Atlas of Genetics and Cytogenetics in Oncology and Haematology

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LIMK1 (LIM domain kinase 1)

Written2009-08Ratna Chakrabarti
Department of Molecular biology, Microbiology, Burnett School of Biomedical Sciences, University of Central Florida, 12722 Research Parkway, Orlando, Florida 32826, USA

(Note : for Links provided by Atlas : click)


Alias (NCBI)EC
HGNC Alias symbLIMK
LocusID (NCBI) 3984
Atlas_Id 41159
Location 7q11.23  [Link to chromosome band 7q11]
Location_base_pair Starts at 74083804 and ends at 74122525 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping LIMK1.png]
Local_order ELN, LIMK1, EIF4H, LAT2.
  LIMK1 gene is located at chromosome 7 on the long arm (q11.23).
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
LIMK1 (7q11.23)::LIMK1 (7q11.23)


  A) LIMK1 gene consists of 16 exons. Exons 2-4 encode two LIM domains in tandem. Exons 4-6 encode a PDZ domain and exons 8-16 encode a serine/threonine kinase domain. B) A splice variant of LIMK1 (dLIMK1), which lacks the kinase domain. In this variant, intron 7 was extended to 61 additional bases at the 5' end of exon 8, which caused a frameshift in the LIMK1 ORF and resulted in premature termination after 12 missense mutations in dLIMK1.
Description The gene starts at 73136092 bp from pter and ends at 73174790 bp from pter. Its size is 38699 bases and its orientation lie in the plus strand. The 5' promoter region (1.5 kb) contains putative sites for transcriptional regulation including Sp1, MZF1, AP1 and NF-E2. No consensus TATA box is evident.
Transcription The transcript contains 16 exons spanning a length of 3.332 kb. The mRNA contains a short 5'UTR but a long 3' end UTR. Two LIM domains, LIM1 and LIM2 are encoded by the exons 2-4. A single PDZ domain is encoded by the exons 2-6. A C-terminal domain is encoded by exons 8-16.
Pseudogene None identified.


  LIMK1 consists of specific domains, nuclear localisation signal (NLS) and nuclear exit signals (NES).
Description The LIMK1 protein is composed of 647 amino acids. It belongs to a unique family of LIM domain containing dual specificity (serine threonine and tyrosine) protein kinase. LIMK1 also has a PDZ domain in the middle of the gene and a kinase domain at the C-terminal end. A stretch of basic amino acids resembling nuclear localisation signal is present in the kinase domain and two nuclear export signal sequences containing hydrophobic residues are present in the PDZ domain.
Expression LIMK1 exhibits tissue specific expression. It is predominantly expressed in brain but to a moderate extent in the heart and skeletal muscle. The least amount of LIMK1 expression was noted in the liver. LIMK1 is also expressed in lesser amounts in various human epithelial cell lines and haematopoetic cell lines.
Localisation LIMK1 is primarily localized in the cytoplasm but also transported to the nucleus. In the cytoplasm, LIMK1 is colocalized with microtubules, and actin at the focal adhesion, stress fiber and at the lamellipodia. In the mitotic cells, LIMK1 is localized to the centrosomes until early telophase and to the cleavage furrow during late telophase.
Function LIMK1 regulates organization of actin cytoskeleton through inactivating phosphorylation of the actin depolymerizing family (ADF) protein cofilin. LIMK1 phosphorylates cofilin at Serine, which inhibits actin depolymerization and results in accumulation of F actin. LIMK1 also regulates microtubule stability and assembly through phosphorylation of p25/TPPP (tubulin polymerization protein), which destabilizes microtubules. Activated LIMK1 associates with gamma-tubulin at the centrosome during mitotic phases. LIMK1 is a multifunctional protein and is involved in regulation of cell motility, cell cycle, cytokinesis and cellular morphology. LIMK1 also regulates neurite growth, synaptic stability, growth cone motility, axon formation through modulation of Golgi dynamics and neuronal differentiation.
Homology LIMK1 has 50% identity overall and 70% identity in the kinase domain with another family member LIMK2. Although both proteins phosphorylate cofilin and regulate actin cytosketon reorganization current studies showed that LIMK2 has also different cellular function.


Germinal Hemizygous deletion of LIMK1 along with Elastin gene in a 1.5 MB deletion has been noted in patients with Williams-Beuren syndrome. Patients with Williams Syndrome exhibit impaired visuospatial constructive cognition possibly because of loss of LIMK1 gene.
SNP: A single nucleotide polymorphism of LIMK1 in a haplotype spanning Elastin gene has been linked to susceptibility of intracranial aneurysm (IA).

Implicated in

Entity Prostate cancer
Disease Prostate cancer is the most prevalent malignancy second to lung cancer in men in the western world. Although slow growing, a subpopulation of prostate cancer patients develops highly invasive metastatic disease that is nonresponsive to anti-androgen therapy and is usually fatal.
Prognosis The gold standard for diagnosis of prostate cancer are the Gleason scores and the serum PSA level. PSA level is also used for prognostic purposes. LIMK1 expression may have prognostic value for identification of metastatic progression as overexpression of LIMK1 has been noted in metastatic prostate cancer cells.
Cytogenetics Through cytogenetics method such as CGH and FISH analysis chromosomal gain in 7q11.2 region or entire chromosome 7 including 7q11.23 locus has been reported in some prostate cancer cases.
Oncogenesis LIMK1 is overexpressed in prostate cancer cells and tissues compared to benign prostatic hyperplasia. Because LIMK1 plays an important role in mitosis, microtubule dynamics and cytokinesis altered expession of LIMK1 may cause mitotic defects. Aberrant expression of LIMK1 is also involved in induction of invasion in prostate cancer cells.
Entity Breast cancer
Disease Breast cancer is one of the major cancers affecting women in the western world after skin cancer and second leading cause of cancer death in women. About 20% of breast cancers are familial and about 10% of breast cancer is because of inheritence of a mutated gene. Although the cure rate has been increased because of the improved diagnostic approaches and early detection, the metastatic disease actually has been increased since 1990.
Prognosis Overexpression of Her2/neu oncogene product is considered to be associated with worse prognosis. LIMK1 expression may have a prognostic value for metastatic breast cancer as overexpression of LIMK1 has been noted in metastatic breast cancer cells.
Cytogenetics CGH analysis indicated a gain in chromosome 7 in majority of the infiltrating ductal carcinoma cases. Some of the chromosomal gains include the region encompassing Elastin and LIMK1 loci.
Oncogenesis Overexpression of LIMK1 has been shown to increase invasion and metastasis in animals. LIMK1 also involved in regulation of EGFR turnover through endocytic pathway in invasive breast cancer cells, which may have implication in development of an agressive disease.
Entity Melanoma
Disease Malignant melanoma is an agressive type of skin cancer, which often metastasize leading to death. The progression of melanoma is unpredictable and sometimes show refractoriness to available chemotherapy.
Cytogenetics Chromosomal analysis using tiling array and CGH showed a gain in chromosome 7 in melanoma cells. Increased expression of LIMK1 in melanoma cells (Skmel 28) harboring a break at 7q11.2 has also been reported.
Entity Williams-Beuren Syndrome (WBS)
Disease WBS is a genetic disorder with autosomal dominant inheritence. WBS is caused by microdeletion at 7q11.23 region with a phenotype of connective tissue abnormalities, growth and psychomotor retardation, muscular hypotonia, loss of visuospatial cognition and behavioural abnormalities.
Prognosis The presence of supravalvular aortic stenosis, pulmonary stenosis, developmental retardation and characteristic facial features in children between 18 to 30 months.
Cytogenetics Chromosome analyses showed a deletion at the LIMK1 locus at 7q11.23 caused by a distal recombination event at the common telomeric breakpoint.
Entity Alzheimer Disease (AD)
Disease Dystrophic neurites are found to be associated with Alzheimer's pathology. Altered structures of axons and dendrites, deposition of amyloid plaques leading to neurofibrillary tangle formation in AD pathology are responsible for dementia and cognitive disorder in Alzheimer's patients.
Prognosis Deposition of fibrillar amyloid beta in the brain is one of the events towards developing Alzheimer Disease. LIMK1 has been shown to be involved in amyloid beta-induced neuronal degeneration. Immunofluorescence analysis showed an increased number of phosphorylated LIMK1 positive neurons in the areas of brain with AD pathology. Inhibition of cofilin phosphorylation prevented neuronal degeneration, which supports the involvement of LIMK1 in AD.
Entity Intracranial Aneurysm
Disease Intracranial aneurysm is the localized dilation of the blood vessel which could be fatal upon rupture causing hemorrhage in the subarachnoid space. It occurs more frequently in adults than children and in women than men. Risk factors include family history of aneurysm and inherited disorders including polycystic kidney disease.
Cytogenetics Genome wide linkage studies indicated a significant association between SNP in LIMK1 promoter sequence at 7q11.2 locus and incidence of IA in Japanese and Korean patients. The SNP in the promoter sequence of LIMK1 [C(-187)T] introduced an additional transcription factor (AP2) binding site, which leads to a reduced transcription of LIMK1 mRNA.


