Tyrosine-protein phosphatase non-receptor type 22

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functionⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityⁱ

• H₂O

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  + O-phospho-L-tyrosyl-[protein]

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  = L-tyrosyl-[protein]

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  + phosphate

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  PROSITE-ProRule annotation

  <p>Manual validated information which has been generated by the UniProtKB automatic annotation system.</p> <p><a href="/manual/evidences#ECO:0000255">More...</a></p> Manual assertion according to rulesⁱ

  • PROSITE-ProRule:PRU10044

  1 Publication

  Manual assertion based on experiment inⁱ

  • Ref.20

    "Substrate specificity of lymphoid-specific tyrosine phosphatase (Lyp) and identification of Src kinase-associated protein of 55 kDa homolog (SKAP-HOM) as a Lyp substrate."
    Yu X., Chen M., Zhang S., Yu Z.H., Sun J.P., Wang L., Liu S., Imasaki T., Takagi Y., Zhang Z.Y.
    J. Biol. Chem. 286:30526-30534(2011) [PubMed] [Europe PMC] [Abstract]

    Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1-294 OF MUTANT SER-227 ALONE AND IN COMPLEX WITH SKAP2 PEPTIDE, SUBSTRATE SPECIFICITY, FUNCTION.
  EC:3.1.3.48
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  • See the description of this EC number in ENZYME.
  PROSITE-ProRule annotation

  Manual assertion according to rulesⁱ

  • PROSITE-ProRule:PRU10044
  1 Publication

  Manual assertion based on experiment inⁱ

  • Ref.20

    "Substrate specificity of lymphoid-specific tyrosine phosphatase (Lyp) and identification of Src kinase-associated protein of 55 kDa homolog (SKAP-HOM) as a Lyp substrate."
    Yu X., Chen M., Zhang S., Yu Z.H., Sun J.P., Wang L., Liu S., Imasaki T., Takagi Y., Zhang Z.Y.
    J. Biol. Chem. 286:30526-30534(2011) [PubMed] [Europe PMC] [Abstract]

    Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1-294 OF MUTANT SER-227 ALONE AND IN COMPLEX WITH SKAP2 PEPTIDE, SUBSTRATE SPECIFICITY, FUNCTION.
  Source: Rhea

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  H₂O

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  +

  O-phospho-L-tyrosyl-[protein]

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  L-tyrosine-phosphate residue

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  =

  L-tyrosyl-[protein]

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  L-tyrosine residue

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  +

  phosphate

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• H₂O

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  + N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine phosphate

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  = N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine

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  + phosphate

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  By similarity

  Manual assertion inferred from sequence similarity toⁱ

  • UniProtKB:P29352 (PTN22_MOUSE)
  This reaction proceeds in the forward

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  • See the description of this reaction in Rhea.

  By similarity

  Manual assertion inferred from sequence similarity toⁱ

  • UniProtKB:P29352 (PTN22_MOUSE)

  direction.
  Source: Rhea

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  H₂O

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  +

  N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine phosphate

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  zoom

  =

  N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine

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  +

  phosphate

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<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationⁱ

Sites

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functionⁱ

• kinase binding Source: BHF-UCL
• non-membrane spanning protein tyrosine phosphatase activity Source: GO_Central <p>Inferred from Biological aspect of Ancestor</p> <p>A type of phylogenetic evidence whereby an aspect of a descendent is inferred through the characterization of an aspect of a ancestral gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#iba">GO evidence code guide</a></p> Inferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• phosphatase activity Source: UniProtKB <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ
  • Ref.14

    "Protein tyrosine phosphatase non-receptor type 22 modulates NOD2-induced cytokine release and autophagy."
    Spalinger M.R., Lang S., Vavricka S.R., Fried M., Rogler G., Scharl M.
    PLoS ONE 8:E72384-E72384(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• protein tyrosine phosphatase activity Source: UniProtKBInferred from direct assayⁱ
  • Ref.15

    "Structure, inhibitor, and regulatory mechanism of Lyp, a lymphoid-specific tyrosine phosphatase implicated in autoimmune diseases."
    Yu X., Sun J.P., He Y., Guo X., Liu S., Zhou B., Hudmon A., Zhang Z.Y.
    Proc. Natl. Acad. Sci. U.S.A. 104:19767-19772(2007) [PubMed] [Europe PMC] [Abstract]

    Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-294 IN COMPLEX WITH INHIBITOR, FUNCTION, PHOSPHORYLATION AT SER-35, MUTAGENESIS OF SER-35 AND THR-36.
• SH3 domain binding Source: BHF-UCL
• ubiquitin protein ligase binding Source: UniProtKB <p>Inferred from Physical Interaction</p> <p>Covers physical interactions between the gene product of interest and another molecule (or ion, or complex).</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ipi">GO evidence code guide</a></p> Inferred from physical interactionⁱ
  • Ref.12

    "The autoimmunity-associated gene PTPN22 potentiates toll-like receptor-driven, type 1 interferon-dependent immunity."
    Wang Y., Shaked I., Stanford S.M., Zhou W., Curtsinger J.M., Mikulski Z., Shaheen Z.R., Cheng G., Sawatzke K., Campbell A.M., Auger J.L., Bilgic H., Shoyama F.M., Schmeling D.O., Balfour H.H. Jr., Hasegawa K., Chan A.C., Corbett J.A.

    , Binstadt B.A., Mescher M.F., Ley K., Bottini N., Peterson E.J.
    Immunity 39:111-122(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, INTERACTION WITH TRAF3.

GO - Biological processⁱ

• autophagy Source: UniProtKB-KW
• cellular response to muramyl dipeptide Source: UniProtKBInferred from direct assayⁱ
  • Ref.14

    "Protein tyrosine phosphatase non-receptor type 22 modulates NOD2-induced cytokine release and autophagy."
    Spalinger M.R., Lang S., Vavricka S.R., Fried M., Rogler G., Scharl M.
    PLoS ONE 8:E72384-E72384(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• lipopolysaccharide-mediated signaling pathway Source: UniProtKB <p>Inferred from Mutant Phenotype</p> <p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypeⁱ
  • Ref.14

    "Protein tyrosine phosphatase non-receptor type 22 modulates NOD2-induced cytokine release and autophagy."
    Spalinger M.R., Lang S., Vavricka S.R., Fried M., Rogler G., Scharl M.
    PLoS ONE 8:E72384-E72384(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• negative regulation of autophagy Source: UniProtKBInferred from mutant phenotypeⁱ
  • Ref.14

    "Protein tyrosine phosphatase non-receptor type 22 modulates NOD2-induced cytokine release and autophagy."
    Spalinger M.R., Lang S., Vavricka S.R., Fried M., Rogler G., Scharl M.
    PLoS ONE 8:E72384-E72384(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• negative regulation of gene expression Source: UniProtKBInferred from mutant phenotypeⁱ
  • Ref.14

    "Protein tyrosine phosphatase non-receptor type 22 modulates NOD2-induced cytokine release and autophagy."
    Spalinger M.R., Lang S., Vavricka S.R., Fried M., Rogler G., Scharl M.
    PLoS ONE 8:E72384-E72384(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• negative regulation of interleukin-6 production Source: UniProtKBInferred from mutant phenotypeⁱ
  • Ref.14

    "Protein tyrosine phosphatase non-receptor type 22 modulates NOD2-induced cytokine release and autophagy."
    Spalinger M.R., Lang S., Vavricka S.R., Fried M., Rogler G., Scharl M.
    PLoS ONE 8:E72384-E72384(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• negative regulation of interleukin-8 production Source: UniProtKBInferred from mutant phenotypeⁱ
  • Ref.14

    "Protein tyrosine phosphatase non-receptor type 22 modulates NOD2-induced cytokine release and autophagy."
    Spalinger M.R., Lang S., Vavricka S.R., Fried M., Rogler G., Scharl M.
    PLoS ONE 8:E72384-E72384(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• negative regulation of JUN kinase activity Source: UniProtKBInferred from mutant phenotypeⁱ
  • Ref.14

    "Protein tyrosine phosphatase non-receptor type 22 modulates NOD2-induced cytokine release and autophagy."
    Spalinger M.R., Lang S., Vavricka S.R., Fried M., Rogler G., Scharl M.
    PLoS ONE 8:E72384-E72384(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway Source: UniProtKBInferred from mutant phenotypeⁱ
  • Ref.14

