Disease	Score

Substances	Interaction	Organism	Category

Substances	Interaction	Organism	Category

     Covered on Genetics Home Reference: ulcerative colitis

     From NCBI Gene: 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] From UniProt: 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.

Condition	Change (log2fold)	Comparison	Species	Experimental variables	Experiment name

Condition	Change (log2fold)	Comparison	Species	Experimental variables	Experiment name

The following transcription factors affect gene expression:

• NF-kappaB
• NF-kappaB1
• STAT5B

Tissue specificity:

Ubiquitously expressed. Isoform 2 is probably the major isoform. Isoform 1 is expressed in T-cells and in placenta.

Induction:

Up-regulated by IL4/interleukin-4 (at protein level).

Molecular Function:

• Protein Tyrosine Phosphatase Activity
• Non-Membrane Spanning Protein Tyrosine Phosphatase Activity
• Integrin Binding
• Protein Kinase Binding
• Syntaxin Binding
• Receptor Tyrosine Kinase Binding

Biological Processes:

• Negative Regulation Of Transcription From Rna Polymerase Ii Promoter
• Negative Regulation Of Cell Proliferation
• Insulin Receptor Signaling Pathway
• Negative Regulation Of Tumor Necrosis Factor-Mediated Signaling Pathway
• Negative Regulation Of Lipid Storage
• B Cell Differentiation
• T Cell Differentiation
• Erythrocyte Differentiation
• Peptidyl-Tyrosine Dephosphorylation
• Negative Regulation Of Epidermal Growth Factor Receptor Signaling Pathway
• Negative Regulation Of Tyrosine Phosphorylation Of Stat1 Protein
• Negative Regulation Of Tyrosine Phosphorylation Of Stat3 Protein
• Negative Regulation Of Tyrosine Phosphorylation Of Stat5 Protein
• Negative Regulation Of Tyrosine Phosphorylation Of Stat6 Protein
• Glucose Homeostasis
• Negative Regulation Of Macrophage Differentiation
• Positive Regulation Of Gluconeogenesis
• Negative Regulation Of Insulin Receptor Signaling Pathway
• Negative Regulation Of Inflammatory Response
• Negative Regulation Of T Cell Receptor Signaling Pathway
• Negative Regulation Of Chemotaxis
• Regulation Of Interferon-Gamma-Mediated Signaling Pathway
• Negative Regulation Of Interferon-Gamma-Mediated Signaling Pathway
• Negative Regulation Of Type I Interferon-Mediated Signaling Pathway
• Negative Regulation Of Protein Tyrosine Kinase Activity
• Negative Regulation Of Interleukin-6-Mediated Signaling Pathway
• Negative Regulation Of Erk1 And Erk2 Cascade
• Regulation Of Hepatocyte Growth Factor Receptor Signaling Pathway
• Negative Regulation Of Interleukin-2-Mediated Signaling Pathway
• Negative Regulation Of Prolactin Signaling Pathway
• Negative Regulation Of Interleukin-4-Mediated Signaling Pathway
• Negative Regulation Of Macrophage Colony-Stimulating Factor Signaling Pathway
• Negative Regulation Of Positive Thymic T Cell Selection
• Positive Regulation Of Endoplasmic Reticulum Stress-Induced Intrinsic Apoptotic Signaling Pathway
• Positive Regulation Of Perk-Mediated Unfolded Protein Response
• Negative Regulation Of Platelet-Derived Growth Factor Receptor-Beta Signaling Pathway

*synonyms