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FLASH GENE
Symbol CIB1 contributors: mct - updated : 06-02-2010
HGNC name calcium and integrin binding 1 (calmyrin)
HGNC id 16920
Location 15q26.1      Physical location : 90.773.477 - 90.777.279
Synonym name
  • calmyrin
  • calcium and integrin binding protein
  • DNA-PK interacting protein
  • SNK-interacting protein 2-28
  • calmyrin
  • kinase-interacting protein
    • Synonym symbol(s) SIP28, PRKDCIP, KIP, SIP2-28, CALMYRIN, CIB
    DNA
    TYPE functioning gene
    STRUCTURE 3.80 kb     7 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 995 22 191 - 2007 17516631
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   predominantly Homo sapiens
    Digestivesalivary gland   highly
    Endocrineparathyroid   highly
    Lymphoid/Immunetonsils   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumcardiacmyocardiummoderately Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • four EF-hand calcium-binding domains, although only the third and fourth C-terminal EF hands functionally bind Ca2+ at physiologic concentrations
  • myristoylation site(s) (can be myristoylated at its N-terminus to mediate plasma membrane localization in multiple cell types)
  • a hydrophobic pocket that has been implicated in ligand binding
  • two canonical Ca2+-binding EF-hand motifs in the C-terminal globular domain
    • conjugated Other
    mono polymer heteromer
    HOMOLOGY
    interspecies ortholog to murine Cibkip pending
    intraspecies homolog to kip2
    homolog to calcineurin B
    homolog to calmodulin
    Homologene
    FAMILY
  • calcium-binding protein family
    • CATEGORY adhesion , regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,nucleus,nucleoplasm
    text
  • membrane-associated colocalized with PS2
  • shifting from nucleus to perinuclear compartment when coexpressed with M17S2
  • localizes primarily to the sarcolemma in myocardium, where it anchors calcineurin to control its activation in coordination with the L-type Ca2+ channel
  • localizes to the plasma membrane in fibroblasts, human venous endothelial cells
    • basic FUNCTION
  • playing a role in kinase-phosphatase regulation of DNA and joining
  • converting the inactive conformation of integrin alpha-IIB/beta 3 to an active form through the binding to the integrin cytoplasmic domain
  • playing a dynamic role in signaling, cell death and Alzheimer's disease
  • negative regulator for PLK2 activity
  • regulates platelet aggregation in hemostasis through a specific interaction with the alphaIIb cytoplasmic domain of platelet integrin alphaIIbbeta3
  • functions as a Ca2+-sensitive negative regulator of MAP3K5-mediated signaling events
  • binds many other proteins including presenilin 2, DNA-dependent protein kinase, the polo-like kinases PLK3 and PLK2
  • having a function working as a Ca2+-sensitive antagonist of stress-induced signaling events
  • functions as a previously undescribed regulator of cardiac hypertrophy through its ability to regulate the association of calcineurin with the sarcolemma and its activation
  • regulator of calcineurin-NFAT signaling and cardiac hypertrophy
  • necessary for pathological but not physiological hypertrophy and contributes to cardiac dysfunction during pressure overload
  • unique regulator of pathological cardiac hypertrophy and calcineurin-NFAT signaling in cardiac myocytes
  • required for permitting activation of calcineurin during maladaptive cardiac hypertrophy
    • CELLULAR PROCESS cell life, cell death/apoptosis
    nucleotide, repair
    PHYSIOLOGICAL PROCESS development
    text double-stand break repair, nervous system
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • regulatory subunit for integrin alpha II beta 3
    • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Ca2+
    • protein
  • DNA-dependent protein kianase (PRKDC)
  • cytoplasmic domain of alpha II b in the heterodimer integrin alpha Iib/beta3
  • presenilin 2 (PS2)
  • activating and inhibiting protein ligand of ITPR1
  • CABP1 and CIB1 are two myristoylated proteins that bind the MYO1C regulatory domain
  • bind integrin alphaIIb and may be involved in outside-in-signaling in platelets
  • targeting apoptosis signal-regulating kinase 1 (MAP3K5), and negatively regulates stress-activated MAPK signaling pathways
  • interacting with NBR1 (M17S2) and FEZ1 suggesting a role in neural development
  • activating and inhibiting protein ligand of ITPR1
  • interacting with PLK2
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility may be Alzheimer disease
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
  • potential molecular target for the development of new therapeutics specific for human disorders whose pathogenesis is linked to MAP3K5-mediated signaling events
  • new strategy for treating hypertrophic heart disease through inhibition of CIB1 or its interaction with calcineurin
    • ANIMAL & CELL MODELS
  • Cib1-deleted mice showed a marked reduction in myocardial hypertrophy, fibrosis, cardiac dysfunction and calcineurin–nuclear factor of activated T cells (NFAT) activity after pressure overload, whereas the degree of physiologic hypertrophy after swimming exercise was not altered