    "Protein tyrosine phosphatase non-receptor type 22 modulates NOD2-induced cytokine release and autophagy."
    Spalinger M.R., Lang S., Vavricka S.R., Fried M., Rogler G., Scharl M.
    PLoS ONE 8:E72384-E72384(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• negative regulation of p38MAPK cascade Source: UniProtKBInferred from mutant phenotypeⁱ
  • Ref.14

    "Protein tyrosine phosphatase non-receptor type 22 modulates NOD2-induced cytokine release and autophagy."
    Spalinger M.R., Lang S., Vavricka S.R., Fried M., Rogler G., Scharl M.
    PLoS ONE 8:E72384-E72384(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• negative regulation of T cell activation Source: BHF-UCLInferred from mutant phenotypeⁱ
  • "Reduced CD4+T cell activation in children with type 1 diabetes carrying the PTPN22/Lyp 620Trp variant."
    Aarnisalo J., Treszl A., Svec P., Marttila J., Oling V., Simell O., Knip M., Korner A., Madacsy L., Vasarhelyi B., Ilonen J., Hermann R.
    J Autoimmun 31:13-21(2008) [PubMed] [Europe PMC] [Abstract]
• negative regulation of T cell receptor signaling pathway Source: UniProtKBInferred from direct assayⁱ
  • Ref.15

    "Structure, inhibitor, and regulatory mechanism of Lyp, a lymphoid-specific tyrosine phosphatase implicated in autoimmune diseases."
    Yu X., Sun J.P., He Y., Guo X., Liu S., Zhou B., Hudmon A., Zhang Z.Y.
    Proc. Natl. Acad. Sci. U.S.A. 104:19767-19772(2007) [PubMed] [Europe PMC] [Abstract]

    Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-294 IN COMPLEX WITH INHIBITOR, FUNCTION, PHOSPHORYLATION AT SER-35, MUTAGENESIS OF SER-35 AND THR-36.
• negative regulation of tumor necrosis factor production Source: UniProtKBInferred from mutant phenotypeⁱ
  • Ref.14

    "Protein tyrosine phosphatase non-receptor type 22 modulates NOD2-induced cytokine release and autophagy."
    Spalinger M.R., Lang S., Vavricka S.R., Fried M., Rogler G., Scharl M.
    PLoS ONE 8:E72384-E72384(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• peptidyl-tyrosine dephosphorylation Source: GO_CentralInferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• phosphoanandamide dephosphorylation Source: BHF-UCL
• positive regulation of CD8-positive, alpha-beta T cell proliferation Source: GO_CentralInferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• positive regulation of defense response to virus by host Source: GO_CentralInferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• positive regulation of ERK1 and ERK2 cascade Source: UniProtKBInferred from mutant phenotypeⁱ
  • Ref.14

    "Protein tyrosine phosphatase non-receptor type 22 modulates NOD2-induced cytokine release and autophagy."
    Spalinger M.R., Lang S., Vavricka S.R., Fried M., Rogler G., Scharl M.
    PLoS ONE 8:E72384-E72384(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• positive regulation of gene expression Source: UniProtKBInferred from mutant phenotypeⁱ
  • Ref.12

    "The autoimmunity-associated gene PTPN22 potentiates toll-like receptor-driven, type 1 interferon-dependent immunity."
    Wang Y., Shaked I., Stanford S.M., Zhou W., Curtsinger J.M., Mikulski Z., Shaheen Z.R., Cheng G., Sawatzke K., Campbell A.M., Auger J.L., Bilgic H., Shoyama F.M., Schmeling D.O., Balfour H.H. Jr., Hasegawa K., Chan A.C., Corbett J.A.

