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WRAP53 (WD repeat containing, antisense to TP53)

Identity

Other namesFLJ10385
TCAB1
WDR79
HGNC (Hugo) WRAP53
LocusID (NCBI) 55135
Location 17p13.1
Location_base_pair Starts at 7589389 and ends at 7606820 bp from pter ( according to hg19-Feb_2009)  [Mapping]

DNA/RNA

Description The WRAP53 gene encompasses 16 kb of DNA; 13 exons (three non-coding alternative start exons: exon 1alpha, 1beta and 1gamma. Exon 1alpha directly overlaps the first exon of TP53 in an antisense fashion by up to 227 base pairs (bp), depending on transcription start site (TSS) usage. Exon 1gamma of WRAP53 is located in the first intron of TP53 overlapping the previously identified transcript Hp53int1 in an antisense fashion.
Transcription At least 17 splice variants. 1.9 kb mRNA; 1647 bp open reading frame.

Regulatory antisense RNA
Expression: widely expressed at low levels.
Localisation: cytoplasm and nucleus.
Function: regulates p53 mRNA levels by interacting with the 5'UTR of p53 mRNA.
Homology: conserved in mouse.
Diseases implication currently not analysed.

Pseudogene Not known.

Protein

Description 548 amino acids; 75 kDa protein; contains from N-term to C-term, a proline-rich region (aa 8-57), a WD40 domain, 5 repeats (160-441), and a glycin-rich region (533-545).
Expression Widely expressed, overexpressed in cancer.
Localisation Cytoplasm and nucleus (enriched in Cajal bodies).
Function Essential for Cajal body formation and maintenance. Targets the SMN complex, scaRNAs and telomerase enzyme (via TERC) to Cajal bodies. Inhibition of WRAP53 triggers mitochondrial-dependent apoptosis specifically in cancer cells.
Homology Highly-conserved in mammals, the WD40 domain is conserved from human to fly.

Mutations

Note Single nucleotide polymorphisms (SNPs) in women with breast cancer (see below).
Germinal Not reported.
Somatic Not reported.

Implicated in

Entity Breast and ovarian cancer
Note Single nucleotide polymorphisms (SNPs) in WRAP53 were found to be overrepresented in women with breast cancer, in particular estrogen receptor negative breast cancer. The same SNPs were also associated with aggressive ovarian cancer. The SNPs are located in the coding region of WRAP53 and results in the amino acid change R68G.
  
Entity Spinal muscular atrophy (SMA)
Note WRAP53 targets the SMN complex to Cajal Bodies. WRAP53 and SMN association is disrupted in SMA patients suggesting a role of WRAP53 in SMA pathogenesis.
Disease Spinal muscular atrophy (SMA) is a common neurodegenerative disorder caused by reduced levels of SMN due to mutations or deletions of the SMN1 gene. SMA is the leading genetic cause of infant mortality worldwide, affecting approximately 1 in 6000 infants.
  

External links

Nomenclature
HGNC (Hugo)WRAP53   25522
Cards
AtlasWRAP53ID50705ch17p13
Entrez_Gene (NCBI)WRAP53  55135  WD repeat containing, antisense to TP53
GeneCards (Weizmann)WRAP53
Ensembl (Hinxton)ENSG00000141499 [Gene_View]  chr17:7589389-7606820 [Contig_View]  WRAP53 [Vega]
ICGC DataPortalENSG00000141499
cBioPortalWRAP53
AceView (NCBI)WRAP53
Genatlas (Paris)WRAP53
WikiGenes55135
SOURCE (Princeton)NM_001143990 NM_001143991 NM_001143992 NM_018081
Genomic and cartography
GoldenPath (UCSC)WRAP53  -  17p13.1   chr17:7589389-7606820 +  17p13.1   [Description]    (hg19-Feb_2009)
EnsemblWRAP53 - 17p13.1 [CytoView]
Mapping of homologs : NCBIWRAP53 [Mapview]
OMIM612661   613988   
Gene and transcription
Genbank (Entrez)AK001247 AK056669 AK092370 AK225273 AK225411
RefSeq transcript (Entrez)NM_001143990 NM_001143991 NM_001143992 NM_018081
RefSeq genomic (Entrez)AC_000149 NC_000017 NC_018928 NG_028245 NT_010718 NW_001838403 NW_004929405
Consensus coding sequences : CCDS (NCBI)WRAP53
Cluster EST : UnigeneHs.408312 [ NCBI ]
CGAP (NCI)Hs.408312
Alternative Splicing : Fast-db (Paris)GSHG0012202
Alternative Splicing GalleryENSG00000141499
Gene ExpressionWRAP53 [ NCBI-GEO ]     WRAP53 [ SEEK ]   WRAP53 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9BUR4 (Uniprot)
NextProtQ9BUR4  [Medical]
With graphics : InterProQ9BUR4
Splice isoforms : SwissVarQ9BUR4 (Swissvar)
Domaine pattern : Prosite (Expaxy)WD_REPEATS_2 (PS50082)    WD_REPEATS_REGION (PS50294)   
Domains : Interpro (EBI)WD40/YVTN_repeat-like_dom [organisation]   WD40_repeat [organisation]   WD40_repeat_dom [organisation]  
Related proteins : CluSTrQ9BUR4
Domain families : Pfam (Sanger)WD40 (PF00400)   
Domain families : Pfam (NCBI)pfam00400   
Domain families : Smart (EMBL)WD40 (SM00320)  
DMDM Disease mutations55135
Blocks (Seattle)Q9BUR4
Human Protein AtlasENSG00000141499 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasQ9BUR4
HPRD07670
IPIIPI00306087   IPI00909820   IPI00887755   IPI00982224   IPI00984156   
Protein Interaction databases
DIP (DOE-UCLA)Q9BUR4
IntAct (EBI)Q9BUR4
FunCoupENSG00000141499
BioGRIDWRAP53
InParanoidQ9BUR4
Interologous Interaction database Q9BUR4
IntegromeDBWRAP53
STRING (EMBL)WRAP53
Ontologies - Pathways
Ontology : AmiGORNA binding  protein binding  nucleus  telomerase holoenzyme complex  nucleolus  cytoplasm  Cajal body  telomere formation via telomerase  positive regulation of telomerase activity  
Ontology : EGO-EBIRNA binding  protein binding  nucleus  telomerase holoenzyme complex  nucleolus  cytoplasm  Cajal body  telomere formation via telomerase  positive regulation of telomerase activity  
Protein Interaction DatabaseWRAP53
Wikipedia pathwaysWRAP53
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)WRAP53
snp3D : Map Gene to Disease55135
SNP (GeneSNP Utah)WRAP53
SNP : HGBaseWRAP53
Genetic variants : HAPMAPWRAP53
Exome VariantWRAP53
1000_GenomesWRAP53 
ICGC programENSG00000141499 
Somatic Mutations in Cancer : COSMICWRAP53 
CONAN: Copy Number AnalysisWRAP53 
Mutations and Diseases : HGMDWRAP53
Mutations and Diseases : intOGenWRAP53
Genomic VariantsWRAP53  WRAP53 [DGVbeta]
dbVarWRAP53
ClinVarWRAP53
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM612661    613988   
MedgenWRAP53
GENETestsWRAP53
Disease Genetic AssociationWRAP53
Huge Navigator WRAP53 [HugePedia]  WRAP53 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneWRAP53
Homology/Alignments : Family Browser (UCSC)WRAP53
Phylogenetic Trees/Animal Genes : TreeFamWRAP53
Chemical/Protein Interactions : CTD55135
Chemical/Pharm GKB GenePA164727568
Clinical trialWRAP53
Cancer Resource (Charite)ENSG00000141499
Other databases
Probes
Litterature
PubMed32 Pubmed reference(s) in Entrez
CoreMineWRAP53
iHOPWRAP53
OncoSearchWRAP53

