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FLASH GENE
Symbol TNIK contributors: mct/npt - updated : 10-11-2014
HGNC name TRAF2 and NCK interacting kinase
HGNC id 30765
Location 3q26.2      Physical location : 170.780.291 - 171.178.197
Synonym symbol(s) KIAA0551, AD 2
EC.number 2.7.11.1
DNA
TYPE functioning gene
STRUCTURE 397.90 kb     33 Exon(s)
MAPPING cloned Y linked N status provisional
Map cen - D3S3656 - D3S3723 - TNIK - D3S2410 - D3S1574 - qter
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
33 - 5816 155 1360 - 2009 19816403
32 - 5792 - 1352 - 2009 19816403
32 - 5729 - 1331 - 2009 19816403
31 - 5705 - 1323 - 2009 19816403
32 - 5651 - 1305 - 2009 19816403
31 - 5627 - 1297 - 2009 19816403
31 - 5564 - 1276 - 2009 19816403
30 - 5540 - 1268 - 2009 19816403
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Endocrinethyroid   highly
Nervousbrain   highly
 nerve   highly
Reproductivemale systemtestis  highly
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • an N-terminal kinase domain homologous to STE20, the Saccharomyces cerevisiae mitogen-activated protein kinase kinase kinase kinase,
  • serine-threonine kinase and scaffold domains
  • C-terminal germinal center kinase homology region (Fu 1999), and regulatory domain termed the citron homology (CNH) domain (Taira 2004)
  • HOMOLOGY
    Homologene
    FAMILY
  • germinal centre kinase family
  • STE Ser/Thr protein kinase family
  • STE20 subfamily
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,cytoskeleton
    intracellular,nucleus
    text earlier reported to localize in the cytoplasm and interact with and phosphorylate cytoskeletal structures, but its presence in the TCF4 transcriptional complex suggested nuclear localization (Mahmoudi 2009)
    basic FUNCTION
  • a member of the germinal center kinase family that activates the c-Jun N-terminal kinase pathway and regulates the cytoskeleton (Fu 1999)
  • inducing disruption of F-actin structure, thereby inhibiting cell spreading, specific effector of RAP2A to regulate actin cytoskeleton (Taira 2004)
  • specific effector of Rap2 proteins (Uechi 2009)
  • is essential for the activation of both the canonical Wnt pathway and the JNK pathway, and serves as a pro-survival factor.
  • is a novel key player in TRAF6-dependent JNK and NF-&
  • 954;B signaling and a transducer of activating and transforming signals in human B-cells.
  • as a critical regulator of cognitive functions and suggest it may play a regulatory role in diseases impacting on its interacting proteins and complexes
  • dynamic change of TNIK offers a way to protect cells from outside stimulus
  • involved in cytoskeleton organization and neuronal dendrite extension
  • is essential for activation of WNT signaling pathway in colon cancer growth
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • NEDD4/RAP2A/TNIK signaling pathway regulates neurite growth and arborization in mammalian neurons
  • a component
  • critical component of the transcriptional regulatory complex in the Wnt-signalling pathway (Mahmoudi 2009)
  • NEDD4, the serine/threonine kinase TNIK, and RAP2A form a complex that controls NEDD4-mediated ubiquitination of RAP2A
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interaction with TANC1 (induced phosphorylation of TANC1) (Nonaka 2008)
  • interacted with RAP2A through its CNH domain but did not interact with RAP1A or Ras(Taira 2004)
  • directly binds both TCF4 and beta-catenin and phosphorylates TCF4 (Mahmoudi 2009)
  • RAP2A acts via TNIK to regulate the stability of LRP6 receptor for WNT/CTNNB signaling
  • by binding to phosphatidic acid enriched at the apical membrane, RAPGEF2 locally activates RAP2A resulting in induction of brush border formation via a pathway that includes the polarity players TNIK, MST4 and Ezrin
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerdigestivestomach
    is a novel therapeutic target in gastric cancer and TNIK amplification can be potentially used for patient selection
    ANIMAL & CELL MODELS