Cask Protein

From Anvita Health Wiki

Contents 1 Function 2 Structure 3 Compartment 4 Alternative-splicing 5 Expression 6 Pathology 7 More General Terms 8 Internet Database 9 References

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

• amyloid precursor protein ( APP)
• neurexins
• syndecans
• 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

• mental retardation X-linked CASK-related (MRXCASK)
• FG syndrome type 4

More General Terms

• guanylate kinase
• serine/threonine kinase

Internet Database

Entrez gene: 8573
Kegg: [1]
OMIM: 300172
OMIM: 300422
OMIM: 300749
Prosite: [2]
Prosite: [3]
Prosite: [4]
Prosite: [5]
Prosite: [6]
Prosite: [7]
Prosite: [8]
Prosite: [9]
UniProt: [10]

References

UniProt [11]

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