LIM domain kinase 1

Details

Name
LIM domain kinase 1
Synonyms
  • 2.7.11.1
  • LIMK
  • LIMK-1
Gene Name
LIMK1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0008608|LIM domain kinase 1
MRLTLLCCTWREERMGEEGSELPVCASCGQRIYDGQYLQALNADWHADCFRCCDCSASLS
HQYYEKDGQLFCKKDYWARYGESCHGCSEQITKGLVMVAGELKYHPECFICLTCGTFIGD
GDTYTLVEHSKLYCGHCYYQTVVTPVIEQILPDSPGSHLPHTVTLVSIPASSHGKRGLSV
SIDPPHGPPGCGTEHSHTVRVQGVDPGCMSPDVKNSIHVGDRILEINGTPIRNVPLDEID
LLIQETSRLLQLTLEHDPHDTLGHGLGPETSPLSSPAYTPSGEAGSSARQKPVLRSCSID
RSPGAGSLGSPASQRKDLGRSESLRVVCRPHRIFRPSDLIHGEVLGKGCFGQAIKVTHRE
TGEVMVMKELIRFDEETQRTFLKEVKVMRCLEHPNVLKFIGVLYKDKRLNFITEYIKGGT
LRGIIKSMDSQYPWSQRVSFAKDIASGMAYLHSMNIIHRDLNSHNCLVRENKNVVVADFG
LARLMVDEKTQPEGLRSLKKPDRKKRYTVVGNPYWMAPEMINGRSYDEKVDVFSFGIVLC
EIIGRVNADPDYLPRTMDFGLNVRGFLDRYCPPNCPPSFFPITVRCCDLDPEKRPSFVKL
EHWLETLRMHLAGHLPLGPQLEQLDRGFWETYRRGESGLPAHPEVPD
Number of residues
647
Molecular Weight
72584.4
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / heat shock protein binding / protein kinase activity / protein serine/threonine kinase activity / zinc ion binding
Processes
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
Components
cytoplasm / cytosol / focal adhesion / membrane / neuron projection / nucleoplasm
General Function
Zinc ion binding
Specific 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).
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0013301|LIM domain kinase 1 (LIMK1)
ATGCTGTTGGCTTCAGCCCCAAGAAGACGCCGCTTCCTCCAGAGGGCTAAGTGTTGTGAC
TGCAGTGCCTCCCTGTCGCACCAGTACTATGAGAAGGATGGGCAGCTCTTCTGCAAGAAG
GACTACTGGGCCCGCTATGGCGAGTCCTGCCATGGGTGCTCTGAGCAAATCACCAAGGGA
CTGGTTATGGTGGCTGGGGAGCTGAAGTACCACCCCGAGTGTTTCATCTGCCTCACGTGT
GGGACCTTTATCGGTGACGGGGACACCTACACGCTGGTGGAGCACTCCAAGCTGTACTGC
GGGCACTGCTACTACCAGACTGTGGTGACCCCCGTCATCGAGCAGATCCTGCCTGACTCC
CCTGGCTCCCACCTGCCCCACACCGTCACCCTGGTGTCCATCCCAGCCTCATCTCATGGC
AAGCGTGGACTTTCAGTCTCCATTGACCCCCCGCACGGCCCACCGGGCTGTGGCACCGAG
CACTCACACACCGTCCGCGTCCAGGGAGTGGATCCGGGCTGCATGAGCCCAGATGTGAAG
AATTCCATCCACGTCGGAGACCGGATCTTGGAAATCAATGGCACGCCCATCCGAAATGTG
CCCCTGGACGAGATTGACCTGCTGATTCAGGAAACCAGCCGCCTGCTCCAGCTGACCCTC
GAGCATGACCCTCACGATACACTGGGCCACGGGCTGGGGCCTGAGACCAGCCCCCTGAGC
TCTCCGGCTTATACTCCCAGCGGGGAGGCGGGCAGCTCTGCCCGGCAGAAACCTGTCTTG
AGGAGCTGCAGCATCGACAGGTCTCCGGGCGCTGGCTCACTGGGCTCCCCGGCCTCCCAG
CGCAAGGACCTGGGTCGCTCTGAGTCCCTCCGCGTAGTCTGCCGGCCACACCGCATCTTC
CGGCCGTCGGACCTCATCCACGGGGAGGTGCTGGGCAAGGGCTGCTTCGGCCAGGCTATC
AAGGTGACACACCGTGAGACAGGTGAGGTGATGGTGATGAAGGAGCTGATCCGGTTCGAC
GAGGAGACCCAGAGGACGTTCCTCAAGGAGGTGAAGGTCATGCGATGCCTGGAACACCCC
AACGTGCTCAAGTTCATCGGGGTGCTCTACAAGGACAAGAGGCTCAACTTCATCACTGAG
TACATCAAGGGCGGCACGCTCCGGGGCATCATCAAGAGCATGGACAGCCAGTACCCATGG
AGCCAGAGAGTGAGCTTTGCCAAGGACATCGCATCAGGGATGGCCTACCTCCACTCCATG
AACATCATCCACCGAGACCTCAACTCCCACAACTGCCTGGTCCGCGAGAACAAGAATGTG
GTGGTGGCTGACTTCGGGCTGGCGCGTCTCATGGTGGACGAGAAGACTCAGCCTGAGGGC
CTGCGGAGCCTCAAGAAGCCAGACCGCAAGAAGCGCTACACCGTGGTGGGCAACCCCTAC
TGGATGGCACCTGAGATGATCAACGGCCGCAGCTATGATGAGAAGGTGGATGTGTTCTCC
TTTGGGATCGTCCTGTGCGAGATCATCGGGCGGGTGAACGCAGACCCTGACTACCTGCCC
CGCACCATGGACTTTGGCCTCAACGTGCGAGGATTCCTGGACCGCTACTGCCCCCCAAAC
TGCCCCCCGAGCTTCTTCCCCATCACCGTGCGCTGTTGCGATCTGGACCCCGAGAAGAGG
CCATCCTTTGTGAAGCTGGAACACTGGCTGGAGACCCTCCGCATGCACCTGGCCGGCCAC
CTGCCACTGGGCCCACAGCTGGAGCAGCTGGACAGAGGTTTCTGGGAGACCTACCGGCGC
GGCGAGAGCGGACTGCCTGCCCACCCTGAGGTCCCCGACTGA
Chromosome Location
7
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP53667
UniProtKB Entry NameLIMK1_HUMAN
HGNC IDHGNC:6613
