LIMK1_MOUSE
ID LIMK1_MOUSE Reviewed; 647 AA.
AC P53668;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=LIM domain kinase 1;
DE Short=LIMK-1;
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:P53667};
DE AltName: Full=KIZ-1;
GN Name=Limk1; Synonyms=Limk;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J;
RX PubMed=7478547;
RA Proeschel C., Blouin M.J., Gutowski N.J., Ludwig R., Noble M.;
RT "Limk1 is predominantly expressed in neural tissues and phosphorylates
RT serine, threonine and tyrosine residues in vitro.";
RL Oncogene 11:1271-1281(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=CD-1;
RX PubMed=8541208; DOI=10.1016/0925-4773(95)00400-u;
RA Cheng A.K., Robertson E.J.;
RT "The murine LIM-kinase gene (limk) encodes a novel serine threonine kinase
RT expressed predominantly in trophoblast giant cells and the developing
RT nervous system.";
RL Mech. Dev. 52:187-197(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129/SvJ;
RX PubMed=11003705; DOI=10.1007/s003350010166;
RA Martindale D.W., Wilson M.D., Wang D., Burke R.D., Chen X., Duronio V.,
RA Koop B.F.;
RT "Comparative genomic sequence analysis of the Williams syndrome region
RT (LIMK1-RFC2) of human chromosome 7q11.23.";
RL Mamm. Genome 11:890-898(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=129/Sv;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 15-647.
RC STRAIN=BALB/cJ;
RX PubMed=7848918;
RA Bernard O., Ganiatsas S., Kannourakis G., Dringen R.;
RT "Kiz-1, a protein with LIM zinc finger and kinase domains, is expressed
RT mainly in neurons.";
RL Cell Growth Differ. 5:1159-1171(1994).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ASP-460.
RX PubMed=15056216; DOI=10.1111/j.1462-5822.2004.00375.x;
RA Dai S., Sarmiere P.D., Wiggan O., Bamburg J.R., Zhou D.;
RT "Efficient Salmonella entry requires activity cycles of host ADF and
RT cofilin.";
RL Cell. Microbiol. 6:459-471(2004).
RN [7]
RP INTERACTION WITH SSH1.
RX PubMed=15660133; DOI=10.1038/sj.emboj.7600543;
RA Soosairajah J., Maiti S., Wiggan O., Sarmiere P., Moussi N., Sarcevic B.,
RA Sampath R., Bamburg J.R., Bernard O.;
RT "Interplay between components of a novel LIM kinase-slingshot phosphatase
RT complex regulates cofilin.";
RL EMBO J. 24:473-486(2005).
RN [8]
RP FUNCTION, INTERACTION WITH RLIM AND RNF6, UBIQUITINATION BY RLIM AND RNF6,
RP SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=16204183; DOI=10.1101/gad.1340605;
RA Tursun B., Schlueter A., Peters M.A., Viehweger B., Ostendorff H.P.,
RA Soosairajah J., Drung A., Bossenz M., Johnsen S.A., Schweizer M.,
RA Bernard O., Bach I.;
RT "The ubiquitin ligase Rnf6 regulates local LIM kinase 1 levels in axonal
RT growth cones.";
RL Genes Dev. 19:2307-2319(2005).
RN [9]
RP INTERACTION WITH NISCH.
RX PubMed=18332102; DOI=10.1128/mcb.01832-07;
RA Ding Y., Milosavljevic T., Alahari S.K.;
RT "Nischarin inhibits LIM kinase to regulate cofilin phosphorylation and cell
RT invasion.";
RL Mol. Cell. Biol. 28:3742-3756(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-210; SER-298 AND SER-310, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [11]
RP INTERACTION WITH CDC42BPA; CDC42BPB AND FAM89B, SUBCELLULAR LOCATION, AND
RP PHOSPHORYLATION AT THR-508.
