Search Results
Overview
| Uniprot ID | P17706 |
|---|---|
| Protein Name | Tyrosine-protein phosphatase non-receptor type 2 |
| Gene Name | PTPN2 |
| Organism | Homo sapiens |
Kla Sites from experimental identification
| Position | Flanking peptide |
|---|---|
| 287 | KGDSSIQKRWKELSK |
| 307 | AFDHSPNKIMTEKYN |
| 312 | PNKIMTEKYNGNRIG |
| 364 | RKATTAQKVQQMKQR |
Function
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. Also plays 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
Protein Sequence
Gene Ontology
| Classification | GO ID | Description |
|---|---|---|
| Biological Process | GO:0038020 | insulin receptor recycling |
| Cellular Component | GO:0005737 | cytoplasm |
| Cellular Component | GO:0005829 | cytosol |
| Cellular Component | GO:0005783 | endoplasmic reticulum |
| Cellular Component | GO:0005793 | endoplasmic reticulum-Golgi intermediate compartment |
| Cellular Component | GO:0031904 | endosome lumen |
| Cellular Component | GO:0005654 | nucleoplasm |
| Cellular Component | GO:0005634 | nucleus |
| Cellular Component | GO:0005886 | plasma membrane |
| Molecular Function | GO:0005178 | integrin binding |
| Molecular Function | GO:0004726 | non-membrane spanning protein tyrosine phosphatase activity |
| Molecular Function | GO:0019901 | protein kinase binding |
| Molecular Function | GO:0004725 | protein tyrosine phosphatase activity |
| Molecular Function | GO:0030971 | receptor tyrosine kinase binding |
| Molecular Function | GO:0097677 | STAT family protein binding |
| Molecular Function | GO:0019905 | syntaxin binding |
| Biological Process | GO:0030183 | B cell differentiation |
| Biological Process | GO:0030218 | erythrocyte differentiation |
| Biological Process | GO:0042593 | glucose homeostasis |
| Biological Process | GO:0008286 | insulin receptor signaling pathway |
| Biological Process | GO:0008285 | negative regulation of cell population proliferation |
| Biological Process | GO:0050922 | negative regulation of chemotaxis |
| Biological Process | GO:0042059 | negative regulation of epidermal growth factor receptor signaling pathway |
| Biological Process | GO:0070373 | negative regulation of ERK1 and ERK2 cascade |
| Biological Process | GO:0050728 | negative regulation of inflammatory response |
| Biological Process | GO:0046627 | negative regulation of insulin receptor signaling pathway |
| Biological Process | GO:1902206 | negative regulation of interleukin-2-mediated signaling pathway |
| Biological Process | GO:1902215 | negative regulation of interleukin-4-mediated signaling pathway |
| Biological Process | GO:0070104 | negative regulation of interleukin-6-mediated signaling pathway |
| Biological Process | GO:0010888 | negative regulation of lipid storage |
| Biological Process | GO:1902227 | negative regulation of macrophage colony-stimulating factor signaling pathway |
| Biological Process | GO:0045650 | negative regulation of macrophage differentiation |
| Biological Process | GO:2000587 | negative regulation of platelet-derived growth factor receptor-beta signaling pathway |
| Biological Process | GO:1902233 | negative regulation of positive thymic T cell selection |
| Biological Process | GO:0046426 | negative regulation of receptor signaling pathway via JAK-STAT |
| Biological Process | GO:0050860 | negative regulation of T cell receptor signaling pathway |
| Biological Process | GO:0010804 | negative regulation of tumor necrosis factor-mediated signaling pathway |
| Biological Process | GO:0060339 | negative regulation of type I interferon-mediated signaling pathway |
| Biological Process | GO:0060336 | negative regulation of type II interferon-mediated signaling pathway |
| Biological Process | GO:0042532 | negative regulation of tyrosine phosphorylation of STAT protein |
| Biological Process | GO:0035335 | peptidyl-tyrosine dephosphorylation |
| Biological Process | GO:1902237 | positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway |
| Biological Process | GO:0045722 | positive regulation of gluconeogenesis |
| Biological Process | GO:1903899 | positive regulation of PERK-mediated unfolded protein response |
| Biological Process | GO:1902202 | regulation of hepatocyte growth factor receptor signaling pathway |
| Biological Process | GO:0060334 | regulation of type II interferon-mediated signaling pathway |
| Biological Process | GO:0030217 | T cell differentiation |
Reference
[1] Yang D, Yin J, Shan L, Yi X, Zhang W et al.. Identification of lysine-lactylated substrates in gastric cancer cells.. iScience 25(7):104630. 2022 Jul 15. PMID: 35800753.
[2] Cheng Z, Huang H, Li M, Chen Y. Proteomic analysis identifies PFKP lactylation in SW480 colon cancer cells.. iScience 27(1):108645. 2024 Jan 19. PMID: 38155775.
[3] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.
[4] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.
[5] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.