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  6. Tyrosine-protein phosphatase non-receptor type 2

Tchem Tyrosine-protein phosphatase non-receptor type 2

Non-receptor type tyrosine-specific phosphatase that dephosphorylates receptor protein tyrosine kinases including INSR, EGFR, CSF1R, PDGFR. Also dephosphorylates non-receptor protein tyrosine kinases like JAK1, JAK2, JAK3, Src family kinases, STAT1, STAT3, STAT5A, STAT5B and STAT6 either in the nucleus or the cytoplasm. Negatively regulates numerous signaling pathways and biological processes like hematopoiesis, inflammatory response, cell proliferation and differentiation, and glucose homeostasis. Plays a multifaceted and important role in the development of the immune system. Functions in T-cell receptor signaling through dephosphorylation of FYN and LCK to control T-cells differentiation and activation. Dephosphorylates CSF1R, negatively regulating its downstream signaling and macrophage differentiation. Negatively regulates cytokine (IL2/interleukin-2 and interferon)-mediated signaling through dephosphorylation of the cytoplasmic kinases JAK1, JAK3 and their substrate STAT1, that propagate signaling downstream of the cytokine receptors. Also regulates the IL6/interleukin-6 and IL4/interleukin-4 cytokine signaling through dephosphorylation of STAT3 and STAT6 respectively. In addition to the immune system, it is involved in anchorage-dependent, negative regulation of EGF-stimulated cell growth. Activated by the integrin ITGA1/ITGB1, it dephosphorylates EGFR and negatively regulates EGF signaling. Dephosphorylates PDGFRB and negatively regulates platelet-derived growth factor receptor-beta signaling pathway and therefore cell proliferation. Negatively regulates tumor necrosis factor-mediated signaling downstream via MAPK through SRC dephosphorylation. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of the hepatocyte growth factor receptor MET. Plays also an important role in glucose homeostasis. For instance, negatively regulates the insulin receptor signaling pathway through the dephosphorylation of INSR and control gluconeogenesis and liver glucose production through negative regulation of the IL6 signaling pathways. Finally, it negatively regulates prolactin-mediated signaling pathway through dephosphorylation of STAT5A and STAT5B. May also bind DNA.

The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. Members of the PTP family share a highly conserved catalytic motif, which is essential for the catalytic activity. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. Epidermal growth factor receptor and the adaptor protein Shc were reported to be substrates of this PTP, which suggested the roles in growth factor mediated cell signaling. Multiple alternatively spliced transcript variants encoding different isoforms have been found. Two highly related but distinctly processed pseudogenes that localize to chromosomes 1 and 13, respectively, have been reported. [provided by RefSeq, May 2011]

 Comments

Property Summary

NCBI Gene PubMed Count 132
Grant Count 55
R01 Count 30
Funding $4,147,831
PubMed Score 269.50
PubTator Score 169.23

Knowledge Summary

Patent

No data available

TINX Plot

  Disease Relevance (25)

Disease Z-score Confidence
Crohn's disease 304 4.235 2.1
diabetes mellitus 1,663 3.914 2.0
Colitis 46 3.084 1.5
Rheumatoid Arthritis 1,160 3.063 1.5
Alopecia areata 37 2.0
Alzheimer's disease 644
Celiac disease 112 2.0
Crohn Disease 97
Diabetes Mellitus, Insulin-Dependent 76
Inflammatory Bowel Diseases 87
Leukemia, T-Cell 5
Malignant neoplasm of esophagus 18
Motor neuron disease 39 1.0
Pick disease 1,893
Precursor T-Cell Lymphoblastic Leukemia-... 18 
Type 1 diabetes mellitus 101 2.0
ependymoma 2,514
glioblastoma 5,572
group 3 medulloblastoma 2,254
malignant mesothelioma 3,162
non-small cell lung cancer 2,798
osteosarcoma 7,933
ovarian cancer 8,484
progressive supranuclear palsy 674
ulcerative colitis 2,087

Expression

  Differential Expression (10)

Disease log2 FC p
malignant mesothelioma 1.600 0.000
ependymoma 1.200 0.014
osteosarcoma 2.635 0.000
glioblastoma 1.400 0.000
non-small cell lung cancer -1.070 0.000
group 3 medulloblastoma 1.300 0.006
Alzheimer's disease 1.100 0.026
Pick disease 1.700 0.000
progressive supranuclear palsy 1.100 0.027
ovarian cancer -1.900 0.000

Synonym

Accession P17706 A8K955 A8MXU3 K7ENG3 Q96AU5 Q96HR2
Symbols PTN2
PTPT
TCPTP
TC-PTP
TCELLPTP

Gene

PTPN2

PANTHER Protein Class (3)

 Grant Application (55)

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PDB

1L8K  

 GO Function (6)

 GO Component (5)

 GO Process (35)

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 Compartment GO Term (28)

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 IMPC Term (2)

 MGI Term (13)

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 GWAS Trait (9)

Pathway (14)

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 UniProt Keyword (12)

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Ligand (158)

