CASK

CASK

Target · Synaptic scaffold kinase

CASK Calcium/calmodulin dependent serine protein kinase · Peripheral plasma membrane protein CASK

CASK (calcium/calmodulin dependent serine protein kinase, also known as LIN2, CAGH39, FGS4 and TNRC8) is a MAGUK family scaffolding protein with Mg(2+)-independent kinase activity. It is located at synapses in the brain, where it anchors transmembrane proteins and supports ion channel trafficking. Browse Assay Genie's current range of CASK research reagents below, or read on for the biology behind the target.

Nucleus, cytoplasm, membraneMAGUK scaffold kinaseLinked to FG syndrome 4
926 aa
Protein length
~105 kDa
Molecular weight
Xp11.4
Gene locus
EC 2.7.11.1
Enzyme class
Target information

What is CASK (calcium/calmodulin dependent serine protein kinase)?

CASK is a multidomain scaffolding protein that also acts as a Mg(2+)-independent protein kinase. It catalyses phosphotransfer from ATP to proteins such as NRXN1, and it plays a role in anchoring synaptic transmembrane proteins and in ion channel trafficking. CASK binds cell-surface proteins including amyloid precursor protein, neurexins and syndecans. Through its interaction with syndecan and the actin/spectrin-binding protein 4.1, it may link the extracellular matrix to the actin cytoskeleton.

CASK also contributes to neural development and to the regulation of gene expression through its interaction with the transcription factor TBR1. It is a component of the LIN-10-LIN-2-LIN-7 complex, which associates with the motor protein KIF17 to carry vesicles containing the NMDA receptor subunit NR2B along microtubules. UniProt records the protein in the nucleus, cytoplasm and cell membrane, consistent with these varied roles. The CASK gene encodes a member of the MAGUK (membrane-associated guanylate kinase) family. HGNC places it in the CASK family alongside the PDZ domain containing and SH3 domain containing groups. Multiple transcript variants encoding different isoforms have been reported. Orthologues are annotated in mouse and rat as Cask.

Mutations in the CASK gene are associated with FG syndrome 4, intellectual disability and microcephaly with pontine and cerebellar hypoplasia, and a form of X-linked intellectual disability. The gene was previously named trinucleotide repeat containing 8 and calcium/calmodulin-dependent serine protein kinase (MAGUK family), and LIN2 reflects its relationship to the LIN-2 component of the LIN-10-LIN-2-LIN-7 complex. Researchers studying CASK protein typically focus on synaptic organisation, neurodevelopment and neurological disease.

Synaptic biology

CASK is a scaffold at brain synapses that anchors transmembrane proteins and supports ion channel trafficking.

Neurodevelopmental disorders

Mutations in CASK are associated with FG syndrome 4, intellectual disability and microcephaly with pontine and cerebellar hypoplasia.

Vesicle and receptor transport

CASK is part of the LIN-10-LIN-2-LIN-7 complex that works with KIF17 to move NR2B-containing vesicles along microtubules.

Gene regulation in neurons

CASK interacts with the transcription factor TBR1, linking a membrane-associated scaffold to neural development and gene expression.

Background

CASK frequently asked questions

What does CASK do?

CASK is a multidomain scaffolding protein with Mg(2+)-independent kinase activity. It phosphorylates substrates such as NRXN1, anchors synaptic transmembrane proteins, aids ion channel trafficking, and binds neurexins, syndecans and amyloid precursor protein. It also interacts with TBR1 to influence neural development and gene expression.

What other names and isoforms does CASK have?

CASK is also known as LIN2, CAGH39, FGS4 and TNRC8. Earlier names include trinucleotide repeat containing 8 and calcium/calmodulin-dependent serine protein kinase (MAGUK family). Multiple transcript variants encoding different isoforms have been described, so check the datasheet of any product for its validated reactivity and isoform coverage.

Is CASK linked to disease and conserved across species?

Mutations in CASK are associated with FG syndrome 4, intellectual disability and microcephaly with pontine and cerebellar hypoplasia, and a form of X-linked intellectual disability. Mouse and rat both carry a Cask orthologue; check the datasheet of any product for its validated reactivity.

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Related targets

Synaptic scaffold proteins, neurexins, transport motors and NMDA receptor subunits connected to CASK biology.

Gene and protein annotations from HGNC, NCBI Gene and UniProt O14936; product specifications from Assay Genie datasheets.

CASK Product listing