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FLASH GENE
Symbol NCS1 contributors: mct - updated : 20-03-2019
HGNC name neuronal calcium sensor 1
HGNC id 3953
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N terminal sequence for myristoylation
  • four EF-hand, calcium binding motif
  • Zn2+-binding sites, which affect its structural and functional properties upon filling
  • C-terminal tail is important for regulating the conformational stability of the Ca(2+)-activated state
  • conjugated LipoP
    HOMOLOGY
    interspecies homolog to murine Freq (100 pc)
    homolog to rattus Freq (100 pc)
    Homologene
    FAMILY
  • recoverin family
  • CATEGORY signaling neurotransmitter
    SUBCELLULAR LOCALIZATION     plasma membrane,junction
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    text peripheral membrane protein, associated with golgi stacks, post-synaptic densities of dendrites, and in the pre-synaptic nerve terminal at neuromuscular junctions
    basic FUNCTION
  • regulator of g-protein coupled receptor phosphorylation in a calcium dependent manner
  • involved in the regulation of dense-core granule exocytosis
  • may be involved in a variety of brain function such a sensory processing, motor control, emotional control, learning and memory
  • can substitute for calmodulin
  • involved in in the regulation of ERK1/2 signaling and inflammatory reactions in mast cells, with PI4KB
  • plays an important role in neurotransmitter release and interacts with a plethora of binding partners mostly through a large solvent-exposed hydrophobic crevice
  • has evolved a remarkable complex interdomain cooperativity and a fundamentally different folding mechanism compared to structurally related proteins
  • Ca2+-binding protein, having an important role in cardiac survival during stress
  • contributes to stress tolerance in cardiomyocytes at least in part by activating certain Ca2+-dependent survival pathways that promote mitochondrial biosynthesis/function and detoxification pathways
  • multi-functional Ca2+-binding protein that affects a range of cellular processes beyond those related to neurons
  • plays a role in the aggressive behavior of a subset of breast cancer
  • in WFS1-deficient cells, NCS1 overexpression not only restored ER-mitochondria interactions and Ca2+ transfer but also rescued mitochondrial dysfunction
  • key role of NCS1 in ER-mitochondria cross-talk
  • regulates many vital processes such as synaptic transmission
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling neurotransmission
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Ca2+ (3 ions via the second, third and fourth EF-hand)
  • protein
  • interacting with IL1RAPL1 and KCND2
  • is an important regulator of immature heart function and hypertrophy, and it functions in part by promoting ITPR1 function
  • interacts with both the G-protein-coupled receptor (GPCR) DRD2, regulating its internalization and surface expression, and the cognate kinases GRK1 and ADBRK1
  • cell & other
    REGULATION
    Other myristated
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    facilitates metastatic spread of liver and breast cancer
    constitutional germinal mutation      
    impairment of the normal cycling of NCS-1 by the R102Q mutation could have subtle effects on neuronal signalling and physiology in the developing and adult brain
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • cardiomyocytes derived from Ncs1-deficient (Ncs1-/-) mice were more susceptible to oxidative and metabolic stress than wild-type (WT) myocytes