Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

P53668

- LIMK1_MOUSE

UniProt

P53668 - LIMK1_MOUSE

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein

LIM domain kinase 1

Gene

Limk1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.By similarity2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei368 – 3681ATPPROSITE-ProRule annotation
Active sitei460 – 4601Curated

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi345 – 3539ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. protein heterodimerization activity Source: MGI
  3. protein serine/threonine kinase activity Source: UniProtKB-KW
  4. zinc ion binding Source: InterPro

GO - Biological processi

  1. negative regulation of ubiquitin-protein transferase activity Source: Ensembl
  2. positive regulation of axon extension Source: MGI
  3. positive regulation of stress fiber assembly Source: MGI
  4. protein phosphorylation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BRENDAi2.7.11.1. 3474.
ReactomeiREACT_198374. Regulation of actin dynamics for phagocytic cup formation.

Names & Taxonomyi

Protein namesi
Recommended name:
LIM domain kinase 1 (EC:2.7.11.1)
Short name:
LIMK-1
Alternative name(s):
KIZ-1
Gene namesi
Name:Limk1
Synonyms:Limk
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 5

Organism-specific databases

MGIiMGI:104572. Limk1.

Subcellular locationi

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

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. focal adhesion Source: MGI
  3. neuron projection Source: UniProtKB
  4. nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi460 – 4601D → G: Abrogates kinase activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 647647LIM domain kinase 1PRO_0000075804Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei210 – 2101PhosphoserineBy similarity
Modified residuei229 – 2291PhosphothreonineBy similarity
Modified residuei302 – 3021PhosphoserineBy similarity
Modified residuei307 – 3071PhosphoserineBy similarity
Modified residuei310 – 3101PhosphoserineBy similarity
Modified residuei323 – 3231Phosphoserine; by MAPKAPK2By similarity
Modified residuei337 – 3371PhosphoserineBy similarity
Modified residuei508 – 5081Phosphothreonine; by ROCK1By similarity

Post-translational modificationi

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).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.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP53668.
PaxDbiP53668.
PRIDEiP53668.

PTM databases

PhosphoSiteiP53668.

Expressioni

Tissue specificityi

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

Developmental stagei

Expressed in ventral neural tube and axonal projections at E12.5-E13 (at protein level).1 Publication

Gene expression databases

BgeeiP53668.
CleanExiMM_LIMK1.
ExpressionAtlasiP53668. baseline and differential.
GenevestigatoriP53668.

Interactioni

Subunit structurei

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.By similarity3 Publications

Protein-protein interaction databases

BioGridi201166. 3 interactions.
MINTiMINT-247675.
STRINGi10090.ENSMUSP00000015137.

Structurei

3D structure databases

ProteinModelPortaliP53668.
SMRiP53668. Positions 22-145, 158-258, 303-637.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini25 – 7551LIM zinc-binding 1PROSITE-ProRule annotationAdd
BLAST
Domaini84 – 13754LIM zinc-binding 2PROSITE-ProRule annotationAdd
BLAST
Domaini165 – 25894PDZPROSITE-ProRule annotationAdd
BLAST
Domaini339 – 604266Protein kinasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 2 LIM zinc-binding domains.PROSITE-ProRule annotation
Contains 1 PDZ (DHR) domain.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

LIM domain, Repeat

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00530000063025.
HOGENOMiHOG000013121.
HOVERGENiHBG052328.
InParanoidiP53668.
KOiK05743.
OMAiCFRCCEC.
OrthoDBiEOG73V6JQ.
PhylomeDBiP53668.
TreeFamiTF318014.

Family and domain databases

Gene3Di2.10.110.10. 2 hits.
2.30.42.10. 1 hit.
InterProiIPR011009. 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]
PfamiPF00412. LIM. 2 hits.
PF00595. PDZ. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSiPR00109. TYRKINASE.
SMARTiSM00132. LIM. 2 hits.
SM00228. PDZ. 1 hit.
[Graphical view]
SUPFAMiSSF50156. SSF50156. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00478. 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]

Sequencei

Sequence statusi: Complete.

