LIM domain kinase 1 - Mus musculus (Mouse)

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P53668 (LIMK1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 124. History...

Clusters with 100%, 90%, 50% identity |

Documents (3) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	647 AA.
Sequence status	Complete.
Protein existence	Evidence 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. 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.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Domain	LIM domain Repeat
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of ubiquitin-protein ligase activity Inferred from electronic annotation. Source: Compara positive regulation of actin filament bundle assembly Inferred from electronic annotation. Source: Compara positive regulation of axon extension Inferred from genetic interaction Ref.8. Source: MGI
Cellular_component	cytoplasm Inferred from direct assay Ref.8. Source: UniProtKB focal adhesion Inferred from direct assay PubMed 15023529 PubMed 16399995. Source: MGI neuron projection Inferred from direct assay Ref.8. Source: UniProtKB nucleus Inferred from direct assay PubMed 15023529 PubMed 16399995. Source: MGI
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 647

647

LIM domain kinase 1

PRO_0000075804

Regions

Domain

25 – 75

LIM zinc-binding 1

Domain

84 – 137

LIM zinc-binding 2

Domain

165 – 258

PDZ

Domain

339 – 604

266

Protein kinase

Nucleotide binding

345 – 353

ATP By similarity

Sites

Active site

460

Probable

Binding site

368

ATP By similarity

Amino acid modifications

Modified residue

210

Phosphoserine By similarity

Modified residue

229

Phosphothreonine By similarity

Modified residue

302

Phosphoserine By similarity

Modified residue

307

Phosphoserine By similarity

Modified residue

310

Phosphoserine By similarity

Modified residue

323

Phosphoserine; by MAPKAPK2 By similarity

Modified residue

337

Phosphoserine By similarity

Modified residue

508

Phosphothreonine; by ROCK1 By similarity

Experimental info

Mutagenesis

460

D → G: Abrogates kinase activity. Ref.6

Sequence conflict

200 – 201

RV → EC in AAC52254. Ref.2

Sequence conflict

269 – 271

DPS → GSQ in AAC52254. Ref.2

Sequence conflict

326 – 327

VV → C in AAC52254. Ref.2

Sequence conflict

523

G → P in AAC52147. Ref.5

Sequences

Sequence

Length

Mass (Da)

Tools

P53668 [UniParc].

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

647

72,793

        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' referencesShow '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. 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.
IPI	IPI00133642.
PIR	I48737.
RefSeq	NP_034847.1. NM_010717.2.
UniGene	Mm.15409.
3D structure databases
ProteinModelPortal	P53668.
SMR	P53668. Positions 25-145, 158-258, 304-637.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-247675.
STRING	10090.ENSMUSP00000015137.
PTM databases
PhosphoSite	P53668.
Proteomic databases
PaxDb	P53668.
PRIDE	P53668.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000015137; ENSMUSP00000015137; ENSMUSG00000029674.
GeneID	16885.
KEGG	mmu:16885.
UCSC	uc008zwt.1. mouse.
Organism-specific databases
CTD	3984.
MGI	MGI:104572. Limk1.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00530000063025.
HOGENOM	HOG000013121.
HOVERGEN	HBG052328.
InParanoid	P53668.
KO	K05743.
OMA	CFRCCEC.
OrthoDB	EOG41C6VP.
Enzyme and pathway databases
BRENDA	2.7.11.1. 3474.
Gene expression databases
ArrayExpress	P53668.
Bgee	P53668.
CleanEx	MM_LIMK1.
Genevestigator	P53668.
GermOnline	ENSMUSG00000029674. Mus musculus.
Family and domain databases
Gene3D	2.10.110.10. 2 hits.
InterPro	IPR011009. Kinase-like_dom. IPR001478. PDZ. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR001245. Ser-Thr/Tyr_kinase_cat_dom. IPR001781. Znf_LIM. [Graphical view]
Pfam	PF00412. LIM. 2 hits. PF00595. PDZ. 1 hit. PF07714. Pkinase_Tyr. 1 hit. [Graphical view]
PRINTS	PR00109. TYRKINASE.
SMART	SM00132. LIM. 2 hits. SM00228. PDZ. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit. SSF50156. PDZ. 1 hit.
PROSITE	PS00478. 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. PS00108. PROTEIN_KINASE_ST. False negative. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	LIMK1. mouse.
NextBio	290892.
SOURCE	Search...

Entry information

Entry name

LIMK1_MOUSE

Accession

Primary (citable) accession number: P53668

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	May 1, 2013
This is version 124 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

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

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents