LIMK2: LIM Domain Kinase 2 – A Key Regulator of Actin Dynamics and Cancer Progression
Comprehensive genomic and functional overview of LIMK2, including its role in cytoskeletal regulation, disease associations, expression patterns, and mutational landscape.
Gene Information Card
| Symbol | LIMK2 |
|---|---|
| Full Name | LIM domain kinase 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 22q12.2 |
| NCBI Gene ID | 3985 ncbi.nlm.nih.gov/gene/3985 |
| Ensembl ID | ENSG00000100241 |
| UniProt ID | P53671 |
| OMIM ID | 601222 |
| HGNC ID | 6614 |
| Aliases | LIMK-2, LIMK2A, LIMK2B |
Description
LIMK2 (LIM domain kinase 2) encodes a serine/threonine kinase that phosphorylates and inactivates cofilin, thereby regulating actin cytoskeleton dynamics. It is involved in cell motility, proliferation, and differentiation. Aberrant expression and mutations of LIMK2 are implicated in various cancers, neurodegenerative disorders, and developmental abnormalities.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Prostate cancer | LIMK2 overexpression promotes cell migration and invasion via cofilin phosphorylation and actin remodeling. | PMID: 21502544; COSMIC |
| Breast cancer | LIMK2 amplification and overexpression correlate with poor prognosis and metastasis. | PMID: 23382219; COSMIC |
| Lung cancer | LIMK2 upregulation enhances tumor cell proliferation and resistance to apoptosis. | PMID: 25636850; COSMIC |
| Neuroblastoma | LIMK2 mutations and altered expression contribute to neuronal differentiation defects. | PMID: 19782033; ClinVar |
| Intellectual disability | Homozygous loss-of-function mutations in LIMK2 are associated with syndromic intellectual disability. | PMID: 28135719; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Lung | 15.2 | Medium |
| Liver | 6.1 | Low |
| Kidney | 10.4 | Medium |
| Prostate | 18.7 | High |
| Breast | 14.3 | Medium |
| Testis | 22.1 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 16.5 | Cervical cancer cell line; moderate expression |
| MCF7 | 19.2 | Breast cancer cell line; high expression |
| PC3 | 21.8 | Prostate cancer cell line; high expression |
| A549 | 14.0 | Lung cancer cell line; moderate expression |
| SH-SY5Y | 11.3 | Neuroblastoma cell line; moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.103C>T (p.Arg35Cys) | Missense | <0.1% | Reduced kinase activity; associated with intellectual disability (ClinVar) |
| c.497G>A (p.Arg166Gln) | Missense | <0.1% | Impaired cofilin phosphorylation; loss-of-function (ClinVar) |
| c.1132G>A (p.Glu378Lys) | Missense | 0.2% | Gain-of-function; increased cell migration in cancer (COSMIC) |
| c.1450_1451insA (p.Thr484Asnfs*5) | Frameshift | <0.1% | Loss-of-function; truncation (COSMIC) |
Mutation functional classification
Loss of Function (LOF)
Mutations such as p.Arg35Cys and p.Arg166Gln reduce or abolish LIMK2 kinase activity, impairing cofilin phosphorylation and actin regulation, linked to neurodevelopmental disorders.
Gain of Function (GOF)
p.Glu378Lys enhances LIMK2 activity, promoting cofilin phosphorylation, actin stabilization, and increased cell motility, observed in cancer.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported for LIMK2 in current databases.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004672 – protein kinase activity | • GO:0005524 – ATP binding |
| • GO:0030036 – actin cytoskeleton organization | • GO:0046777 – protein autophosphorylation |
| • GO:0051014 – actin filament severing | • GO:0035556 – intracellular signal transduction |
| • GO:0005737 – cytoplasm | • GO:0005829 – cytosol |
Pathways
• Regulation of actin cytoskeleton (KEGG: hsa04810)
• Signaling by Rho GTPases (Reactome: R-HSA-194315)
• Cofilin phosphorylation by LIM kinases (Reactome: R-HSA-5663213)
• Axon guidance (KEGG: hsa04360)
Protein Summary
LIMK2 is a 638-amino-acid protein containing two N-terminal LIM domains and a C-terminal kinase domain. It phosphorylates cofilin at Ser3, inactivating its actin-severing activity, thereby promoting actin filament stabilization. LIMK2 activity is regulated by Rho/ROCK and PAK signaling. It plays critical roles in cell migration, neurite outgrowth, and cell cycle progression. Dysregulation of LIMK2 is linked to cancer metastasis and neurological disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LIMK2 Knockout HEK293 Cell Line | EDJ-KQ5124 | Human | 3985 | Details Get a Quote |
| LIMK2 Knockout A-549 Cell Line | EDJ-KQ28074 | Human | 3985 | Details Get a Quote |
| LIMK2 Knockout HCT 116 Cell Line | EDJ-KQ28075 | Human | 3985 | Details Get a Quote |
| LIMK2 Knockout HeLa Cell Line | EDJ-KQ26848 | Human | 3985 | Details Get a Quote |
| LIMK2 Knockout HAP1 Cell Line | EDC09093 | Human | 3985 | Details Get a Quote |
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