RC TISSUE=Brain;
RX PubMed=25107909; DOI=10.1074/jbc.m114.588079;
RA Lee I.C., Leung T., Tan I.;
RT "Adaptor protein LRAP25 mediates myotonic dystrophy kinase-related Cdc42-
RT binding kinase (MRCK) regulation of LIMK1 protein in lamellipodial F-actin
RT dynamics.";
RL J. Biol. Chem. 289:26989-27003(2014).
CC -!- FUNCTION: Serine/threonine-protein kinase that plays an essential role
CC in the regulation of actin filament dynamics (PubMed:15056216,
CC PubMed:16204183). Acts downstream of several Rho family GTPase signal
CC transduction pathways (PubMed:15056216). Activated by upstream kinases
CC including ROCK1, PAK1 and PAK4, which phosphorylate LIMK1 on a
CC threonine residue located in its activation loop. LIMK1 subsequently
CC phosphorylates and inactivates the actin binding/depolymerizing factors
CC cofilin-1/CFL1, cofilin-2/CFL2 and destrin/DSTN, thereby preventing the
CC cleavage of filamentous actin (F-actin), and stabilizing the actin
CC cytoskeleton. In this way LIMK1 regulates several actin-dependent
CC biological processes including cell motility, cell cycle progression,
CC and differentiation. Phosphorylates TPPP on serine residues, thereby
CC promoting microtubule disassembly. Stimulates axonal outgrowth and may
CC be involved in brain development (By similarity).
CC {ECO:0000250|UniProtKB:P53667, ECO:0000269|PubMed:15056216,
CC ECO:0000269|PubMed:16204183}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000250|UniProtKB:P53667};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990;
CC Evidence={ECO:0000250|UniProtKB:P53667};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:P53667};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46609;
CC Evidence={ECO:0000250|UniProtKB:P53667};
CC -!- SUBUNIT: Self-associates to form homodimers. Interacts with HSP90AA1;
CC this interaction promotes LIMK1 dimerization and subsequent
CC transphosphorylation. Interacts with CDKN1C (By similarity). Interacts
CC (via LIM domain) with the cytoplasmic domain of NRG1 (By similarity).
CC Interacts with NISCH (PubMed:18332102). Interacts with SSH1
CC (PubMed:15660133). Interacts with RLIM and RNF6 (PubMed:16204183).
CC Interacts (via LIM zinc-binding domains) with FAM89B/LRAP25 (via LRR
CC repeat). Forms a tripartite complex with CDC42BPA, CDC42BPB and
CC FAM89B/LRAP25 (PubMed:25107909). {ECO:0000250|UniProtKB:P53667,
CC ECO:0000269|PubMed:15660133, ECO:0000269|PubMed:16204183,
CC ECO:0000269|PubMed:18332102, ECO:0000269|PubMed:25107909}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16204183}. Nucleus
CC {ECO:0000250|UniProtKB:P53667}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:P53667}. Cell projection, lamellipodium
CC {ECO:0000269|PubMed:25107909}. Note=Predominantly found in the
CC cytoplasm (By similarity). Localizes in the lamellipodium in a
CC CDC42BPA, CDC42BPB and FAM89B/LRAP25-dependent manner.
CC {ECO:0000269|PubMed:25107909}.
CC -!- TISSUE SPECIFICITY: Highest expression in the nervous system,
CC particularly in the spinal cord and the cranial nerve and dorsal root
CC ganglia.
CC -!- DEVELOPMENTAL STAGE: Expressed in ventral neural tube and axonal
CC projections at 12.5 dpc-13 dpc (at protein level).
CC {ECO:0000269|PubMed:16204183}.
CC -!- PTM: Autophosphorylated. Phosphorylated on Thr-508 by ROCK1 and PAK1,
CC resulting in activation. Phosphorylated by PAK4 which increases the
CC ability of LIMK1 to phosphorylate cofilin. Phosphorylated at Ser-323 by
CC MAPKAPK2 during activation of VEGFA-induced signaling, which results in
CC activation of LIMK1 and promotion of actin reorganization, cell
CC migration, and tubule formation of endothelial cells. Dephosphorylated
CC and inactivated by SSH1. Phosphorylated by CDC42BP (By similarity).
