3tac

Structural highlights

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. [LIPA2_HUMAN] Alters PTPRF cellular localization and induces PTPRF clustering. May regulate the disassembly of focal adhesions. May localize receptor-like tyrosine phosphatases type 2A at specific sites on the plasma membrane, possibly regulating their interaction with the extracellular environment and their association with substrates.^[3]

References

1. ↑ 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
2. ↑ 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
3. ↑ Serra-Pages C, Medley QG, Tang M, Hart A, Streuli M. Liprins, a family of LAR transmembrane protein-tyrosine phosphatase-interacting proteins. J Biol Chem. 1998 Jun 19;273(25):15611-20. PMID:9624153
4. ↑ Wei Z, Zheng S, Spangler SA, Yu C, Hoogenraad CC, Zhang M. Liprin-mediated large signaling complex organization revealed by the liprin-alpha/CASK and liprin-alpha/liprin-beta complex structures. Mol Cell. 2011 Aug 19;43(4):586-98. PMID:21855798 doi:10.1016/j.molcel.2011.07.021