LIMK1_HUMAN - dbPTM
LIMK1_HUMAN - PTM Information in dbPTM
Basic Information of Protein
UniProt ID LIMK1_HUMAN
UniProt AC P53667
Protein Name LIM domain kinase 1
Gene Name LIMK1
Organism Homo sapiens (Human).
Sequence Length 647
Subcellular Localization Cytoplasm. Nucleus. Cell projection, lamellipodium . Predominantly found in the cytoplasm. Localizes in the lamellipodium in a CDC42BPA, CDC42BPB and FAM89B/LRAP25-dependent manner.
Protein Description 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)..
Protein Sequence MRLTLLCCTWREERMGEEGSELPVCASCGQRIYDGQYLQALNADWHADCFRCCDCSASLSHQYYEKDGQLFCKKDYWARYGESCHGCSEQITKGLVMVAGELKYHPECFICLTCGTFIGDGDTYTLVEHSKLYCGHCYYQTVVTPVIEQILPDSPGSHLPHTVTLVSIPASSHGKRGLSVSIDPPHGPPGCGTEHSHTVRVQGVDPGCMSPDVKNSIHVGDRILEINGTPIRNVPLDEIDLLIQETSRLLQLTLEHDPHDTLGHGLGPETSPLSSPAYTPSGEAGSSARQKPVLRSCSIDRSPGAGSLGSPASQRKDLGRSESLRVVCRPHRIFRPSDLIHGEVLGKGCFGQAIKVTHRETGEVMVMKELIRFDEETQRTFLKEVKVMRCLEHPNVLKFIGVLYKDKRLNFITEYIKGGTLRGIIKSMDSQYPWSQRVSFAKDIASGMAYLHSMNIIHRDLNSHNCLVRENKNVVVADFGLARLMVDEKTQPEGLRSLKKPDRKKRYTVVGNPYWMAPEMINGRSYDEKVDVFSFGIVLCEIIGRVNADPDYLPRTMDFGLNVRGFLDRYCPPNCPPSFFPITVRCCDLDPEKRPSFVKLEHWLETLRMHLAGHLPLGPQLEQLDRGFWETYRRGESGLPAHPEVPD
Overview of Protein Modification Sites with Functional and Structural Information
Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations Modification Substrate Peptides
&
Secondary Structure		 ASA (%) Reference Orthologous
Protein Cluster
7S-palmitoylation-MRLTLLCCTWREER
-CCEEEEEEEECHHH		1.8725884247
8S-palmitoylationMRLTLLCCTWREERM
CCEEEEEEEECHHHC		4.0525884247
58PhosphorylationRCCDCSASLSHQYYE
HHCCCCCCCCCEEEE		17.7030576142
64PhosphorylationASLSHQYYEKDGQLF
CCCCCEEEECCCEEE		15.2130576142
154PhosphorylationIEQILPDSPGSHLPH
HHHHCCCCCCCCCCC		29.2628348404
157PhosphorylationILPDSPGSHLPHTVT
HCCCCCCCCCCCEEE		25.8228348404
162PhosphorylationPGSHLPHTVTLVSIP
CCCCCCCEEEEEEEC		17.1628348404
164PhosphorylationSHLPHTVTLVSIPAS
CCCCCEEEEEEECCC		23.6928348404
180UbiquitinationHGKRGLSVSIDPPHG
CCCCCEEEEECCCCC		7.5629967540
196PhosphorylationPGCGTEHSHTVRVQG
CCCCCCCCCEEEEEC		18.0218691976
210PhosphorylationGVDPGCMSPDVKNSI
CCCCCCCCCCCCCCE		23.2525159151
210 (in isoform 3)Phosphorylation-23.25-
214UbiquitinationGCMSPDVKNSIHVGD
CCCCCCCCCCEECCC		52.9729967540
229PhosphorylationRILEINGTPIRNVPL
EEEEECCEECCCCCH		15.8525159151
229 (in isoform 3)Phosphorylation-15.85-
253 (in isoform 3)Phosphorylation-19.69-
253PhosphorylationTSRLLQLTLEHDPHD
HHHHHHHHHCCCCCC		19.6917192257
261 (in isoform 3)Phosphorylation-31.44-
261PhosphorylationLEHDPHDTLGHGLGP
HCCCCCCCCCCCCCC		31.4418691976
264PhosphorylationDPHDTLGHGLGPETS
CCCCCCCCCCCCCCC		31.2732645325
270PhosphorylationGHGLGPETSPLSSPA
CCCCCCCCCCCCCCC		38.4920873877
271PhosphorylationHGLGPETSPLSSPAY
CCCCCCCCCCCCCCC		23.3720873877
274 (in isoform 3)Phosphorylation-37.35-
274PhosphorylationGPETSPLSSPAYTPS
CCCCCCCCCCCCCCC		37.3517192257
275PhosphorylationPETSPLSSPAYTPSG
CCCCCCCCCCCCCCC		22.6420873877
