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FLASH GENE
Symbol FLII contributors: mct - updated : 10-12-2017
HGNC name flightless I homolog (Drosophila)
HGNC id 3750
Location 17p11.2      Physical location : 18.148.152 - 18.162.055
Synonym name flightless I homolog
Synonym symbol(s) FLIR, FLIR1, FLI, FLIR2, FLIL, MGC39265, FLI2
DNA
TYPE functioning gene
SPECIAL FEATURE overlapping, gene in gene, opposite orientation, tail to tail
text overlapping 3'end of LLGL1
STRUCTURE 14.10 kb     30 Exon(s)
10 Kb 5' upstream gene genomic sequence study
text structure 3' and overlaps with the 3' and OFLLGL1 gene
MAPPING cloned Y linked   status confirmed
Map see SMCR (phenotype)
regionally located within the Smith-Magenis critical region
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
30 - 4176 - 1269 - 2002 11971982
29 - 4222 - 1214 - 2002 11971982
30 - 4208 - 1258 - 2002 11971982
EXPRESSION
Type
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   highly
Respiratorylung   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularstriatumcardiac  
Muscularstriatumskeletal  
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • sixteen N terminal, leucine-rich repeat motifs (LRR), with LXXLL motif within the LRR domain of FLII interacting directly with the DNA-binding domain of PPARG
  • five C terminal gelsolin-like domains, involved in capping and severing actin filaments
  • HOMOLOGY
    interspecies homolog to Drosophila flightless (fli) 1
    homolog to murine Fliih
    Homologene
    FAMILY
  • gelsolin superfamily of actin-remodeling proteins
  • CATEGORY motor/contractile
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton
    intracellular,nucleus,nucleoplasm
    text
  • distributed throughout the cytosol and in focal adhesions
  • basic FUNCTION
  • playing a key role in embryonic cellularization by interacting with both the cytoskeleton and other cellular components
  • actin-remodeling protein that influences diverse processes including cell migration and gene transcription and links signal transduction with cytoskeletal regulation 0)
  • regulates cell migration through its localization to focal adhesions and its ability to cap actin filaments, which collectively affect focal adhesion maturation
  • may contribute to the inhibitory effect of chronic wound fluid on fibroblast function
  • is a component of the MLXIPL transcriptional complex and negatively regulates MLXIPL function in cancer cells
  • important role for FLII in the development and regulation of the epidermal barrier, which may contribute to the impaired healing and skin fragility of epidermolysis bullosa (EB) patients
  • functions in PPARG activation as a molecular switch to repress transcriptional activity by interrupting formation of the PPARG/RXRA complex
  • is a negative regulator of wound healing
  • actin remodeling protein that affects cellular processes including adhesion, proliferation and migration
  • enhances cutaneous squamous cell carcinoma tumor progression by decreasing apoptosis and enhancing tumor cell invasion
  • FLII and LRRFIP2 repress caspase-1 activation, which could be restored through the severing of actin filaments in a Ca2+-dependent process
  • both LRRFIP2 and FliI control the localization of NLRP3 with F-actin as well as the activity of NLRP3 inflammasome
  • CELLULAR PROCESS cell organization/biogenesis
    PHYSIOLOGICAL PROCESS
    text muscle contraction
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • is a substrate of SGK3 that functions downstream of PI 3-kinase and SGK3 can associate with FLII and phosphorylate FLII at residues Ser(436) and Thr(818)
  • FLII can bind directly to both ESR1 and ACTL6A, an actin-related component of the SWI/SNF complex, suggesting that FLII may recruit SWI/SNF to ESR1 target genes via interaction with ACTL6A
  • FLII is a novel NXN-binding partner (binds to NXN and other related proteins, such as Rod-derived cone viability factor (NXNL1)
  • with FLAp (linking FLII to the actin cytoskeleton)
  • three regulators of the actin cytoskeleton--AMOTL2, SPATA13 and FLII--interact with PHLDB2
  • LRRFIP2 enhances the interaction between FLII and CASP1, facilitating the inhibitory effect of FLII on CASP1 activation
  • FLII binds directly to and suppresses the transcriptional activity of PPARG
  • FLII interacts with MYH9 to promote cell extension formation, which enables collagen remodeling in fibroblasts
  • FLII is recruited to the NLRP3 inflammasome by leucine-rich repeat FliI-interaction protein 2 (LRRFIP2), an NLRP3-associated protein
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   deletion    
    constantly, in Smith-Magenis syndrome (SMCR)
    constitutional     --over  
    increased in the blistered skin of patients with epidermolysis bullosa (EB)
    tumoral     --over  
    negatively regulated MLXIPL mediated transcription in cancer cells
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerskin 
    targeting FLII may be a potential strategy for reducing the severity of cutaneous squamous cell carcinoma
    obesity  
    FLII may serve as a novel therapeutic target in the treatment of adiposity-related metabolic syndromes
    ANIMAL & CELL MODELS