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3c0g

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Revision as of 13:11, 7 November 2018

CASK CaM-Kinase Domain- 3'-AMP complex, P1 form

Structural highlights

3c0g 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.
Ligands:
Related:	3c0h, 3c0i
Gene:	CASK (HUMAN)
Activity:	Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[CSKP_HUMAN] Defects in CASK are the cause of mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH) [MIM:300749]. A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. Patients with mental retardation X-linked CASK-related can manifest a severe phenotype consisting of severe intellectual deficit, congenital or postnatal microcephaly, disproportionate brainstem and cerebellar hypoplasia. A milder phenotype consists of mental retardation alone or associated with nystagmus.^[1] Defects in CASK are the cause of FG syndrome type 4 (FGS4) [MIM:300422]. FG syndrome (FGS) is an X-linked disorder characterized by mental retardation, relative macrocephaly, hypotonia and constipation.^[2]

Function

[CSKP_HUMAN] Multidomain scaffolding protein with a role in synaptic transmembrane protein anchoring and ion channel trafficking. Contributes to neural development and regulation of gene expression via interaction with the transcription factor TRB1. Binds to cell-surface proteins, including amyloid precursor protein, neurexins and syndecans. May mediate a link between the extracellular matrix and the actin cytoskeleton via its interaction with syndecan and with the actin/spectrin-binding protein 4.1.

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

CASK is a unique MAGUK protein that contains an N-terminal CaM-kinase domain besides the typical MAGUK domains. The CASK CaM-kinase domain is presumed to be a catalytically inactive pseudokinase because it lacks the canonical DFG motif required for Mg2+ binding that is thought to be indispensable for kinase activity. Here we show, however, that CASK functions as an active protein kinase even without Mg2+ binding. High-resolution crystal structures reveal that the CASK CaM-kinase domain adopts a constitutively active conformation that binds ATP and catalyzes phosphotransfer without Mg2+. The CASK CaM-kinase domain phosphorylates itself and at least one physiological interactor, the synaptic protein neurexin-1, to which CASK is recruited via its PDZ domain. Thus, our data indicate that CASK combines the scaffolding activity of MAGUKs with an unusual kinase activity that phosphorylates substrates recuited by the scaffolding activity. Moreover, our study suggests that other pseudokinases (10% of the kinome) could also be catalytically active.

CASK Functions as a Mg2+-independent neurexin kinase.,Mukherjee K, Sharma M, Urlaub H, Bourenkov GP, Jahn R, Sudhof TC, Wahl MC Cell. 2008 Apr 18;133(2):328-39. PMID:18423203^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Najm J, Horn D, Wimplinger I, Golden JA, Chizhikov VV, Sudi J, Christian SL, Ullmann R, Kuechler A, Haas CA, Flubacher A, Charnas LR, Uyanik G, Frank U, Klopocki E, Dobyns WB, Kutsche K. Mutations of CASK cause an X-linked brain malformation phenotype with microcephaly and hypoplasia of the brainstem and cerebellum. Nat Genet. 2008 Sep;40(9):1065-7. doi: 10.1038/ng.194. PMID:19165920 doi:10.1038/ng.194
↑ Piluso G, D'Amico F, Saccone V, Bismuto E, Rotundo IL, Di Domenico M, Aurino S, Schwartz CE, Neri G, Nigro V. A missense mutation in CASK causes FG syndrome in an Italian family. Am J Hum Genet. 2009 Feb;84(2):162-77. doi: 10.1016/j.ajhg.2008.12.018. Epub 2009, Feb 5. PMID:19200522 doi:10.1016/j.ajhg.2008.12.018
↑ Mukherjee K, Sharma M, Urlaub H, Bourenkov GP, Jahn R, Sudhof TC, Wahl MC. CASK Functions as a Mg2+-independent neurexin kinase. Cell. 2008 Apr 18;133(2):328-39. PMID:18423203 doi:10.1016/j.cell.2008.02.036

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3c0g"

@@ Line 1: / Line 1: @@
 ==CASK CaM-Kinase Domain- 3'-AMP complex, P1 form==
 <StructureSection load='3c0g' size='340' side='right' caption='[[3c0g]], [[Resolution|resolution]] 2.19&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CASK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3c0g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3c0g OCA], [http://pdbe.org/3c0g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3c0g RCSB], [http://www.ebi.ac.uk/pdbsum/3c0g PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3c0g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3c0g OCA], [http://pdbe.org/3c0g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3c0g RCSB], [http://www.ebi.ac.uk/pdbsum/3c0g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3c0g ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 17: / Line 18: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c0/3c0g_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c0/3c0g_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 34: / Line 35: @@
 ==See Also==
+*[[Calcium/Calmodulin-dependent protein kinase|Calcium/Calmodulin-dependent protein kinase]]
 *[[Pseudoenzyme|Pseudoenzyme]]
 == References ==

3c0g

From Proteopedia

Revision as of 13:11, 7 November 2018

CASK CaM-Kinase Domain- 3'-AMP complex, P1 form

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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