Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol LIMK1 contributors: mct - updated : 05-09-2019
HGNC name LIM domain kinase 1
HGNC id 6613
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • two N-terminal cysteine-rich LIM/double zinc finger motifs
  • a proline serine rich region with several putative casein kinase and MAP kinase recognition sites
  • a PDZ domain (PSD95/disc large/ZO-1)
  • a C terminal serine/threonine kinase domain
    • HOMOLOGY
    interspecies homolog to Limk1
    Homologene
    FAMILY
  • protein kinase superfamily
  • TKL Ser/Thr protein kinase family
    • CATEGORY regulatory , signaling , receptor membrane
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
    text
  • phosphorylated LIMK1 is recruited to the centrosomes during early prophase, where it colocalizes with TUBG
  • regulator of actin cytoskeleton dynamics, found to localize at the mitotic centrosome
    • basic FUNCTION
  • ceramide-induced gene, regulating actin dynamics through phosphorylation of cofilin, which leads to accumulation of F-actin, playing a role in brain development
  • maybe responsible for the cognitive defect of the Williams syndrome
  • may act as a link between stress-induced ceramide formation and reorganization of the actin cytoskeleton
  • involved with elastin in the same actin depolymerization signaling pathway
  • regulate actin cytoskeletal reorganization through phosphorylating and inactivating cofilin, an actin-depolymerizing factor of actin filaments
  • its activity is required for thrombin-induced modulation of microtubule destabilization and actin polymerization and may coordinate microtubules and actin cytoskeleton
  • mitotic LIMK1 activation is critical for accurate spindle orientation in cells
  • regulates actin dynamics by phosphorylating and inactivating cofilin, an actin-depolymerizing protein
  • may mediate TGF-beta-dependent signaling during ocular inflammation
  • regulates actin cytoskeletal remodeling by phosphorylating and inactivating cofilin, an actin filament-disassembling factor
  • has a dual role in regulating lamellipodium extension by decelerating actin retrograde flow and polymerization
  • plays a facilitative role in lamellipodium extension by promoting the efficient conversion of the force of actin polymerization into extension by decelerating the rate of actin retrograde flow via cofilin inactivation
  • critical role of LIMK1-mediated CFL1 pathway and actin dynamics in modulating retinoid receptor mediated function
  • modulator of actin and microtubule dynamics, is involved in the mitotic process through inactivating phosphorylation of cofilin
  • LIMK1 and LIMK2 affect centrosome focusing
  • LIMK1 activity helps promote human placental development in utero
  • LIMK1 negatively regulated neuronal migration by affecting the neuronal cytoskeleton and its effects were partly mediated by cofilin phosphorylation
  • involvement in the regulation of mitotic centrosome integrity
  • LIMK1 phosphorylation regulates cytoplasmic dynein function in centrosomal protein transport, which in turn impacts mitotic spindle pole integrity
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling neurotransmission
  • signaling cascade that involves FAM89B-CDC42BPA and LIMK1-cofilin in the regulation of lamellipodial F-actin dynamics important for cell protrusion and migration
    • a component
  • forms a complex with tubulin via the PDZ domain
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • witn proneuregulin 1
  • cell-type dependent functional interaction between PARK2 and LIMK1 (links parkin and LIMK1 in the pathogenesis of familial PD)
  • interacting with PINK1
  • with cofilin (induces actin remodeling by phosphorylating and inactivating cofilin, an actin-depolymerizing factor, and LIMK1-mediated cofilin phosphorylation is required for accurate spindle orientation by stabilizing cortical actin networks during mitosis)
  • LIMK1-mediated CFL1 phosphorylation is critical for ionomycin-induced neurite outgrowth and CAMK4 mediates ionomycin-induced LIMK1 activation
  • CDKN1C interacts with the actin cytoskeleton modifying enzyme, LIM-kinase 1 (LIMK1) but not LIMK2 (CDKN1C control of LIMK1 ultimately affects cell mobility negativel)
  • Coagulation Factor F10 inhibits cancer cell migration via LIMK1-mediated cofilin inactivation
  • AURKA physically associates with LIMK1 and activates it through phosphorylation, which is important for its centrosomal and spindle pole localization
  • CAMK2D and PPP3CA provide likely a switch-like mechanism that controls Ca-dependent LIMK1, SSH1 and CFL1 activation, and subsequently actin cytoskeletal reorganization
  • LIMK1 was required for CDKN1C death promoting effect
  • PAK4 kinase activity and associated LIMK1 activity are essential for carcinoma cell motility, highlighting PAK4 as a potential anti-metastatic therapeutic target
  • novel interaction between LIMK1 and NTRK2, which is required for the BDNF-induced axonal elongation
  • LIMK1 or SSH1 depletion inhibited RELA phosphorylation at Ser(536), a critical event conferring transcriptional competency to the bound NFKB
  • lamellipodium-localized FAM89B-CDC42BPA complex is essential for the regulation of local LIMK1 and its downstream F-actin regulatory factor cofilin
  • LIMK1 interacts and regulates the activity of cyclic AMP response element-binding protein (CREB1)
  • PLCH2 specifically interacts with LIMK1 in Neuro2A cells
  • ROCK1 via LIMK1, LIMK2 regulates growth, maturation and actin based functions in mast cells
  • is a serine/threonine protein kinase that mediates actin dynamics by regulating actin depolymerization factor/cofilin
  • WDR1 interacts with Lim domain kinase 1 (LIMK1), a well known phosphorylation kinase of CFL1
    • cell & other
    REGULATION
    activated by by binding to the BMP receptor, BMPRII (regulating BMP-dependent dendritogenesis)
    MAPKAPK2 for a novel signaling pathway in VEGFA-induced cell migration
    Other palmitoylation is critical for LIMK1 function because this modification not only controls LIMK1 targeting, but is also essential for LIMK1 activation by its membrane-localized upstream activator PAK
    ASSOCIATED DISORDERS
    corresponding disease(s) WBS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   deletion    
    in Williams syndrome
    tumoral     --over  
    significantly promoted colon cancer cell migration and invasion
    Susceptibility to intracranial aneurysm
    Variant & Polymorphism SNP promoter C(-187)T SNP increasing the risk of intracranial aneurysm
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    immunologyautoimmune 
    downregulating LIMK1 expression may provide a novel therapy for suppression and prevention of ocular inflammation and fibrosis
    ANIMAL & CELL MODELS