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| | <StructureSection load='2wzj' size='340' side='right'caption='[[2wzj]], [[Resolution|resolution]] 2.79Å' scene=''> | | <StructureSection load='2wzj' size='340' side='right'caption='[[2wzj]], [[Resolution|resolution]] 2.79Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2wzj]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WZJ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2WZJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2wzj]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WZJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WZJ FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1y8g|1y8g]], [[1zmw|1zmw]], [[1zmu|1zmu]], [[1zmv|1zmv]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.786Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2wzj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wzj OCA], [https://pdbe.org/2wzj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wzj RCSB], [https://www.ebi.ac.uk/pdbsum/2wzj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wzj ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2wzj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wzj OCA], [http://pdbe.org/2wzj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2wzj RCSB], [http://www.ebi.ac.uk/pdbsum/2wzj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2wzj ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/MARK2_RAT MARK2_RAT] Serine/threonine-protein kinase involved in cell polarity and microtubule dynamics regulation. Phosphorylates CRTC2/TORC2, DCX, HDAC7, KIF13B, MAP2, MAP4, MAPT/TAU and RAB11FIP2. Plays a key role in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Regulates epithelial cell polarity by phosphorylating RAB11FIP2. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Regulates axogenesis by phosphorylating KIF13B, promoting interaction between KIF13B and 14-3-3 and inhibiting microtubule-dependent accumulation of KIF13B. Also required for neurite outgrowth and establishment of neuronal polarity. 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. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). Modulates the developmental decision to build a columnar versus a hepatic epithelial cell apparently by promoting a switch from a direct to a transcytotic mode of apical protein delivery. Essential for the asymmetric development of membrane domains of polarized epithelial cells.<ref>PMID:14517247</ref> <ref>PMID:15466480</ref> <ref>PMID:14741102</ref> <ref>PMID:16717194</ref> <ref>PMID:18509032</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Non-specific serine/threonine protein kinase]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Mandelkow, E]] | + | [[Category: Mandelkow E]] |
| - | [[Category: Mandelkow, E M]] | + | [[Category: Mandelkow E-M]] |
| - | [[Category: Marx, A]] | + | [[Category: Marx A]] |
| - | [[Category: Panneerselvam, S]] | + | [[Category: Panneerselvam S]] |
| - | [[Category: Developmental protein]]
| + | |
| - | [[Category: Differentiation]]
| + | |
| - | [[Category: S/t protein kinase]]
| + | |
| - | [[Category: Serine/threonine-protein kinase]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Uba domain]]
| + | |
| Structural highlights
Function
MARK2_RAT Serine/threonine-protein kinase involved in cell polarity and microtubule dynamics regulation. Phosphorylates CRTC2/TORC2, DCX, HDAC7, KIF13B, MAP2, MAP4, MAPT/TAU and RAB11FIP2. Plays a key role in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Regulates epithelial cell polarity by phosphorylating RAB11FIP2. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Regulates axogenesis by phosphorylating KIF13B, promoting interaction between KIF13B and 14-3-3 and inhibiting microtubule-dependent accumulation of KIF13B. Also required for neurite outgrowth and establishment of neuronal polarity. 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. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). Modulates the developmental decision to build a columnar versus a hepatic epithelial cell apparently by promoting a switch from a direct to a transcytotic mode of apical protein delivery. Essential for the asymmetric development of membrane domains of polarized epithelial cells.[1] [2] [3] [4] [5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Kinases of the MARK/Par-1 family of S/T protein kinases are regulators of diverse cellular processes in Caenorhabditis elegans, Drosophila, yeast, and mammalian cells. They are involved in nematode embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. MARK phosphorylates microtubule-associated proteins such as tau and is a key regulator of microtubule-based intracellular transport. Hyperphosphorylation of tau causes defects in neuronal transport and may induce abnormal aggregation of tau in Alzheimer disease and other tauopathies. Recent high-resolution structure analysis of MARK fragments covering the kinase domain and accessory regulatory domains has revealed important details regarding the autoregulation of MARK, but their interpretation has remained controversial. Here we focus on the structural aspects of MARK activity and autoregulation. Comparison of the available MARK structures with related kinases of the AMPK family and with new structures of MARK isoforms (MARK2 and 3) reveals unexpected structural similarities between these kinases that may help to resolve the existing controversies.
Structure and function of polarity-inducing kinase family MARK/Par-1 within the branch of AMPK/Snf1-related kinases.,Marx A, Nugoor C, Panneerselvam S, Mandelkow E FASEB J. 2010 Jun;24(6):1637-48. Epub 2010 Jan 13. PMID:20071654[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Timm T, Li XY, Biernat J, Jiao J, Mandelkow E, Vandekerckhove J, Mandelkow EM. MARKK, a Ste20-like kinase, activates the polarity-inducing kinase MARK/PAR-1. EMBO J. 2003 Oct 1;22(19):5090-101. PMID:14517247 doi:http://dx.doi.org/10.1093/emboj/cdg447
- ↑ Mandelkow EM, Thies E, Trinczek B, Biernat J, Mandelkow E. MARK/PAR1 kinase is a regulator of microtubule-dependent transport in axons. J Cell Biol. 2004 Oct 11;167(1):99-110. Epub 2004 Oct 4. PMID:15466480 doi:http://dx.doi.org/10.1083/jcb.200401085
- ↑ Schaar BT, Kinoshita K, McConnell SK. Doublecortin microtubule affinity is regulated by a balance of kinase and phosphatase activity at the leading edge of migrating neurons. Neuron. 2004 Jan 22;41(2):203-13. PMID:14741102
- ↑ Chen YM, Wang QJ, Hu HS, Yu PC, Zhu J, Drewes G, Piwnica-Worms H, Luo ZG. Microtubule affinity-regulating kinase 2 functions downstream of the PAR-3/PAR-6/atypical PKC complex in regulating hippocampal neuronal polarity. Proc Natl Acad Sci U S A. 2006 May 30;103(22):8534-9. Epub 2006 May 22. PMID:16717194 doi:http://dx.doi.org/10.1073/pnas.0509955103
- ↑ Sapir T, Sapoznik S, Levy T, Finkelshtein D, Shmueli A, Timm T, Mandelkow EM, Reiner O. Accurate balance of the polarity kinase MARK2/Par-1 is required for proper cortical neuronal migration. J Neurosci. 2008 May 28;28(22):5710-20. doi: 10.1523/JNEUROSCI.0911-08.2008. PMID:18509032 doi:http://dx.doi.org/10.1523/JNEUROSCI.0911-08.2008
- ↑ Marx A, Nugoor C, Panneerselvam S, Mandelkow E. Structure and function of polarity-inducing kinase family MARK/Par-1 within the branch of AMPK/Snf1-related kinases. FASEB J. 2010 Jun;24(6):1637-48. Epub 2010 Jan 13. PMID:20071654 doi:10.1096/fj.09-148064
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