PTPN22

This gene encodes of member of the non-receptor class 4 subfamily of the protein-tyrosine phosphatase family. The encoded protein is a lymphoid-specific intracellular phosphatase that associates with the molecular adapter protein CBL and may be involved in regulating CBL function in the T-cell receptor signaling pathway. Mutations in this gene may be associated with a range of autoimmune disorders including Type 1 Diabetes, rheumatoid arthritis, systemic lupus erythematosus and Graves' disease. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq]

protein tyrosine phosphatase, non-receptor type 22 (lymphoid)

Acts as negative regulator of T-cell receptor (TCR) signaling by direct dephosphorylation of the Src family kinases LCK and FYN, ITAMs of the TCRz/CD3 complex, as well as ZAP70, VAV, VCP and other key signaling molecules (PubMed:16461343, PubMed:18056643).
Associates with and probably dephosphorylates CBL. Dephosphorylates LCK at its activating 'Tyr-394' residue (PubMed:21719704).
Dephosphorylates ZAP70 at its activating 'Tyr-493' residue (PubMed:16461343).
Dephosphorylates the immune system activator SKAP2 (PubMed:21719704).
Positively regulates toll-like receptor (TLR)-induced type 1 interferon production (PubMed:23871208).
Promotes host antiviral responses mediated by type 1 interferon (By similarity).
Regulates NOD2-induced pro-inflammatory cytokine secretion and autophagy (PubMed:23991106).
Dephosphorylates phospho-anandamide (p-AEA), an endocannabinoid to anandamide (also called N-arachidonoylethanolamide) (By similarity).

AutophagyIEA:UniProtKB-KW
Cellular response to muramyl dipeptideManual Assertion Based On ExperimentIDA:UniProtKB
Lipid metabolic processIEA:UniProtKB-KW
Lipopolysaccharide-mediated signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of autophagyManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of gene expressionManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of interleukin-6 productionManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of interleukin-8 productionManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of JUN kinase activityManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of p38MAPK cascadeManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of T cell activationManual Assertion Based On ExperimentIMP:BHF-UCL
Negative regulation of T cell receptor signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of tumor necrosis factor productionManual Assertion Based On ExperimentIMP:UniProtKB
Peptidyl-tyrosine dephosphorylationManual Assertion Based On ExperimentIBA:GO_Central
Phosphoanandamide dephosphorylationISS:BHF-UCL
Positive regulation of CD8-positive, alpha-beta T cell proliferationManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of defense response to virus by hostManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of ERK1 and ERK2 cascadeManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of gene expressionManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of granzyme B productionManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of interferon-gamma productionManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of protein K63-linked ubiquitinationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of toll-like receptor 3 signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of toll-like receptor 4 signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of toll-like receptor 7 signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of toll-like receptor 9 signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of type I interferon productionManual Assertion Based On ExperimentIMP:UniProtKB
Protein dephosphorylationManual Assertion Based On ExperimentIDA:BHF-UCL
Regulation of B cell receptor signaling pathway1 PublicationNAS:BHF-UCL
Regulation of innate immune response1 PublicationIC:BHF-UCL
Regulation of natural killer cell proliferationManual Assertion Based On ExperimentIDA:BHF-UCL
Regulation of NIK/NF-kappaB signalingManual Assertion Based On ExperimentIMP:UniProtKB
Response to lipopolysaccharideManual Assertion Based On ExperimentIMP:UniProtKB
T cell differentiationISS:BHF-UCL
T cell receptor signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central

Cytoplasm

Systemic lupus erythematosus (SLE):
A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.
Diabetes mellitus, insulin-dependent (IDDM):
A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
Rheumatoid arthritis (RA):
An inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures.
Vitiligo (VTLG):
A pigmentary disorder of the skin and mucous membranes. It is characterized by circumscribed depigmented macules and patches, commonly on extensor aspects of extremities, on the face or neck and in skin folds. Vitiligo is a progressive disorder in which some or all of the melanocytes in the affected skin are selectively destroyed. It is a multifactorial disorder with a complex etiology probably including autoimmune mechanisms, and is associated with an elevated risk of other autoimmune diseases.

Phosphorylation on Ser-35 by PKC/PRKCD abrogates its ability to dephosphorylate and inactivate the SRC family kinases.