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PPP1R13L (protein phosphatase 1, regulatory (inhibitor) subunit 13 like)

Written2006-12Ulla Vogel
National Research Centre for the Working Environment, Lersø Parkalle 105, DK-2100 Copenhagen O, Denmark

(Note : for Links provided by Atlas : click)

Identity

Alias_namesprotein phosphatase 1, regulatory (inhibitor) subunit 13 like
protein phosphatase 1, regulatory subunit 13 like
Alias_symbol (synonym)RAI
IASPP
HGNC (Hugo) PPP1R13L
LocusID (NCBI) 10848
Atlas_Id 42997
Location 19q13.32  [Link to chromosome band 19q13]
Location_base_pair Starts at 45882892 and ends at 45909607 bp from pter ( according to hg19-Feb_2009)  [Mapping PPP1R13L.png]
Fusion genes
(updated 2016)
BICD1 (12p11.21) / PPP1R13L (19q13.32)CCDC120 (Xp11.23) / PPP1R13L (19q13.32)PPP1R13L (19q13.32) / OPA3 (19q13.32)
PPP6R2 (22q13.33) / PPP1R13L (19q13.32)

DNA/RNA

Description 26,674 bp 13 exons.
Transcription 3,076 bps.

Protein

Description 828 amino acids.
Function PPP1R13L was originally named RAI, an acronym for RelA associated inhibitor. It was originally identified by yeast two-hybrid screening using RelA as bait. PPP1R13L was shown to associate specifically with relA and inhibit relA mediated NF-kappaB activated transcription when NF-kappaB specific transcription was activated by TNF. Yang et al. found no interaction with p53. The mRNA expression was examined in several tissues and was found to be high in heart, placenta, prostate tissues and detectable in lung, kidney, pancreas, spleen thymus, ovary, small intestine and colon. Bergamaschi et al found that PPP1R13L interacts with p53. Antisense RNA or RNAi mediated down regulation of PPP1R13L expression and induced apoptosis. Increased expression of PPP1R13L lead to increased resistance towards cisplatin and UV-induced apoptosis. This indicates that RAI inhibits apoptosis.
Several studies provide evidence that PPP1R13L expression is increased in tumor tissue. In a study of colorectal adenomas and colorectal cancers, PPP1R13L expression was found to be substantially higher in lesions than in the normal tissue from the same patient. PPP1R13L expression has also been found to be increased in breast carcinomas and in blood cells in patients with acute leukemia.
In a prospective study of lung cancer among 265 lung cancer cases and 272 controls nested within the population based 'Diet, Cancer and Health study', PPP1R13L expression in mononuclear blood cells (isolated by buffy coat) was not associated with risk of lung cancer. mRNA levels were found to be 41% higher in women than in men.

Mutations

Note Genetic Epidemiology:
The most frequently studied polymorphism in PPP1R13L is PPP1R13L IVS1 A4364G (rs1970764). Carriers of the variant allele have been shown to be at decreased risk of basal cell carcinoma among younger persons (< 50 years), breast cancer (<55 years) and lung cancer (<56 years).
The polymorphism is part of a haplotype, which has a stronger association with risk of cancer than the polymorphism itself. Homozygous carriers of the haplotype ERCC1 Asn118AsnA, ASE-1 G-21AG, PPP1R13L IVS1 A4364GA have been shown to be at increased risk of breast cancer and lung cancer. Thus, women who were homozygous carriers of the haplotype ERCC1 Asn118AsnA, ASE-1 G-21AG, RAI IVS1 A4364GA, had a 9.5-fold higher risk of breast cancer before 55 years of age than women who were not homozygous carriers of the haplotype. Older women and heterozygous carriers were not at an increased risk of breast cancer. Homozygous carriers of the haplotype were found to be at 4.9-fold increased risk of lung cancer in the age interval 50-55 years. The association was stronger among women than among men, although the difference was not statistically significant. In subsequent study including more cases and a larger comparison group, a statistically significant difference between genders was found. Furthermore, it was found that the haplotype interacts with smoking intensity. Thus, among women, who were carriers of the haplotype, additional smoking at high smoking intensity (>20 cigarettes/day) was associated with increased lung cancer risk. This was not seen among women who were not homozygous carriers of the haplotype or among men.
The haplotype was not associated with risk of testis cancer or with risk of colorectal adenomas or colorectal cancer. Furthermore, the haplotype was not associated with risk of basal cell carcinoma among older persons (>60 years).
These results indicate that the haplotype may be associated with risk of cancer primarily among young and middle aged persons and that it may be specific for women.

