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FLASH GENE
Symbol CASC5 contributors: mct - updated : 18-05-2015
HGNC name cancer susceptibility candidate 5
HGNC id 24054
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • distinct and essential binding domains for BUB1 and BUB1B (here designated Bubs) at the N terminus
  • a conserved motif directly interacting with and targeting protein phosphatase 1 (PP1) to the outer kinetochore (
  • a C terminal bipartite nuclear localization signal, with essential binding domains for ZWINT and NSL1
  • HOMOLOGY
    interspecies homolog to rattus Rad51_predicted
    homolog to murine Casc5
    Homologene
    FAMILY Spc105/Spc7/KNL-1 family
    CATEGORY unknown/unspecified
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome,kinetochore
    text acrosome
    basic FUNCTION
  • playing in important roles in spermatogenesis, especially in the formation and maintenance of the acrosome
  • may function normally to suppress cell growth and/or enhance maturation
  • centromeric form may be the base to anchor the MIS12 core complex that is enriched with coiled coils and extends to outer ZWINT during mitosis
  • may be the center of the network for generating kinetochore-based checkpoint signaling
  • CASC5 and CENPK, a subunit of a constitutively centromere-associated complex, coordinately direct NDC80 complex localization and kinetochore assembly
  • mixed-lineage leukemia (MLL) fusion partner and a kinetochore component
  • microtubule binding by CASC5 functions in checkpoint silencing by sensing microtubules attached to kinetochores and relaying their presence to eliminate generation of the checkpoint signal
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • NDC80, MIS12, and CASC5 complexes form the core of the KMN network
  • KMN network (for CASC5, MIS12 and NDC80 complexes) is a hub for signalling at the outer kinetochore
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • directly links spindle checkpoint proteins BUB1B and BUB1 to kinetochores and is required for spindle checkpoint and chromosome alignment
  • DSN1 is required to shape an interface between the MIS12 complex and CASC5
  • directly binds to several structural and regulatory proteins
  • PPP2R5D opposes TTK phosphorylation of CASC5 and thereby promotes spindle assembly checkpoint silencing
  • cell & other
    REGULATION
    Other phosphorylation by Aurora B disrupts the CASC5-PP1 interaction
    ASSOCIATED DISORDERS
    corresponding disease(s) MCPH4
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion translocation    
    fused to MLL by t(11;15) (q23;q14) in acute myeloid leukemia
    tumoral     --over  
    in lung cancer of smockers
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS