Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures
Basic Information
Protein Name :  LIM domain kinase 1  

UniProtKB / Swiss-Prot ID :  LIMK1_HUMAN

Gene Name (Synonyms) : 
LIMK1, LIMK  

Species :  Homo sapiens (Human). 

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

Protein 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. 

Protein Sequence MRLTLLCCTWREERMGEEGSELPVCASCGQRIYDGQYLQALNADWHADCFRCCDCSASLSHQYYEKDGQL...
Predicted Secondary Structure CEEEEEEECCCCCCCCCCCCCCCCCCCCCCCCCCHHHHHHHHHHHCCCCEEECCCCCHHHHHHCCCCCCE...
Protein Variant
LocationDescription
190G -> A (in dbSNP:rs35827364). VAR_042246
247S -> N (in dbSNP:rs55661242). VAR_042247
422R -> Q (in dbSNP:rs55679316). VAR_042248
580F -> Y (in dbSNP:rs178412). VAR_050148
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Overview of Protein Modification Sites with Functional and Structural Information
Accessible Surface Area (ASA)
Pred. Secondary
Real Secondary
Disorder Prediction
Protein Domain
&
Experimental PTM Sites
Predicted PTM Sites
Protein Variant
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Experimental Post-Translational Modification Sites Download
Locations
Modification
Substrate Sites
&
Secondary Structure
Accessible Surface Area (%)
Resource
Reference
Structural Characterization
Orthologous
Protein Cluster
196PhosphoserineGTEHSHTVR
CCCCCCCCC
18.02SysPTM
Link-
210PhosphoserinePGCMSPDVK
CCCCCCCCC
23.25HPRD
Link-
210PhosphoserinePGCMSPDVK
CCCCCCCCC
23.25Phosphositeplus
Link-
210Phosphoserine.PGCMSPDVK
CCCCCCCCC
23.25UniProtKB
Link-
229PhosphothreonineEINGTPIRN
CCCCCCCCC
15.85HPRD
Link-
229PhosphothreonineEINGTPIRN
CCCCCCCCC
15.85Phosphositeplus
Link-
229PhosphothreonineEINGTPIRN
CCCCCCCCC
15.85SysPTM
Link-
229Phosphothreonine.EINGTPIRN
CCCCCCCCC
15.85UniProtKB
Link-
253PhosphothreonineLLQLTLEHD
CCCCCCCCC
19.69HPRD
Link-
253PhosphothreonineLLQLTLEHD
CCCCCCCCC
19.69Phosphositeplus
Link-
261PhosphothreonineDPHDTLGHG
CCHHHHHHC
31.44HPRD
Link-
261Phosphothreonine.DPHDTLGHG
CCHHHHHHC
31.44UniProtKB
Link-
270PhosphothreonineLGPETSPLS
CCCCCCCCC
38.49Phosphositeplus
Link-
270Phosphothreonine.LGPETSPLS
CCCCCCCCC
38.49UniProtKB
Link-
274PhosphoserineTSPLSSPAY
CCCCCCCCC
37.35HPRD
Link-
274PhosphoserineTSPLSSPAY
CCCCCCCCC
37.35Phosphositeplus
Link-
296PhosphoserinePVLRSCSID
CCCCCCCCC
14.19SysPTM
Link-
296Phosphoserine.PVLRSCSID
CCCCCCCCC
14.19UniProtKB
Link-
298PhosphoserineLRSCSIDRS
CCCCCCCCC
28.86PhosphoELM
Link-
298PhosphoserineLRSCSIDRS
CCCCCCCCC
28.86Phosphositeplus
Link-
298PhosphoserineLRSCSIDRS
CCCCCCCCC
28.86SysPTM
Link-
298Phosphoserine (LIMK1)LRSCSIDRS
CCCCCCCCC
28.86HPRD
Link-
298Phosphoserine.LRSCSIDRS
CCCCCCCCC
28.86UniProtKB
Link-
302PhosphoserineSIDRSPGAG
CCCCCCCCC
24.76HPRD
Link-
302PhosphoserineSIDRSPGAG
CCCCCCCCC
24.76PhosphoELM
Link-
302PhosphoserineSIDRSPGAG
CCCCCCCCC
24.76Phosphositeplus
Link-
302PhosphoserineSIDRSPGAG
CCCCCCCCC
24.76SysPTM
Link-
302Phosphoserine.SIDRSPGAG
CCCCCCCCC
24.76UniProtKB
Link-
307PhosphoserinePGAGSLGSP
CCCCCCCCC
29.08HPRD
