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P53668

- LIMK1_MOUSE

UniProt

P53668 - LIMK1_MOUSE

Protein

LIM domain kinase 1

Gene

Limk1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 138 (01 Oct 2014)
      Sequence version 1 (01 Oct 1996)
      Previous versions | rss
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    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 binding Source: UniProtKB
    3. protein heterodimerization activity Source: MGI
    4. protein serine/threonine kinase activity Source: UniProtKB-KW
    5. 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

    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

    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.
    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, 304-637.
    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

    MRLTLLCCTW REERMGEEGS ELPVCASCGQ RIYDGQYLQA LNADWHADCF    50
    RCCECSVSLS HQYYEKDGQL FCKKDYWARY GESCHGCSEH ITKGLVMVAG 100
    ELKYHPECFI CLACGNFIGD GDTYTLVEHS KLYCGQCYYQ TVVTPVIEQI 150
    LPDSPGSHLP HTVTLVSIPA SAHGKRGLSV SIDPPHGPPG CGTEHSHTVR 200
    VQGVDPGCMS PDVKNSIHVG DRILEINGTP IRNVPLDEID LLIQETSRLL 250
    QLTLEHDPHD SLGHGPVSDP SPLSSPVHTP SGQAASSARQ KPVLRSCSID 300
    TSPGTSSLAS PASQRKDLGR SESLRVVCRP HRIFRPSDLI HGEVLGKGCF 350
    GQAIKVTHRE TGEVMVMKEL IRFDEETQRT FLKEVKVMRC LEHPNVLKFI 400
    GVLYKDKRLN FITEYIKGGT LRGIIKNMDS QYPWSQRVSF AKDIASGMAY 450
    LHSMNIIHRD LNSHNCLVRE NRNVVVADFG LARLMIDEKN QSEDLRSLKK 500
    PDRKKRYTVV GNPYWMAPEM INGRSYDEKV DVFSFGIVLC EIIGRVNADP 550
    DYLPRTMDFG LNVRGFLDRY CPPNCPPSFF PITVRCCDLD PEKRPSFVKL 600
    EQWLETLRMH LSGHLPLGPQ LEQLERGFWE TYRRGESSLP AHPEVPD 647
    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, 304-637.
    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.
    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

    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 1, 2014
    This is version 138 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