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P53668 (LIMK1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 132. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
LIM domain kinase 1

Short name=LIMK-1
EC=2.7.11.1
Alternative name(s):
KIZ-1
Gene names
Name:Limk1
Synonyms:Limk
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length647 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. axonal outgrowth and may be involved in brain development. Required for atypical chemokine receptor ACKR2-induced phosphorylation of cofilin (CFL1) By similarity. Stimulates axonal outgrowth and may be involved in brain development. Ref.6 Ref.8

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Subunit structure

Self-associates to form homodimers. Interacts with HSP90AA1; this interaction promotes LIMK1 dimerization and subsequent transphosphorylation. Interacts with CDN1C By similarity. Interacts (via LIM domain) with the cytoplasmic domain of NRG1. Interacts with NISCH and SSH1. Interacts with RLIM and RNF6. Ref.7 Ref.8 Ref.9

Subcellular location

Cytoplasm. Nucleus. Note: Predominantly found in the cytoplasm By similarity. Ref.6 Ref.8

Tissue specificity

Highest expression in the nervous system, particularly in the spinal cord and the cranial nerve and dorsal root ganglia.

Developmental stage

Expressed in ventral neural tube and axonal projections at E12.5-E13 (at protein level). Ref.8

Post-translational modification

Autophosphorylated. Phosphorylated on Thr-508 by ROCK1 and PAK1, resulting in activation. Phosphorylated by PAK4 which increases the ability of LIMK1 to phosphorylate cofilin. Phosphorylated at Ser-323 by MAPKAPK2 during activation of VEGFA-induced signaling, which results in activation of LIMK1 and promotion of actin reorganization, cell migration, and tubule formation of endothelial cells. Dephosphorylated and inactivated by SSH1. Phosphorylated by CDC42BP By similarity.

Ubiquitinated. 'Lys-48'-linked polyubiquitination by RNF6 leads to proteasomal degradation through the 26S proteasome, modulating LIMK1 levels in the growth cone and its effect on axonal outgrowth. Also polyubiquitinated by RLIM. Ref.8

Sequence similarities

Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.

Contains 2 LIM zinc-binding domains.

Contains 1 PDZ (DHR) domain.

Contains 1 protein kinase domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 647647LIM domain kinase 1
PRO_0000075804

Regions

Domain25 – 7551LIM zinc-binding 1
Domain84 – 13754LIM zinc-binding 2
Domain165 – 25894PDZ
Domain339 – 604266Protein kinase
Nucleotide binding345 – 3539ATP By similarity

Sites

Active site4601 Probable
Binding site3681ATP By similarity

Amino acid modifications

Modified residue2101Phosphoserine By similarity
Modified residue2291Phosphothreonine By similarity
Modified residue3021Phosphoserine By similarity
Modified residue3071Phosphoserine By similarity
Modified residue3101Phosphoserine By similarity
Modified residue3231Phosphoserine; by MAPKAPK2 By similarity
Modified residue3371Phosphoserine By similarity
Modified residue5081Phosphothreonine; by ROCK1 By similarity

Experimental info

Mutagenesis4601D → G: Abrogates kinase activity. Ref.6
Sequence conflict200 – 2012RV → EC in AAC52254. Ref.2
Sequence conflict269 – 2713DPS → GSQ in AAC52254. Ref.2
Sequence conflict326 – 3272VV → C in AAC52254. Ref.2
Sequence conflict5231G → P in AAC52147. Ref.5

Sequences

Sequence LengthMass (Da)Tools
P53668 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: 46E8992425A77883

FASTA64772,793
        10         20         30         40         50         60 
MRLTLLCCTW REERMGEEGS ELPVCASCGQ RIYDGQYLQA LNADWHADCF RCCECSVSLS 

        70         80         90        100        110        120 
HQYYEKDGQL FCKKDYWARY GESCHGCSEH ITKGLVMVAG ELKYHPECFI CLACGNFIGD 

       130        140        150        160        170        180 
GDTYTLVEHS KLYCGQCYYQ TVVTPVIEQI LPDSPGSHLP HTVTLVSIPA SAHGKRGLSV 

       190        200        210        220        230        240 
SIDPPHGPPG CGTEHSHTVR VQGVDPGCMS PDVKNSIHVG DRILEINGTP IRNVPLDEID 

       250        260        270        280        290        300 
LLIQETSRLL QLTLEHDPHD SLGHGPVSDP SPLSSPVHTP SGQAASSARQ KPVLRSCSID 

       310        320        330        340        350        360 
TSPGTSSLAS PASQRKDLGR SESLRVVCRP HRIFRPSDLI HGEVLGKGCF GQAIKVTHRE 

       370        380        390        400        410        420 
TGEVMVMKEL IRFDEETQRT FLKEVKVMRC LEHPNVLKFI GVLYKDKRLN FITEYIKGGT 

       430        440        450        460        470        480 
LRGIIKNMDS QYPWSQRVSF AKDIASGMAY LHSMNIIHRD LNSHNCLVRE NRNVVVADFG 