Link-
307PhosphoserinePGAGSLGSP
CCCCCCCCC
29.08PhosphoELM
Link-
307PhosphoserinePGAGSLGSP
CCCCCCCCC
29.08Phosphositeplus
Link-
307PhosphoserinePGAGSLGSP
CCCCCCCCC
29.08SysPTM
Link-
307Phosphoserine.PGAGSLGSP
CCCCCCCCC
29.08UniProtKB
Link-
310PhosphoserineGSLGSPASQ
CCCCCCCCC
23.68PhosphoELM
Link-
310PhosphoserineGSLGSPASQ
CCCCCCCCC
23.68Phosphositeplus
Link-
310Phosphoserine (LIMK1)GSLGSPASQ
CCCCCCCCC
23.68HPRD
Link-
310Phosphoserine.GSLGSPASQ
CCCCCCCCC
23.68UniProtKB
Link-
313PhosphoserineGSPASQRKD
CCCCCCCCC
33.62HPRD
Link-
313PhosphoserineGSPASQRKD
CCCCCCCCC
33.62Phosphositeplus
Link-
313Phosphoserine.GSPASQRKD
CCCCCCCCC
33.62UniProtKB
Link-
323PhosphoserineGRSESLRVV
CCCCCCCCC
23.79Phosphositeplus
Link-
323Phosphoserine; by MAPKAPK2.GRSESLRVV
CCCCCCCCC
23.79UniProtKB
Link-
337PhosphoserineIFRPSDLIH
CCCHHHEEE
40.57HPRD
Link
337PhosphoserineIFRPSDLIH
CCCHHHEEE
40.57Phosphositeplus
Link
337PhosphoserineIFRPSDLIH
CCCHHHEEE
40.57SysPTM
Link
337Phosphoserine.IFRPSDLIH
CCCHHHEEE
40.57UniProtKB
Link
415PhosphotyrosineFITEYIKGG
EEEEECCCC
10.16Phosphositeplus
Link
427PhosphoserineGIIKSMDSQ
HHHHHCCCC
19.88HPRD
Link
439PhosphoserineSQRVSFAKD
HHHHHHHHH
22.98HPRD
Link
508PhosphothreonineKKRYTVVGN
CCCEEECCC
16.85Phosphositeplus
Link
508Phosphothreonine (CDC42BPA)KKRYTVVGN
CCCEEECCC
16.85HPRD
Link
508Phosphothreonine (PAK1)KKRYTVVGN
CCCEEECCC
16.85HPRD
Link
508Phosphothreonine (ROCK1)KKRYTVVGN
CCCEEECCC
16.85HPRD
Link
508Phosphothreonine (ROCK_group;PAK1;MRCKa)KKRYTVVGN
CCCEEECCC
16.85PhosphoELM
Link
508Phosphothreonine; by ROCK1 and PAK1.KKRYTVVGN
CCCEEECCC
16.85UniProtKB
Link
637PhosphoserineRRGESGLPA
CCCCCCCCC
48.75Phosphositeplus
Link-
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Protein-Protein Interactions
      Interacting Protein      
Interaction type
Source ID
      Resource      
      Pubmed ID      
Domain-Domain Interactions
PAK2_HUMANdirect interaction
phosphorylation
EBI-1182678
EBI-1187058
intact16837009
16837009
1433Z_HUMANphysical interactionEBI-445599
intact12361576
LATS1_HUMANcolocalization
physical interaction
physical interaction
physical interaction
physical interaction
EBI-444493
EBI-444464
EBI-444
intact15220930
15220930
15220930
15220930
15220930
NRG1_HUMANin vitro
yeast 2-hybrid
HPRD:03210HPRD9685409
RNF12_HUMANin vitroHPRD:03210HPRD10431247
1433Z_HUMANin vitro
in vivo
yeast 2-hybrid
HPRD:03210HPRD12323073
COF1_HUMANin vitro
in vivo
HPRD:03210HPRD9655398
11418599
11340065
11925442
16456544
COF2_HUMANin vitro
in vivo
HPRD:03210HPRD9655398
12684437
8824278
BMPR2_HUMANin vitro
in vivo
yeast 2-hybrid
HPRD:03210HPRD12963706
CDN1C_HUMANin vitro
in vivo
yeast 2-hybrid
HPRD:03210HPRD14530263
LIMK1_HUMANin vitro
in vivo
HPRD:03210HPRD8980133
SSH3_HUMANin vitroHPRD:03210HPRD15660133
LATS1_HUMANENSP00000336740STRING
COF2_HUMANENSP00000336740STRING
COF1_HUMANENSP00000336740STRING
SSH3_HUMANENSP00000336740STRING
SSH1_HUMANENSP00000336740STRING
PAK4_HUMANENSP00000336740STRING
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Disease Reference
