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FLASH GENE
Symbol CIB1 contributors: mct - updated : 08-10-2018
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, CaMy1
    DNA
    TYPE functioning gene
    STRUCTURE 35.50 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 - 2017 28542214
    CIB1
    7 - 1104 - 231 - 2017 28542214
  • CIB1A
  • CIB1A is a novel mediator of PRKD2-driven carcinogenesis and a potentially interesting therapeutic target
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   predominantly Homo sapiens
    Endocrineparathyroid   highly
    Lymphoid/Immunetonsils   highly
    Nervousbrain   highly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumcardiacmyocardiummoderately Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron 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,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    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
  • potential role of the CIB1/LMO3 complex is to inhibit cell proliferation
  • 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
  • EF-hand Ca(2+)-binding protein expressed in several cell types, including brain neurons
  • CIB1 regulates endomitosis
  • emerging roles of CIB1 in regulating cancer cell survival and angiogenesis
  • is an EF-hand calcium binding protein, which is involved in many cellular processes, including calcium signaling, cell survival and proliferation, cell migration, cell adhesion and apoptosis
  • 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
  • calcium- and integrin-binding protein CIB1 is an LMO3-binding protein, which binds via the second LIM domain (LIM2) of LMO3
  • 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
  • CIB1 via STMN2 couples Ca(2+) signals with the dynamics of microtubules during neuronal outgrowth in the developing brain
  • CIB1 is involved in regulating endomitosis, perhaps through its interaction with PLK3
  • CIB1 could bind to all integrin complexes and act as a broad regulator of integrin function
  • CIB1 may be involved in the pathogenesis of oligoasthenozoospermia by the CDK1 signaling pathway
  • role for CIB1 in neoplastic transformation, revaeling a novel mechanism facilitating oncogenic signalling by HRAS and PAPSS1
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in the oligoasthenozoospermia patients
    Susceptibility may be Alzheimer disease
    Variant & Polymorphism
    Candidate gene
    Marker
  • significant correlation between the urine CIB1 and serum pro-BNP levels in patients with acute ischemic heart failure (significantly higher)
  • Therapy target
  • potential molecular target for the development of new therapeutics specific for human disorders whose pathogenesis is linked to MAP3K5-mediated signaling events
  • SystemTypeDisorderPubmed
    cancerreproductivebreast
    is a novel therapeutic target for triple-negative breast cancer
    cardiovascularaquiredheart failure
    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
  • Cib1 expression is increased in primary mouse megakaryocytes compared to mononuclear bone marrow cells