Implicated in

Note
Entity General increased cancer risk
Note No human disease has been linked to inactivation of PPP1R13L. However, polymorphisms in PPP1R13L may be associated with increased cancer risk (see above).
  

Bibliography

iASPP oncoprotein is a key inhibitor of p53 conserved from worm to human.
Bergamaschi D, Samuels Y, O'Neil NJ, Trigiante G, Crook T, Hsieh JK, O'Connor DJ, Zhong S, Campargue I, Tomlinson ML, Kuwabara PE, Lu X
Nature genetics. 2003 ; 33 (2) : 162-167.
PMID 12524540
 
Polymorphisms in RAI and in genes of nucleotide and base excision repair are not associated with risk of testicular cancer.
Laska MJ, Nex&oring; BA, Vistisen K, Poulsen HE, Loft S, Vogel U
Cancer letters. 2005 ; 225 (2) : 245-251.
PMID 15885892
 
Clinical management of women with metastatic breast cancer: a descriptive study according to age group.
Manders K, van de Poll-Franse LV, Creemers GJ, Vreugdenhil G, van der Sangen MJ, Nieuwenhuijzen GA, Roumen RM, Voogd AC
BMC cancer. 2006 ; 6 : page 179.
PMID 16824210
 
A specific haplotype of single nucleotide polymorphisms on chromosome 19q13.2-3 encompassing the gene RAI is indicative of post-menopausal breast cancer before age 55.
Nex&oring; BA, Vogel U, Olsen A, Ketelsen T, Bukowy Z, Thomsen BL, Wallin H, Overvad K, Tj&oring;nneland A
Carcinogenesis. 2003 ; 24 (5) : 899-904.
PMID 12771034
 
Two regions in chromosome 19q13.2-3 are associated with risk of lung cancer.
Vogel U, Laros I, Jacobsen NR, Thomsen BL, Bak H, Olsen A, Bukowy Z, Wallin H, Overvad K, Tj&oring;nneland A, Nex&oring; BA, Raaschou-Nielsen O
Mutation research. 2004 ; 546 (1-2) : 65-74.
PMID 14757194
 
ERCC1, XPD and RAI mRNA levels in lymphocytes are not associated with lung cancer risk in a prospective study of Danes.
Vogel U, Nex&oring; BA, Tj&oring;nneland A, Wallin H, Hertel O, Raaschou-Nielsen O
Mutation research. 2006 ; 593 (1-2) : 88-96.
PMID 16054657
 
Effect of polymorphisms in XPD, RAI, ASE-1 and ERCC1 on the risk of basal cell carcinoma among Caucasians after age 50.
Vogel U, Olsen A, Wallin H, Overvad K, Tj&oring;nneland A, Nex&oring; BA
Cancer detection and prevention. 2005 ; 29 (3) : 209-214.
PMID 15936590
 
Gene-environment interactions between smoking and a haplotype of RAI, ASE-1 and ERCC1 polymorphisms among women in relation to risk of lung cancer in a population-based study.
Vogel U, S&oring;rensen M, Hansen RD, Tj&oring;nneland A, Overvad K, Wallin H, Nex&oring; BA, Raaschou-Nielsen O
Cancer letters. 2007 ; 247 (1) : 159-165.
PMID 16690207
 
Identification of a novel inhibitor of nuclear factor-kappaB, RelA-associated inhibitor.
Yang JP, Hori M, Sanda T, Okamoto T
The Journal of biological chemistry. 1999 ; 274 (22) : 15662-15670.
PMID 10336463
 
Multiple single nucleotide polymorphisms on human chromosome 19q13.2-3 associate with risk of Basal cell carcinoma.
Yin J, Rockenbauer E, Hedayati M, Jacobsen NR, Vogel U, Grossman L, Bolund L, Nex&oring; BA
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2002 ; 11 (11) : 1449-1453.
PMID 12433725
 