    , Binstadt B.A., Mescher M.F., Ley K., Bottini N., Peterson E.J.
    Immunity 39:111-122(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, INTERACTION WITH TRAF3.
  • Ref.14

    "Protein tyrosine phosphatase non-receptor type 22 modulates NOD2-induced cytokine release and autophagy."
    Spalinger M.R., Lang S., Vavricka S.R., Fried M., Rogler G., Scharl M.
    PLoS ONE 8:E72384-E72384(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• positive regulation of granzyme B production Source: GO_CentralInferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• positive regulation of interferon-gamma production Source: UniProtKBInferred from mutant phenotypeⁱ
  • Ref.14

    "Protein tyrosine phosphatase non-receptor type 22 modulates NOD2-induced cytokine release and autophagy."
    Spalinger M.R., Lang S., Vavricka S.R., Fried M., Rogler G., Scharl M.
    PLoS ONE 8:E72384-E72384(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• positive regulation of protein K63-linked ubiquitination Source: UniProtKBInferred from mutant phenotypeⁱ
  • Ref.12

    "The autoimmunity-associated gene PTPN22 potentiates toll-like receptor-driven, type 1 interferon-dependent immunity."
    Wang Y., Shaked I., Stanford S.M., Zhou W., Curtsinger J.M., Mikulski Z., Shaheen Z.R., Cheng G., Sawatzke K., Campbell A.M., Auger J.L., Bilgic H., Shoyama F.M., Schmeling D.O., Balfour H.H. Jr., Hasegawa K., Chan A.C., Corbett J.A.

    , Binstadt B.A., Mescher M.F., Ley K., Bottini N., Peterson E.J.
    Immunity 39:111-122(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, INTERACTION WITH TRAF3.
• positive regulation of toll-like receptor 3 signaling pathway Source: UniProtKBInferred from mutant phenotypeⁱ
  • Ref.12

    "The autoimmunity-associated gene PTPN22 potentiates toll-like receptor-driven, type 1 interferon-dependent immunity."
    Wang Y., Shaked I., Stanford S.M., Zhou W., Curtsinger J.M., Mikulski Z., Shaheen Z.R., Cheng G., Sawatzke K., Campbell A.M., Auger J.L., Bilgic H., Shoyama F.M., Schmeling D.O., Balfour H.H. Jr., Hasegawa K., Chan A.C., Corbett J.A.

    , Binstadt B.A., Mescher M.F., Ley K., Bottini N., Peterson E.J.
    Immunity 39:111-122(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, INTERACTION WITH TRAF3.
• positive regulation of toll-like receptor 4 signaling pathway Source: UniProtKBInferred from mutant phenotypeⁱ
  • Ref.12

    "The autoimmunity-associated gene PTPN22 potentiates toll-like receptor-driven, type 1 interferon-dependent immunity."
    Wang Y., Shaked I., Stanford S.M., Zhou W., Curtsinger J.M., Mikulski Z., Shaheen Z.R., Cheng G., Sawatzke K., Campbell A.M., Auger J.L., Bilgic H., Shoyama F.M., Schmeling D.O., Balfour H.H. Jr., Hasegawa K., Chan A.C., Corbett J.A.

    , Binstadt B.A., Mescher M.F., Ley K., Bottini N., Peterson E.J.
    Immunity 39:111-122(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, INTERACTION WITH TRAF3.
• positive regulation of toll-like receptor 7 signaling pathway Source: GO_CentralInferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• positive regulation of toll-like receptor 9 signaling pathway Source: GO_CentralInferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• positive regulation of type I interferon production Source: UniProtKBInferred from mutant phenotypeⁱ
  • Ref.12

    "The autoimmunity-associated gene PTPN22 potentiates toll-like receptor-driven, type 1 interferon-dependent immunity."
    Wang Y., Shaked I., Stanford S.M., Zhou W., Curtsinger J.M., Mikulski Z., Shaheen Z.R., Cheng G., Sawatzke K., Campbell A.M., Auger J.L., Bilgic H., Shoyama F.M., Schmeling D.O., Balfour H.H. Jr., Hasegawa K., Chan A.C., Corbett J.A.

