Gene Symbol: Cask
Description: calcium/calmodulin-dependent serine protein kinase (MAGUK family)
Alias: DXPri1, DXRib1, LIN-2, Pals3, mLin-2, peripheral plasma membrane protein CASK
Species: mouse
Products:     Cask

Top Publications

  1. Hsueh Y. Calcium/calmodulin-dependent serine protein kinase and mental retardation. Ann Neurol. 2009;66:438-43 pubmed publisher
    Calcium/calmodulin-dependent serine protein kinase (CASK) belongs to the membrane-associated guanylate kinase protein family...
  2. Misawa H, Kawasaki Y, Mellor J, Sweeney N, Jo K, Nicoll R, et al. Contrasting localizations of MALS/LIN-7 PDZ proteins in brain and molecular compensation in knockout mice. J Biol Chem. 2001;276:9264-72 pubmed
    ..Interestingly, MALS-3 protein is dramatically induced in the MALS-1/2 double knockouts, implying that dynamic changes in protein expression may play an important regulatory role for this family of synaptic PDZ proteins. ..
  3. Atasoy D, Schoch S, Ho A, Nadasy K, Liu X, Zhang W, et al. Deletion of CASK in mice is lethal and impairs synaptic function. Proc Natl Acad Sci U S A. 2007;104:2525-30 pubmed
    b>CASK is an evolutionarily conserved multidomain protein composed of an N-terminal Ca2+/calmodulin-kinase domain, central PDZ and SH3 domains, and a C-terminal guanylate kinase domain...
  4. Marquez Rosado L, Singh D, Rincón Arano H, Solan J, Lampe P. CASK (LIN2) interacts with Cx43 in wounded skin and their coexpression affects cell migration. J Cell Sci. 2012;125:695-702 pubmed publisher
    ..Co-immunoprecipitation, in vitro binding and far western experiments demonstrate that mammalian CASK (also known as LIN2) directly interacts with Cx43...
  5. Laverty H, Wilson J. Murine CASK is disrupted in a sex-linked cleft palate mouse mutant. Genomics. 1998;53:29-41 pubmed of genes in which the encoded proteins combine these domains, termed here, the CAMGUKs, including rat CASK, Caenorhabditis elegans lin-2, and Drosophila caki/camguk...
  6. Hsueh Y, Wang T, Yang F, Sheng M. Nuclear translocation and transcription regulation by the membrane-associated guanylate kinase CASK/LIN-2. Nature. 2000;404:298-302 pubmed
    ..b>CASK/LIN-2, a MAGUK required for EGF receptor localization and signalling in Caenorhabditis elegans, contains a ..
  7. Setou M, Nakagawa T, Seog D, Hirokawa N. Kinesin superfamily motor protein KIF17 and mLin-10 in NMDA receptor-containing vesicle transport. Science. 2000;288:1796-802 pubmed
    ..tail with a PDZ domain of mLin-10 (Mint1/X11), which is a constituent of a large protein complex including mLin-2 (CASK), mLin-7 (MALS/Velis), and the NR2B subunit...
  8. Lee S, Fan S, Makarova O, Straight S, Margolis B. A novel and conserved protein-protein interaction domain of mammalian Lin-2/CASK binds and recruits SAP97 to the lateral surface of epithelia. Mol Cell Biol. 2002;22:1778-91 pubmed
    Mammalian Lin-2 (mLin-2)/CASK is a membrane-associated guanylate kinase (MAGUK) and contains multidomain modules that mediate protein-protein interactions important for the establishment and maintenance of neuronal and epithelial cell ..
  9. Samuels B, Hsueh Y, Shu T, Liang H, Tseng H, Hong C, et al. Cdk5 promotes synaptogenesis by regulating the subcellular distribution of the MAGUK family member CASK. Neuron. 2007;56:823-37 pubmed
    ..One protein recruited to developing terminals by SynCAM and Neurexins/Neuroligins is the MAGUK family member CASK. We found that Cdk5 phosphorylates and regulates CASK distribution to membranes...

More Information


  1. Gardner K, Sanford J, Mays T, Rafael Fortney J. CASK localizes to nuclei in developing skeletal muscle and motor neuron culture models and is agrin-independent. J Cell Physiol. 2006;206:196-202 pubmed
    ..Calmodulin-associated serine/threonine kinase (CASK) stabilizes the integrity of synapses in the brain...