General References
  1. Mizuno K, Okano I, Ohashi K, Nunoue K, Kuma K, Miyata T, Nakamura T: Identification of a human cDNA encoding a novel protein kinase with two repeats of the LIM/double zinc finger motif. Oncogene. 1994 Jun;9(6):1605-12. [Article]
  2. Frangiskakis JM, Ewart AK, Morris CA, Mervis CB, Bertrand J, Robinson BF, Klein BP, Ensing GJ, Everett LA, Green ED, Proschel C, Gutowski NJ, Noble M, Atkinson DL, Odelberg SJ, Keating MT: LIM-kinase1 hemizygosity implicated in impaired visuospatial constructive cognition. Cell. 1996 Jul 12;86(1):59-69. [Article]
  3. 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: Identification of genes from a 500-kb region at 7q11.23 that is commonly deleted in Williams syndrome patients. Genomics. 1996 Sep 1;36(2):328-36. [Article]
  4. Edwards DC, Gill GN: Structural features of LIM kinase that control effects on the actin cytoskeleton. J Biol Chem. 1999 Apr 16;274(16):11352-61. [Article]
  5. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  6. Hillier LW, Fulton RS, Fulton LA, Graves TA, Pepin KH, Wagner-McPherson C, Layman D, Maas J, Jaeger S, Walker R, Wylie K, Sekhon M, Becker MC, O'Laughlin MD, Schaller ME, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Cordes M, Du H, Sun H, Edwards J, Bradshaw-Cordum H, Ali J, Andrews S, Isak A, Vanbrunt A, Nguyen C, Du F, Lamar B, Courtney L, Kalicki J, Ozersky P, Bielicki L, Scott K, Holmes A, Harkins R, Harris A, Strong CM, Hou S, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Leonard S, Rohlfing T, Rock SM, Tin-Wollam AM, Abbott A, Minx P, Maupin R, Strowmatt C, Latreille P, Miller N, Johnson D, Murray J, Woessner JP, Wendl MC, Yang SP, Schultz BR, Wallis JW, Spieth J, Bieri TA, Nelson JO, Berkowicz N, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Bedell JA, Mardis ER, Clifton SW, Chissoe SL, Marra MA, Raymond C, Haugen E, Gillett W, Zhou Y, James R, Phelps K, Iadanoto S, Bubb K, Simms E, Levy R, Clendenning J, Kaul R, Kent WJ, Furey TS, Baertsch RA, Brent MR, Keibler E, Flicek P, Bork P, Suyama M, Bailey JA, Portnoy ME, Torrents D, Chinwalla AT, Gish WR, Eddy SR, McPherson JD, Olson MV, Eichler EE, Green ED, Waterston RH, Wilson RK: The DNA sequence of human chromosome 7. Nature. 2003 Jul 10;424(6945):157-64. [Article]
  7. Edwards DC, Sanders LC, Bokoch GM, Gill GN: Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics. Nat Cell Biol. 1999 Sep;1(5):253-9. [Article]
  8. Maekawa M, Ishizaki T, Boku S, Watanabe N, Fujita A, Iwamatsu A, Obinata T, Ohashi K, Mizuno K, Narumiya S: Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase. Science. 1999 Aug 6;285(5429):895-8. [Article]
  9. Ohashi K, Nagata K, Maekawa M, Ishizaki T, Narumiya S, Mizuno K: Rho-associated kinase ROCK activates LIM-kinase 1 by phosphorylation at threonine 508 within the activation loop. J Biol Chem. 2000 Feb 4;275(5):3577-82. [Article]
  10. Sumi T, Matsumoto K, Shibuya A, Nakamura T: Activation of LIM kinases by myotonic dystrophy kinase-related Cdc42-binding kinase alpha. J Biol Chem. 2001 Jun 22;276(25):23092-6. Epub 2001 May 4. [Article]
  11. Dan C, Kelly A, Bernard O, Minden A: Cytoskeletal changes regulated by the PAK4 serine/threonine kinase are mediated by LIM kinase 1 and cofilin. J Biol Chem. 2001 Aug 24;276(34):32115-21. Epub 2001 Jun 18. [Article]
  12. Niwa R, Nagata-Ohashi K, Takeichi M, Mizuno K, Uemura T: Control of actin reorganization by Slingshot, a family of phosphatases that dephosphorylate ADF/cofilin. Cell. 2002 Jan 25;108(2):233-46. [Article]
