LIMK1

LIMK1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3S95, 5L6W, 5HVK, 5HVJ
Identifiers
Aliases	LIMK1 , LIMK, LIMK-1, LIM domain kinase 1
External IDs	OMIM: 601329 MGI: 104572 HomoloGene: 1738 GeneCards: LIMK1
Gene location (Human) Chr. Chromosome 7 (human) [1] Band 7q11.23 Start 74,082,933 bp [1] End 74,122,525 bp [1]
Gene location (Mouse) Chr. Chromosome 5 (mouse) [2] Band 5 74.73 cM|5 G2 Start 134,684,893 bp [2] End 134,717,452 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in stromal cell of endometrium cingulate gyrus prefrontal cortex amygdala Brodmann area 9 ganglionic eminence monocyte hypothalamus nucleus accumbens canal of the cervix Top expressed in motor neuron internal carotid artery substantia nigra external carotid artery pontine nuclei medial vestibular nucleus anterior horn of spinal cord supraoptic nucleus trigeminal ganglion fossa More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity nucleotide binding heat shock protein binding metal ion binding kinase activity protein binding protein heterodimerization activity ATP binding protein kinase activity protein serine/threonine kinase activity signal transducer activity Cellular component membrane focal adhesion cytoplasm nucleus Golgi apparatus cytosol nuclear speck neuron projection lamellipodium cell projection Biological process Fc-gamma receptor signaling pathway involved in phagocytosis phosphorylation nervous system development negative regulation of ubiquitin-protein transferase activity Rho protein signal transduction positive regulation of actin filament bundle assembly actin cytoskeleton organization signal transduction positive regulation of axon extension protein phosphorylation positive regulation of stress fiber assembly Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3984 16885 Ensembl ENSG00000106683 ENSMUSG00000029674 UniProt P53667 P53668 RefSeq (mRNA) NM_016735 NM_001204426 NM_002314 NM_010717 NM_001305875 RefSeq (protein) NP_001191355 NP_002305 NP_001292804 NP_034847 Location (UCSC) Chr 7: 74.08 – 74.12 Mb Chr 5: 134.68 – 134.72 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

LIM domain kinase 1 is an enzyme that in humans is encoded by the LIMK1 gene. ^{[5] [6]}

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, a central PDZ domain, and a C-terminal protein kinase domain. LIMK1 is likely to be a component of an intracellular signaling pathway and may be involved in brain development. ^[7]

Clinical significance

LIMK1 hemizygosity is implicated in the impaired visuospatial constructive cognition of Williams syndrome. ^[7]

Interactions

LIMK1 has been shown to interact with:

• CFL1, ^{[8] [9]}
• CDKN1C, ^[10]
• NRG1, ^[11]
• PAK1, ^[12]
• PAK4, ^[13] and
• YWHAZ. ^[14]