  2. Kamberov E, Makarova O, Roh M, Liu A, Karnak D, Straight S, et al. Molecular cloning and characterization of Pals, proteins associated with mLin-7. J Biol Chem. 2000;275:11425-31 pubmed
    ..Pals proteins represent a new subfamily of membrane-associated guanylate kinases that allow for multiple targeting complexes containing mLin-7. ..
  3. Olsen O, Moore K, Fukata M, Kazuta T, Trinidad J, Kauer F, et al. Neurotransmitter release regulated by a MALS-liprin-alpha presynaptic complex. J Cell Biol. 2005;170:1127-34 pubmed
    ..The MALS/Veli-CASK-Mint-1 complex of PDZ proteins occurs on both sides of the synapse and has the potential to link transsynaptic ..
  4. Bamji S, Shimazu K, Kimes N, Huelsken J, Birchmeier W, Lu B, et al. Role of beta-catenin in synaptic vesicle localization and presynaptic assembly. Neuron. 2003;40:719-31 pubmed
    ..This study defines a specific role for cadherins and catenins in synapse organization beyond their roles in mediating cell adhesion. ..
  5. Chen C, Lin C, Chang C, Jiang S, Hsueh Y. Sarm1, a negative regulator of innate immunity, interacts with syndecan-2 and regulates neuronal morphology. J Cell Biol. 2011;193:769-84 pubmed publisher
    ..These functions likely involve Sarm1-mediated regulation of microtubule stability, as Sarm1 influenced tubulin acetylation. This study thus reveals the molecular mechanism underlying the action of Sarm1 in neuronal morphogenesis. ..
  6. Revil T, Jerome Majewska L. During embryogenesis, esrp1 expression is restricted to a subset of epithelial cells and is associated with splicing of a number of developmentally important genes. Dev Dyn. 2013;242:281-90 pubmed publisher
    ..5 to E13.5. Our results suggest that Esrp1 could play an important role in the morphological changes underlying embryogenesis of the placenta and embryo. ..
  7. Gerke P, Benzing T, Höhne M, Kispert A, Frotscher M, Walz G, et al. Neuronal expression and interaction with the synaptic protein CASK suggest a role for Neph1 and Neph2 in synaptogenesis. J Comp Neurol. 2006;498:466-75 pubmed
    ..Here it colocalizes with the synaptic scaffolder calmodulin-associated serin/threonin kinase (CASK), and both Neph1 and Neph2 interact with the PDZ domain of CASK via their cytoplasmic tail...
  8. Yao I, Takagi H, Ageta H, Kahyo T, Sato S, Hatanaka K, et al. SCRAPPER-dependent ubiquitination of active zone protein RIM1 regulates synaptic vesicle release. Cell. 2007;130:943-57 pubmed
    ..Thus, SCRAPPER has an essential function in regulating proteasome-mediated degradation of RIM1 required for synaptic tuning. ..
  9. Aravindan R, Fomin V, Naik U, Modelski M, Naik M, Galileo D, et al. CASK interacts with PMCA4b and JAM-A on the mouse sperm flagellum to regulate Ca2+ homeostasis and motility. J Cell Physiol. 2012;227:3138-50 pubmed publisher
    ..Investigating the mechanism involved, we used co-immunoprecipitation studies to show that CASK (Ca(2+) /calmodulin-dependent serine kinase), identified for the first time on the sperm flagellum where it co-..
  10. Sanford J, Mays T, Rafael Fortney J. CASK and Dlg form a PDZ protein complex at the mammalian neuromuscular junction. Muscle Nerve. 2004;30:164-71 pubmed
    ..Calcium, calmodulin-associated serine/threonine kinase (CASK) is a MAGUK that is critical at synapses in the central nervous system and at cell-cell junctions because of its ..
  11. Weng H, Kim C, Valavanis C, Wang Z, Schwartz L. Acheron, an novel LA antigen family member, binds to CASK and forms a complex with Id transcription factors. Cell Mol Biol Lett. 2009;14:273-87 pubmed publisher
    ..Using Acheron as bait, we performed a yeast two-hybrid screen with a mouse embryo cDNA library and identified CASK-C, a novel CASK/Lin-2 isoform, as an Acheron binding partner...
  12. Lozovatsky L, Abayasekara N, Piawah S, Walther Z. CASK deletion in intestinal epithelia causes mislocalization of LIN7C and the DLG1/Scrib polarity complex without affecting cell polarity. Mol Biol Cell. 2009;20:4489-99 pubmed publisher
    b>CASK is the mammalian ortholog of LIN2, a component of the LIN2/7/10 protein complex that targets epidermal growth factor receptor (EGFR) to basolateral membranes in Caenorhabditis elegans...