       490        500        510        520        530        540 
LARLMIDEKN QSEDLRSLKK PDRKKRYTVV GNPYWMAPEM INGRSYDEKV DVFSFGIVLC 

       550        560        570        580        590        600 
EIIGRVNADP DYLPRTMDFG LNVRGFLDRY CPPNCPPSFF PITVRCCDLD PEKRPSFVKL 

       610        620        630        640 
EQWLETLRMH LSGHLPLGPQ LEQLERGFWE TYRRGESSLP AHPEVPD 

« Hide

References

« Hide 'large scale' references
[1]"Limk1 is predominantly expressed in neural tissues and phosphorylates serine, threonine and tyrosine residues in vitro."
Proeschel C., Blouin M.J., Gutowski N.J., Ludwig R., Noble M.
Oncogene 11:1271-1281(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: C57BL/6.
[2]"The murine LIM-kinase gene (limk) encodes a novel serine threonine kinase expressed predominantly in trophoblast giant cells and the developing nervous system."
Cheng A.K., Robertson E.J.
Mech. Dev. 52:187-197(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: CD-1.
[3]"Comparative genomic sequence analysis of the Williams syndrome region (LIMK1-RFC2) of human chromosome 7q11.23."
Martindale D.W., Wilson M.D., Wang D., Burke R.D., Chen X., Duronio V., Koop B.F.
Mamm. Genome 11:890-898(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: 129/SvJ.
[4]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: 129/Sv.
[5]"Kiz-1, a protein with LIM zinc finger and kinase domains, is expressed mainly in neurons."
Bernard O., Ganiatsas S., Kannourakis G., Dringen R.
Cell Growth Differ. 5:1159-1171(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 15-647.
Strain: BALB/c.
[6]"Efficient Salmonella entry requires activity cycles of host ADF and cofilin."
Dai S., Sarmiere P.D., Wiggan O., Bamburg J.R., Zhou D.
Cell. Microbiol. 6:459-471(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-460.
[7]"Interplay between components of a novel LIM kinase-slingshot phosphatase 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) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SSH1.
[8]"The ubiquitin ligase Rnf6 regulates local LIM kinase 1 levels in axonal growth cones."
Tursun B., Schlueter A., Peters M.A., Viehweger B., Ostendorff H.P., Soosairajah J., Drung A., Bossenz M., Johnsen S.A., Schweizer M., Bernard O., Bach I.
Genes Dev. 19:2307-2319(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH RLIM AND RNF6, UBIQUITINATION BY RLIM AND RNF6, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE.
[9]"Nischarin inhibits LIM kinase to regulate cofilin phosphorylation and cell invasion."
Ding Y., Milosavljevic T., Alahari S.K.
Mol. Cell. Biol. 28:3742-3756(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NISCH.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X86569 mRNA. Translation: CAA60377.1.
U15159 mRNA. Translation: AAC52254.1.
AF139987 Genomic DNA. Translation: AAD34858.1.
AF289665 Genomic DNA. Translation: AAF99334.1.
U14166 mRNA. Translation: AAC52147.1.
PIRI48737.
RefSeqNP_034847.1. NM_010717.2.
UniGeneMm.15409.

3D structure databases

ProteinModelPortalP53668.
SMRP53668. Positions 22-145, 158-258, 304-637.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid201166. 3 interactions.
MINTMINT-247675.
STRING10090.ENSMUSP00000015137.

PTM databases

PhosphoSiteP53668.

Proteomic databases

PaxDbP53668.
PRIDEP53668.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000015137; ENSMUSP00000015137; ENSMUSG00000029674.
GeneID16885.
KEGGmmu:16885.
UCSCuc008zwt.1. mouse.

Organism-specific databases

CTD3984.
MGIMGI:104572. Limk1.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00530000063025.
HOGENOMHOG000013121.
HOVERGENHBG052328.
InParanoidP53668.
KOK05743.
OMACFRCCEC.
OrthoDBEOG73V6JQ.
TreeFamTF318014.

Enzyme and pathway databases

BRENDA2.7.11.1. 3474.

Gene expression databases

ArrayExpressP53668.
BgeeP53668.
CleanExMM_LIMK1.
GenevestigatorP53668.

Family and domain databases

Gene3D2.10.110.10. 2 hits.
InterProIPR011009. Kinase-like_dom.
IPR001478. PDZ.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR001781. Znf_LIM.
[Graphical view]
PfamPF00412. LIM. 2 hits.
PF00595. PDZ. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSPR00109. TYRKINASE.
SMARTSM00132. LIM. 2 hits.
SM00228. PDZ. 1 hit.
[Graphical view]
SUPFAMSSF50156. SSF50156. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS00478. LIM_DOMAIN_1. 2 hits.
PS50023. LIM_DOMAIN_2. 2 hits.
PS50106. PDZ. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSLIMK1. mouse.
NextBio290892.
PROP53668.
SOURCESearch...

Entry information

Entry nameLIMK1_MOUSE
AccessionPrimary (citable) accession number: P53668
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: February 19, 2014
This is version 132 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot