ID:MARK1_HUMAN DESCRIPTION: RecName: Full=Serine/threonine-protein kinase MARK1; EC=2.7.11.1; EC=2.7.11.26; AltName: Full=MAP/microtubule affinity-regulating kinase 1; AltName: Full=PAR1 homolog c; Short=Par-1c; Short=Par1c; FUNCTION: Serine/threonine-protein kinase involved in cell polarity and microtubule dynamics regulation. Phosphorylates DCX, MAP2, MAP4 and MAPT/TAU. 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). CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CATALYTIC ACTIVITY: ATP + [tau protein] = ADP + [tau protein] phosphate. COFACTOR: Magnesium (By similarity). ENZYME REGULATION: Inhibited by phosphorylation at Ser-219 (By similarity). Activated by phosphorylation on Thr-215. SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein. Cytoplasm, cytoskeleton (By similarity). Note=Appears to localize to an intracellular network (By similarity). TISSUE SPECIFICITY: Highly expressed in heart, skeletal muscle, brain, fetal brain and fetal kidney. 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). DOMAIN: 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). PTM: 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. DISEASE: Note=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. MISCELLANEOUS: Phosphorylation of MAPT/tau by MARK1 could play a role in early steps of Alzheimer disease. Pathological aggregation of MAPT/tau to neurofibrillary tangles, filamentous structures consisting of paired helical filaments (PHFs), is one of the hallmarks of Alzheimer disease. Hyperphosphorylation by MARK1 could be the initial step for this abnormal aggregation of tau in Alzheimer disease and animal models of tauopathy (PubMed:11089574). SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily. SIMILARITY: Contains 1 KA1 (kinase-associated) domain. SIMILARITY: Contains 1 protein kinase domain. SIMILARITY: Contains 1 UBA domain. SEQUENCE CAUTION: Sequence=BAA96001.1; Type=Erroneous initiation; Sequence=BAB55152.1; Type=Frameshift; Positions=763;
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.
ModBase Predicted Comparative 3D Structure on Q9P0L2
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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.
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
