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FLASH GENE
Symbol FLNA contributors: mct - updated : 27-02-2017
HGNC name filamin A, alpha
HGNC id 3754
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
48 - 8557 280 2647 - 2001 11336782
47 - 8533 - 2639 - 2001 11336782
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveesophagus   highly
Reproductivefemale systemuterus  highly
 male systemprostate  highly
Respiratoryrespiratory tractlarynx  highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectivebone   
Nervouscentral   
Nervousperipherous   
cells
SystemCellPubmedSpeciesStageRna symbol
Cardiovascularendothelial cell
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period fetal, pregnancy
Text highly, in the cortex (migratory neurons)
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N terminal filamentous with two calponin
  • homology domains (CHD1 and CHD2, actin-binding domain (ABD), between the initial two methionines crucial for proper enteric neuron development, and calponin homology domain 1 (CHD1), within the filamin A (FLNa) actin-binding domain, is the minimal fragment sufficient for ASB2-mediated degradation
  • 24 Ig-like domains, filamin repeats terminating in a 24th-dimerisation domain
  • a membrane glycoprotein binding domain
  • C terminal self-association domain
  • mono polymer homomer , heteromer , dimer
    HOMOLOGY
    interspecies homolog to murine Flna
    intraspecies homolog to flnc
    Homologene
    FAMILY
  • filamin family
  • CATEGORY chaperone/stress , motor/contractile , signaling
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton
    intracellular,nucleus,nucleolus
    text
  • localize to podosomes, and the defects seen in patients carrying FLNA mutations could be related to the capacity of certain cell types to form podosomes
  • basic FUNCTION
  • dimeric actin cross-linking phosphoprotein
  • required for locomotion of many cell types
  • anchor protein, playing essential roles in intercellular junctions
  • having a critical function in neural-crest and non-neural crest, and playing a role either in organizing endothelial cells or in the interaction of endothelial and mesenchymal cells
  • required for cell-cell contact in vascular development and cardiac morphogenesis
  • playing a crucial role in enteric-neuron structure and function
  • playing an important role in actin cytoskeleton organization, membrane stabilization, and anchoring of transmembrane proteins
  • involved in Ca2+ -sensing receptor signaling (silencing of filamin A gene expression inhibits Ca2+ -sensing receptor signaling)
  • CAV1-dependent target in IGF1-stimulated cancer cell migration
  • required for an efficient recombinational DNA double strand break repair
  • required for membrane stability, providing protection from force-induced cell death in an integrin-dependent manner for which the AB Domain is essential
  • enhances MAP2K7 activation and is important for synergistic stress-induced JNK activation
  • actin-binding protein that participates in cell attachment, plays important additional roles in signal transduction and modulation of transcriptional responses
  • stimulates CDC25C function and promotes entry into mitosis
  • required to maintain the F-actin-dependent linear distribution of caveolin-1
  • plays a critical role in cytoskeletal organization, cell motility and cellular signaling
  • actin-binding protein that is a central mechanotransduction element of the cytoskeleton
  • has a crucial role in the normal processes of ciliogenesis and basal body positioning
  • role in mesenchymal migration, which could be directly related to the defects in cell migration described during the embryonic development in FLNA-defective patients
  • unique role for FLNA as a nucleolar protein that associates with the RNA polymerase I (Pol I) transcription machinery to suppress rRNA gene transcription
  • positive role for FLNA in platelet adhesion under high shear
  • non-muscle actin binding protein, which organizes filamentous actin into orthogonal networks and stress fibers
  • ASB2-resistant filamins protect cells from ASB2-mediated inhibition of spreading
  • CELLULAR PROCESS cell communication
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • heterodimer FLNA/FLNB
  • repeat 24 and the second hinge domain are important for dimer formation
  • dimeric protein that binds to actin filaments via its actin-binding domain
  • forms
  • V
    -shaped tail-to-tail homodimers that cross-link F-actin into orthogonal networks
  • forms a complex with CDC25C and binds preferentially to the mitotic form of CDC25C
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • LNK regulatory role through its association with LNK
  • FLNB to allow for proper neuronal migration
  • SP1 transcriptional activation
  • interacting with MAP3K4
  • ASB2 targets the actin-binding proteins filamin A and B for proteasomal degradation
  • interactions between FLNA and transmembrane or signalling proteins, mediated at least in part by immunoglobulin domains 19 to 21 are important for both cell spreading and initiation of migration can bind MAP2K7 and MAP2K4, connecting the in close proximity
  • interacting with IGFBP5 (IGFBP5 leads to dephosphorylation of FLNA with subsequent FLNA cleavage)
  • interacting with CFTR
  • in melanoma cells RRAS and FLNA may cooperatively promote metastasis by enhancing cell migration
  • interactions with intermediate filaments and protein kinase C enable tight regulation of ITGB1 function and consequently early events in cell adhesion and migration on extracellular matrix proteins
  • in endothelial cells endogenous RRAS interacts with endogenous FLNA, to maintain endothelial barrier function
  • TMEM67 forms a functional complex with FLNA that is disrupted in MKS3 and causes defects in neuronal migration and Wnt signalling
  • NPHS1 recruits and regulates a protein complex that includes INPPL1, FLNA and RAPH1, proteins important in regulation of actin and focal adhesion dynamics, as well as lamellipodia formation
  • FLNA, FLNB but not Janus kinases are substrates of the ASB2 cullin-ring E3 ubiquitin ligase in hematopoietic cells
  • ARFGEF2 regulates filamin A phosphorylation and neuronal migration
  • reduces SCNN1A channel function through direct interaction on the cell surface
  • FLNA binds to ARHGAP24 at F-actin-enriched sites, such as at the leading edge of the cell where RAC1 activity is controlled to inhibit actin assembly
  • FLNA regulates neuronal migration through ARFGEF2-dependent ARF1 activation
  • interaction between the antiviral endoribonuclease RNASEL and the actin-binding protein FLNA that enhances host defense by preventing viral entry into naive cells
  • FLNA-PACSIN2 interaction regulates membrane tubulation in megakaryocyte (MK) and platelets and likely contributes to demarcation membrane system (DMS)formation
  • ASB2, by driving degradation of filamin A (FLNA) and filamin B (FLNB), is responsible for the difference in FLNA and FLNB abundance in the different spleen Conventional dendritic cells (cDCs) subsets
  • FLNA loss leads to diminished expression of Beta1-integrin, whereas FLNB loss promotes integrin expression
  • FLNA is known to play roles in cytoskeleton organization and to be required for heart function, and its degradation mediated by ASB2 ensures essential functions in differentiating cardiac progenitors
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) BPNH , OPD2 , MLNS , FMTD , OPD1 , PVNH4 , CIPO2 , FGS2 , ODPF
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    inhibited neuronal migration
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS