ID:TAOK2_HUMAN DESCRIPTION: RecName: Full=Serine/threonine-protein kinase TAO2; EC=2.7.11.1; AltName: Full=Kinase from chicken homolog C; Short=hKFC-C; AltName: Full=Prostate-derived sterile 20-like kinase 1; Short=PSK-1; Short=PSK1; Short=Prostate-derived STE20-like kinase 1; AltName: Full=Thousand and one amino acid protein kinase 2; FUNCTION: Serine/threonine-protein kinase involved in different processes such as membrane blebbing and apoptotic bodies formation DNA damage response and MAPK14/p38 MAPK stress-activated MAPK cascade. Phosphorylates itself, MBP, activated MAPK8, MAP2K3, MAP2K6 and tubulins. Activates the MAPK14/p38 MAPK signaling pathway through the specific activation and phosphorylation of the upstream MAP2K3 and MAP2K6 kinases. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress-activated MAPK cascade, probably by mediating phosphorylation of upstream MAP2K3 and MAP2K6 kinases. Isoform 1, but not isoform 2, plays a role in apoptotic morphological changes, including cell contraction, membrane blebbing and apoptotic bodies formation. This function, which requires the activation of MAPK8/JNK and nuclear localization of C-terminally truncated isoform 1, may be linked to the mitochondrial CASP9-associated death pathway. Isoform 1 binds to microtubules and affects their organization and stability independently of its kinase activity. Prevents MAP3K7-mediated activation of CHUK, and thus NF-kappa-B activation, but not that of MAPK8/JNK. May play a role in the osmotic stress-MAPK8 pathway. Isoform 2, but not isoform 1, is required for PCDH8 endocytosis. Following homophilic interactions between PCDH8 extracellular domains, isoform 2 phosphorylates and activates MAPK14/p38 MAPK which in turn phosphorylates isoform 2. This process leads to PCDH8 endocytosis and CDH2 cointernalization. Both isoforms are involved in MAPK14 phosphorylation. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. COFACTOR: Magnesium (By similarity). ENZYME REGULATION: Selectively inhibited by the enantiopure organoruthenium inhibitor 9E1. Activated following arsenic trioxide (As(2)O(3)) treatment. SUBUNIT: Interacts with MAP2K3 and MAP2K6 (By similarity). Self- associates. Interacts with tubulins through the C-terminal domain. Interacts with MAP3K7 and interfers with MAP3K7-binding to CHUK and thus prevents NF-kappa-B activation. Isoform 2 interacts with PCDH8; this complex may also include CDH2 (By similarity). SUBCELLULAR LOCATION: Cytoplasmic vesicle membrane; Multi-pass membrane protein (Potential). Cytoplasm, cytoskeleton. Nucleus. Note=Catalytically active full-length phosphorylated isoform 1 localizes to microtubules in the cytoplasm predominantly on microtubule cables positioned around the nucleus. A C-terminally truncated form of isoform 1 is present in the nucleus; isoform 2 and kinase-defective, as well as full-length isoform 1 are excluded from the nucleus. SUBCELLULAR LOCATION: Isoform 2: Cell projection, dendrite. Note=In dendrites, colocalizes with PCDH8 (By similarity). TISSUE SPECIFICITY: Ubiquitously expressed, with a higher level of expression in testis and brain. PTM: Isoforms 1 and 2 are autophosphorylated. PTM: C-terminal cleavage of isoform 1 and subsequent nuclear localization requires CASP9 activity. PTM: Isoform 2 is phosphorylated at 'Ser-1031' by MAPK14. This phosphorylation is required PCDH8 for endocytosis (By similarity). Autophosphorylated. Phosphorylated by ATM. SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily. SIMILARITY: Contains 1 protein kinase domain. SEQUENCE CAUTION: Sequence=AAQ89301.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=BAA74904.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF00069 - Protein kinase domain PF07714 - Protein tyrosine and serine/threonine kinase
SCOP Domains: 48371 - ARM repeat 56112 - Protein kinase-like (PK-like)
ModBase Predicted Comparative 3D Structure on Q9UL54
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000186 activation of MAPKK activity GO:0000187 activation of MAPK activity GO:0001558 regulation of cell growth GO:0006468 protein phosphorylation GO:0006612 protein targeting to membrane GO:0006915 apoptotic process GO:0006974 cellular response to DNA damage stimulus GO:0007095 mitotic G2 DNA damage checkpoint GO:0007257 activation of JUN kinase activity GO:0007346 regulation of mitotic cell cycle GO:0007399 nervous system development GO:0007409 axonogenesis GO:0008360 regulation of cell shape GO:0016310 phosphorylation GO:0016477 cell migration GO:0030036 actin cytoskeleton organization GO:0031954 positive regulation of protein autophosphorylation GO:0032147 activation of protein kinase activity GO:0032874 positive regulation of stress-activated MAPK cascade GO:0032956 regulation of actin cytoskeleton organization GO:0042981 regulation of apoptotic process GO:0046330 positive regulation of JNK cascade GO:0046777 protein autophosphorylation GO:0048041 focal adhesion assembly GO:0051403 stress-activated MAPK cascade
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