A haplotype spanning two genes, ELN and LIMK1, decreases their transcripts and confers susceptibility to intracranial aneurysms.
Akagawa H, Tajima A, Sakamoto Y, Krischek B, Yoneyama T, Kasuya H, Onda H, Hori T, Kubota M, Machida T, Saeki N, Hata A, Hashiguchi K, Kimura E, Kim CJ, Yang TK, Lee JY, Kimm K, Inoue I.
Hum Mol Genet. 2006 May 15;15(10):1722-34. Epub 2006 Apr 12.
PMID 16611674
Identification of genetic markers for prostatic cancer progression.
Alers JC, Rochat J, Krijtenburg PJ, Hop WC, Kranse R, Rosenberg C, Tanke HJ, Schroder FH, van Dekken H.
Lab Invest. 2000 Jun;80(6):931-42.
PMID 10879743
LIM kinase 1 increases tumor metastasis of human breast cancer cells via regulation of the urokinase-type plasminogen activator system.
Bagheri-Yarmand R, Mazumdar A, Sahin AA, Kumar R.
Int J Cancer. 2006 Jun 1;118(11):2703-10.
PMID 16381000
Phosphorylated LIM kinases colocalize with gamma-tubulin in centrosomes during early stages of mitosis.
Chakrabarti R, Jones JL, Oelschlager DK, Tapia T, Tousson A, Grizzle WE.
Cell Cycle. 2007 Dec 1;6(23):2944-52. Epub 2007 Aug 30.
PMID 18000399
LIM kinase 1 is essential for the invasive growth of prostate epithelial cells: implications in prostate cancer.
Davila M, Frost AR, Grizzle WE, Chakrabarti R.
J Biol Chem. 2003 Sep 19;278(38):36868-75. Epub 2003 Jun 23.
PMID 12821664
LIM Kinase1 controls synaptic stability downstream of the type II BMP receptor.
Eaton BA, Davis GW.
Neuron. 2005 Sep 1;47(5):695-708.
PMID 16129399
Structural features of LIM kinase that control effects on the actin cytoskeleton.
Edwards DC, Gill GN.
J Biol Chem. 1999 Apr 16;274(16):11352-61.
PMID 10196227
Control of growth cone motility and morphology by LIM kinase and Slingshot via phosphorylation and dephosphorylation of cofilin.
Endo M, Ohashi K, Sasaki Y, Goshima Y, Niwa R, Uemura T, Mizuno K.
J Neurosci. 2003 Apr 1;23(7):2527-37.
PMID 12684437
LIM kinase 1 coordinates microtubule stability and actin polymerization in human endothelial cells.
Gorovoy M, Niu J, Bernard O, Profirovic J, Minshall R, Neamu R, Voyno-Yasenetskaya T.
J Biol Chem. 2005 Jul 15;280(28):26533-42. Epub 2005 May 16.
PMID 15897190
Phosphorylation of actin-depolymerizing factor/cofilin by LIM-kinase mediates amyloid beta-induced degeneration: a potential mechanism of neuronal dystrophy in Alzheimer's disease.
Heredia L, Helguera P, de Olmos S, Kedikian G, Sola Vigo F, LaFerla F, Staufenbiel M, de Olmos J, Busciglio J, Caceres A, Lorenzo A.
J Neurosci. 2006 Jun 14;26(24):6533-42.
PMID 16775141
Inhibition of activated Ras-induced neuronal differentiation of PC12 cells by the LIM domain of LIM-kinase 1.
Higuchi O, Amano T, Yang N, Mizuno K.
Oncogene. 1997 Apr 17;14(15):1819-25.
PMID 9150388
A molecular cytogenetic analysis of 7q31 in prostate cancer.
Jenkins RB, Qian J, Lee HK, Huang H, Hirasawa K, Bostwick DG, Proffitt J, Wilber K, Lieber MM, Liu W, Smith DI.
Cancer Res. 1998 Feb 15;58(4):759-66.
PMID 9485032
Genomic profiling of malignant melanoma using tiling-resolution arrayCGH.
Jonsson G, Dahl C, Staaf J, Sandberg T, Bendahl PO, Ringner M, Guldberg P, Borg A.
Oncogene. 2007 Jul 12;26(32):4738-48. Epub 2007 Jan 29.
PMID 17260012
Identification of a human cDNA encoding a novel protein kinase with two repeats of the LIM/double zinc finger motif.
Mizuno K, Okano I, Ohashi K, Nunoue K, Kuma K, Miyata T, Nakamura T.
Oncogene. 1994 Jun;9(6):1605-12.
PMID 8183554
A role of LIM kinase 1/cofilin pathway in regulating endocytic trafficking of EGF receptor in human breast cancer cells.
Nishimura Y, Yoshioka K, Bernard O, Bereczky B, Itoh K.
Histochem Cell Biol. 2006 Nov;126(5):627-38. Epub 2006 Jun 9.
PMID 16763828
Seven novel and stable translocations associated with oncogenic gene expression in malignant melanoma.
Okamoto I, Pirker C, Bilban M, Berger W, Losert D, Marosi C, Haas OA, Wolff K, Pehamberger H.
Neoplasia. 2005 Apr;7(4):303-11.
PMID 15967107
LIMK1 regulates Golgi dynamics, traffic of Golgi-derived vesicles, and process extension in primary cultured neurons.
Rosso S, Bollati F, Bisbal M, Peretti D, Sumi T, Nakamura T, Quiroga S, Ferreira A, Caceres A.
Mol Biol Cell. 2004 Jul;15(7):3433-49. Epub 2004 Apr 16.
PMID 15090620
LIM-kinase deleted in Williams syndrome.
Tassabehji M, Metcalfe K, Fergusson WD, Carette MJ, Dore JK, Donnai D, Read AP, Proschel C, Gutowski NJ, Mao X, Sheer D.
Nat Genet. 1996 Jul;13(3):272-3.
PMID 8673124
A role for LIM kinase in cancer invasion.
Yoshioka K, Foletta V, Bernard O, Itoh K.
Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):7247-52. Epub 2003 May 30.
PMID 12777619


This paper should be referenced as such :
Chakrabarti, R
LIMK1 (LIM domain kinase 1)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(7):641-644.
Free journal version : [ pdf ]   [ DOI ]

External links


HGNC (Hugo)LIMK1   6613
Atlas Explorer : (Salamanque)LIMK1
Entrez_Gene (NCBI)LIMK1    LIM domain kinase 1
AliasesLIMK; LIMK-1
GeneCards (Weizmann)LIMK1
Ensembl hg19 (Hinxton)ENSG00000106683 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000106683 [Gene_View]  ENSG00000106683 [Sequence]  chr7:74083804-74122525 [Contig_View]  LIMK1 [Vega]
ICGC DataPortalENSG00000106683
TCGA cBioPortalLIMK1
Genatlas (Paris)LIMK1
SOURCE (Princeton)LIMK1
Genetics Home Reference (NIH)LIMK1
Genomic and cartography
GoldenPath hg38 (UCSC)LIMK1  -     chr7:74083804-74122525 +  7q11.23   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)LIMK1  -     7q11.23   [Description]    (hg19-Feb_2009)
GoldenPathLIMK1 - 7q11.23 [CytoView hg19]  LIMK1 - 7q11.23 [CytoView hg38]
Genome Data Viewer NCBILIMK1 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AB209557 AF134379 AK026544 AK125156 AK290162
RefSeq transcript (Entrez)NM_001204426 NM_002314 NM_016735
Consensus coding sequences : CCDS (NCBI)LIMK1
Gene ExpressionLIMK1 [ NCBI-GEO ]   LIMK1 [ EBI - ARRAY_EXPRESS ]   LIMK1 [ SEEK ]   LIMK1 [ MEM ]
Gene Expression Viewer (FireBrowse)LIMK1 [ Firebrowse - Broad ]
GenevisibleExpression of LIMK1 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)3984
GTEX Portal (Tissue expression)LIMK1
Human Protein AtlasENSG00000106683-LIMK1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP53667   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP53667  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP53667
Domaine pattern : Prosite (Expaxy)LIM_DOMAIN_1 (PS00478)    LIM_DOMAIN_2 (PS50023)    PDZ (PS50106)    PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)   
Domains : Interpro (EBI)Kinase-like_dom_sf    PDZ    PDZ_sf    Prot_kinase_dom    Protein_kinase_ATP_BS    Ser-Thr/Tyr_kinase_cat_dom    Znf_LIM   
Domain families : Pfam (Sanger)LIM (PF00412)    PDZ (PF00595)    PK_Tyr_Ser-Thr (PF07714)   
Domain families : Pfam (NCBI)pfam00412    pfam00595    pfam07714   
Domain families : Smart (EMBL)LIM (SM00132)  PDZ (SM00228)  
Conserved Domain (NCBI)LIMK1
PDB (RSDB)3S95    5HVJ    5HVK    5L6W    5NXC    6WLY   
PDB Europe3S95    5HVJ    5HVK    5L6W    5NXC    6WLY   
PDB (PDBSum)3S95    5HVJ    5HVK    5L6W    5NXC    6WLY   
PDB (IMB)3S95    5HVJ    5HVK    5L6W    5NXC    6WLY   
Structural Biology KnowledgeBase3S95    5HVJ    5HVK    5L6W    5NXC    6WLY   
SCOP (Structural Classification of Proteins)3S95    5HVJ    5HVK    5L6W    5NXC    6WLY   
CATH (Classification of proteins structures)3S95    5HVJ    5HVK    5L6W    5NXC    6WLY   
AlphaFold pdb e-kbP53667   
Human Protein Atlas [tissue]ENSG00000106683-LIMK1 [tissue]
Protein Interaction databases
IntAct (EBI)P53667
Ontologies - Pathways
