Covered on Genetics Home Reference: rheumatoid arthritisFrom NCBI Gene: Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-positive, NK cell-positiveHepatitis c virus, susceptibility toFrom UniProt: Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-positive/NK-cell-positive (T(-)B(+)NK(+) SCID): A form of severe combined immunodeficiency (SCID), a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development. [MIM:608971] Multiple sclerosis (MS): A multifactorial, inflammatory, demyelinating disease of the central nervous system. Sclerotic lesions are characterized by perivascular infiltration of monocytes and lymphocytes and appear as indurated areas in pathologic specimens (sclerosis in plaques). The pathological mechanism is regarded as an autoimmune attack of the myelin sheath, mediated by both cellular and humoral immunity. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia and bladder dysfunction. Genetic and environmental factors influence susceptibility to the disease. [MIM:126200]

     From NCBI Gene: The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitosis, and oncogenic transformation. This PTP contains an extracellular domain, a single transmembrane segment and two tandem intracytoplasmic catalytic domains, and thus is classified as a receptor type PTP. This PTP has been shown to be an essential regulator of T- and B-cell antigen receptor signaling. It functions through either direct interaction with components of the antigen receptor complexes, or by activating various Src family kinases required for the antigen receptor signaling. This PTP also suppresses JAK kinases, and thus functions as a regulator of cytokine receptor signaling. Alternatively spliced transcripts variants of this gene, which encode distinct isoforms, have been reported. [provided by RefSeq, Jun 2012] From UniProt: Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor. Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first PTPase domain has enzymatic activity, while the second one seems to affect the substrate specificity of the first one. Upon T-cell activation, recruits and dephosphorylates SKAP1 and FYN. Dephosphorylates LYN, and thereby modulates LYN activity.

The following transcription factors affect gene expression:

• Nkx2-5
• STAT1
• STAT1alpha
• STAT1beta
• AP-1
• c-Jun
• GR-beta
• GR-alpha
• GR

Molecular Function:

• Protein Tyrosine Phosphatase Activity
• Transmembrane Receptor Protein Tyrosine Phosphatase Activity
• Protein Kinase Binding

Biological Processes:

• Negative Regulation Of T Cell Mediated Cytotoxicity
• Negative Regulation Of Cytokine-Mediated Signaling Pathway
• Hematopoietic Progenitor Cell Differentiation
• Immunoglobulin Biosynthetic Process
• Negative Regulation Of Protein Kinase Activity
• Protein Dephosphorylation
• Negative Regulation Of Cell Adhesion Involved In Substrate-Bound Cell Migration
• Cell Surface Receptor Signaling Pathway
• Dephosphorylation
• T Cell Differentiation
• Positive Regulation Of B Cell Proliferation
• B Cell Proliferation
• Positive Regulation Of T Cell Proliferation
• Cell Cycle Phase Transition
• Positive Regulation Of Protein Kinase Activity
• Bone Marrow Development
• Stem Cell Development
• T Cell Receptor Signaling Pathway
• B Cell Receptor Signaling Pathway
• Positive Regulation Of Antigen Receptor-Mediated Signaling Pathway
• Release Of Sequestered Calcium Ion Into Cytosol
• Defense Response To Virus
• Regulation Of Cell Cycle
• Positive Regulation Of Hematopoietic Stem Cell Migration
• Positive Regulation Of Stem Cell Proliferation