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FLASH GENE
Symbol TYK2 contributors: mct/npt - updated : 06-09-2017
HGNC name tyrosine kinase 2
HGNC id 12440
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a pseudokinase domain tandemly linked to the N site of the former
  • five JAK homology (JH) domains, and JH2, which did not show phosphotransfer activity, but binds ATP and the nucleotide binding stabilizes the protein without inducing major conformational changes
  • C terminal kinase domain
  • HOMOLOGY
    Homologene
    FAMILY
  • protein kinase superfamily
  • Tyr protein kinase family
  • JAK subfamily
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton
    intracellular,nucleus
    basic FUNCTION
  • important modulator of the urokinase-directed vascular smooth muscle cell functional behaviour at the place of injury
  • mediating the activation of STAT proteins
  • involved in signal transduction of cytokine receptors
  • specifically interacts with the proapoptotic protein SIVA1 via its N-terminus region and augments the apoptotic effects induced by SIVA1 through the TYK2-SIVA1 interaction independently of the phosphorylation of SIVA1 by TYK2
  • role of TYK2 in suppressing the growth and metastasis of breast cancer
  • mediates signals triggered by various cytokines, which are related to the pathogenesis of psoriasis
  • essential for proper signaling in immune responses and development
  • protein kinase involved in interleukin 12 (IL12) pathway, which is a well-known player in the pathogenesis of systemic sclerosis (SSc)
  • participates in signaling through cytokine receptors involved in immune responses and inflammation
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • forms a functional complex with SIVA1 and participates in the transduction of signals that inhibit B lymphocyte growth
  • fundamental component of IFNR complex
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • PTPN1 in response to interferon stimulation
  • interacting with IFNAR1 and IRF5
  • TYK2 controls STAT1 and STAT6 activation in response to IL13 stimulation
  • biological processes that require TYK2 catalytic function in humans are restricted to the IL12 and IL23 pathway (pMID: 23894201)
  • TYK2 directly regulated IL22-dependent inflammation and epidermal hyperplasia
  • TYK2-IFNAR1 interface reveals an unexpected receptor-binding mode that mimics a SH2 domain-phosphopeptide interaction, with a glutamate replacing the canonical phosphotyrosine residue
  • TYK2 protects against acute colitis in part by amplifying inflammation-induced epithelial IL22 signaling to STAT3
  • like SRC, TYK2 can also inhibit gap junction communication by phosphorylating GJA1 (
  • cell & other
    REGULATION
    activated by exposure of cells to different cytokines and growth factors
    ASSOCIATED DISORDERS
    corresponding disease(s) HIES3 , MSSL6
    Susceptibility
  • to lupus erythematosus
  • to multiple sclerosis
  • to systemic sclerosis (SSc)
  • Variant & Polymorphism SNP
  • increasing the risk of lupus erythematosus
  • rare functional variant within the TYK2 gene (rs34536443) has been reported as protective in multiple sclerosis (Ban 2009)
  • strong association observed for V362F with SSc
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    immunologyautoimmune 
    TYK2 pseudokinase stabilizers, represent a novel approach to the design of potent and selective agents for the treatment of autoimmunity
    dermatologyskin 
    therapeutic potential of TYK2 inhibition in human psoriasis
    ANIMAL & CELL MODELS