LIM domain kinase 1; LIMK-1 (LIMK1, LIMK)

Function

• protein kinase which regulates actin filament dynamics
• phosphorylates & inactivates the actin binding/depolymerizing factor cofilin, thereby stabilizing the actin cytoskeleton
• isoform 3 has a dominant negative effect on actin cytoskeletal changes
• potent activator of serum response factor
• may be involved in brain development
• self-associates
• the LIM domain interacts with the cytoplasmic domain of NRG1
• binds ROCK1
• phosphorylated on Ser &/or Thr & activated by ROCK1
• interacts with SSH1
• may be dephosphorylated & inactivated by SSH1
• interacts with NISCH (putative)
• autophosphorylated (putative)

Structure

• belongs to the protein kinase superfamily, TKL Ser/Thr protein kinase family
• contains 2 LIM Zn+2-binding domains
• contains 1 PDZ domain (DHR domain)
• contains 1 protein kinase domain

Compartment

cytoplasm

Alternative splicing

named isoforms=3

Expression

• highest expression in both adult & fetal nervous system
• detected ubiquitously throughout the different regions of adult brain, with highest levels in the cerebral cortex
• expressed to a lesser extent in heart & skeletal muscle

Pathology

• haploinsufficiency of LIMK1 may be the cause of certain cardiovascular & musculo-skeletal abnormalities observed in Williams-Beuren syndrome

Notes

• may be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay

More general terms

• LIM domain protein
• serine/threonine kinase

Additional terms

• Williams-Beuren syndrome

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=3984
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:3984
• OMIM: https://mirror.omim.org/entry/194050
• OMIM: https://mirror.omim.org/entry/601329
• UniProt: http://www.uniprot.org/uniprot/P53667.html