Kegg disease
There are no disease associations of PTM sites.
Drug Reference
DrugBank
DB08912Dabrafenib
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Related Literatures of Post-Translational Modification
Phosphorylation
ReferencePubMed
"Rho-associated kinase ROCK activates LIM-kinase 1 by phosphorylationat threonine 508 within the activation loop.";
Ohashi K., Nagata K., Maekawa M., Ishizaki T., Narumiya S., Mizuno K.;
J. Biol. Chem. 275:3577-3582(2000).
Cited for: PHOSPHORYLATION AT THR-508, MUTAGENESIS OF THR-508, AND INTERACTIONWITH ROCK1.
"Interplay between components of a novel LIM kinase-slingshotphosphatase complex regulates cofilin.";
Soosairajah J., Maiti S., Wiggan O., Sarmiere P., Moussi N.,Sarcevic B., Sampath R., Bamburg J.R., Bernard O.;
EMBO J. 24:473-486(2005).
Cited for: FUNCTION, INTERACTION WITH SSH1, PHOSPHORYLATION AT THR-508, ANDDEPHOSPHORYLATION.
"MAPKAPK-2-mediated LIM-kinase activation is critical for VEGF-inducedactin remodeling and cell migration.";
Kobayashi M., Nishita M., Mishima T., Ohashi K., Mizuno K.;
EMBO J. 25:713-726(2006).
Cited for: PHOSPHORYLATION AT SER-323 BY MAPKAPK2.
"Proteomics analysis of protein kinases by target class-selectiveprefractionation and tandem mass spectrometry.";
Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R.,Keri G., Wehland J., Daub H.;
Mol. Cell. Proteomics 6:537-547(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-298 AND SER-310, ANDMASS SPECTROMETRY.
"Kinase-selective enrichment enables quantitative phosphoproteomics ofthe kinome across the cell cycle.";
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,Greff Z., Keri G., Stemmann O., Mann M.;
Mol. Cell 31:438-448(2008).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-210; THR-229; SER-298;SER-310 AND SER-337, AND MASS SPECTROMETRY.
"A quantitative atlas of mitotic phosphorylation.";
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,Elledge S.J., Gygi S.P.;
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-302; SER-307 ANDSER-310, AND MASS SPECTROMETRY.
"Lys-N and trypsin cover complementary parts of the phosphoproteome ina refined SCX-based approach.";
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,Mohammed S.;
Anal. Chem. 81:4493-4501(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-298 AND SER-310, ANDMASS SPECTROMETRY.
"Large-scale proteomics analysis of the human kinome.";
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,Mann M., Daub H.;
Mol. Cell. Proteomics 8:1751-1764(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-210; THR-229; THR-261;THR-270; SER-296; SER-298; SER-302; SER-307; SER-310 AND SER-313, ANDMASS SPECTROMETRY.
"Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signallingto actin cytoskeletal dynamics.";
Edwards D.C., Sanders L.C., Bokoch G.M., Gill G.N.;
Nat. Cell Biol. 1:253-259(1999).
Cited for: PHOSPHORYLATION AT THR-508 BY PAK1.
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Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures