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| | <StructureSection load='2r0i' size='340' side='right'caption='[[2r0i]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='2r0i' size='340' side='right'caption='[[2r0i]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2r0i]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2R0I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2R0I FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2r0i]] is a 2 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=2R0I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2R0I FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MARK2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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]] 2.202Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://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=2r0i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r0i OCA], [https://pdbe.org/2r0i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2r0i RCSB], [https://www.ebi.ac.uk/pdbsum/2r0i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2r0i ProSAT]</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=2r0i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r0i OCA], [https://pdbe.org/2r0i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2r0i RCSB], [https://www.ebi.ac.uk/pdbsum/2r0i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2r0i ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == 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>
| + | [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: Kin1]]
| + | |
| - | [[Category: Mark]]
| + | |
| - | [[Category: Par-1]]
| + | |
| - | [[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.
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
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