  13. Giangreco A, Jensen K, Takai Y, Miyoshi J, Watt F. Necl2 regulates epidermal adhesion and wound repair. Development. 2009;136:3505-14 pubmed publisher
    ..of Necl2 in cultured human keratinocytes led to upregulation of calcium/calmodulin-associated Ser/Thr kinase (CASK), increased calcium-independent intercellular adhesion, and inhibition of cell motility and in vitro wound healing...
  14. Ahn S, Kim Y, Kim S, Swat W, Miner J. Scaffolding proteins DLG1 and CASK cooperate to maintain the nephron progenitor population during kidney development. J Am Soc Nephrol. 2013;24:1127-38 pubmed publisher
    DLG1 (discs-large homolog 1) and CASK (calcium/calmodulin-dependent serine protein kinase) interact at membrane-cytoskeleton interfaces and function as scaffolding proteins that link signaling molecules, receptors, and other scaffolding ..
  15. Wentzel C, Sommer J, Nair R, Stiefvater A, Sibarita J, Scheiffele P. mSYD1A, a mammalian synapse-defective-1 protein, regulates synaptogenic signaling and vesicle docking. Neuron. 2013;78:1012-23 pubmed publisher
    ..Thus, mSYD1A is a regulator of presynaptic release sites at central synapses. ..
  16. Tabuchi K, Biederer T, Butz S, Sudhof T. CASK participates in alternative tripartite complexes in which Mint 1 competes for binding with caskin 1, a novel CASK-binding protein. J Neurosci. 2002;22:4264-73 pubmed
    b>CASK, an adaptor protein of the plasma membrane, is composed of an N-terminal calcium/calmodulin-dependent protein (CaM) kinase domain, central PSD-95, Dlg, and ZO-1/2 domain (PDZ) and Src homology 3 (SH3) domains, and a C-terminal ..
  17. Macdiarmid J, Stevenson D, Campbell D, Wilson J. The latent membrane protein 1 of Epstein-Barr virus and loss of the INK4a locus: paradoxes resolve to cooperation in carcinogenesis in vivo. Carcinogenesis. 2003;24:1209-18 pubmed
    ..In addition, loss of the INK4a locus accelerates the development of a more aggressive lesion. Conversely, complete loss of the INK4a locus in an otherwise normal cell might inhibit lesion formation. ..
  18. LaConte L, Chavan V, Liang C, Willis J, Schönhense E, Schoch S, et al. CASK stabilizes neurexin and links it to liprin-? in a neuronal activity-dependent manner. Cell Mol Life Sci. 2016;73:3599-621 pubmed publisher
    b>CASK, a MAGUK family protein, is an essential protein present in the presynaptic compartment...
  19. Naim E, Bernstein A, Bertram J, Caruana G. Mutagenesis of the epithelial polarity gene, discs large 1, perturbs nephrogenesis in the developing mouse kidney. Kidney Int. 2005;68:955-65 pubmed
    ..of Dlg1 in epithelial cells, and the ability of Dlg1 to bind to calmodulin-associated serine/threonine kinase (CASK)...
  20. Borg J, Straight S, Kaech S, de Taddèo Borg M, Kroon D, Karnak D, et al. Identification of an evolutionarily conserved heterotrimeric protein complex involved in protein targeting. J Biol Chem. 1998;273:31633-6 pubmed
    ..Here, we report that X11alpha directly binds to the mammalian homologue of Lin-2 (mLin-2), also known as CASK. This binding is mediated by direct interaction between the Calmodulin Kinase II (CKII)-like domain of mLin-2 and ..
  21. Douglas K, Camper S. Partial transcriptome of the developing pituitary gland. Genomics. 2000;70:335-46 pubmed
    ..The tissue distribution, cell specificity, and developmental regulation were determined for a subset of the transcripts. ..
  22. Fallon L, Moreau F, Croft B, Labib N, Gu W, Fon E. Parkin and CASK/LIN-2 associate via a PDZ-mediated interaction and are co-localized in lipid rafts and postsynaptic densities in brain. J Biol Chem. 2002;277:486-91 pubmed
    ..truncated by a Parkinson's disease-causing mutation, functions as a class II PDZ-binding motif that binds CASK, the mammalian homolog of Caenorhabditis elegans Lin-2, but not other PDZ proteins in brain extracts...