    , Binstadt B.A., Mescher M.F., Ley K., Bottini N., Peterson E.J.
    Immunity 39:111-122(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, INTERACTION WITH TRAF3.
• protein dephosphorylation Source: BHF-UCLInferred from direct assayⁱ
  • Ref.1

    "Cloning and characterization of a lymphoid-specific, inducible human protein tyrosine phosphatase, Lyp."
    Cohen S., Dadi H., Shaoul E., Sharfe N., Roifman C.M.
    Blood 93:2013-2024(1999) [PubMed] [Europe PMC] [Abstract]

    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), INTERACTION WITH CBL.
• regulation of B cell receptor signaling pathway Source: BHF-UCL <p>Non-traceable Author Statement</p> <p>Used for statements in the abstract, introduction or discussion of a paper that cannot be traced back to another publication.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#nas">GO evidence code guide</a></p> Non-traceable author statementⁱ
  • Ref.27

    "Cutting edge: the PTPN22 allelic variant associated with autoimmunity impairs B cell signaling."
    Arechiga A.F., Habib T., He Y., Zhang X., Zhang Z.Y., Funk A., Buckner J.H.
    J. Immunol. 182:3343-3347(2009) [PubMed] [Europe PMC] [Abstract]

    Cited for: VARIANT TRP-620, CHARACTERIZATION OF VARIANT TRP-620.
• regulation of innate immune response Source: BHF-UCL <p>Inferred by Curator</p> <p>Used for cases where an annotation is not supported by any evidence but can be reasonably inferred by a curator from other GO annotations for which evidence<br />is available.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ic">GO evidence code guide</a></p> Inferred by curatorⁱ
  • "PTPN22 gene regulates natural killer cell proliferation during in vitro expansion."
    Douroudis K., Shcherbakova A., Everaus H., Aints A.
    Tissue Antigens 76:315-318(2010) [PubMed] [Europe PMC] [Abstract]
• regulation of natural killer cell proliferation Source: BHF-UCLInferred from direct assayⁱ
  • "PTPN22 gene regulates natural killer cell proliferation during in vitro expansion."
    Douroudis K., Shcherbakova A., Everaus H., Aints A.
    Tissue Antigens 76:315-318(2010) [PubMed] [Europe PMC] [Abstract]
• regulation of NIK/NF-kappaB signaling Source: UniProtKBInferred from mutant phenotypeⁱ
  • Ref.14

    "Protein tyrosine phosphatase non-receptor type 22 modulates NOD2-induced cytokine release and autophagy."
    Spalinger M.R., Lang S., Vavricka S.R., Fried M., Rogler G., Scharl M.
    PLoS ONE 8:E72384-E72384(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• response to lipopolysaccharide Source: UniProtKBInferred from mutant phenotypeⁱ
  • Ref.12

    "The autoimmunity-associated gene PTPN22 potentiates toll-like receptor-driven, type 1 interferon-dependent immunity."
    Wang Y., Shaked I., Stanford S.M., Zhou W., Curtsinger J.M., Mikulski Z., Shaheen Z.R., Cheng G., Sawatzke K., Campbell A.M., Auger J.L., Bilgic H., Shoyama F.M., Schmeling D.O., Balfour H.H. Jr., Hasegawa K., Chan A.C., Corbett J.A.

    , Binstadt B.A., Mescher M.F., Ley K., Bottini N., Peterson E.J.
    Immunity 39:111-122(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, INTERACTION WITH TRAF3.
• T cell differentiation Source: BHF-UCL
• T cell receptor signaling pathway Source: GO_CentralInferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsⁱ

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyⁱ

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationⁱ

• UniProt annotation
• GO - Cellular component

Keywords - Cellular componentⁱ

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechⁱ

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseaseⁱ

Mutagenesis

Keywords - Diseaseⁱ

Organism-specific databases

Miscellaneous databases

Chemistry databases

Genetic variation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingⁱ

Molecule processing

Amino acid modifications

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationⁱ

Keywords - PTMⁱ

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressionⁱ

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityⁱ

<p>This subsection of the 'Expression' section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductionⁱ

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactionⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structureⁱ

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsⁱ

GO - Molecular functionⁱ

• kinase binding Source: BHF-UCL
• SH3 domain binding Source: BHF-UCL
• ubiquitin protein ligase binding Source: UniProtKBInferred from physical interactionⁱ
  • Ref.12

    "The autoimmunity-associated gene PTPN22 potentiates toll-like receptor-driven, type 1 interferon-dependent immunity."
    Wang Y., Shaked I., Stanford S.M., Zhou W., Curtsinger J.M., Mikulski Z., Shaheen Z.R., Cheng G., Sawatzke K., Campbell A.M., Auger J.L., Bilgic H., Shoyama F.M., Schmeling D.O., Balfour H.H. Jr., Hasegawa K., Chan A.C., Corbett J.A.