The expression of iASPP in acute leukemias.
Zhang X, Wang M, Zhou C, Chen S, Wang J
Leukemia research. 2005 ; 29 (2) : 179-183.
PMID 15607367
 

Citation

This paper should be referenced as such :
Vogel, U
PPP1R13L (protein phosphatase 1, regulatory (inhibitor) subunit 13 like)
Atlas Genet Cytogenet Oncol Haematol. 2007;11(2):105-106.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/PPP1R13LID42997ch19q13.html


External links

Nomenclature
HGNC (Hugo)PPP1R13L   18838
Cards
AtlasPPP1R13LID42997ch19q13
Entrez_Gene (NCBI)PPP1R13L  10848  protein phosphatase 1 regulatory subunit 13 like
AliasesIASPP; NKIP1; RAI; RAI4
GeneCards (Weizmann)PPP1R13L
Ensembl hg19 (Hinxton)ENSG00000104881 [Gene_View]  chr19:45882892-45909607 [Contig_View]  PPP1R13L [Vega]
Ensembl hg38 (Hinxton)ENSG00000104881 [Gene_View]  chr19:45882892-45909607 [Contig_View]  PPP1R13L [Vega]
ICGC DataPortalENSG00000104881
TCGA cBioPortalPPP1R13L
AceView (NCBI)PPP1R13L
Genatlas (Paris)PPP1R13L
WikiGenes10848
SOURCE (Princeton)PPP1R13L
Genetics Home Reference (NIH)PPP1R13L
Genomic and cartography
GoldenPath hg19 (UCSC)PPP1R13L  -     chr19:45882892-45909607 -  19q13.32   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)PPP1R13L  -     19q13.32   [Description]    (hg38-Dec_2013)
EnsemblPPP1R13L - 19q13.32 [CytoView hg19]  PPP1R13L - 19q13.32 [CytoView hg38]
Mapping of homologs : NCBIPPP1R13L [Mapview hg19]  PPP1R13L [Mapview hg38]
OMIM607463   
Gene and transcription
Genbank (Entrez)AF078036 AF078037 AJ888472 AK130326 AY869712
RefSeq transcript (Entrez)NM_001142502 NM_006663
RefSeq genomic (Entrez)NC_000019 NC_018930 NT_011109 NW_004929415
Consensus coding sequences : CCDS (NCBI)PPP1R13L
Cluster EST : UnigeneHs.466937 [ NCBI ]
CGAP (NCI)Hs.466937
Alternative Splicing GalleryENSG00000104881
Gene ExpressionPPP1R13L [ NCBI-GEO ]   PPP1R13L [ EBI - ARRAY_EXPRESS ]   PPP1R13L [ SEEK ]   PPP1R13L [ MEM ]
Gene Expression Viewer (FireBrowse)PPP1R13L [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)10848
GTEX Portal (Tissue expression)PPP1R13L
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ8WUF5   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ8WUF5  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ8WUF5
Splice isoforms : SwissVarQ8WUF5
PhosPhoSitePlusQ8WUF5
Domaine pattern : Prosite (Expaxy)ANK_REP_REGION (PS50297)    ANK_REPEAT (PS50088)    SH3 (PS50002)   
Domains : Interpro (EBI)Ankyrin_rpt    Ankyrin_rpt-contain_dom    iASPP    SH3_domain   
Domain families : Pfam (Sanger)Ank_2 (PF12796)    SH3_9 (PF14604)   
Domain families : Pfam (NCBI)pfam12796    pfam14604   
Domain families : Smart (EMBL)ANK (SM00248)  SH3 (SM00326)  
Conserved Domain (NCBI)PPP1R13L
DMDM Disease mutations10848
Blocks (Seattle)PPP1R13L
PDB (SRS)2VGE   
PDB (PDBSum)2VGE   
PDB (IMB)2VGE   
PDB (RSDB)2VGE   
Structural Biology KnowledgeBase2VGE   
SCOP (Structural Classification of Proteins)2VGE   
CATH (Classification of proteins structures)2VGE   
SuperfamilyQ8WUF5
Human Protein AtlasENSG00000104881
Peptide AtlasQ8WUF5
HPRD09195
IPIIPI00439948   IPI01018117   IPI00181006   IPI00747179   
Protein Interaction databases
DIP (DOE-UCLA)Q8WUF5
IntAct (EBI)Q8WUF5
FunCoupENSG00000104881
BioGRIDPPP1R13L
STRING (EMBL)PPP1R13L
ZODIACPPP1R13L
Ontologies - Pathways
QuickGOQ8WUF5