  23. Tindi J, Chávez A, Cvejic S, Calvo Ochoa E, Castillo P, Jordan B. ANKS1B Gene Product AIDA-1 Controls Hippocampal Synaptic Transmission by Regulating GluN2B Subunit Localization. J Neurosci. 2015;35:8986-96 pubmed publisher
    ..Our work provides an explanation for how AIDA-1 dysfunction might contribute to neuropsychiatric conditions, such as schizophrenia. ..
  24. Garcia Mata R, Dubash A, Sharek L, Carr H, Frost J, Burridge K. The nuclear RhoA exchange factor Net1 interacts with proteins of the Dlg family, affects their localization, and influences their tumor suppressor activity. Mol Cell Biol. 2007;27:8683-97 pubmed
    ..Together, our results suggest that the interaction between Net1 and Dlg1 may contribute to the mechanism of Net1-mediated transformation. ..
  25. Joch M, Ase A, Chen C, MacDonald P, Kontogiannea M, Corera A, et al. Parkin-mediated monoubiquitination of the PDZ protein PICK1 regulates the activity of acid-sensing ion channels. Mol Biol Cell. 2007;18:3105-18 pubmed
  26. Gnanasekaran A, Sundukova M, Hullugundi S, Birsa N, Bianchini G, Hsueh Y, et al. Calcium/calmodulin-dependent serine protein kinase (CASK) is a new intracellular modulator of P2X3 receptors. J Neurochem. 2013;126:102-12 pubmed publisher
    ..The present study investigated the role of calcium/calmodulin-dependent serine protein kinase (CASK) in interacting and controlling P2X3 receptor expression and function in mouse trigeminal ganglia...
  27. Cimerman J, Waldhaus J, Harasztosi C, Duncker S, Dettling J, Heidrych P, et al. Generation of somatic electromechanical force by outer hair cells may be influenced by prestin-CASK interaction at the basal junction with the Deiter's cell. Histochem Cell Biol. 2013;140:119-35 pubmed publisher
    ..9b as the bait in a yeast two-hybrid assay, we identified a calcium/calmodulin-dependent serine protein kinase (CASK) as an interaction partner of prestin...
  28. Srivastava S, McMillan R, Willis J, Clark H, Chavan V, Liang C, et al. X-linked intellectual disability gene CASK regulates postnatal brain growth in a non-cell autonomous manner. Acta Neuropathol Commun. 2016;4:30 pubmed publisher
    The phenotypic spectrum among girls with heterozygous mutations in the X-linked intellectual disability (XLID) gene CASK (calcium/calmodulin-dependent serine protein kinase) includes postnatal microcephaly, ponto-cerebellar hypoplasia, ..
  29. Huang T, Hsueh Y. Calcium/calmodulin-dependent serine protein kinase (CASK), a protein implicated in mental retardation and autism-spectrum disorders, interacts with T-Brain-1 (TBR1) to control extinction of associative memory in male mice. J Psychiatry Neurosci. 2017;42:37-47 pubmed
    Human genetic studies have indicated that mutations in calcium/calmodulin-dependent serine protein kinase (CASK) result in X-linked mental retardation and autism-spectrum disorders...
  30. Eichel C, Beuriot A, Chevalier M, Rougier J, Louault F, Dilanian G, et al. Lateral Membrane-Specific MAGUK CASK Down-Regulates NaV1.5 Channel in Cardiac Myocytes. Circ Res. 2016;119:544-56 pubmed publisher
    ..To test the hypothesis that the MAGUK (membrane-associated guanylate kinase) protein CASK (calcium/calmodulin-dependent serine protein kinase) interacts with and regulates NaV1.5 in cardiac myocytes...
  31. Ojeh N, Pekovic V, Jahoda C, Määttä A. The MAGUK-family protein CASK is targeted to nuclei of the basal epidermis and controls keratinocyte proliferation. J Cell Sci. 2008;121:2705-17 pubmed publisher
    The Ca2+/calmodulin-associated Ser/Thr kinase (CASK) binds syndecans and other cell-surface proteins through its PDZ domain and has been implicated in synaptic assembly, epithelial polarity and neuronal gene transcription...
  32. Sanford J, Mays T, Varian K, Wilson J, Janssen P, Rafael Fortney J. Truncated CASK does not alter skeletal muscle or protein interactors. Muscle Nerve. 2008;38:1116-27 pubmed publisher
    b>CASK (Ca2+, calmodulin-associated serine/threonine kinase) is an essential mammalian cell junction protein and is also crucial at Drosophila neuromuscular synapses...