Ontology : AmiGOprotein kinase activity  protein serine/threonine kinase activity  protein serine/threonine kinase activity  protein serine/threonine kinase activity  protein serine/threonine/tyrosine kinase activity  protein binding  ATP binding  nucleus  cytoplasm  cytoplasm  cytosol  cytosol  cytoskeleton  focal adhesion  protein phosphorylation  protein phosphorylation  signal transduction  Rho protein signal transduction  nervous system development  membrane  nuclear speck  lamellipodium  actin cytoskeleton organization  heat shock protein binding  positive regulation of actin filament bundle assembly  Fc-gamma receptor signaling pathway involved in phagocytosis  neuron projection  neuron projection  positive regulation of axon extension  metal ion binding  negative regulation of ubiquitin-protein transferase activity  positive regulation of stress fiber assembly  protein serine kinase activity  
Ontology : EGO-EBIprotein kinase activity  protein serine/threonine kinase activity  protein serine/threonine kinase activity  protein serine/threonine kinase activity  protein serine/threonine/tyrosine kinase activity  protein binding  ATP binding  nucleus  cytoplasm  cytoplasm  cytosol  cytosol  cytoskeleton  focal adhesion  protein phosphorylation  protein phosphorylation  signal transduction  Rho protein signal transduction  nervous system development  membrane  nuclear speck  lamellipodium  actin cytoskeleton organization  heat shock protein binding  positive regulation of actin filament bundle assembly  Fc-gamma receptor signaling pathway involved in phagocytosis  neuron projection  neuron projection  positive regulation of axon extension  metal ion binding  negative regulation of ubiquitin-protein transferase activity  positive regulation of stress fiber assembly  protein serine kinase activity  
REACTOMEP53667 [protein]
REACTOME PathwaysR-HSA-5627123 [pathway]   
NDEx NetworkLIMK1
Atlas of Cancer Signalling NetworkLIMK1
Wikipedia pathwaysLIMK1
Orthology - Evolution
GeneTree (enSembl)ENSG00000106683
Phylogenetic Trees/Animal Genes : TreeFamLIMK1
Homologs : HomoloGeneLIMK1
Homology/Alignments : Family Browser (UCSC)LIMK1
Gene fusions - Rearrangements
Fusion : FusionHubBAZ1B--LIMK1    COL1A1--LIMK1    DIS3--LIMK1    IGFBP3--LIMK1    LIMK1--ELN    LIMK1--GGA1    LIMK1--GNAT3    LIMK1--LIMK1    LIMK1--POLR2J    LIMK1--TYW1   
Fusion : QuiverLIMK1
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerLIMK1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)LIMK1
Exome Variant ServerLIMK1
GNOMAD BrowserENSG00000106683
Varsome BrowserLIMK1
ACMGLIMK1 variants
Genomic Variants (DGV)LIMK1 [DGVbeta]
DECIPHERLIMK1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisLIMK1 
ICGC Data PortalLIMK1 
TCGA Data PortalLIMK1 
Broad Tumor PortalLIMK1
OASIS PortalLIMK1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICLIMK1  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DLIMK1
Mutations and Diseases : HGMDLIMK1
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)LIMK1
DoCM (Curated mutations)LIMK1
CIViC (Clinical Interpretations of Variants in Cancer)LIMK1
NCG (London)LIMK1
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry LIMK1
NextProtP53667 [Medical]
Target ValidationLIMK1
Huge Navigator LIMK1 [HugePedia]
ClinGenLIMK1 (curated)
Clinical trials, drugs, therapy
Protein Interactions : CTDLIMK1
Pharm GKB GenePA30386
Clinical trialLIMK1
DataMed IndexLIMK1
PubMed158 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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