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

General

LIM domain protein serine/threonine kinase

Properties

SIZE: entity length = 647 aa MW = 73 kD COMPARTMENT: cytoplasm STATE: active state MOTIF: LIM domain {25-75} MOTIF: cysteine residue (6) histidine residue Zn+2-binding site LIM domain {84-137} MOTIF: cysteine residue (6) histidine residue Zn+2-binding site PDZ domain NAME: PDZ domain SITE: 165-258 MOTIF: Ser phosphorylation site {S210} Thr phosphorylation site {T229} Ser phosphorylation site {S298} Ser phosphorylation site {S302} Ser phosphorylation site {S307} Ser phosphorylation site {S310} Ser phosphorylation site {S337} kinase domain SITE: 339-604 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 345-353 ATP-binding site NAME: ATP-binding site SITE: 368-368 aspartate residue {D460} Thr phosphorylation site {T508}

Database Correlations

OMIM correlations UniProt P53667 PFAM correlations Entrez Gene 3984 Kegg hsa:3984 ENZYME 2.7.11.1

References

UniProt :accession P53667