LIMK2

LIM domain kinase 2
PDB rendering based on 1x6a.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1X6A​, 4TPT​
Identifiers
Symbol	LIMK2
External IDs	OMIM: 601988 MGI: 1197517 HomoloGene: 55911 ChEMBL: 5932 GeneCards: LIMK2 Gene
EC number	2.7.11.1
Gene ontology Molecular function • protein serine/threonine kinase activity • protein binding • ATP binding • zinc ion binding • protein heterodimerization activity Cellular component • nucleus • cytoplasm • cis-Golgi network Biological process • protein phosphorylation • spermatogenesis • phosphorylation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3985	16886
Ensembl	ENSG00000182541	ENSMUSG00000020451
UniProt	P53671	O54785
RefSeq (mRNA)	NM_001031801	NM_001034030
RefSeq (protein)	NP_001026971	NP_001029202
Location (UCSC)	Chr 22: 31.21 – 31.28 Mb	Chr 11: 3.34 – 3.41 Mb
PubMed search

LIM domain kinase 2 is an enzyme that in humans is encoded by the LIMK2 gene.^[1][2][3]

Function

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. The protein encoded by this gene is phosphorylated and activated by ROCK, a downstream effector of Rho, and the encoded protein, in turn, phosphorylates cofilin, inhibiting its actin-depolymerizing activity. It is thought that this pathway contributes to Rho-induced reorganization of the actin cytoskeleton. At least three transcript variants encoding different isoforms have been found for this gene.^[3]

References

1. Okano I, Hiraoka J, Otera H, Nunoue K, Ohashi K, Iwashita S, Hirai M, Mizuno K (Dec 1995). "Identification and characterization of a novel family of serine/threonine kinases containing two N-terminal LIM motifs". The Journal of Biological Chemistry 270 (52): 31321–30. doi:10.1074/jbc.270.52.31321. PMID 8537403.
2. Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP (Dec 1999). "The DNA sequence of human chromosome 22". Nature 402 (6761): 489–95. doi:10.1038/990031. PMID 10591208.
3. "Entrez Gene: LIMK2 LIM domain kinase 2".

Further reading

• Scott RW, Olson MF (Jun 2007). "LIM kinases: function, regulation and association with human disease". Journal of Molecular Medicine (Berlin, Germany) 85 (6): 555–68. doi:10.1007/s00109-007-0165-6. PMID 17294230.
• Osada H, Hasada K, Inazawa J, Uchida K, Ueda R, Takahashi T, Takahashi T (13 Dec 1996). "Subcellular localization and protein interaction of the human LIMK2 gene expressing alternative transcripts with tissue-specific regulation". Biochemical and Biophysical Research Communications 229 (2): 582–9. doi:10.1006/bbrc.1996.1847. PMID 8954941.
• Hiraoka J, Okano I, Higuchi O, Yang N, Mizuno K (9 Dec 1996). "Self-association of LIM-kinase 1 mediated by the interaction between an N-terminal LIM domain and a C-terminal kinase domain". FEBS Letters 399 (1-2): 117–21. doi:10.1016/S0014-5793(96)01303-8. PMID 8980133.
• Yang N, Higuchi O, Ohashi K, Nagata K, Wada A, Kangawa K, Nishida E, Mizuno K (Jun 1998). "Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin reorganization". Nature 393 (6687): 809–12. doi:10.1038/31735. PMID 9655398.
• Nomoto S, Tatematsu Y, Takahashi T, Osada H (Aug 1999). "Cloning and characterization of the alternative promoter regions of the human LIMK2 gene responsible for alternative transcripts with tissue-specific expression". Gene 236 (2): 259–71. doi:10.1016/S0378-1119(99)00280-2. PMID 10452946.
• Sumi T, Matsumoto K, Takai Y, Nakamura T (27 Dec 1999). "Cofilin phosphorylation and actin cytoskeletal dynamics regulated by rho- and Cdc42-activated LIM-kinase 2". The Journal of Cell Biology 147 (7): 1519–32. doi:10.1083/jcb.147.7.1519. PMC 2174243. PMID 10613909.
• Sumi T, Matsumoto K, Nakamura T (Jan 2001). "Specific activation of LIM kinase 2 via phosphorylation of threonine 505 by ROCK, a Rho-dependent protein kinase". The Journal of Biological Chemistry 276 (1): 670–6. doi:10.1074/jbc.M007074200. PMID 11018042.
• Hartley JL, Temple GF, Brasch MA (Nov 2000). "DNA cloning using in vitro site-specific recombination". Genome Research 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
• Amano T, Tanabe K, Eto T, Narumiya S, Mizuno K (Feb 2001). "LIM-kinase 2 induces formation of stress fibres, focal adhesions and membrane blebs, dependent on its activation by Rho-associated kinase-catalysed phosphorylation at threonine-505". The Biochemical Journal 354 (Pt 1): 149–59. doi:10.1042/0264-6021:3540149. PMC 1221639. PMID 11171090.
• Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A (Mar 2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Research 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.
• Sumi T, Matsumoto K, Shibuya A, Nakamura T (Jun 2001). "Activation of LIM kinases by myotonic dystrophy kinase-related Cdc42-binding kinase alpha". The Journal of Biological Chemistry 276 (25): 23092–6. doi:10.1074/jbc.C100196200. PMID 11340065.
• Toshima J, Toshima JY, Takeuchi K, Mori R, Mizuno K (Aug 2001). "Cofilin phosphorylation and actin reorganization activities of testicular protein kinase 2 and its predominant expression in testicular Sertoli cells". The Journal of Biological Chemistry 276 (33): 31449–58. doi:10.1074/jbc.M102988200. PMID 11418599.
• Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, Meil A, Wojcik J, Legrain P, Gauthier JM (Jul 2004). "Functional proteomics mapping of a human signaling pathway". Genome Research 14 (7): 1324–32. doi:10.1101/gr.2334104. PMC 442148. PMID 15231748.
• Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, Goward ME, Aguado B, Mallya M, Mokrab Y, Huckle EJ, Beare DM, Dunham I (2005). "A genome annotation-driven approach to cloning the human ORFeome". Genome Biology 5 (10): R84. doi:10.1186/gb-2004-5-10-r84. PMC 545604. PMID 15461802.
• Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A (Oct 2004). "From ORFeome to biology: a functional genomics pipeline". Genome Research 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336.
• Vardouli L, Moustakas A, Stournaras C (Mar 2005). "LIM-kinase 2 and cofilin phosphorylation mediate actin cytoskeleton reorganization induced by transforming growth factor-beta". The Journal of Biological Chemistry 280 (12): 11448–57. doi:10.1074/jbc.M402651200. PMID 15647284.

External links

• LIMK2 Info with links in the Cell Migration Gateway