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

2006-12-01   Ulla Vogel 

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

Identity

HGNC
LOCATION
19q13.32
LOCUSID
ALIAS
IASPP,NKIP1,RAI,RAI4
FUSION GENES

DNA/RNA

Description

26,674 bp 13 exons.

Transcription

3,076 bps.

Proteins

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 (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

Entity name
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

Pubmed IDLast YearTitleAuthors
125245402003iASPP oncoprotein is a key inhibitor of p53 conserved from worm to human.Bergamaschi D et al
158858922005Polymorphisms in RAI and in genes of nucleotide and base excision repair are not associated with risk of testicular cancer.Laska MJ et al
168242102006Clinical management of women with metastatic breast cancer: a descriptive study according to age group.Manders K et al
127710342003A 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.Nexø BA et al
147571942004Two regions in chromosome 19q13.2-3 are associated with risk of lung cancer.Vogel U et al
160546572006ERCC1, XPD and RAI mRNA levels in lymphocytes are not associated with lung cancer risk in a prospective study of Danes.Vogel U et al
159365902005Effect of polymorphisms in XPD, RAI, ASE-1 and ERCC1 on the risk of basal cell carcinoma among Caucasians after age 50.Vogel U et al
166902072007Gene-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 et al
103364631999Identification of a novel inhibitor of nuclear factor-kappaB, RelA-associated inhibitor.Yang JP et al
124337252002Multiple single nucleotide polymorphisms on human chromosome 19q13.2-3 associate with risk of Basal cell carcinoma.Yin J et al
156073672005The expression of iASPP in acute leukemias.Zhang X et al

Other Information

Locus ID:

NCBI: 10848
MIM: 607463
HGNC: 18838
Ensembl: ENSG00000104881

Variants:

dbSNP: 10848
ClinVar: 10848
TCGA: ENSG00000104881
COSMIC: PPP1R13L

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000104881ENST00000360957Q8WUF5
ENSG00000104881ENST00000360957A0A024R0Q5
ENSG00000104881ENST00000418234Q8WUF5
ENSG00000104881ENST00000418234A0A024R0Q5
ENSG00000104881ENST00000589371K7EML6
ENSG00000104881ENST00000591986K7ENG6
ENSG00000104881ENST00000592134K7EPP1
ENSG00000104881ENST00000593226K7EN03

Expression (GTEx)

0
50
100
150
200
250

Pathways

PathwaySourceExternal ID
Gene ExpressionREACTOMER-HSA-74160
Generic Transcription PathwayREACTOMER-HSA-212436
Transcriptional Regulation by TP53REACTOMER-HSA-3700989
Regulation of TP53 ActivityREACTOMER-HSA-5633007
Regulation of TP53 Activity through Association with Co-factorsREACTOMER-HSA-6804759

Protein levels (Protein atlas)

Not detected
Low
Medium
High

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA164713176Platinum compoundsChemicalClinicalAnnotationassociatedPD19203783
PA444937MesotheliomaDiseaseClinicalAnnotationassociatedPD
PA445204Ovarian NeoplasmsDiseaseClinicalAnnotationassociatedPD19203783
PA449014cisplatinChemicalClinicalAnnotationassociatedPD
PA449748gemcitabineChemicalClinicalAnnotationassociatedPD

References

Pubmed IDYearTitleCitations
169642642006iASPP preferentially binds p53 proline-rich region and modulates apoptotic function of codon 72-polymorphic p53.92
191163882009A field synopsis on low-penetrance variants in DNA repair genes and cancer susceptibility.63
179066392007The prolyl isomerase Pin1 orchestrates p53 acetylation and dissociation from the apoptosis inhibitor iASPP.55
218973692011iASPP/p63 autoregulatory feedback loop is required for the homeostasis of stratified epithelia.35
172229382007Genetic polymorphisms and treatment response in advanced non-small cell lung cancer.29
219261652011iASPP and chemoresistance in ovarian cancers: effects on paclitaxel-mediated mitotic catastrophe.29
156073672005The expression of iASPP in acute leukemias.28
182758172008Biochemical and structural studies of ASPP proteins reveal differential binding to p53, p63, and p73.27
236915142013MicroRNA-124 regulates the proliferation of colorectal cancer cells by targeting iASPP.26
196921682010Genetic susceptibility to distinct bladder cancer subphenotypes.25

Citation

Ulla Vogel

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

Atlas Genet Cytogenet Oncol Haematol. 2006-12-01

Online version: http://atlasgeneticsoncology.org/gene/42997/ppp1r13l