  33. Feng W, Long J, Zhang M. A unified assembly mode revealed by the structures of tetrameric L27 domain complexes formed by mLin-2/mLin-7 and Patj/Pals1 scaffold proteins. Proc Natl Acad Sci U S A. 2005;102:6861-6 pubmed
    ..Our results provide a unified picture for L27 domain-mediated protein-protein interactions. ..
  34. Burkin H, Zhao L, Miller D. CASK is in the mammalian sperm head and is processed during epididymal maturation. Mol Reprod Dev. 2004;68:500-6 pubmed
    ..b>CASK is an adaptor protein that has been implicated in coupling neuronal cell adhesion to regulated exocytosis...
  35. Karnak D, Lee S, Margolis B. Identification of multiple binding partners for the amino-terminal domain of synapse-associated protein 97. J Biol Chem. 2002;277:46730-5 pubmed SAP97 called the MAGUK recruitment (MRE) domain binds the LIN-2,7 amino-terminal (L27N) domain of mLIN-2/CASK, a MAGUK known to bind mLIN-7. Here we show that SAP97 binds two other mLIN-7 binding MAGUK proteins...
  36. Spiegel I, Salomon D, Erne B, Schaeren Wiemers N, Peles E. Caspr3 and caspr4, two novel members of the caspr family are expressed in the nervous system and interact with PDZ domains. Mol Cell Neurosci. 2002;20:283-97 pubmed
    ..the cytoplasmic tails of Caspr3 and Caspr4 interacted differentially with PDZ domain-containing proteins of the CASK/Lin2-Veli/Lin7-Mint1/Lin10 complex...
  37. Sun Q, Kelly G. Post-translational modification of CASK leads to its proteasome-dependent degradation. Int J Biochem Cell Biol. 2010;42:90-7 pubmed publisher
    b>CASK is a member of the membrane-associated guanylate kinase family. In mammals it is an essential protein, as CASK knockout mice die after birth and its deletion in humans has developmental consequences...
  38. Fairless R, Masius H, Rohlmann A, Heupel K, Ahmad M, Reissner C, et al. Polarized targeting of neurexins to synapses is regulated by their C-terminal sequences. J Neurosci. 2008;28:12969-81 pubmed publisher
    ..bassoon colabeling demonstrate that these carriers are not active zone precursor vesicles, but colocalization with CASK, RIM1alpha, and calcium channels suggests that they may carry additional components of the exocytotic machinery...
  39. Lin C, Huang T, Wang G, Kuo T, Yen T, Hsueh Y. Neural activity- and development-dependent expression and distribution of CASK interacting nucleosome assembly protein in mouse brain. J Comp Neurol. 2006;494:606-19 pubmed
    b>CASK interacting nucleosome assembly protein (CINAP) modulates gene expression and its abundance in cultured neurons is regulated by synaptic activity...
  40. Wang T, Ding C, Wang G, Luo S, Lin Y, Ruan Y, et al. Identification of Tbr-1/CASK complex target genes in neurons. J Neurochem. 2004;91:1483-92 pubmed
    ..Luciferase reporter assays using cultured hippocampal neurons showed that overexpression of Tbr-1 and CASK-enhanced promoter activities of some of these putative target genes, including NMDAR subunit 2b (NR2b), glycine ..
  41. Leonoudakis D, Conti L, Radeke C, McGuire L, Vandenberg C. A multiprotein trafficking complex composed of SAP97, CASK, Veli, and Mint1 is associated with inward rectifier Kir2 potassium channels. J Biol Chem. 2004;279:19051-63 pubmed
    ..and co-immunoprecipitations from brain and transfected cells, we demonstrated that a complex composed of SAP97, CASK, Veli, and Mint1 associates with Kir2 channels via the C-terminal PDZ-binding motif...
  42. Biederer T, Sara Y, Mozhayeva M, Atasoy D, Liu X, Kavalali E, et al. SynCAM, a synaptic adhesion molecule that drives synapse assembly. Science. 2002;297:1525-31 pubmed
  43. Wilson J, Ferguson M, Jenkins N, Lock L, Copeland N, Levine A. Transgenic mouse model of X-linked cleft palate. Cell Growth Differ. 1993;4:67-76 pubmed
    ..The disrupted cellular sequences have been mapped to the proximal region of the mouse X chromosome. The disrupted locus may represent the mouse counterpart to a human locus mutated in an X-linked cleft secondary palate syndrome. ..
  44. Wilson J, Weinberg W, Johnson R, Yuspa S, Levine A. Expression of the BNLF-1 oncogene of Epstein-Barr virus in the skin of transgenic mice induces hyperplasia and aberrant expression of keratin 6. Cell. 1990;61:1315-27 pubmed