InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PTPN2

Summary

InnateDB Protein

IDBP-1169.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PTPN2

Protein Name

protein tyrosine phosphatase, non-receptor type 2

Synonyms

PTN2; PTPT; TC-PTP; TCELLPTP; TCPTP;

Species

Homo sapiens

Ensembl Protein

ENSP00000320546

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}.

Comments

Interactions

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]
RNA-RNA	0
DNA-RNA	0

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

PDB ID

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

PRINTS

PR00700

PIRSF

PIRSF000926

SMART

SM00194
SM00404

TIGRFAMs

Post-translational Modifications

Modification

Cross-References