RGD Reference Report - CASK Functions as a Mg2+-independent neurexin kinase. - Rat Genome Database

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CASK Functions as a Mg2+-independent neurexin kinase.

Authors: Mukherjee, K  Sharma, M  Urlaub, H  Bourenkov, GP  Jahn, R  Sudhof, TC  Wahl, MC 
Citation: Mukherjee K, etal., Cell. 2008 Apr 18;133(2):328-39. doi: 10.1016/j.cell.2008.02.036.
RGD ID: 8553987
Pubmed: PMID:18423203   (View Abstract at PubMed)
PMCID: PMC3640377   (View Article at PubMed Central)
DOI: DOI:10.1016/j.cell.2008.02.036   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Nrxn1Ratprotein binding enablesIPIUniProtKB:O14936PMID:18423203IntAct 

Objects Annotated

Genes (Rattus norvegicus)
Nrxn1  (neurexin 1)

Additional Information