Names & Taxonomy

Uniprot ID:
P53667
Entry Name:
LIMK1_HUMAN
Status:
reviewed
Protein Names:
LIM domain kinase 1 (LIMK-1) (EC 2.7.11.1)
Gene Names:
LIMK1 LIMK
Gene Names Primary:
LIMK1
Organism:
Homo sapiens (Human)

Structure

Length:
647
Sequence:
MRLTLLCCTWREERMGEEGSELPVCASCGQRIYDGQYLQALNADWHADCFRCCDCSASLSHQYYEKDGQLFCKKDYWARYGESCHGCSEQITKGLVMVAGELKYHPECFICLTCGTFIGDGDTYTLVEHSKLYCGHCYYQTVVTPVIEQILPDSPGSHLPHTVTLVSIPASSHGKRGLSVSIDPPHGPPGCGTEHSHTVRVQGVDPGCMSPDVKNSIHVGDRILEINGTPIRNVPLDEIDLLIQETSRLLQLTLEHDPHDTLGHGLGPETSPLSSPAYTPSGEAGSSARQKPVLRSCSIDRSPGAGSLGSPASQRKDLGRSESLRVVCRPHRIFRPSDLIHGEVLGKGCFGQAIKVTHRETGEVMVMKELIRFDEETQRTFLKEVKVMRCLEHPNVLKFIGVLYKDKRLNFITEYIKGGTLRGIIKSMDSQYPWSQRVSFAKDIASGMAYLHSMNIIHRDLNSHNCLVRENKNVVVADFGLARLMVDEKTQPEGLRSLKKPDRKKRYTVVGNPYWMAPEMINGRSYDEKVDVFSFGIVLCEIIGRVNADPDYLPRTMDFGLNVRGFLDRYCPPNCPPSFFPITVRCCDLDPEKRPSFVKLEHWLETLRMHLAGHLPLGPQLEQLDRGFWETYRRGESGLPAHPEVPD
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Cytoplasm. Nucleus. Note=Predominantly found in the cytoplasm.

Function

Function:
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).
Catalytic Activity:
ATP + a protein = ADP + a phosphoprotein.
Active Site:
ACT_SITE 460 460
Cross Reference Drug Bank:
DB08912
Gene Ontology Go:
axonal growth cone
cytoplasm
cytosol
focal adhesion
Golgi apparatus
membrane
neuron projection
nucleoplasm
perinuclear region of cytoplasm
ATP binding
heat shock protein binding
protein kinase activity
protein serine/threonine kinase activity
zinc ion binding
actin cytoskeleton organization
axon guidance
ephrin receptor signaling pathway
Fc-gamma receptor signaling pathway involved in phagocytosis
innate immune response
negative regulation of ubiquitin-protein transferase activity
nervous system development
positive regulation of actin filament bundle assembly
positive regulation of axon extension
positive regulation of stress fiber assembly
protein phosphorylation
Rho protein signal transduction
signal transduction
small GTPase mediated signal transduction
Gene Ontology Biological Process:
actin cytoskeleton organization
axon guidance
ephrin receptor signaling pathway
Fc-gamma receptor signaling pathway involved in phagocytosis
innate immune response
negative regulation of ubiquitin-protein transferase activity
nervous system development
positive regulation of actin filament bundle assembly
positive regulation of axon extension
positive regulation of stress fiber assembly
protein phosphorylation
Rho protein signal transduction
signal transduction
small GTPase mediated signal transduction
Gene Ontology Molecular Function:
ATP binding
heat shock protein binding
protein kinase activity
protein serine/threonine kinase activity
zinc ion binding
Gene Ontology Cellular Component:
axonal growth cone
cytoplasm
cytosol
focal adhesion
Golgi apparatus
membrane
neuron projection
nucleoplasm
perinuclear region of cytoplasm
Keywords:
3D-structure
ATP-binding
Alternative splicing
Complete proteome
Cytoplasm
Kinase
LIM domain
Metal-binding
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
Repeat
Serine/threonine-protein kinase
Transferase
Ubl conjugation
Williams-Beuren syndrome
Zinc
Interacts With:
P29066; P29067; P23528; O95835; P50281; Q13153; Q13177; Q8WYL5

Publication

PubMed ID:
8183554 8689688 8812460 10196227 14702039 12853948 10559936 10436159 10652353 11340065 11413130 11832213 12807904 14530263 14759258 15660133 16230460 16456544 16641196 18028908 17188549 18691976 18669648 19413330 19369195 22886629 21682918 23633677 17344846