MARK1
Domain
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 (By similarity).
The KA1 domain mediates binding to phospholipids and targeting to membranes. Binds phosphatidic acid (PA), phosphatidylserine (PtdSer) and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2).
Function
Serine/threonine-protein kinase (PubMed:23666762). Involved in cell polarity and microtubule dynamics regulation. Phosphorylates DCX, MAP2 and MAP4. Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:23666762). Involved in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3).
Involvement in disease
Genetic variations in MARK1 may be associated with susceptibility to autism. MARK1 is overexpressed in the prefrontal cortex of patients with autism and causes changes in the function of cortical dendrites.
Post-translational modifications
Phosphorylation at Thr-613 by PRKCZ/aPKC in polarized epithelial cells inhibits the kinase activity (By similarity). Phosphorylated at Thr-215 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Phosphorylation at Thr-215 by TAOK1 activates the kinase activity, leading to phosphorylation and detachment of MAPT/TAU from microtubules. Phosphorylation at Ser-219 by GSK3-beta (GSK3B) inhibits the kinase activity.
Sequence Similarities
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.
Tissue Specificity
Highly expressed in heart, skeletal muscle, brain, fetal brain and fetal kidney.
Cellular localization
- Cell membrane
- Peripheral membrane protein
- Cytoplasm
- Cytoskeleton
- Cytoplasm
- Cell projection
- Dendrite
- Appears to localize to an intracellular network.
Alternative names
KIAA1477, MARK, MARK1, Serine/threonine-protein kinase MARK1, MAP/microtubule affinity-regulating kinase 1, PAR1 homolog c, Par-1c, Par1c