYP2W1 (select a term)
intoGenCYP2W1
NCG5 (London)CYP2W1
Cancer3DCYP2W1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM615967   
Orphanet
MedgenCYP2W1
Genetic Testing Registry CYP2W1
NextProtQ8TAV3 [Medical]
TSGene54905
GENETestsCYP2W1
Target ValidationCYP2W1
Huge Navigator CYP2W1 [HugePedia]
snp3D : Map Gene to Disease54905
BioCentury BCIQCYP2W1
ClinGenCYP2W1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD54905
Chemical/Pharm GKB GenePA134992665
Clinical trialCYP2W1
Miscellaneous
canSAR (ICR)CYP2W1 (select the gene name)
Probes
Litterature
PubMed24 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineCYP2W1
EVEXCYP2W1
GoPubMedCYP2W1
iHOPCYP2W1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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