Structural highlights
3fe3 is a 2 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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| Related: | 2hak, 2qnj, 2y8g, 2zmu, 2zmv, 2zmw, 2r0i |
| Gene: | MARK3 (HUMAN) |
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[MARK3_HUMAN] Involved in the specific phosphorylation of microtubule-associated proteins for tau, MAP2 and MAP4. Phosphorylates CDC25C on 'Ser-216'. 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.[1]
Publication Abstract from PubMed
The Ser/Thr kinase MARK2 phosphorylates tau protein at sites that cause detachment from microtubules in Alzheimer neurofibrillary degeneration. Homologs of MARK2 include Par-1 in C. elegans and Drosophila, which generates embryonic polarity. We report the X-ray structure of the catalytic and ubiquitin-associated domains (UBA) of human MARK2. The activity was altered by mutations in the ATP binding site and/or activation loop. The catalytic domain shows the small and large lobes typical of kinases. The substrate cleft is in an inactive, open conformation in the inactivated and the wild-type structure. The UBA domain is attached via a taut linker to the large lobe of the kinase domain and leans against a hydrophobic patch on the small lobe. The UBA structure is unusual because the orientation of its third helix is inverted, relative to previous structures. Possible implications of the structure for the regulation of kinase activity are discussed.
Structure of the catalytic and ubiquitin-associated domains of the protein kinase MARK/Par-1.,Panneerselvam S, Marx A, Mandelkow EM, Mandelkow E Structure. 2006 Feb;14(2):173-83. PMID:16472737[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Dequiedt F, Martin M, Von Blume J, Vertommen D, Lecomte E, Mari N, Heinen MF, Bachmann M, Twizere JC, Huang MC, Rider MH, Piwnica-Worms H, Seufferlein T, Kettmann R. New role for hPar-1 kinases EMK and C-TAK1 in regulating localization and activity of class IIa histone deacetylases. Mol Cell Biol. 2006 Oct;26(19):7086-102. PMID:16980613 doi:http://dx.doi.org/10.1128/MCB.00231-06
- ↑ Panneerselvam S, Marx A, Mandelkow EM, Mandelkow E. Structure of the catalytic and ubiquitin-associated domains of the protein kinase MARK/Par-1. Structure. 2006 Feb;14(2):173-83. PMID:16472737 doi:10.1016/j.str.2005.09.022
