peripheral plasma membrane protein CASK; hCASK; Ca+2/calmodulin-dependent serine protein kinase; protein lin-2 homolog (CASK, LIN2)

Function: - multidomain scaffolding protein with a role in synaptic transmembrane protein anchoring & ion channel trafficking - contributes to neural development & regulation of gene expression via interaction with the transcription factor TRB1 - binds to cell-surface proteins, including a) amyloid precursor protein (APP) b) neurexins c) syndecans d) actin-binding band 4.1 protein - may mediate a link between the extracellular matrix & the actin cytoskeleton via its interaction with syndecan & with the actin/spectrin-binding protein 4.1 - differs from archetypal CaMK members in that the kinase domain exhibits a constitutively active conformation & the autoinhibitory region does not engage in direct contact with the ATP-binding cleft, although it still binds Ca⁺²/CAM - binds WHRN & NRXN1 cytosolic tail - interacts with CASKIN1, APBA1, LIN7(A/B/C) & L27 domain of DLG1 & isoform 2 of DLG4 (putative) - CASK & LIN7 form two mutually exclusive tripartite complexes with APBA1 or CASKIN1 (putative) - interacts with FCHSD2 - interacts with TSPYL2 - part of a complex containing CASK, TRB1 & TSPYL2 (putative) - interacts with KIRREL3 Kinetic parameters: - KM=563 uM for ATP Cofactor: - unlike other protein kinases, does not require a divalent cation such as Mg⁺² for catalytic activity Structure: - the first L27 domain binds DLG1 & the second L27 domain probably binds LIN7 (putative) - the protein kinase domain mediates the interaction with FCHSD2 - in the N-terminal section; belongs to the protein kinase superfamily, CAMK Ser/Thr protein kinase family, CaMK subfamily - belongs to the MAGUK family - contains 1 guanylate kinase-like domain - contains 2 L27 domains - contains 1 PDZ domain (DHR domain) - contains 1 protein kinase domain - contains 1 SH3 domain Compartment: - nucleus (putative). cytoplasm - cell membrane; peripheral membrane protein Alternative splicing: named isoforms=6 Expression: - ubiquitous - expression is significantly greater in brain relative to kidney, lung, & liver & in fetal brain & kidney relative to lung & liver Pathology: - defects in CASK are the cause of a) mental retardation X-linked CASK-related (MRXCASK) b) FG syndrome type 4

General

guanylate kinase serine/threonine kinase

Properties

SIZE: entity length = 926 aa MW = 105 kD COMPARTMENT: cytoplasm cell nucleus STATE: active state MOTIF: kinase domain SITE: 12-276 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 18-26 ATP-binding site NAME: ATP-binding site SITE: 41-41 aspartate residue {D141} Ser phosphorylation site {S151} Ser phosphorylation site {S155} binding site SITE: 305-315 FOR-BINDING-OF: calmodulin L27 1 {343-398} L27 2 {402-455} PDZ domain NAME: PDZ domain SITE: 489-564 Tyr phosphorylation site {Y571} src homology 3 [SH3] domain SITE: 615-682 domain {739-911} HOMOLOGY: guanylate kinase

Database Correlations

OMIM correlations UniProt O14936 PFAM correlations Entrez Gene 8573 Kegg hsa:8573 ENZYME 2.7.11.1

References

UniProt :accession O14936