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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
Location 14q22.1      Physical location : 53.323.989 - 53.417.815
Synonym name
  • kindlin 2
  • mitogen-inducible gene 2 protein
  • pleckstrin homology domain containing, family C (with FERM domain) member 1
  • Synonym symbol(s) MIG2, KIND2, mig-2, UNC112, PLEKHC1, UNC112B, FLJ34213, FLJ44462, DKFZp686G11125
    DNA
    TYPE functioning gene
    STRUCTURE 93.71 kb     15 Exon(s)
    regulatory sequence Promoter
    Binding site
    text structure
  • core promoter of Kindlin-2 is a 39 base pair long GC rich fragment located -122/-83 upstream of the Kindlin-2 transcription start site, and SP1 plays an important role in regulation of Kindlin-2 expression (PMI : 21922223)
  • MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    15 - 3351 77 680 - 2008 18997731
    16 - 3372 78.5 687 - 2008 18997731
    15 - 2161 72.3 633 - 2008 18997731
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveintestinelarge intestinecolon  
    Endocrinepancreas    
    Reproductivefemale systemovary   
     male systemprostate   
    Respiratorylung    
    Skin/Tegumentskin    
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveinterstitialdermis highly
    Muscularstriatumcardiac highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    cell cycle     cell cycle, G1, S
    Text placenta
    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)
  • 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