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FLASH GENE
Symbol CFL1 contributors: mct/shn/pgu - updated : 20-11-2018
HGNC name cofilin 1 (non-muscle)
HGNC id 1874
Location 11q13.1      Physical location : 65.622.286 - 65.625.804
Synonym name
  • actin depolymerizing factor
  • 18 kDa phosphoprotein
  • cofilin, non-muscle isoform
  • epididymis secretory protein Li 15
    • Synonym symbol(s) ADF, CFL, HEL-S-15
    DNA
    TYPE functioning gene
    STRUCTURE 3.52 kb     4 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map cen - D11S4205 - D11S1883 - CFL1 - D11S913 - D11S1889 - qter
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 - 1260 - 166 - 2003 12684437
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivesalivary gland   highly
    Lymphoid/Immunetonsils   highly
    Skin/Tegumentskin   highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    HOMOLOGY
    interspecies ortholog to Cfl1, Mus musculus
    ortholog to Cfl1, Rattus norvegicus
    ortholog to CFL1, Pan troglodytes
    Homologene
    FAMILY
  • actin-binding proteins ADF family
    • CATEGORY structural protein
    SUBCELLULAR LOCALIZATION     plasma membrane,junction
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,cytosolic,vesicle
    intracellular,cytoplasm,cytoskeleton
    intracellular,nucleus
    intracellular,nuclear envelope
    text
  • localization in lamellipodia and membrane ruffles, and can also accumulate in the tips and shafts of filopodia
    • basic FUNCTION
  • actin-binding protein, depolymerisation factor of F-actin to G-actin
  • interfering with immunological synapse formation and T-cell activation
  • plays an essential role for the rapid turnover of actin filaments by severing and depolymerizing them
  • actin-filament-severing activity of cofilin is critical for growth cone motility and neurite extension
  • target for Tight junction permeability regulation in epithelial cells
  • with CORO2A, are implicated as factors that can regulate a subset of focal-adhesion-turnover events
  • responsible for the formation of the actin cytoskeleton and is indispensable for cell cycle control
  • cofilin expression and its regulation of CDKN1B expression is important for the control of G(1) phase progression
  • plays an important role in cortical cytoplasmic organization during embryo compaction
  • cofilin expression and its regulation of CDKN1B expression is important for the control of G(1) phase progression
  • major regulator of actin dynamics involved in the regulation of cell spreading and migration through its actin depolymerizing and severing activities
  • ADF/cofilin-mediated actin dynamics regulated AMPA receptor (AMPAR) trafficking during synaptic potentiation
  • temporally regulated ADF/cofilin activities function in postsynaptic modifications of receptor number and spine size during synaptic plasticity (
  • its activation is required for FAS-stimulated formation of membrane protrusions and increased tumour cell invasion)
  • FSCN1 and CFL1 act synergistically in filament severing
  • cooperates with FSCN1 to disassemble filopodial actin filaments
  • essential and conserved modulator of actin dynamics in eukaryotic cells
  • CFL1 and VANGL2 cooperate likely in the initiation of planar cell polarity in the embryo
  • Cofilin/actin rod formation by dysregulation of CFL1 activity is a central initial step in neurodegeneration
  • CFL1 is required for the activation of apical actomyosin required for neural tube closure
  • actin dynamic reassembly and CFL1 phosphorylation loop is involved in the control of stromal (skeletal) stem cells (hMSCs) proliferation and osteoblasts differentiation
  • control actin stress fibers, nuclear integrity, and cell survival
  • key protein in the regulation of actin dynamics and migration
  • actin-binding protein and a major actin depolymerization factor in the central nervous system (CNS)
  • CFL1 induces Epithelial-mesenchymal transition (EMT) by promoting cytoskeletal rearrangement 5)
  • actin filament length regulators CFL1, CAPZB and DIAPH1 regulate mitotic cortex thickness and both increasing and decreasing thickness decreases tension in mitosis
