Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol FLNA contributors: mct - updated : 27-02-2014
HGNC name filamin A, alpha
HGNC id 3754
Corresponding disease
BPNH bilateral periventricular nodular heterotopia in females
CIPO2 intestinal pseudoobstruction, neuronal, chronic idiopathic 2
FGS2 FG syndrome 2
FMTD frontometaphyseal dysplasia
MLNS Melnick-Needles syndrome
ODPF terminous osseous dysplasia and pigmentary defect
OPD1 otopalatodigital syndrome, type 1
OPD2 otopalatodigital syndrome, type 2
PVNH4 periventricular heterotopia 4, Ehlers-Danlos variant
Location Xq28      Physical location : 153.576.899 - 153.603.006
Synonym name
  • filamin A, alpha (actin binding protein 280)
  • actin binding phosphoprotein, dystrophin-like (APB280)
  • actin binding protein 280
  • endothelial actin-binding protein
  • non-muscle filamin
  • Synonym symbol(s) ABP280, ABPX, FLN1, NHBP, MNS, FMD, DKFZp434P031
    DNA
    TYPE functioning gene
    STRUCTURE 26.11 kb     48 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map cen - RGCP@ - TKTL1 - FLNA - EMD EMD - DNASE1L1 - TAZ - ATP6AP1 - GDI1 - (FAM50A - PLXNA3 ) - LAGE3 - UBL4A - (SLC10A3 )- DXS253E - FAM3A - G6PD - ERVK2 - MPP1 - F8 - DXS115 - DXS459 - DXYS64X - qter
    Authors PMID: 8577758
    Text see CVG@
    Physical map
    MECP2 Xq28 methyl CpG binding protein 2 (Rett syndrome) OPN1LW Xq28 opsin 1 (cone pigments), long-wave-sensitive (color blindness, protan) OPN1MW Xq28 opsin 1 (cone pigments), medium-wave-sensitive (color blindness, deutan) CXorf2 Xq28 chromosome X open reading frame 2 TKTL1 Xq28 transketolase-like 1 FLNA Xq28 filamin A, alpha (actin binding protein 280) EMD Xq28 emerin (Emery-Dreifuss muscular dystrophy) RPL10 Xq28 ribosomal protein L10 DNASE1L1 Xq28 deoxyribonuclease I-like 1 TAZ Xq28 tafazzin (cardiomyopathy, dilated 3A (X-linked); endocardial fibroelastosis 2; Barth syndrome) ATP6AP1 Xq28 ATPase, H+ transporting, lysosomal accessory protein 1 GDI1 Xq28 GDP dissociation inhibitor 1 DXS9928E Xq28 DNA segment on chromosome X (unique) 9928 expressed sequence PLXN3 Xq28 likely ortholog of mouse plexin 3 DXS9879E Xq28 DNA segment on chromosome X (unique) 9879 expressed sequence UBL4 Xq28 ubiquitin-like 4 SLC10A3 Xq28 solute carrier family 10 (sodium/bile acid cotransporter family), member 3 FAM3A Xq28 family with sequence similarity 3, member A G6PD Xq28 glucose-6-phosphate dehydrogenase IKBKG Xq28 inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma
    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
  • 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
  • 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
  • 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
  • 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