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FLASH GENE
Symbol FERMT2 contributors: mct/pgu - updated : 27-06-2017
HGNC name fermitin family homolog 2 (Drosophila)
HGNC id 15767
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N terminus of kindlin-2 (K2-N), with a conserved positively charged surface that binds to membrane enriched with negatively charged phosphatidylinositol-(4,5)-bisphosphate
  • a pleckstrin homology (PH) domain
  • two C-terminal FERM domains, similar with that of talin
  • HOMOLOGY
    interspecies ortholog to C.elegans UNC-112
    ortholog to murine Plekhc1
    intraspecies homolog to URP1,URP2
    Homologene
    FAMILY
  • kindlin family
  • CATEGORY adhesion , regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    text localizes to cell–ECM-adhesion sites
    basic FUNCTION
  • playing an indispensable role for proper control of cell shape change
  • being a novel and essential element of bidirectional integrin signaling
  • regulator of integrin activation and functions as a coactivator
  • required for talin-induced integrin activation, and is a novel and essential element of bidirectional integrin signaling
  • novel integrin adaptor protein important for muscle differentiation, and critical regulator of myocyte elongation
  • cytoplasmic component of cell/ECM adhesions that bind to beta-integrin cytoplasmic tails directly and cooperate with talin in integrin activation
  • essential role for integrin signalling and cell/ECM adhesion regulation
  • essential component of the intercalated disc, that is necessary for cytoskeletal organization at sites of membrane attachment, and required for vertebrate myocardial formation and function
  • integrin adaptor protein important for muscle differentiation, and critical regulator of myocyte elongation
  • focal adhesion proteins implicated in integrin activation
  • physiological role for kindlin-2 in skin fibroblasts under normal steady-state conditions and during tissue regeneration
  • important functions of kindlin-2 in the regulation of podocyte-matrix adhesion and matrix deposition
  • focal adhesion protein that regulate integrin signaling
  • governs RAC1 activation, which controls osteoblast function, and is a critical mediator for osteoblast physiology
  • capable of promoting integrin activation, but such ability is significantly reduced for its membrane-binding defective mutant
  • potential membrane-binding function of its ubiquitin-like domain, which is likely common for all kindlins to promote their localization to the plasma membrane and control integrin activation
  • FBLIM1 may work in concert with its binding partners FERMT2 and filamin in bone
  • SRC, FERMT2 and FBLIM1 together constitute a positive feedback loop that controls SRC activity and regulates integrin-mediated cellular functions
  • is a focal adhesion protein that regulates the activation of integrins
  • in Pancreatic stellate cells (PSCs) promoted the progression of pancreatic cancer
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    text actin cytoskeleton organization and biogenesis
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • FBLP1
  • interact with many components of cell-ECM adhesions, such as migfilin and integrin-linked kinase to promote cytoskeletal reorganization
  • interacts directly with the focal-adhesion proteins ILK and migfilin
  • binds directly to the C terminal region of beta integrin cytoplasmic tails and exerts intergrin-specific activation effects
  • interacts with multiple phosphoinositides, preferentially with phosphatidylinositol 3,4,5-trisphosphate
  • FERMT2 and filamin, which directly bind FBLIM1, have been implicated in regulation of bone remodeling
  • regulatory loop between FERMT2 and GLI1, an effector of Hedgehog signaling pathway (FERMT2 is transcriptionally downregulated via GLI1 occupancy on the FERMT2 promoter)
  • FERMT2 is a novel ACTN2-interacting protein and plays an important role in the regulation of cardiac structure and function
  • cell & other
    REGULATION
    induced by serum in diploid fibroblast cell line
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in breast tumors
    constitutional        
    resulting in early embryonic lethality
    tumoral        
    in leiomyomas compared with normal myometrium
    tumoral     --low  
    greatly decreased in leiomyosarcomas
    tumoral     --over  
    in malignant mesothelioma, and heightened expression of Kindlin-2 might contribute to tumor progression
    Susceptibility to sporadic Alzheimer disease (SAD)
    Variant & Polymorphism SNP
  • rs17125944 in FERMT2 is associated with sporadic AD (SAD) patients
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductiveprostate
    targeting the FERMT2-GLI1 feedback loop may facilitate the killing of prostate cancer cells
    ANIMAL & CELL MODELS