The Caskin1 protein interacts with the CASK protein via this region []. CASK and Caskin1 are synaptic scaffolding proteins. The binding motif on human Caskin1 is EEIWVLRK. A similar motif is found on protein MINT1 and protein TIAM1, both shown to be able to bind to CASK though the motif. However, MINT1 and TIAM1 are not included in this entry []. This region is predicted to be natively unstructured.This entry also matches Caskin2, a Caskin1 homologue deprived of the CASK interaction domain (CID) []. Caskin1 and caskin2 consist of multiple ankyrin repeats, two SAM domains and one SH3 domain. In Caskin1 the CID is located between the SH3 and SAM domains [].
CASK is a scaffolding protein that is highly expressed in the mammalian nervous system and plays roles in synaptic protein targeting, neural development, and gene expression regulation. CASK interacts with many different binding partners including parkin, neurexin, syndecans, calcium channel proteins, caskin, among others, to perform specific functions in different subcellular locations []. Disruption of the CASK gene in mice results in neonatal lethality []while mutations in the human gene have been associated with X-linked mental retardation []. Drosophila CASK is associated with both pre- and postsynaptic membranes and is crucial in synaptic transmission and vesicle cycling []. CASK contains an N-terminal calmodulin-dependent kinase (CaMK)-like domain, two L27 domains, followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK) []. In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain [].
There are three mammalian LIN7 homologues, LIN7A/B/C []. LIN7 contains single L27 and PDZ domains. Protein lin-7 plays a role in establishing and maintaining the asymmetric distribution of channels and receptors at the plasma membrane of polarized cells []. The three components LIN7A, B and C form a complex with CASK and APBA1 which is thought to have roles in neurone synapses [].
Caskin-1 and Caskin-2 are multidomain proteins containing six N-terminal ankyrin repeats, a single SH3 domain, and two sterile alpha motif (SAM) domains followed by a long proline-rich sequence and a short conserved C-terminal domain. Caskin-1 may link the scaffolding protein CASK to downstream intracellular effectors []. Caskin-1 polymerises, via the tandem SAM domains, to form long, 8 nM wide fibres, upon which other proteins can assemble [].
This entry represents the SH3 domain of Caskin-1 (CASK-interacting protein 1).Caskin-1 and Caskin-2 are multidomain proteins containing six N-terminal ankyrin repeats, a single SH3 domain, and two sterile alpha motif (SAM) domains followed by a long proline-rich sequence and a short conserved C-terminal domain. Caskin-1 may link the scaffolding protein CASK to downstream intracellular effectors []. Caskin-1 polymerises, via the tandem SAM domains, to form long, 8 nM wide fibres, upon which other proteins can assemble [].
Caskin2 is a multidomain adaptor protein that contains six ankyrin repeats, a single SH3 domain, tandem sterile alpha motif (SAM) domains, and a long disordered proline-rich region. It shares a domain architecture with Caskin1, but does not bind CASK [, ]. The CASKIN2 SH3 domain has two substitutions that prevent it from binding typical polyproline ligands, which indicates that it could be a nonfunctional remnant in this protein [].
