Tchem LIMK1 LIM domain kinase 1

Protein Summary

Description

Serine/threonine-protein kinase that plays an essential role in the regulation of actin filament dynamics. Acts downstream of several Rho family GTPase signal transduction pathways. Activated by upstream kinases including ROCK1, PAK1 and PAK4, which phosphorylate LIMK1 on a threonine residue located in its activation loop. LIMK1 subsequently phosphorylates and inactivates the actin binding/depolymerizing factors cofilin-1/CFL1, cofilin-2/CFL2 and destrin/DSTN, thereby preventing the cleavage of filamentous actin (F-actin), and stabilizing the actin cytoskeleton. In this way LIMK1 regulates several actin-dependent biological processes including cell motility, cell cycle progression, and differentiation. Phosphorylates TPPP on serine residues, thereby promoting microtubule disassembly. Stimulates axonal outgrowth and may be involved in brain development. Isoform 3 has a dominant negative effect on actin cytoskeletal changes. Required for atypical chemokine receptor ACKR2-induced phosphorylation of cofilin (CFL1). 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.[provided by RefSeq, Feb 2011]

Uniprot Accession IDs

• P53667
• B7Z6I8
• D3DXF4
• D3DXF5
• O15283
• Q15820
• Q15821
• Q75MU3
• Q9Y5Q1
• LIMK-1

Gene Name

• LIMK1

Ensembl ID

• ENST00000336180
• ENSP00000336740
• ENSG00000106683
• ENST00000435201
• ENSP00000414606
• ENST00000538333
• ENSP00000444452

Symbol

• LIMK
• LIMK
• LIMK-1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	0.98
biological process	0.91
kinase	0.86
protein domain	0.85
transcription factor perturbation	0.84

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Tkl Group / Lisk Family / Limk Subfamily / Lim Domain Kinase 1

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 326.83   (req: < 5)

Gene RIFs: 99   (req: <= 3)

Antibodies: 887   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 326.83   (req: >= 5)

Gene RIFs: 99   (req: > 3)

Antibodies: 887   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 16

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 61

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 1