Structure of CHEMBL56711

CHEMBL56711
pKi 6.00

Structure of CHEMBL379196

CHEMBL379196
pKi 6.00

Structure of CHEMBL1938829

CHEMBL1938829
pIC50 6.00

Structure of CHEMBL1163239

CHEMBL1163239
pIC50 6.01

Structure of CHEMBL1242827

CHEMBL1242827
pIC50 6.01

Structure of CHEMBL1242363

CHEMBL1242363
pIC50 6.02

Structure of CHEMBL266753

CHEMBL266753
pIC50 6.03

Structure of CHEMBL55799

CHEMBL55799
pKi 6.05

Structure of CHEMBL1938816

CHEMBL1938816
pIC50 6.06

Structure of CHEMBL1938828

CHEMBL1938828
pIC50 6.06

Structure of CHEMBL504291

CHEMBL504291
pIC50 6.07

Structure of CHEMBL448797

CHEMBL448797
pIC50 6.07

Structure of CHEMBL292849

CHEMBL292849
pKi 6.09

Structure of CHEMBL214378

CHEMBL214378
pKi 6.09

Structure of CHEMBL445491

CHEMBL445491
pIC50 6.10

Structure of CHEMBL1241469

CHEMBL1241469
pIC50 6.10

Structure of CHEMBL3098857

CHEMBL3098857
pIC50 6.10

Structure of CHEMBL3822604

CHEMBL3822604
pIC50 6.12

Structure of CHEMBL443663

CHEMBL443663
pIC50 6.13

Structure of CHEMBL450403

CHEMBL450403
pIC50 6.13

Gene RIF (89)

PMID Text
26734582 role of PTPN2 in type 1 diabetes and Crohn's disease (review)
26344020 rs2542151 SNP in The PTPN2 gene is associated with T1DM in Chinese Han children
26208487 Loss of protein tyrosine phosphatase, non-receptor type 2 is associated with activation of AKT and tamoxifen resistance in breast cancer.
26139109 PTPN2 is linked to the pathogenesis of rheumatoid arthritis via synovial fibroblasts. It is a regulator of lnterleukin-6 production in rheumatoid arthritis synovial fibroblasts.
26090670 Angiopoietin-1 Regulates Brain Endothelial Permeability through PTPN-2 Mediated Tyrosine Dephosphorylation of Occludin
26026268 demonstrate that SIPAR directly interacts with T cell protein tyrosine phosphatase TC45 and enhances its association with STAT3
25492475 dysfunction of PTPN2 results in aberrant T-cell differentiation and intestinal dysbiosis similar to those observed in human CD. Our findings indicate a novel and crucial role for PTPN2 in chronic intestinal inflammation.
25489960 Single-nucleotide polymorphism in PTPN2 gene is associated with Crohn's disease.
25460303 PTPN2 and genes of the vitamin D pathway may have roles in risk of juvenile idiopathic arthritis
25311528 FGFR3 regulation by PTPN1 and PTPN2 depend on FGFR3 localization and A-loop sequence.
More...

AA Sequence 

MPTTIEREFEELDTQRRWQPLYLEIRNESHDYPHRVAKFPENRNRNRYRDVSPYDHSRVKLQNAENDYIN      1 - 70
ASLVDIEEAQRSYILTQGPLPNTCCHFWLMVWQQKTKAVVMLNRIVEKESVKCAQYWPTDDQEMLFKETG     71 - 140
FSVKLLSEDVKSYYTVHLLQLENINSGETRTISHFHYTTWPDFGVPESPASFLNFLFKVRESGSLNPDHG    141 - 210
PAVIHCSAGIGRSGTFSLVDTCLVLMEKGDDINIKQVLLNMRKYRMGLIQTPDQLRFSYMAIIEGAKCIK    211 - 280
GDSSIQKRWKELSKEDLSPAFDHSPNKIMTEKYNGNRIGLEEEKLTGDRCTGLSSKMQDTMEENSESALR    281 - 350
KRIREDRKATTAQKVQQMKQRLNENERKRKRWLYWQPILTKMGFMSVILVGAFVGWTLFFQQNAL         351 - 415
//

Text Mined References (143)

PMID Year Title
26734582 2015 Genetic Variations of PTPN2 and PTPN22: Role in the Pathogenesis of Type 1 Diabetes and Crohn's Disease.
26344020 2015 Genetic Variants of PTPN2 Gene in Chinese Children with Type 1 Diabetes Mellitus.
26208487 2015 Loss of protein tyrosine phosphatase, non-receptor type 2 is associated with activation of AKT and tamoxifen resistance in breast cancer.
26139109 2015 Protein tyrosine phosphatase nonreceptor type 2: an important regulator of lnterleukin-6 production in rheumatoid arthritis synovial fibroblasts.
26090670 2015 Angiopoietin-1 Regulates Brain Endothelial Permeability through PTPN-2 Mediated Tyrosine Dephosphorylation of Occludin.
26026268 2015 Nuclear termination of STAT3 signaling through SIPAR (STAT3-Interacting Protein As a Repressor)-dependent recruitment of T cell tyrosine phosphatase TC-PTP.
25492475 2015 PTPN2 controls differentiation of CD4? T cells and limits intestinal inflammation and intestinal dysbiosis.
25489960 2015 Immunochip analysis identification of 6 additional susceptibility loci for Crohn's disease in Koreans.
25460303 2015 Epistasis amongst PTPN2 and genes of the vitamin D pathway contributes to risk of juvenile idiopathic arthritis.
25311528 2015 Differential regulation of FGFR3 by PTPN1 and PTPN2.
More...