    , Binstadt B.A., Mescher M.F., Ley K., Bottini N., Peterson E.J.
    Immunity 39:111-122(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, INTERACTION WITH TRAF3.

Protein-protein interaction databases

Chemistry databases

Miscellaneous databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structureⁱ

Secondary structure

3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsⁱ

Domains and Repeats

Region

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesⁱ

Phylogenomic databases

Family and domain databases

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (6+)ⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusⁱ: Complete.

This entry has 6 described isoforms and 7 potential isoforms that are computationally mapped.Show allAlign All

        10         20         30         40         50
MDQREILQKF LDEAQSKKIT KEEFANEFLK LKRQSTKYKA DKTYPTTVAE 
        60         70         80         90        100
KPKNIKKNRY KDILPYDYSR VELSLITSDE DSSYINANFI KGVYGPKAYI 
       110        120        130        140        150
ATQGPLSTTL LDFWRMIWEY SVLIIVMACM EYEMGKKKCE RYWAEPGEMQ 
       160        170        180        190        200
LEFGPFSVSC EAEKRKSDYI IRTLKVKFNS ETRTIYQFHY KNWPDHDVPS 
       210        220        230        240        250
SIDPILELIW DVRCYQEDDS VPICIHCSAG CGRTGVICAI DYTWMLLKDG 
       260        270        280        290        300
IIPENFSVFS LIREMRTQRP SLVQTQEQYE LVYNAVLELF KRQMDVIRDK 
       310        320        330        340        350
HSGTESQAKH CIPEKNHTLQ ADSYSPNLPK STTKAAKMMN QQRTKMEIKE 
       360        370        380        390        400
SSSFDFRTSE ISAKEELVLH PAKSSTSFDF LELNYSFDKN ADTTMKWQTK 
       410        420        430        440        450
AFPIVGEPLQ KHQSLDLGSL LFEGCSNSKP VNAAGRYFNS KVPITRTKST 
       460        470        480        490        500
PFELIQQRET KEVDSKENFS YLESQPHDSC FVEMQAQKVM HVSSAELNYS 
       510        520        530        540        550
LPYDSKHQIR NASNVKHHDS SALGVYSYIP LVENPYFSSW PPSGTSSKMS 
       560        570        580        590        600
LDLPEKQDGT VFPSSLLPTS STSLFSYYNS HDSLSLNSPT NISSLLNQES 
       610        620        630        640        650
AVLATAPRID DEIPPPLPVR TPESFIVVEE AGEFSPNVPK SLSSAVKVKI 
       660        670        680        690        700
GTSLEWGGTS EPKKFDDSVI LRPSKSVKLR SPKSELHQDR SSPPPPLPER 
       710        720        730        740        750
TLESFFLADE DCMQAQSIET YSTSYPDTME NSTSSKQTLK TPGKSFTRSK 
       760        770        780        790        800
SLKILRNMKK SICNSCPPNK PAESVQSNNS SSFLNFGFAN RFSKPKGPRN 

