Homo sapiens Protein: PTPN2
InnateDB Protein IDBP-1167.7
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol PTPN2
Protein Name protein tyrosine phosphatase, non-receptor type 2
Species Homo sapiens
Ensembl Protein ENSP00000320298
InnateDB Gene IDBG-1165 (PTPN2)
Protein Structure
UniProt Annotation
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, 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. {ECO:0000269PubMed:10734133, ECO:0000269PubMed:11909529, ECO:0000269PubMed:12138178, ECO:0000269PubMed:12612081, ECO:0000269PubMed:14966296, ECO:0000269PubMed:15592458, ECO:0000269PubMed:18819921, ECO:0000269PubMed:22080863, ECO:0000269PubMed:9488479}.
Subcellular Localization Isoform 1: Endoplasmic reticulum {ECO:0000269PubMed:7593185}. Endoplasmic reticulum-Golgi intermediate compartment {ECO:0000269PubMed:7593185}. Note=Targeted to the endoplasmic reticulum by its C-terminal hydrophobic region. {ECO:0000269PubMed:7593185}.Isoform 2: Nucleus. Cytoplasm. Cell membrane. Note=Predominantly localizes to chromatin (By similarity). Able to shuttle between the nucleus and the cytoplasm and to dephosphorylate plasma membrane receptors (PubMed:9488479). Recruited by activated ITGA1 at the plasma membrane. {ECO:0000250, ECO:0000269PubMed:9488479}.
Disease Associations
Tissue Specificity Ubiquitously expressed. Isoform 2 is probably the major isoform. Isoform 1 is expressed in T-cells and in placenta. {ECO:0000269PubMed:1731319, ECO:0000269PubMed:2546150}.
Number of Interactions This gene and/or its encoded proteins are associated with 25 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.
Experimentally validated
Total 25 [view]
Protein-Protein 24 [view]
Protein-DNA 0
Protein-RNA 0
DNA-DNA 1 [view]
Predicted by orthology
Total 1 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0004725 protein tyrosine phosphatase activity
GO:0005178 integrin binding
GO:0005515 protein binding
GO:0016791 phosphatase activity
GO:0019901 protein kinase binding
GO:0019905 syntaxin binding
GO:0030971 receptor tyrosine kinase binding
Biological Process
GO:0006470 protein dephosphorylation
GO:0008285 negative regulation of cell proliferation
GO:0008286 insulin receptor signaling pathway
GO:0010804 negative regulation of tumor necrosis factor-mediated signaling pathway
GO:0010888 negative regulation of lipid storage
GO:0016311 dephosphorylation
GO:0019221 cytokine-mediated signaling pathway
GO:0030183 B cell differentiation
GO:0030217 T cell differentiation
GO:0030218 erythrocyte differentiation
GO:0035335 peptidyl-tyrosine dephosphorylation
GO:0042059 negative regulation of epidermal growth factor receptor signaling pathway
GO:0042512 negative regulation of tyrosine phosphorylation of Stat1 protein
GO:0042518 negative regulation of tyrosine phosphorylation of Stat3 protein
GO:0042524 negative regulation of tyrosine phosphorylation of Stat5 protein
GO:0042527 negative regulation of tyrosine phosphorylation of Stat6 protein
GO:0042593 glucose homeostasis
GO:0045087 innate immune response (InnateDB)
GO:0045650 negative regulation of macrophage differentiation
GO:0045722 positive regulation of gluconeogenesis
GO:0046627 negative regulation of insulin receptor signaling pathway
GO:0050728 negative regulation of inflammatory response
GO:0050860 negative regulation of T cell receptor signaling pathway
GO:0050922 negative regulation of chemotaxis
GO:0060333 interferon-gamma-mediated signaling pathway
GO:0060334 regulation of interferon-gamma-mediated signaling pathway
GO:0060336 negative regulation of interferon-gamma-mediated signaling pathway
GO:0060339 negative regulation of type I interferon-mediated signaling pathway
GO:0070104 negative regulation of interleukin-6-mediated signaling pathway
GO:0070373 negative regulation of ERK1 and ERK2 cascade
GO:1902202 regulation of hepatocyte growth factor receptor signaling pathway
GO:1902206 negative regulation of interleukin-2-mediated signaling pathway
GO:1902212 negative regulation of prolactin signaling pathway
GO:1902215 negative regulation of interleukin-4-mediated signaling pathway
GO:1902227 negative regulation of macrophage colony-stimulating factor signaling pathway
GO:1902233 negative regulation of positive thymic T cell selection
GO:2000587 negative regulation of platelet-derived growth factor receptor-beta signaling pathway
Cellular Component
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005783 endoplasmic reticulum
GO:0005793 endoplasmic reticulum-Golgi intermediate compartment
GO:0005886 plasma membrane
Protein Structure and Domains
InterPro IPR000242 Protein-tyrosine phosphatase, receptor/non-receptor type
IPR000387 Protein-tyrosine/Dual specificity phosphatase
IPR003595 Protein-tyrosine phosphatase, catalytic
IPR012265 Protein-tyrosine phosphatase, non-receptor type-1/2
IPR029021 Protein-tyrosine phosphatase-like
PFAM PF00102
Post-translational Modifications
SwissProt P17706
PhosphoSite PhosphoSite-P17706
UniProt Splice Variant
Entrez Gene 5771
UniGene Hs.654527
RefSeq NP_536347
OMIM 176887
HPRD 06768
EMBL AK290649 AK292570 AP001077 AP002449 AP005482 BC008244 BC016727 CH471113 EF445017 M25393 M81478
GenPept AAA65997 AAH08244 AAH16727 ACA06062 ACA06063 ACA06064 BAF83338 BAF85259 EAX01532 EAX01533 EAX01539