P53668-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MRLTLLCCTW REERMGEEGS ELPVCASCGQ RIYDGQYLQA LNADWHADCF
60 70 80 90 100
RCCECSVSLS HQYYEKDGQL FCKKDYWARY GESCHGCSEH ITKGLVMVAG
110 120 130 140 150
ELKYHPECFI CLACGNFIGD GDTYTLVEHS KLYCGQCYYQ TVVTPVIEQI
160 170 180 190 200
LPDSPGSHLP HTVTLVSIPA SAHGKRGLSV SIDPPHGPPG CGTEHSHTVR
210 220 230 240 250
VQGVDPGCMS PDVKNSIHVG DRILEINGTP IRNVPLDEID LLIQETSRLL
260 270 280 290 300
QLTLEHDPHD SLGHGPVSDP SPLSSPVHTP SGQAASSARQ KPVLRSCSID
310 320 330 340 350
TSPGTSSLAS PASQRKDLGR SESLRVVCRP HRIFRPSDLI HGEVLGKGCF
360 370 380 390 400
GQAIKVTHRE TGEVMVMKEL IRFDEETQRT FLKEVKVMRC LEHPNVLKFI
410 420 430 440 450
GVLYKDKRLN FITEYIKGGT LRGIIKNMDS QYPWSQRVSF AKDIASGMAY
460 470 480 490 500
LHSMNIIHRD LNSHNCLVRE NRNVVVADFG LARLMIDEKN QSEDLRSLKK
510 520 530 540 550
PDRKKRYTVV GNPYWMAPEM INGRSYDEKV DVFSFGIVLC EIIGRVNADP
560 570 580 590 600
DYLPRTMDFG LNVRGFLDRY CPPNCPPSFF PITVRCCDLD PEKRPSFVKL
610 620 630 640
EQWLETLRMH LSGHLPLGPQ LEQLERGFWE TYRRGESSLP AHPEVPD
Length:647
Mass (Da):72,793
Last modified:October 1, 1996 - v1
Checksum:i46E8992425A77883
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti200 – 2012RV → EC in AAC52254. (PubMed:8541208)Curated
Sequence conflicti269 – 2713DPS → GSQ in AAC52254. (PubMed:8541208)Curated
Sequence conflicti326 – 3272VV → C in AAC52254. (PubMed:8541208)Curated
Sequence conflicti523 – 5231G → P in AAC52147. (PubMed:7848918)Curated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS19724.1.
PIRiI48737.
RefSeqiNP_034847.1. NM_010717.2.
UniGeneiMm.15409.

Genome annotation databases

EnsembliENSMUST00000015137; ENSMUSP00000015137; ENSMUSG00000029674.
GeneIDi16885.
KEGGimmu:16885.
UCSCiuc008zwt.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS19724.1.
PIRi I48737.
RefSeqi NP_034847.1. NM_010717.2.
UniGenei Mm.15409.

3D structure databases

ProteinModelPortali P53668.
SMRi P53668. Positions 22-145, 158-258, 303-637.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 201166. 3 interactions.
MINTi MINT-247675.
STRINGi 10090.ENSMUSP00000015137.

PTM databases

PhosphoSitei P53668.

Proteomic databases

MaxQBi P53668.
PaxDbi P53668.
PRIDEi P53668.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000015137 ; ENSMUSP00000015137 ; ENSMUSG00000029674 .
GeneIDi 16885.
KEGGi mmu:16885.
UCSCi uc008zwt.1. mouse.

Organism-specific databases

CTDi 3984.
MGIi MGI:104572. Limk1.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00530000063025.
HOGENOMi HOG000013121.
HOVERGENi HBG052328.
InParanoidi P53668.
KOi K05743.
OMAi CFRCCEC.
OrthoDBi EOG73V6JQ.
PhylomeDBi P53668.
TreeFami TF318014.

Enzyme and pathway databases

BRENDAi 2.7.11.1. 3474.
Reactomei REACT_198374. Regulation of actin dynamics for phagocytic cup formation.

Miscellaneous databases

ChiTaRSi LIMK1. mouse.
NextBioi 290892.
PROi P53668.
SOURCEi Search...

Gene expression databases

Bgeei P53668.
CleanExi MM_LIMK1.
ExpressionAtlasi P53668. baseline and differential.
Genevestigatori P53668.

Family and domain databases

Gene3Di 2.10.110.10. 2 hits.
2.30.42.10. 1 hit.
InterProi IPR011009. 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 ]
Pfami PF00412. LIM. 2 hits.
PF00595. PDZ. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view ]
PRINTSi PR00109. TYRKINASE.
SMARTi SM00132. LIM. 2 hits.
SM00228. PDZ. 1 hit.
[Graphical view ]
SUPFAMi SSF50156. SSF50156. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEi 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.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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. 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.

Entry informationi

Entry nameiLIMK1_MOUSE
AccessioniPrimary (citable) accession number: P53668
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: October 29, 2014
This is version 139 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3