InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: LIMK1

Summary

InnateDB Protein

IDBP-586814.3

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

LIMK1

Protein Name

LIM domain kinase 1

Synonyms

LIMK; LIMK-1;

Species

Homo sapiens

Ensembl Protein

ENSP00000444452

InnateDB Gene

IDBG-20945 (LIMK1)

Protein Structure

UniProt Annotation

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). {ECO:0000269PubMed:10196227, ECO:0000269PubMed:10436159, ECO:0000269PubMed:11832213, ECO:0000269PubMed:12807904, ECO:0000269PubMed:15660133, ECO:0000269PubMed:16230460, ECO:0000269PubMed:18028908, ECO:0000269PubMed:23633677}.

Subcellular Localization

Cytoplasm. Nucleus. Note=Predominantly found in the cytoplasm.

Disease Associations

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.

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.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 55 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.

Experimentally validated
Total	55 [view]
Protein-Protein	52 [view]
Protein-DNA	2 [view]
Protein-RNA	1 [view]
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	3 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008270	zinc ion binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0016773	phosphotransferase activity, alcohol group as acceptor
GO:0031072	heat shock protein binding

Biological Process

GO:0006468	protein phosphorylation
GO:0007165	signal transduction
GO:0007266	Rho protein signal transduction
GO:0007399	nervous system development
GO:0007411	axon guidance
GO:0009103	lipopolysaccharide biosynthetic process
GO:0030036	actin cytoskeleton organization
GO:0032233	positive regulation of actin filament bundle assembly
GO:0038096	Fc-gamma receptor signaling pathway involved in phagocytosis
GO:0045087	innate immune response
GO:0045773	positive regulation of axon extension
GO:0051444	negative regulation of ubiquitin-protein transferase activity

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0016020	membrane
GO:0043005	neuron projection

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR001478 PDZ domain
IPR001781 Zinc finger, LIM-type
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR010440 Lipopolysaccharide kinase
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714
PF00595
PF13180
PF00412
PF06293

PRINTS

PR00109

PIRSF

SMART

SM00228
SM00132
SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt