PTPN13 (Protein tyrosine phosphatase, non-receptor type 13)

2008-09-01   Alessandro Beghini 

University of Milan, Medical Faculty, Department of Biology, Genetics for Medical Sciences, via Viotti 5, 20133-Milan, Italy

Identity

HGNC
LOCATION
4q21.3
IMAGE
Atlas Image
LEGEND
Genomic view
LOCUSID
ALIAS
FAP-1,PNP1,PTP-BAS,PTP-BL,PTP1E,PTPL1,PTPLE,hPTP1E
FUSION GENES

DNA/RNA

Description

The gene covers 220.87 kb (from 87734485 to 87955350-NCBI) and contains 48 exons and 51 different introns (49 gt-ag, 2 gc-ag), initiates transcription within exon 2 and terminates in exon 48.

Transcription

Transcription produces 13 different mRNAs, 9 alternatively spliced variants and 4 unspliced forms. RefSeq annotates 4 representative transcripts, but Homo sapiens cDNA sequences in GenBank support at least 9 spliced variants.

Proteins

Description

The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP is a large protein that possesses a PTP domain at C-terminus, and multiple noncatalytic domains, which include a domain with similarity to band 4.1 superfamily of cytoskeletal-associated proteins, a region consisting of five PDZ domains, and a leucine zipper motif. This PTP was found to interact with, and dephosphorylate Fas receptor, as well as IkappaBalpha through the PDZ domains, which suggested its role in Fas mediated programmed cell death. This PTP was also shown to interact with GTPase-activating protein, and thus may function as a regulator of Rho signaling pathway. Eight spliced and the unspliced mRNAs putatively encode good proteins.
Atlas Image
Schematic representation of PTPN13 structure and boxes represent functional domains. The KIND domain has been identified in silico by sequence homology.

Expression

In all human normal tissues, including lymph node and peripheral blood mononuclear cells samples, PTPN13 is ubiquitously expressed.

Localisation

The FERM domain binds to phosphatidylinositol 4,5-biphosphate leading to the enrichment of PTPN13 at a juxtamembrane localization. However, the PTPN13 protein is also detected throughout the cytoplasm. In HeLa cells, PTPN13 localizes to the centrosomes during metaphase.

Function

Functionally, the gene has been tested for association to diseases (Bone Neoplasms; Carcinoma; Colorectal Neoplasms; Liver Neoplasms; lymphoma; Sarcoma, Ewings ), proposed to participate in a pathway (FAS signaling pathway ( CD95 )) and a process (protein amino acid dephosphorylation). Proteins are expected to have molecular functions (non-membrane spanning protein tyrosine phosphatase activity, hydrolase activity, protein binding, structural molecule activity) and to localize in various compartments (nucleus, cytoplasm, cytoskeleton).

Mutations

Note

Different somatic mutations was identified in colorectal tumors (19% of the colorectal cancer samples analyzed), predicted to result in missense or non-sense mutations. Some of these mutant proteins led to reduce phosphatase activity.
Atlas Image
Distribution of mutations in PTPN13, black arrows indicate location of missense mutations, red arrows indicate location of nonsense mutations or frameshifts.

Implicated in

Entity name
Colorectal cancers
Disease
A large-scale study that looked at the mutations in the tyrosine phosphatome from colorectal cancers identified PTPN13. The authors identified 19 mutations, non-sense and missense, seven of which were in the PTP domain.
Entity name
Lymphomas (Hodgkin and non-Hodgkin), gastric and hepatocellular tumors
Disease
Hypermethylation of the PTPN13 promoter or allelic loss was observed leading to downregulation of PTPN13 mRNA.