  • optogenetic regulation of CEFL1 revealed its critical role for controlling timing, turnover and dynamics of F-actin assembly inside daughter cell nuclei
  • CFL1 and WDR1 are evolutionally conserved proteins that cooperatively sever actin filaments
    • CELLULAR PROCESS cell organization/biogenesis
    cell communication
    PHYSIOLOGICAL PROCESS
    text putatively recycling actin in stationary cells
    PATHWAY
    metabolism
    signaling
    a component
  • complexes with cofilin, ERBB2 and PLCG1
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • Actin interacting protein 1, Aip1
  • alpha subunit of Na,K-ATPase
  • N-terminal domain of CAP, adenylate cyclase-associated protein 1, CAP1
  • ADF/cofilins complex bind both G-actin and F-actin
  • 14-3-3 zeta isoform
  • triose-phosphate isomerase, TPI
  • chloride transporter ClC-5
  • Hsp105alpha
  • interacting with HUNK (disrupts the ability of PPP2R4 to bind to CFL1 while sparing its capacity to bind to other substrates such as ERK or AKT
  • LIMK1-mediated phosphocycling of CFL1 plays a crucial role in maintaining actin homeostasis and receptor activity
  • CAMK2D and PPP3CA provide likely a switch-like mechanism that controls Ca-dependent LIMK1, SSH1 and CFL1 activation, and subsequently actin cytoskeletal reorganization
  • plays an important role in regulating actin reorganization of spreading cell on fibronectin via phosphorylating CFL1
  • WDR1 enhances CFL1-mediated actin disassembly in the apical region of precluster cells to promote remodeling of adherens junctions (AJs) and thus intercellular movement, but also robust actin polymerization promotes AJ general adhesion and integrity during the remodeling process
  • WDR1 is a major co-factor that collaborates with CFL1 to disassemble F-actin
  • is required for actin and P-type ATPase secretory pathway calcium ATPase (ATP2C1)-dependent sorting of secretory proteins at the trans-Golgi network (TGN)
  • association of IRS4 with SSH1 contributes likely to localized activation of CFL1 in membrane protrusions
  • WDR1 interacts with Lim domain kinase 1 (LIMK1), a well known phosphorylation kinase of CFL1
  • causal relationship between increased RAC1/CFL1 signaling, synaptic defects, and impaired sensory processing in FRAXA and role for impaired RAC1/CFL1 signaling in the aberrant spine morphology and spine density associated with FRAXA
  • WDR1, an actin interacting protein, enhances CFL1 capacity to accelerate depolymerization of F-actin filaments
  • WDR1 is essential for the localization of CFL1 to the platelet membrane skeleton
    • cell & other
    REGULATION
    Phosphorylated by also phosphorylated by testis-specific kinase 1 (TESK1)
    Other phosphorylated by LIM Kinase 1, LIMK-1
    regulated by SRC through tyrosine phosphorylation at Y68 that triggers the degradation of cofilin through ubiquitination-proteosome pathway and consequently inhibits cofilin activity in reducing cellular F-actin contents and cell spreading
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    cofilin aggregation may contribute to neurodegeneration and brain aging by blocking intracellular trafficking and inducing synaptic loss
    tumoral     --over  
    significant association between overexpression of nuclear CFL1 with bladder cancer progression
    tumoral     --over  
    simultaneous overexpression of AURKA and CFL1 correlated with lymph node metastasis in thyroid cancer tissue
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • not only the higher levels of CFL1, but also its nuclear localization can be proposed as marker of worse outcome of patients with melanoma
  • positive expression of UGP2 and CFL1 can serve a valuable prognostic factor in pancreatic cancer
  • cytoskeletal cofilin is potential tumor marker of invasive bladder cancer
    • Therapy target
    SystemTypeDisorderPubmed
    cancerurinary 
    targetable platforms for the treatment of invasive bladder cancer
    cancerendocrinethyroid
    possibility of targeting AURKA and CFL1 for more effective treatment of thyroid cancer
    cancerhemopathy 
    targeting CFL1 might therefore provide another novel approach for treatment of Ewing sarcoma
    ANIMAL & CELL MODELS
  • Loss of n-cofilin impairs radial migration, resulting in the lack of intermediate cortical layers