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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 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. 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

Ligand Count 158
NCBI Gene PubMed Count 141
PubMed Score 297.25
PubTator Score 169.23

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (7)

Disease Target Count Z-score Confidence
Carcinoma 11493 0.0 0.5
Disease Target Count Z-score Confidence
diabetes mellitus 1728 3.934 2.0
Colitis 54 3.164 1.6
Retinitis pigmentosa 4 38 3.112 1.6

Expression

  Differential Expression (10)

Disease log2 FC p
Alzheimer's disease 1.100 2.6e-02
ependymoma 1.200 1.4e-02
glioblastoma 1.400 1.8e-04
group 3 medulloblastoma 1.300 6.0e-03
malignant mesothelioma 1.600 3.7e-05
non-small cell lung cancer -1.070 1.4e-10
osteosarcoma 2.635 7.3e-07
ovarian cancer -1.900 1.5e-10
Pick disease 1.700 1.8e-05
progressive supranuclear palsy 1.100 2.7e-02

Synonym

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

Gene

PTPN2

PDB

1L8K  

  Ortholog (1)

Species Source Disease
Chimp OMA EggNOG

 UniProt Keyword (13)

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 GO Function (7)

 GO Component (6)

 GO Process (32)

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 Compartment GO Term (29)

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 IMPC Phenotype (2)

 MGI Phenotype (13)

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 GWAS Trait (15)

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 HCA RNA Cell Line (56)

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Pathway (19)

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Protein-protein Interaction (1)

COL5A1  

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 (98)

AA Sequence 

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

Text Mined References (152)

PMID Year Title