LIMK1 Antibody – Rabbit Polyclonal

There are approximately 40 known eukaryotic LIM proteins, so named for the LIM domains they contain. LIM domains are highly conserved cysteine-rich structures containing 2 zinc fingers. Although zinc fingers usually function by binding to DNA or RNA, the LIM motif probably mediates protein-protein interactions. LIM kinase-1 and LIM kinase-2 belong to a small subfamily with a unique combination of 2 N-terminal LIM motifs and a C-terminal protein kinase domain. LIMK1 is a serine/threonine kinase that regulates actin polymerization via phosphorylation and inactivation of the actin binding factor cofilin. This protein is ubiquitously expressed during development and plays a role in many cellular processes associated with cytoskeletal structure. This protein also stimulates axon growth and may play a role in brain development. LIMK1 hemizygosity is implicated in the impaired visuospatial constructive cognition of Williams syndrome. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Function: Protein kinase which regulates actin filament dynamics. Phosphorylates and inactivates the actin binding/depolymerizing factor cofilin, thereby stabilizing the actin cytoskeleton. Stimulates axonal outgrowth and may be involved in brain development. Isoform 3 has a dominant negative effect on actin cytoskeletal changes. Ref.4 Ref.7 Ref.9 Ref.10 Ref.12 Ref.13

Catalytic activity: ATP + a protein = ADP + a phosphoprotein.

Subunit structure: Self-associates. The LIM domain interacts with the cytoplasmic domain of NRG1. Binds ROCK1. Interacts with SSH1. Interacts with NISCH

By similarity. Interacts with RLIM and RNF6

By similarity. Interacts with TPPP. Ref.7 Ref.8 Ref.12 Ref.14

Subcellular location: Cytoplasm. Cell projection › growth cone

By similarity Ref.4 Ref.13.

Tissue specificity: Highest expression in both adult and 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 and skeletal muscle.

Post-translational modification: Autophosphorylated

By similarity. Ref.8 Ref.12 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19Phosphorylated on serine and/or threonine residues by ROCK1. May be dephosphorylated and inactivated by SSH1. Ref.8 Ref.12 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19Ubiquitinated. 'Lys-48'-linked polyubiquitination by RNF6 leads to proteasomal degradation through the 26S proteasome, modulating LIMK1 levels in the growth cone and its effect on axonal outgrowth. Also polyubiquitinated by RLIM

Involvement in disease: Note=LIMK1 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region.

Sequence similarities: Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.Contains 2 LIM zinc-binding domains.Contains 1 PDZ (DHR) domain.Contains 1 protein kinase domain.