MARK1 - Serine/threonine-protein kinase MARK1 - human protein (Function)
 
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MARK1 »  Serine/threonine-protein kinase MARK1   [ EC 2.7.11.26EC 2.7.11.1 ]
 
Protein also known as:  MAP/microtubule affinity-regulating kinase 1.
Gene name:  MARK1
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
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).  
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GO molecular function 
ATP bindingdefinition[GO:0005524]  
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Magnesium ion bindingdefinition[GO:0000287]  
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Phosphatidic acid bindingdefinition[GO:0070300]  
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Phosphatidylinositol-4,5-bisphosphate bindingdefinition[GO:0005546]  
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Phosphatidylserine bindingdefinition[GO:0001786]  
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Protein serine/threonine kinase activitydefinition[GO:0004674]  
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Tau-protein kinase activitydefinition[GO:0050321]  
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GO biological process 
Cytoskeleton organizationdefinition[GO:0007010]  
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Intracellular signal transductiondefinition[GO:0035556]  
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Neuron migrationdefinition[GO:0001764]  
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Protein phosphorylationdefinition[GO:0006468]  
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Wnt signaling pathwaydefinition[GO:0016055]  
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Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reactions
EC 2.7.11.1: ATP + a protein ADP + a phosphoprotein.  
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EC 2.7.11.26: ATP + [tau protein] ADP + [tau protein] phosphate.  
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It requires the following cofactor
 Mg(2+)  
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It is regulated in the following manner
Inhibited by phosphorylation at Ser-219 (By similarity). Activated by phosphorylation on Thr-215.  
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Note 
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 (PubMed11089574).  
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Keywords

Biological process 
Wnt signaling pathway  definition   [KW-0879]
Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: MARK1
GenomeRNAi: 4139
PRO: PR:Q9P0L2
Chemistry
GuidetoPHARMACOLOGY: 2097