PPPTWNI                                                

        10         20         30         40         50
MDQREILQKF LDEAQSKKIT KEEFANEFLK LKRQSTKYKA DKTYPTTVAE 
        60         70         80         90        100
KPKNIKKNRY KDILPYDYSR VELSLITSDE DSSYINANFI KGVYGPKAYI 
       110        120        130        140        150
ATQGPLSTTL LDFWRMIWEY SVLIIVMACM EYEMGKKKCE RYWAEPGEMQ 
       160        170        180        190        200
LEFGPFSVSC EAEKRKSDYI IRTLKVKFNS ETRTIYQFHY KNWPDHDVPS 
       210        220        230        240        250
SIDPILELIW DVRCYQEDDS VPICIHCSAG CGRTGVICAI DYTWMLLKDG 
       260        270        280        290        300
IIPENFSVFS LIREMRTQRP SLVQTQEQYE LVYNAVLELF KRQMDVIRDK 
       310        320        330        340        350
HSGTESQAKH CIPEKNHTLQ ADSYSPNLPK STTKAAKMMN QQRTKMEIKE 
       360        370        380        390        400
SSSFDFRTSE ISAKEELVLH PAKSSTSFDF LELNYSFDKN ADTTMKWQTK 
       410        420        430        440        450
AFPIVGEPLQ KHQSLDLGSL LFEGCSNSKP VNAAGRYFNS KVPITRTKST 
       460        470        480        490        500
PFELIQQRET KEVDSKENFS YLESQPHDSC FVEMQAQKVM HVSSAELNYS 
       510        520        530        540        550
LPYDSKHQIR NASNVKHHDS SALGVYSYIP LVENPYFSSW PPSGTSSKMS 
       560        570        580        590        600
LDLPEKQDGT VFPSSLLPTS STSLFSYYNS HDSLSLNSPT NISSLLNQES 
       610        620        630        640        650
AVLATAPRID DEIPPPLPVR TPESFIVVEE AGEFSPNVPK SLSSAVKVKI 
       660        670        680        690 
GTSLEWGGTS EPKKFDDSVI LRPSKSVKLR SPKSGKNFSW L          

        10         20         30         40         50
MDQREILQKF LDEAQSKKIT KEEFANEFLK LKRQSTKYKA DKTYPTTVAE 
        60         70         80         90        100
KPKNIKKNRY KDILPYDYSR VELSLITSDE DSSYINANFI KGVYGPKAYI 
       110        120        130        140        150
ATQGPLSTTL LDFWRMIWEY SVLIIVMACM EYEMGKKKCE RYWAEPGEMQ 
       160        170        180        190        200
LEFGPFSVSC EAEKRKSDYI IRTLKVKFNS ETRTIYQFHY KNWPDHDVPS 
       210        220        230        240        250
SIDPILELIW DVRCYQEDDS VPICIHCSAG CGRTGVICAI DYTWMLLKDG 
       260        270        280        290        300
SQAKHCIPEK NHTLQADSYS PNLPKSTTKA AKMMNQQRTK MEIKESSSFD 
       310        320        330        340        350
FRTSEISAKE ELVLHPAKSS TSFDFLELNY SFDKNADTTM KWQTKAFPIV 
       360        370        380        390        400
GEPLQKHQSL DLGSLLFEGC SNSKPVNAAG RYFNSKVPIT RTKSTPFELI 
       410        420        430        440        450
QQRETKEVDS KENFSYLESQ PHDSCFVEMQ AQKVMHVSSA ELNYSLPYDS 
       460        470        480        490        500
KHQIRNASNV KHHDSSALGV YSYIPLVENP YFSSWPPSGT SSKMSLDLPE 
       510        520        530        540        550
KQDGTVFPSS LLPTSSTSLF SYYNSHDSLS LNSPTNISSL LNQESAVLAT 
       560        570        580        590        600
APRIDDEIPP PLPVRTPESF IVVEEAGEFS PNVPKSLSSA VKVKIGTSLE 
       610        620        630        640        650
WGGTSEPKKF DDSVILRPSK SVKLRSPKSE LHQDRSSPPP PLPERTLESF 
       660        670        680        690        700
FLADEDCMQA QSIETYSTSY PDTMENSTSS KQTLKTPGKS FTRSKSLKIL 
       710        720        730        740        750
RNMKKSICNS CPPNKPAESV QSNNSSSFLN FGFANRFSKP KGPRNPPPTW 

