Structural highlights
3ose is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , |
| Related: | 3osm, 3ost |
| Gene: | MARK1, KIAA1477, MARK (HUMAN) |
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
[MARK1_HUMAN] 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.
Function
[MARK1_HUMAN] 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).[1] [2]
Publication Abstract from PubMed
Phospholipid-binding modules such as PH, C1, and C2 domains play crucial roles in location-dependent regulation of many protein kinases. Here, we identify the KA1 domain (kinase associated-1 domain), found at the C terminus of yeast septin-associated kinases (Kcc4p, Gin4p, and Hsl1p) and human MARK/PAR1 kinases, as a membrane association domain that binds acidic phospholipids. Membrane localization of isolated KA1 domains depends on phosphatidylserine. Using X-ray crystallography, we identified a structurally conserved binding site for anionic phospholipids in KA1 domains from Kcc4p and MARK1. Mutating this site impairs membrane association of both KA1 domains and intact proteins and reveals the importance of phosphatidylserine for bud neck localization of yeast Kcc4p. Our data suggest that KA1 domains contribute to "coincidence detection," allowing kinases to bind other regulators (such as septins) only at the membrane surface. These findings have important implications for understanding MARK/PAR1 kinases, which are implicated in Alzheimer's disease, cancer, and autism.
Kinase associated-1 domains drive MARK/PAR1 kinases to membrane targets by binding acidic phospholipids.,Moravcevic K, Mendrola JM, Schmitz KR, Wang YH, Slochower D, Janmey PA, Lemmon MA Cell. 2010 Dec 10;143(6):966-77. PMID:21145462[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sun TQ, Lu B, Feng JJ, Reinhard C, Jan YN, Fantl WJ, Williams LT. PAR-1 is a Dishevelled-associated kinase and a positive regulator of Wnt signalling. Nat Cell Biol. 2001 Jul;3(7):628-36. PMID:11433294 doi:10.1038/35083016
- ↑ Kojima Y, Miyoshi H, Clevers HC, Oshima M, Aoki M, Taketo MM. Suppression of tubulin polymerization by the LKB1-microtubule-associated protein/microtubule affinity-regulating kinase signaling. J Biol Chem. 2007 Aug 10;282(32):23532-40. Epub 2007 Jun 15. PMID:17573348 doi:10.1074/jbc.M700590200
- ↑ Moravcevic K, Mendrola JM, Schmitz KR, Wang YH, Slochower D, Janmey PA, Lemmon MA. Kinase associated-1 domains drive MARK/PAR1 kinases to membrane targets by binding acidic phospholipids. Cell. 2010 Dec 10;143(6):966-77. PMID:21145462 doi:10.1016/j.cell.2010.11.028