276PhosphorylationETSPLSSPAYTPSGE
CCCCCCCCCCCCCCC		26.3833259812
278PhosphorylationSPLSSPAYTPSGEAG
CCCCCCCCCCCCCCC		23.6727080861
279PhosphorylationPLSSPAYTPSGEAGS
CCCCCCCCCCCCCCC		17.0627080861
281PhosphorylationSSPAYTPSGEAGSSA
CCCCCCCCCCCCCCC		41.2727080861
286PhosphorylationTPSGEAGSSARQKPV
CCCCCCCCCCCCCCE		28.0720873877
287PhosphorylationPSGEAGSSARQKPVL
CCCCCCCCCCCCCEE		26.9320873877
296PhosphorylationRQKPVLRSCSIDRSP
CCCCEEEECCCCCCC		14.1923927012
298PhosphorylationKPVLRSCSIDRSPGA
CCEEEECCCCCCCCC		28.8623401153
302PhosphorylationRSCSIDRSPGAGSLG
EECCCCCCCCCCCCC		24.7629255136
307PhosphorylationDRSPGAGSLGSPASQ
CCCCCCCCCCCCHHH		29.0829255136
310PhosphorylationPGAGSLGSPASQRKD
CCCCCCCCCHHHCCC		23.6819664994
313PhosphorylationGSLGSPASQRKDLGR
CCCCCCHHHCCCCCC		33.6230266825
320MethylationSQRKDLGRSESLRVV
HHCCCCCCCCCEEEE		44.54115385899
321PhosphorylationQRKDLGRSESLRVVC
HCCCCCCCCCEEEEE		29.7328555341
323PhosphorylationKDLGRSESLRVVCRP
CCCCCCCCEEEEECC		23.7922817900
337PhosphorylationPHRIFRPSDLIHGEV
CCCCCCHHHCCCCEE		40.5721712546
368UbiquitinationTGEVMVMKELIRFDE
CCCEEEEEEEECCCH		37.65-
415PhosphorylationRLNFITEYIKGGTLR
CHHHHHHHCCCCCHH		10.1622817900
427PhosphorylationTLRGIIKSMDSQYPW
CHHHHHHCCCCCCCH		19.8820068231
430PhosphorylationGIIKSMDSQYPWSQR
HHHHCCCCCCCHHHH		23.9927732954
432PhosphorylationIKSMDSQYPWSQRVS
HHCCCCCCCHHHHHH		15.6027732954
435PhosphorylationMDSQYPWSQRVSFAK
CCCCCCHHHHHHHHH		12.0127732954
439PhosphorylationYPWSQRVSFAKDIAS
CCHHHHHHHHHHHHH		22.9820068231
489MalonylationARLMVDEKTQPEGLR
EEHHCCCCCCCCHHH		48.2526320211
497PhosphorylationTQPEGLRSLKKPDRK
CCCCHHHHCCCCCCC		49.9728555341
508PhosphorylationPDRKKRYTVVGNPYW
CCCCCCEEEECCCCC		16.8516219803
534PhosphorylationDEKVDVFSFGIVLCE
CCCCCEEEHHHHHHH		23.55-
637PhosphorylationETYRRGESGLPAHPE
HHHHCCCCCCCCCCC		48.7522817900
Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)
Modified Location Modified Residue Modification Type of Upstream Proteins Gene Name of Upstream Proteins UniProt AC of Upstream Proteins Sources
307SPhosphorylationKinaseAURAO14965
PSP
310SPhosphorylationKinaseMAPK14Q16539
GPS
310SPhosphorylationKinaseP38-SUBFAMILY-GPS
323SPhosphorylationKinaseMAPKAPK2P49137
Uniprot
508TPhosphorylationKinaseAURAO14965
PSP
508TPhosphorylationKinaseCDC42BPAQ5VT25
GPS
508TPhosphorylationKinasePAK1Q13153
Uniprot
508TPhosphorylationKinasePAK4O96013
PSP
508TPhosphorylationKinasePAK6Q9NQU5
PSP
508TPhosphorylationKinasePAK6Q3ULB5
PSP
508TPhosphorylationKinaseROCK1Q13464
Uniprot
508TPhosphorylationKinaseROCK-SUBFAMILY-GPS
508TPhosphorylationKinaseROCK_GROUP-PhosphoELM
-KUbiquitinationE3 ubiquitin ligaseRLIMQ9NVW2
PMID:22199232
-KUbiquitinationE3 ubiquitin ligaseRNF6Q9Y252
PMID:16204183
-KUbiquitinationE3 ubiquitin ligaseLHX1P48742
PMID:22199232
-KUbiquitinationE3 ubiquitin ligasePRKNO60260
PMID:17512523
Functions of PTM Sites
Modified Location Modified Residue Modification Function Reference
323SPhosphorylation