NI                                                     

        10         20         30         40         50
MDQREILQKF LDEAQSKKIT KEEFANEFLK LKRQSTKYKA DKTYPTTVAE 
        60         70         80         90        100
KPKNIKKNRY KDILPYDYSR VELSLITSDE DSSYINANFI KGVYGPKAYI 
       110        120        130        140        150
ATQGPLSTTL LDFWRMIWEY SVLIIVMACM EYEMGKKKCE RYWAEPGEMQ 
       160        170        180        190        200
LEFGPFSVSC EAEKRKSDYI IRTLKVKFNS ETRTIYQFHY KNWPDHDVPS 
       210        220        230        240        250
SIDPILELIW DVRCYQEDDS VPICIHCSAG CGRTGVICAI DYTWMLLKDG 
       260        270        280        290        300
IIPENFSVFS LIREMRTQRP SLVQTQEQYE LVYNAVLELF KRQMDVIRDK 
       310        320        330        340        350
HSGTESQAKH CIPEKNHTLQ ADSYSPNLPK STTKAAKMMN QQRTKMEIKE 
       360        370        380        390        400
SSSFDFRTSE ISAKEELVLH PAKSSTSFDF LELNYSFDKN ADTTMKWQTK 
       410        420        430        440        450
AFPIVGEPLQ KHQSLDLGSL LFEGCSNSKP VNAAGRYFNS KVPITRTKST 
       460        470        480        490        500
PFELIQQRET KEVDSKENFS YLESQPHDSC FVEMQAQKVM HVSSAELNYS 
       510        520        530        540        550
LPYDSKHQIR NASNVKHHDS SALGVYSYIP LVENPYFSSW PPSGTSSKMS 
       560        570        580        590        600
LDLPEKQDGT VFPSSLLPTS STSLFSYYNS HDSLSLNSPT NISSLLNQES 
       610        620        630        640        650
AVLATAPRID DEIPPPLPVR TPESFIVVEE AGEFSPNVPK SLSSAVKSVK 
       660        670        680        690        700
LRSPKSELHQ DRSSPPPPLP ERTLESFFLA DEDCMQAQSI ETYSTSYPDT 
       710        720        730        740        750
MENSTSSKQT LKTPGKSFTR SKSLKILRNM KKSICNSCPP NKPAESVQSN 
       760        770 
NSSSFLNFGF ANRFSKPKGP RNPPPTWNI                        

        10         20         30         40         50
MDQREILQKF LDEAQSKKIT KEEFANEFLK LKRQSTKYKA DKTYPTTVAE 
        60         70         80         90        100
KPKNIKKNRY KDILPYDYSR VELSLITSDE DSSYINANFI KGVYGPKAYI 
       110        120        130        140        150
ATQGPLSTTL LDFWRMIWEY SVLIIVMACM EYEMGKEAEK RKSDYIIRTL 
       160        170 
KVKFNSVSVI LAHQTSLQNL FSQITPAHF                        

        10         20         30         40         50
MDQREILQKF LDEAQSKKIT KEEFANEFLK LKRQSTKYKA DKTYPTTVAE 
        60         70         80         90        100
KPKNIKKNRY KDILPYDYSR VELSLITSDE DSSYINANFI KGVYGPKAYI 
       110        120        130        140        150
ATQGPLSTTL LDFWRMIWEY SVLIIPENFS VFSLIREMRT QRPSLVQTQE 
       160        170        180        190        200
QYELVYNAVL ELFKRQMDVI RDKHSGTESQ AKHCIPEKNH TLQADSYSPN 
       210        220        230        240        250
LPKSTTKAAK MMNQQRTKME IKESSSFDFR TSEISAKEEL VLHPAKSSTS 
       260        270        280        290        300
FDFLELNYSF DKNADTTMKW QTKAFPIVGE PLQKHQSLDL GSLLFEGCSN 
       310        320        330        340        350
SKPVNAAGRY FNSKVPITRT KSTPFELIQQ RETKEVDSKE NFSYLESQPH 
       360        370        380        390        400
DSCFVEMQAQ KVMHVSSAEL NYSLPYDSKH QIRNASNVKH HDSSALGVYS 
       410        420        430        440        450
YIPLVENPYF SSWPPSGTSS KMSLDLPEKQ DGTVFPSSLL PTSSTSLFSY 
       460        470        480        490        500
YNSHDSLSLN SPTNISSLLN QESAVLATAP RIDDEIPPPL PVRTPESFIV 
       510        520        530        540        550
VEEAGEFSPN VPKSLSSAVK VKIGTSLEWG GTSEPKKFDD SVILRPSKSV 
       560        570        580        590        600
KLRSPKSELH QDRSSPPPPL PERTLESFFL ADEDCMQAQS IETYSTSYPD 
       610        620        630        640        650
TMENSTSSKQ TLKTPGKSFT RSKSLKILRN MKKSICNSCP PNKPAESVQS 
       660 
NNSSSFLNFG MCVILLKS                                    

Experimental Info

Natural variant