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FLASH GENE
Symbol LIMK1 contributors: mct - updated : 05-09-2019
HGNC name LIM domain kinase 1
HGNC id 6613
Corresponding disease
WBS Williams Beuren syndrome
Location 7q11.23      Physical location : 73.498.155 - 73.536.854
Synonym name LIM motif-containing protein kinase
Synonym symbol(s) LIMK, LIMK-1
EC.number 2.7.11.1
DNA
TYPE functioning gene
STRUCTURE 38.75 kb     16 Exon(s)
10 Kb 5' upstream gene genomic sequence study
motif repetitive sequence   ALU
MAPPING cloned Y linked N status confirmed
Map cen - LIMK1 - WBSCR1 - RFC2 - LAT2 - qter
Physical map
LOC389516 7 hypothetical gene supported by BC002581; NM_012447 LOC389517 7 similar to Williams Beuren syndrome chromosome region 19 GTF2IP1 7q11.23 general transcription factor II, i, pseudogene 1 LOC389518 7 similar to Neutrophil cytosolic factor 1 LOC389519 7 similar to transcription factor GTF2IRD2 LOC389520 7 similar to Nuclear envelope pore membrane protein POM 121 (Pore membrane protein of 121 kDa) (P145) WBSCR20A 7q11.23 Williams Beuren syndrome chromosome region 20A TRIM50A 7q11.23 tripartite motif-containing 50A FKBP6 7q11.23 FK506 binding protein 6, 36kDa FZD9 7q11.23 frizzled homolog 9 (Drosophila) BAZ1B 7q11.23 bromodomain adjacent to zinc finger domain, 1B BCL7B 7q11.23 B-cell CLL/lymphoma 7B TBL2 7q11.23 transducin (beta)-like 2 WBSCR14 7q11.23 Williams Beuren syndrome chromosome region 14 WBSCR24 7q11.23 Williams Beuren syndrome chromosome region 24 STX1A 7q11.23 syntaxin 1A (brain) WBSCR18 7q11.23 Williams Beuren syndrome chromosome region 18 WBSCR22 7q11.23 Williams Beuren syndrome chromosome region 22 WBSCR21 7q11.23 Williams Beuren syndrome chromosome region 21 CLDN3 7q11.23 claudin 3 CLDN4 7q11.23 claudin 4 WBSCR27 7q11.23 claudin 4 WBSCR28 7q11.23 Williams-Beuren syndrome critical region 28 ELN 7q11.23 elastin (supravalvular aortic stenosis, Williams-Beuren syndrome) LIMK1 7q11.23 LIM domain kinase 1 WBSCR1 7q11.23 Williams-Beuren syndrome chromosome region 1 WBSCR5 7q11.23 Williams-Beuren syndrome chromosome region 5 RFC2 7q11.23 replication factor C (activator 1) 2, 40kDa CYLN2 7q11.23 cytoplasmic linker 2 GTF2IRD1 7q11.23 GTF2I repeat domain containing 1 LOC389521 7 LOC389521 WBSCR23 7q11.23 Williams-Beuren syndrome chromosome region 23 GTF2I 7q11.23 general transcription factor II, i GTF2IRD2 7q11.23 transcription factor GTF2IRD2 LOC389522 7 similar to Cohesin subunit SA-3 (Stromal antigen 3) (SCC3 homolog 3) PMS2L5 7q11-q22 postmeiotic segregation increased 2-like 5 LOC389523 7 similar to opposite strand transcription unit to Stag3; Gats protein WBSCR16 7q11.23 Williams-Beuren syndrome chromosome region 16
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
16 - 3332 - 647 - 1995 8537403
also called LIMK1I1
15 - 3175 - 613 - 1994 8183554
also called dLIMK
- - 3270 - 305 - 1994 8183554
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   lowly
Nervousbrainforebraincerebral cortex highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularstriatumskeletal  
Nervousperipherous   
cells
SystemCellPubmedSpeciesStageRna symbol
Nervousneuron
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period fetal
Text nervous system
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)
  • 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