Ontology : AmiGOnegative regulation of transcription from RNA polymerase II promoter  cardiac right ventricle morphogenesis  ventricular cardiac muscle tissue development  transcription corepressor activity  protein binding  nucleus  nucleoplasm  cytoplasm  transcription, DNA-templated  apoptotic process  transcription factor binding  post-embryonic development  cell junction  embryonic camera-type eye development  multicellular organism growth  hair cycle  identical protein binding  intercellular bridge  positive regulation of cell differentiation  multicellular organismal homeostasis  cardiac muscle contraction  regulation of signal transduction by p53 class mediator  
Ontology : EGO-EBInegative regulation of transcription from RNA polymerase II promoter  cardiac right ventricle morphogenesis  ventricular cardiac muscle tissue development  transcription corepressor activity  protein binding  nucleus  nucleoplasm  cytoplasm  transcription, DNA-templated  apoptotic process  transcription factor binding  post-embryonic development  cell junction  embryonic camera-type eye development  multicellular organism growth  hair cycle  identical protein binding  intercellular bridge  positive regulation of cell differentiation  multicellular organismal homeostasis  cardiac muscle contraction  regulation of signal transduction by p53 class mediator  
NDEx NetworkPPP1R13L
Atlas of Cancer Signalling NetworkPPP1R13L
Wikipedia pathwaysPPP1R13L
Orthology - Evolution
OrthoDB10848
GeneTree (enSembl)ENSG00000104881
Phylogenetic Trees/Animal Genes : TreeFamPPP1R13L
HOVERGENQ8WUF5
HOGENOMQ8WUF5
Homologs : HomoloGenePPP1R13L
Homology/Alignments : Family Browser (UCSC)PPP1R13L
Gene fusions - Rearrangements
Fusion : MitelmanPPP1R13L/OPA3 [19q13.32/19q13.32]  
Fusion: TCGAPPP1R13L 19q13.32 OPA3 19q13.32 LUAD
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPPP1R13L [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PPP1R13L
dbVarPPP1R13L
ClinVarPPP1R13L
1000_GenomesPPP1R13L 
Exome Variant ServerPPP1R13L
ExAC (Exome Aggregation Consortium)PPP1R13L (select the gene name)
Genetic variants : HAPMAP10848
Genomic Variants (DGV)PPP1R13L [DGVbeta]
DECIPHER (Syndromes)19:45882892-45909607  ENSG00000104881
CONAN: Copy Number AnalysisPPP1R13L 
Mutations
ICGC Data PortalPPP1R13L 
TCGA Data PortalPPP1R13L 
Broad Tumor PortalPPP1R13L
OASIS PortalPPP1R13L [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICPPP1R13L  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDPPP1R13L
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 PPP1R13L
DgiDB (Drug Gene Interaction Database)PPP1R13L
DoCM (Curated mutations)PPP1R13L (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)PPP1R13L (select a term)
intoGenPPP1R13L
NCG5 (London)PPP1R13L
Cancer3DPPP1R13L(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM607463   
Orphanet
MedgenPPP1R13L
Genetic Testing Registry PPP1R13L
NextProtQ8WUF5 [Medical]
TSGene10848
GENETestsPPP1R13L
Huge Navigator PPP1R13L [HugePedia]
snp3D : Map Gene to Disease10848
BioCentury BCIQPPP1R13L
ClinGenPPP1R13L
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD10848
Chemical/Pharm GKB GenePA134952588
Clinical trialPPP1R13L
Miscellaneous
canSAR (ICR)PPP1R13L (select the gene name)
Probes
Litterature
PubMed84 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMinePPP1R13L
EVEXPPP1R13L
GoPubMedPPP1R13L
iHOPPPP1R13L
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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