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MGP004571

UniProt Annotations

Entry Information
Gene NameTRAF2 and NCK interacting kinase
Protein EntryTNIK_HUMAN
UniProt IDQ9UKE5
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=8; Name=1; IsoId=Q9UKE5-1; Sequence=Displayed; Name=2; IsoId=Q9UKE5-2; Sequence=VSP_004889; Name=3; IsoId=Q9UKE5-3; Sequence=VSP_004890; Name=4; IsoId=Q9UKE5-4; Sequence=VSP_004891; Name=5; IsoId=Q9UKE5-5; Sequence=VSP_004889, VSP_004890; Name=6; IsoId=Q9UKE5-6; Sequence=VSP_004889, VSP_004891; Name=7; IsoId=Q9UKE5-7; Sequence=VSP_004890, VSP_004891; Name=8; IsoId=Q9UKE5-8; Sequence=VSP_004889, VSP_004890, VSP_004891;
Catalytic ActivityATP + a protein = ADP + a phosphoprotein. {ECO:0000269|PubMed:10521462}.
FunctionSerine/threonine kinase that acts as an essential activator of the Wnt signaling pathway. Recruited to promoters of Wnt target genes and required to activate their expression. May act by phosphorylating TCF4/TCF7L2. Appears to act upstream of the JUN N-terminal pathway. May play a role in the response to environmental stress. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. More generally, it may play a role in cytoskeletal rearrangements and regulate cell spreading. Phosphorylates SMAD1 on Thr-322. {ECO:0000269|PubMed:10521462, ECO:0000269|PubMed:15342639, ECO:0000269|PubMed:19061864, ECO:0000269|PubMed:19816403, ECO:0000269|PubMed:20159449, ECO:0000269|PubMed:21690388}.
InteractionP35222:CTNNB1; NbExp=3; IntAct=EBI-1051794, EBI-491549; Q6F6B3:Tanc1 (xeno); NbExp=2; IntAct=EBI-1051794, EBI-2133582; Q9NQB0:TCF7L2; NbExp=3; IntAct=EBI-1051794, EBI-924724;
PtmAutophosphorylated. Autophosphorylation is activated by RAP2A and induces association to the cytoskeletal fraction. {ECO:0000269|PubMed:15144186, ECO:0000269|PubMed:18088087, ECO:0000269|PubMed:18669648, ECO:0000269|PubMed:18691976, ECO:0000269|PubMed:19369195, ECO:0000269|PubMed:21406692}.
Sequence CautionSequence=BAA25477.2; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
SimilarityBelongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily. {ECO:0000305}.
SimilarityContains 1 CNH domain. {ECO:0000255|PROSITE- ProRule:PRU00795}.
SimilarityContains 1 protein kinase domain. {ECO:0000255|PROSITE-ProRule:PRU00159}.
Subcellular LocationNucleus. Cytoplasm. Recycling endosome. Cytoplasm, cytoskeleton. Note=Associated with recycling endosomes and the cytoskeletal fraction upon RAP2A overexpression.
SubunitInteracts (via the CNH domain) with RAP2A (GTP-bound form preferentially); the interaction is direct and required for the activation of TNIK by RAP2A. Interacts with NEDD4; recruits RAP2A to NEDD4. Interacts with TRAF2 and NCK. Interacts with TCF7L2/TCF4 and CTNNB1; the interaction is direct. Interacts with TANC1. {ECO:0000269|PubMed:10521462, ECO:0000269|PubMed:15342639, ECO:0000269|PubMed:18930710, ECO:0000269|PubMed:19816403, ECO:0000269|PubMed:20159449}.
Tissue SpecificityExpressed ubiquitously. Highest levels observed in heart, brain and skeletal muscle. Expressed in normal colonic epithelia and colorectal cancer tissues. {ECO:0000269|PubMed:10521462, ECO:0000269|PubMed:19816403}.
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