References

1. GRCh38: Ensembl release 89: ENSG00000106683 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000029674 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Tassabehji M, Metcalfe K, Fergusson WD, Carette MJ, Dore JK, Donnai D, Read AP, Pröschel C, Gutowski NJ, Mao X, Sheer D (Aug 1996). "LIM-kinase deleted in Williams syndrome". Nat. Genet. 13 (3): 272–3. doi:10.1038/ng0796-272. PMID   8673124. S2CID   138698.
6. Osborne LR, Martindale D, Scherer SW, Shi XM, Huizenga J, Heng HH, Costa T, Pober B, Lew L, Brinkman J, Rommens J, Koop B, Tsui LC (Jan 1997). "Identification of genes from a 500-kb region at 7q11.23 that is commonly deleted in Williams syndrome patients". Genomics. 36 (2): 328–36. doi: 10.1006/geno.1996.0469 . PMID   8812460.
7. "Entrez Gene: LIMK1 LIM domain kinase 1".
8. Foletta VC, Lim MA, Soosairajah J, Kelly AP, Stanley EG, Shannon M, He W, Das S, Massague J, Bernard O, Soosairaiah J (September 2003). "Direct signaling by the BMP type II receptor via the cytoskeletal regulator LIMK1". J. Cell Biol. 162 (6): 1089–98. doi:10.1083/jcb.200212060. PMC   2172847 . PMID   12963706.
9. Maekawa M, Ishizaki T, Boku S, Watanabe N, Fujita A, Iwamatsu A, Obinata T, Ohashi K, Mizuno K, Narumiya S (August 1999). "Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase". Science. 285 (5429): 895–8. doi:10.1126/science.285.5429.895. PMID   10436159.
10. Yokoo T, Toyoshima H, Miura M, Wang Y, Iida KT, Suzuki H, Sone H, Shimano H, Gotoda T, Nishimori S, Tanaka K, Yamada N (December 2003). "p57Kip2 regulates actin dynamics by binding and translocating LIM-kinase 1 to the nucleus". J. Biol. Chem. 278 (52): 52919–23. doi: 10.1074/jbc.M309334200 . PMID   14530263.
11. Wang JY, Frenzel KE, Wen D, Falls DL (August 1998). "Transmembrane neuregulins interact with LIM kinase 1, a cytoplasmic protein kinase implicated in development of visuospatial cognition". J. Biol. Chem. 273 (32): 20525–34. doi: 10.1074/jbc.273.32.20525 . PMID   9685409.
12. Edwards DC, Sanders LC, Bokoch GM, Gill GN (September 1999). "Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics". Nat. Cell Biol. 1 (5): 253–9. doi:10.1038/12963. PMID   10559936. S2CID   25250183.
13. Dan C, Kelly A, Bernard O, Minden A (August 2001). "Cytoskeletal changes regulated by the PAK4 serine/threonine kinase are mediated by LIM kinase 1 and cofilin". J. Biol. Chem. 276 (34): 32115–21. doi: 10.1074/jbc.M100871200 . PMID   11413130.
14. Birkenfeld J, Betz H, Roth D (January 2003). "Identification of cofilin and LIM-domain-containing protein kinase 1 as novel interaction partners of 14-3-3 zeta". Biochem. J. 369 (Pt 1): 45–54. doi:10.1042/BJ20021152. PMC   1223062 . PMID   12323073.

Further reading

• Scott RW, Olson MF (2007). "LIM kinases: function, regulation and association with human disease". J. Mol. Med. 85 (6): 555–68. doi:10.1007/s00109-007-0165-6. PMID   17294230. S2CID   8881246.
• Mizuno K, Okano I, Ohashi K, Nunoue K, Kuma K, Miyata T, Nakamura T (1994). "Identification of a human cDNA encoding a novel protein kinase with two repeats of the LIM/double zinc finger motif". Oncogene. 9 (6): 1605–12. PMID   8183554.
• Okano I, Hiraoka J, Otera H, Nunoue K, Ohashi K, Iwashita S, Hirai M, Mizuno K (1995). "Identification and characterization of a novel family of serine/threonine kinases containing two N-terminal LIM motifs". J. Biol. Chem. 270 (52): 31321–30. doi: 10.1074/jbc.270.52.31321 . PMID   8537403.
• Frangiskakis JM, Ewart AK, Morris CA, Mervis CB, Bertrand J, Robinson BF, Klein BP, Ensing GJ, Everett LA, Green ED, Pröschel C, Gutowski NJ, Noble M, Atkinson DL, Odelberg SJ, Keating MT (1996). "LIM-kinase1 hemizygosity implicated in impaired visuospatial constructive cognition". Cell. 86 (1): 59–69. doi: 10.1016/S0092-8674(00)80077-X . PMID   8689688. S2CID   17786888.
• Nebl G, Meuer SC, Samstag Y (1996). "Dephosphorylation of serine 3 regulates nuclear translocation of cofilin". J. Biol. Chem. 271 (42): 26276–80. doi: 10.1074/jbc.271.42.26276 . PMID   8824278.
• Hiraoka J, Okano I, Higuchi O, Yang N, Mizuno K (1996). "Self-association of LIM-kinase 1 mediated by the interaction between an N-terminal LIM domain and a C-terminal kinase domain". FEBS Lett. 399 (1–2): 117–21. doi: 10.1016/S0014-5793(96)01303-8 . PMID   8980133. S2CID   2815035.
• Yang N, Higuchi O, Ohashi K, Nagata K, Wada A, Kangawa K, Nishida E, Mizuno K (1998). "Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin reorganization". Nature. 393 (6687): 809–12. Bibcode:1998Natur.393..809Y. doi:10.1038/31735. PMID   9655398. S2CID   4326365.
• Wang JY, Frenzel KE, Wen D, Falls DL (1998). "Transmembrane neuregulins interact with LIM kinase 1, a cytoplasmic protein kinase implicated in development of visuospatial cognition". J. Biol. Chem. 273 (32): 20525–34. doi: 10.1074/jbc.273.32.20525 . PMID   9685409.
• Edwards DC, Gill GN (1999). "Structural features of LIM kinase that control effects on the actin cytoskeleton". J. Biol. Chem. 274 (16): 11352–61. doi: 10.1074/jbc.274.16.11352 . PMID   10196227.
• Sotiropoulos A, Gineitis D, Copeland J, Treisman R (1999). "Signal-regulated activation of serum response factor is mediated by changes in actin dynamics". Cell. 98 (2): 159–69. doi: 10.1016/S0092-8674(00)81011-9 . PMID   10428028. S2CID   15781260.
• Bach I, Rodriguez-Esteban C, Carrière C, Bhushan A, Krones A, Rose DW, Glass CK, Andersen B, Izpisúa Belmonte JC, Rosenfeld MG (1999). "RLIM inhibits functional activity of LIM homeodomain transcription factors via recruitment of the histone deacetylase complex". Nat. Genet. 22 (4): 394–9. doi:10.1038/11970. PMID   10431247. S2CID   22326394.
• Maekawa M, Ishizaki T, Boku S, Watanabe N, Fujita A, Iwamatsu A, Obinata T, Ohashi K, Mizuno K, Narumiya S (1999). "Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase". Science. 285 (5429): 895–8. doi:10.1126/science.285.5429.895. PMID   10436159.
• Edwards DC, Sanders LC, Bokoch GM, Gill GN (1999). "Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics". Nat. Cell Biol. 1 (5): 253–9. doi:10.1038/12963. PMID   10559936. S2CID   25250183.
• Ohashi K, Nagata K, Maekawa M, Ishizaki T, Narumiya S, Mizuno K (2000). "Rho-associated kinase ROCK activates LIM-kinase 1 by phosphorylation at threonine 508 within the activation loop". J. Biol. Chem. 275 (5): 3577–82. doi: 10.1074/jbc.275.5.3577 . PMID   10652353.
• Martindale DW, Wilson MD, Wang D, Burke RD, Chen X, Duronio V, Koop BF (2000). "Comparative genomic sequence analysis of the Williams syndrome region (LIMK1-RFC2) of human chromosome 7q11.23". Mamm. Genome. 11 (10): 890–8. doi:10.1007/s003350010166. PMID   11003705. S2CID   8575994.
• Sumi T, Matsumoto K, Shibuya A, Nakamura T (2001). "Activation of LIM kinases by myotonic dystrophy kinase-related Cdc42-binding kinase alpha". J. Biol. Chem. 276 (25): 23092–6. doi: 10.1074/jbc.C100196200 . PMID   11340065.
• Dan C, Kelly A, Bernard O, Minden A (2001). "Cytoskeletal changes regulated by the PAK4 serine/threonine kinase are mediated by LIM kinase 1 and cofilin". J. Biol. Chem. 276 (34): 32115–21. doi: 10.1074/jbc.M100871200 . PMID   11413130.
• Toshima J, Toshima JY, Takeuchi K, Mori R, Mizuno K (2001). "Cofilin phosphorylation and actin reorganization activities of testicular protein kinase 2 and its predominant expression in testicular Sertoli cells". J. Biol. Chem. 276 (33): 31449–58. doi: 10.1074/jbc.M102988200 . PMID   11418599.

External links

• LIMK1 Info with links in the Cell Migration Gateway Archived 2014-12-11 at the Wayback Machine