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Overview

Uniprot IDP35233
Protein NameTyrosine-protein phosphatase non-receptor type 2
Gene NamePtpn2
OrganismRattus norvegicus

Kla Sites from experimental identification

Position Flanking peptide
359 RKATTAQKVQQMRQR

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 (By similarity)

Protein Sequence

10 MSATIEREFE 20 ELDAQCRWQP 30 LYLEIRNESH 40 DYPHRVAKFP 50 ENRNRNRYRD 60 VSPYDHSRVK 70 LQSAENDYIN 80 ASLVDIEEAQ 90 RSYILTQGPL 100 PNTCCHFWLM 110 VWQQKTRAVV 120 MLNRTVEKES 130 VKCAQYWPTD 140 DREMVFKETG 150 FSVKLLSEDV 160 KSYYTVHLLQ 170 LENINSGETR 180 TISHFHYTTW 190 PDFGVPESPA 200 SFLNFLFKVR 210 ESGSLNPDHG 220 PAVIHCSAGI 230 GRSGTFSLVD 240 TCLVLMEKGE 250 DVNVKQILLS 260 MRKYRMGLIQ 270 TPDQLRFSYM 280 AIIEGAKYTK 290 GDSNIQKRWK 300 ELSKEDLSPV 310 CRHSQNRTMT 320 EKYNGKRIGS 330 EDEKLTGLSS 340 KVPDTVEESS 350 ESILRKRIRE 360 DRKATTAQKV 370 QQMRQRLNET 380 ERKRKRWLYW 390 QPILTKMGFV 400 SVILVGALVG 410 WTLLFQLNVL PRLTDT

Gene Ontology

Classification GO ID Description
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:0031965 nuclear membrane
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0005886 plasma membrane
Molecular Function GO:0003677 DNA binding
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:0038020 insulin receptor recycling
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:0000122 negative regulation of transcription by RNA polymerase II
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:0006470 protein dephosphorylation
Biological Process GO:1902202 regulation of hepatocyte growth factor receptor signaling pathway
Biological Process GO:0030217 T cell differentiation

Reference

[1] Sheng L, Xu H, Wang Y, Ni J, Xiang T et al.. Systematic analysis of lysine lactylation in nucleus pulposus cells.. iScience 27(11):111157. 2024 Nov 15. PMID: 39524337.