Bibliography

Pubmed IDLast YearTitleAuthors
182659462008PTPL1: a large phosphatase with a split personality.Abaan OD et al
80713591994A novel protein-tyrosine phosphatase with homology to both the cytoskeletal proteins of the band 4.1 family and junction-associated guanylate kinases.Banville D et al
88248091996PTPN13, a fas-associated protein tyrosine phosphatase, is located on the long arm of chromosome 4 at band q21.3.Inazawa J et al
82879771994Molecular cloning of a novel protein-tyrosine phosphatase containing a membrane-binding domain and GLGF repeats.Maekawa K et al
79290601994Cloning and characterization of PTPL1, a protein tyrosine phosphatase with similarities to cytoskeletal-associated proteins.Saras J et al
151559502004Mutational analysis of the tyrosine phosphatome in colorectal cancers.Wang Z et al
164890622006Genetic characterization of fas-associated phosphatase-1 as a putative tumor suppressor gene on chromosome 4q21.3 in hepatocellular carcinoma.Yeh SH et al
165722032006Epigenetic disruption of two proapoptotic genes MAPK10/JNK3 and PTPN13/FAP-1 in multiple lymphomas and carcinomas through hypermethylation of a common bidirectional promoter.Ying J et al
124361992002Head-to-head juxtaposition of Fas-associated phosphatase-1 (FAP-1) and c-Jun NH2-terminal kinase 3 (JNK3) genes: genomic structure and seven polymorphisms of the FAP-1 gene.Yoshida S et al
88938251996The gene (PTPN13) encoding the protein tyrosine phosphatase PTP-BL/PTP-BAS is located in mouse chromosome region 5E/F and human chromosome region 4q21.van den Maagdenberg AM et al

Other Information

Locus ID:

NCBI: 5783
MIM: 600267
HGNC: 9646
Ensembl: ENSG00000163629

Variants:

dbSNP: 5783
ClinVar: 5783
TCGA: ENSG00000163629
COSMIC: PTPN13

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000163629ENST00000316707Q12923
ENSG00000163629ENST00000411767Q12923
ENSG00000163629ENST00000427191Q12923
ENSG00000163629ENST00000436978Q12923
ENSG00000163629ENST00000502971D6R9M4
ENSG00000163629ENST00000507902D6R9X4
ENSG00000163629ENST00000511467Q12923

Expression (GTEx)

0
10
20
30
40
50
60

Pathways

PathwaySourceExternal ID
ApoptosisKEGGko04210
ApoptosisKEGGhsa04210
MetabolismREACTOMER-HSA-1430728
Metabolism of lipids and lipoproteinsREACTOMER-HSA-556833
Phospholipid metabolismREACTOMER-HSA-1483257
PI MetabolismREACTOMER-HSA-1483255
Synthesis of PIPs at the plasma membraneREACTOMER-HSA-1660499

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
243166732014Autophagy variation within a cell population determines cell fate through selective degradation of Fap-1.83
192400612009Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling.75
206209602010miR-200c regulates induction of apoptosis through CD95 by targeting FAP-1.67
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
236043172013FBXL2- and PTPL1-mediated degradation of p110-free p85β regulatory subunit controls the PI(3)K signalling cascade.46
165722032006Epigenetic disruption of two proapoptotic genes MAPK10/JNK3 and PTPN13/FAP-1 in multiple lymphomas and carcinomas through hypermethylation of a common bidirectional promoter.38
127244202003FAP-1 association with Fas (Apo-1) inhibits Fas expression on the cell surface.34
179824842008Protein tyrosine phosphatase PTPN13 negatively regulates Her2/ErbB2 malignant signaling.34
197349412009Impaired PTPN13 phosphatase activity in spontaneous or HPV-induced squamous cell carcinomas potentiates oncogene signaling through the MAP kinase pathway.31
176388922007The putative tumor suppressor gene PTPN13/PTPL1 induces apoptosis through insulin receptor substrate-1 dephosphorylation.30

Citation

Alessandro Beghini

PTPN13 (Protein tyrosine phosphatase, non-receptor type 13)

Atlas Genet Cytogenet Oncol Haematol. 2008-09-01

Online version: http://atlasgeneticsoncology.org/gene/41912/ptpn13