Serine/threonine-protein kinase (PubMed:23666762). Involved in cell polarity and microtubule dynamics regulation. Phosphorylates CRTC2/TORC2, DCX, HDAC7, KIF13B, MAP2, MAP4 and RAB11FIP2. Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:23666762). Plays a key role in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Regulates epithelial cell polarity by phosphorylating RAB11FIP2. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Regulates axogenesis by phosphorylating KIF13B, promoting interaction between KIF13B and 14-3-3 and inhibiting microtubule-dependent accumulation of KIF13B. Also required for neurite outgrowth and establishment of neuronal polarity. Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). Modulates the developmental decision to build a columnar versus a hepatic epithelial cell apparently by promoting a switch from a direct to a transcytotic mode of apical protein delivery. Essential for the asymmetric development of membrane domains of polarized epithelial cells. ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein] ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein] ATP + L-seryl-[tau protein] = ADP + H(+) + O-phospho-L-seryl-[tau protein] ATP + L-threonyl-[tau protein] = ADP + H(+) + O-phospho-L-threonyl-[tau protein] Inhibited by PAK5; inhibition is independent of the kinase activity of PAK5 (By similarity). Activated by phosphorylation on Thr-208. Inhibited by phosphorylation at Ser-212 and Thr-596. Inhibited by hymenialdisine. Specifically inhibited by the H.pylori CagA peptide FPLKRHDKVDDLSK that mimics host substrates and binds to the kinase substrate-binding site. Homodimer. Interacts with PAK5; leading to inhibit the protein kinase activity (By similarity). Interacts with MAPT/TAU (PubMed:23666762). Interacts with MTCL1 isoform 1; the interaction is direct and increases MARK2 microtubule-binding ability (PubMed:23902687). Interacts (when phosphorylated at Thr-596) with YWHAZ (PubMed:15324659). Interacts with YWHAB, YWHAG and YWHAQ (PubMed:16959763). (Microbial infection) In case of infection, interacts with H.pylori CagA, leading to inhibit kinase activity and junctional and polarity defects. Phosphorylation at Thr-596 by PRKCZ/aPKC and subsequent interaction with 14-3-3 protein YWHAZ promotes relocation from the cell membrane to the cytoplasm. High levels of expression in heart, brain, skeletal muscle and pancreas, lower levels observed in lung, liver and kidney. The UBA domain does not seem to bind ubiquitin and ubiquitin-like and might play a role in regulating the enzyme conformation and localization. Activation of the kinase activity following phosphorylation at Thr-208 is accompanied by a conformational change that alters the orientation of the UBA domain with respect to the catalytic domain. The KA1 domain mediates binding to phospholipids and targeting to membranes. Autophosphorylated. Phosphorylated at Thr-208 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Phosphorylation at Thr-208 by TAOK1 activates the kinase activity, leading to phosphorylation and detachment of MAPT/TAU from microtubules. Phosphorylation at Ser-212 by GSK3-beta (GSK3B) inhibits the kinase activity. Phosphorylation by CaMK1 promotes activity and is required to promote neurite outgrowth. Phosphorylation at Thr-596 by PRKCZ/aPKC in polarized epithelial cells inhibits the kinase activity and promotes binding to 14-3-3 protein YWHAZ, leading to relocation from cell membrane to cytoplasm. Produced by alternative promoter usage. Produced by alternative splicing of isoform 6. Produced by alternative splicing of isoform 6. Produced by alternative splicing of isoform 1. Produced by alternative splicing of isoform 1. Produced by alternative promoter usage. Produced by alternative splicing of isoform 6. Produced by alternative splicing of isoform 1. Produced by alternative splicing of isoform 1. Produced by alternative splicing of isoform 6. Produced by alternative splicing of isoform 1. Produced by alternative splicing of isoform 6. Produced by alternative splicing of isoform 6. Produced by alternative splicing of isoform 6. Produced by alternative splicing of isoform 1. Produced by alternative splicing of isoform 1. Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily. Truncated N-terminus.