a serine/threonine-protein kinase of the STE20 family. Activates the p38 MAPK signaling pathway through the specific activation of the upstream kinases MKK3 and MKK6. A potential multi-pass membrane protein. Activated in the DNA damage response and regulates the G2/M transition DNA damage checkpoint. Interacts with tubulins through the C-terminal domain. Involved in apoptotic processes such as membrane blebbing and apoptotic body formation. Prevents TAK1-mediated activation of IKK-alpha, and thus NF-kappa-B activation. May play a role in the osmotic stress-JNK1 pathway. An autism spectrum disorder susceptibility gene. Affects basal dendrite formation and axonal projections in cortical pyramidal neurons. Interacts with NRP1 (neuropilin 1), a receptor for the secreted guidance protein semaphorin 3A (Sema3A). Influences the formation of basal dendrites through the activation of JNK. Three isoforms of the human protein are produced by alternative splicing. Isoform 2, but not isoform 1, is required for PCDH8 endocytosis. Isoform 2 and kinase-defective, as well as full-length isoform 1 are excluded from the nucleus. 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. Note: This description may include information from UniProtKB.
Protein type: Kinase, protein; EC 184.108.40.206; Protein kinase, Ser/Thr (non-receptor); Protein kinase, STE; Membrane protein, integral; Apoptosis; Membrane protein, multi-pass; STE group; STE20 family; TAO subfamily
Cellular Component: cytoskeleton; cytoplasmic vesicle membrane; cytoplasm; cytoplasmic membrane-bound vesicle; dendrite; integral to membrane; nucleolus; nucleus; receptor complex
Molecular Function: protein serine/threonine kinase activity; MAP kinase kinase kinase activity; mitogen-activated protein kinase kinase binding; ATP binding
Biological Process: focal adhesion formation; cell migration; activation of MAPKK activity; apoptosis; stress-activated MAPK cascade; positive regulation of JNK cascade; protein amino acid phosphorylation; positive regulation of stress-activated MAPK cascade; regulation of cell shape; response to stress; regulation of cell growth; G2/M transition DNA damage checkpoint; actin cytoskeleton organization and biogenesis; protein targeting to membrane; response to DNA damage stimulus
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.