16456544
508TPhosphorylation

10196227
Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location Modification Variant Position
(Distance <= 10) 		Residue Change SAP Related Disease Reference

Oops, there are no SNP-PTM records of LIMK1_HUMAN !!
Protein-Protein Interaction
Interacting Protein Gene Name Interaction Type PPI Reference Domain-Domain Interactions
NRG1_HUMANNRG1physical
9685409
BMPR2_HUMANBMPR2physical
12963706
CDN1C_HUMANCDKN1Cphysical
14530263
COF1_HUMANCFL1physical
12963706
PAK4_HUMANPAK4physical
11413130
COF1_HUMANCFL1physical
10436159
LIMK1_HUMANLIMK1physical
8980133
LIMK2_HUMANLIMK2physical
8980133
PRKN_HUMANPARK2physical
17512523
H11_HUMANHIST1H1Aphysical
8537403
MBP_HUMANMBPphysical
8537403
LATS1_HUMANLATS1physical
15220930
COF1_HUMANCFL1physical
15220930
A4_HUMANAPPphysical
21832049
COF1_HUMANCFL1physical
16278681
COF1_HUMANCFL1physical
17500066
BAD_HUMANBADphysical
26496610
BLMH_HUMANBLMHphysical
26496610
FYN_HUMANFYNphysical
26496610
ITA1_HUMANITGA1physical
26496610
RPB4_HUMANPOLR2Dphysical
26496610
RRAS_HUMANRRASphysical
26496610
UXT_HUMANUXTphysical
26496610
RAD54_HUMANRAD54Lphysical
26496610
TADA3_HUMANTADA3physical
26496610
RTEL1_HUMANRTEL1physical
26496610
LTOR1_HUMANLAMTOR1physical
26496610
ERBIN_HUMANERBB2IPphysical
26496610
MIIP_HUMANMIIPphysical
26496610
SARNP_HUMANSARNPphysical
26496610
OSBL5_HUMANOSBPL5physical
26496610
SPD2B_HUMANSH3PXD2Bphysical
26496610
Drug and Disease Associations
Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
There are no disease associations of PTM sites.
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
DB08912Dabrafenib
Regulatory Network of LIMK1_HUMAN

loading...

Related Literatures of Post-Translational Modification
Phosphorylation
ReferencePubMed
"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.
"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.
"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.
"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.
"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.
"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.
"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.
"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.
"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.

TOP
© 2024 Institute of Bioinformatics and Systems Biology, NYCU | Designed by : BiOmics Laboratory