  13. Kaji N, Ohashi K, Shuin M, Niwa R, Uemura T, Mizuno K: Cell cycle-associated changes in Slingshot phosphatase activity and roles in cytokinesis in animal cells. J Biol Chem. 2003 Aug 29;278(35):33450-5. Epub 2003 Jun 14. [Article]
  14. Yokoo T, Toyoshima H, Miura M, Wang Y, Iida KT, Suzuki H, Sone H, Shimano H, Gotoda T, Nishimori S, Tanaka K, Yamada N: p57Kip2 regulates actin dynamics by binding and translocating LIM-kinase 1 to the nucleus. J Biol Chem. 2003 Dec 26;278(52):52919-23. Epub 2003 Oct 6. [Article]
  15. Hillman RT, Green RE, Brenner SE: An unappreciated role for RNA surveillance. Genome Biol. 2004;5(2):R8. Epub 2004 Feb 2. [Article]
  16. Soosairajah J, Maiti S, Wiggan O, Sarmiere P, Moussi N, Sarcevic B, Sampath R, Bamburg JR, Bernard O: Interplay between components of a novel LIM kinase-slingshot phosphatase complex regulates cofilin. EMBO J. 2005 Feb 9;24(3):473-86. Epub 2005 Jan 20. [Article]
  17. Nishita M, Tomizawa C, Yamamoto M, Horita Y, Ohashi K, Mizuno K: Spatial and temporal regulation of cofilin activity by LIM kinase and Slingshot is critical for directional cell migration. J Cell Biol. 2005 Oct 24;171(2):349-59. Epub 2005 Oct 17. [Article]
  18. Kobayashi M, Nishita M, Mishima T, Ohashi K, Mizuno K: MAPKAPK-2-mediated LIM-kinase activation is critical for VEGF-induced actin remodeling and cell migration. EMBO J. 2006 Feb 22;25(4):713-26. Epub 2006 Feb 2. [Article]
  19. Li R, Soosairajah J, Harari D, Citri A, Price J, Ng HL, Morton CJ, Parker MW, Yarden Y, Bernard O: Hsp90 increases LIM kinase activity by promoting its homo-dimerization. FASEB J. 2006 Jun;20(8):1218-20. Epub 2006 Apr 26. [Article]
  20. Acevedo K, Li R, Soo P, Suryadinata R, Sarcevic B, Valova VA, Graham ME, Robinson PJ, Bernard O: The phosphorylation of p25/TPPP by LIM kinase 1 inhibits its ability to assemble microtubules. Exp Cell Res. 2007 Dec 10;313(20):4091-106. [Article]
  21. Bernard O: Lim kinases, regulators of actin dynamics. Int J Biochem Cell Biol. 2007;39(6):1071-6. Epub 2006 Nov 28. [Article]
  22. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [Article]
  23. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [Article]
  24. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [Article]
  25. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [Article]
  26. Manetti F: LIM kinases are attractive targets with many macromolecular partners and only a few small molecule regulators. Med Res Rev. 2012 Sep;32(5):968-98. doi: 10.1002/med.20230. Epub 2011 Jan 16. [Article]
  27. McConnell BV, Koto K, Gutierrez-Hartmann A: Nuclear and cytoplasmic LIMK1 enhances human breast cancer progression. Mol Cancer. 2011 Jun 18;10:75. doi: 10.1186/1476-4598-10-75. [Article]
  28. Borroni EM, Cancellieri C, Vacchini A, Benureau Y, Lagane B, Bachelerie F, Arenzana-Seisdedos F, Mizuno K, Mantovani A, Bonecchi R, Locati M: beta-arrestin-dependent activation of the cofilin pathway is required for the scavenging activity of the atypical chemokine receptor D6. Sci Signal. 2013 Apr 30;6(273):ra30.1-11, S1-3. doi: 10.1126/scisignal.2003627. [Article]
  29. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB08912Dabrafenibapproved, investigationalunknowninhibitorDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails
DB11718Encorafenibapproved, investigationalyesinhibitorDetails