Bibliography

Common genetic variation in TP53 and its flanking genes, WDR79 and ATP1B2, and susceptibility to breast cancer.
Garcia-Closas M, Kristensen V, Langerod A, Qi Y, Yeager M, Burdett L, Welch R, Lissowska J, Peplonska B, Brinton L, Gerhard DS, Gram IT, Perou CM, Borresen-Dale AL, Chanock S.
Int J Cancer. 2007 Dec 1;121(11):2532-8.
PMID 17683073
 
Wrap53, a natural p53 antisense transcript required for p53 induction upon DNA damage.
Mahmoudi S, Henriksson S, Corcoran M, Mendez-Vidal C, Wiman KG, Farnebo M.
Mol Cell. 2009 Feb 27;33(4):462-71.
PMID 19250907
 
Single nucleotide polymorphisms in the TP53 region and susceptibility to invasive epithelial ovarian cancer.
Schildkraut JM, Goode EL, Clyde MA, Iversen ES, Moorman PG, Berchuck A, Marks JR, Lissowska J, Brinton L, Peplonska B, Cunningham JM, Vierkant RA, Rider DN, Chenevix-Trench G, Webb PM, Beesley J, Chen X, Phelan C, Sutphen R, Sellers TA, Pearce L, Wu AH, Van Den Berg D, Conti D, Elund CK, Anderson R, Goodman MT, Lurie G, Carney ME, Thompson PJ, Gayther SA, Ramus SJ, Jacobs I, Kruger Kjaer S, Hogdall E, Blaakaer J, Hogdall C, Easton DF, Song H, Pharoah PD, Whittemore AS, McGuire V, Quaye L, Anton-Culver H, Ziogas A, Terry KL, Cramer DW, Hankinson SE, Tworoger SS, Calingaert B, Chanock S, Sherman M, Garcia-Closas M; Australian Ovarian Cancer Study Group.
Cancer Res. 2009 Mar 15;69(6):2349-57. Epub 2009 Mar 10.
PMID 19276375
 
A conserved WD40 protein binds the Cajal body localization signal of scaRNP particles.
Tycowski KT, Shu MD, Kukoyi A, Steitz JA.
Mol Cell. 2009 Apr 10;34(1):47-57. Epub 2009 Mar 12.
PMID 19285445
 
A human telomerase holoenzyme protein required for Cajal body localization and telomere synthesis.
Venteicher AS, Abreu EB, Meng Z, McCann KE, Terns RM, Veenstra TD, Terns MP, Artandi SE.
Science. 2009 Jan 30;323(5914):644-8.
PMID 19179534
 
WRAP53 is essential for Cajal body formation and for targeting the survival of motor neuron complex to Cajal bodies.
Mahmoudi S, Henriksson S, Weibrecht I, Smith S, Soderberg O, Stromblad S, Wiman KG, Farnebo M.
PLoS Biol. 2010 Nov 2;8(11):e1000521.
PMID 21072240
 
WRAP53 promotes cancer cell survival and is a potential target for cancer therapy.
Mahmoudi S, Henriksson S, Farnebo L, Roberg K, Farnebo M.
Cell Death Dis. 2011;2:e114;doi:10.1038/cddis.2010.90.
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written11-2010Marianne Farnebo
Karolinska Institutet, Cancer Center Karolinska (CCK) R8 :04, 17176 Stockholm, Sweden

Citation

This paper should be referenced as such :
Farnebo, M
WRAP53 (WD repeat containing, antisense to TP53)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(7):596-597.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/WRAP53ID50705ch17p13.html

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indexed on : Tue Aug 26 15:24:59 CEST 2014

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