CC {ECO:0000250|UniProtKB:P53667}.
CC -!- PTM: Ubiquitinated. 'Lys-48'-linked polyubiquitination by RNF6 leads to
CC proteasomal degradation through the 26S proteasome, modulating LIMK1
CC levels in the growth cone and its effect on axonal outgrowth. Also
CC polyubiquitinated by RLIM. {ECO:0000269|PubMed:16204183}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
CC protein kinase family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X86569; CAA60377.1; -; mRNA.
DR EMBL; U15159; AAC52254.1; -; mRNA.
DR EMBL; AF139987; AAD34858.1; -; Genomic_DNA.
DR EMBL; AF289665; AAF99334.1; -; Genomic_DNA.
DR EMBL; U14166; AAC52147.1; -; mRNA.
DR CCDS; CCDS19724.1; -.
DR PIR; I48737; I48737.
DR RefSeq; NP_034847.1; NM_010717.3.
DR AlphaFoldDB; P53668; -.
DR SMR; P53668; -.
DR BioGRID; 201166; 6.
DR MINT; P53668; -.
DR STRING; 10090.ENSMUSP00000015137; -.
DR iPTMnet; P53668; -.
DR PhosphoSitePlus; P53668; -.
DR SwissPalm; P53668; -.
DR jPOST; P53668; -.
DR MaxQB; P53668; -.
DR PaxDb; P53668; -.
DR PRIDE; P53668; -.
DR ProteomicsDB; 292259; -.
DR Antibodypedia; 14576; 1025 antibodies from 42 providers.
DR DNASU; 16885; -.
DR Ensembl; ENSMUST00000015137; ENSMUSP00000015137; ENSMUSG00000029674.
DR GeneID; 16885; -.
DR KEGG; mmu:16885; -.
DR UCSC; uc008zwt.1; mouse.
DR CTD; 3984; -.
DR MGI; MGI:104572; Limk1.
DR VEuPathDB; HostDB:ENSMUSG00000029674; -.
DR eggNOG; KOG1187; Eukaryota.
DR GeneTree; ENSGT00940000156345; -.
DR HOGENOM; CLU_000288_7_23_1; -.
DR InParanoid; P53668; -.
DR OMA; FDGQYLQ; -.
DR OrthoDB; 988822at2759; -.
DR PhylomeDB; P53668; -.
DR TreeFam; TF318014; -.
DR BRENDA; 2.7.11.1; 3474.
DR Reactome; R-MMU-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-MMU-399954; Sema3A PAK dependent Axon repulsion.
DR Reactome; R-MMU-5627123; RHO GTPases activate PAKs.
DR BioGRID-ORCS; 16885; 3 hits in 63 CRISPR screens.
DR ChiTaRS; Limk1; mouse.
DR PRO; PR:P53668; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; P53668; protein.
DR Bgee; ENSMUSG00000029674; Expressed in motor neuron and 237 other tissues.
DR ExpressionAtlas; P53668; baseline and differential.
DR Genevisible; P53668; MM.
DR GO; GO:0044295; C:axonal growth cone; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005925; C:focal adhesion; IDA:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0001673; C:male germ cell nucleus; IDA:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0043005; C:neuron projection; IDA:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0031072; F:heat shock protein binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0030036; P:actin cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0048675; P:axon extension; IGI:MGI.
DR GO; GO:0051444; P:negative regulation of ubiquitin-protein transferase activity; ISO:MGI.
DR GO; GO:0032233; P:positive regulation of actin filament bundle assembly; ISO:MGI.
DR GO; GO:0045773; P:positive regulation of axon extension; IGI:MGI.
DR GO; GO:0051496; P:positive regulation of stress fiber assembly; IGI:MGI.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0043149; P:stress fiber assembly; IGI:MGI.
DR Gene3D; 2.30.42.10; -; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR036034; PDZ_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR001781; Znf_LIM.
DR Pfam; PF00412; LIM; 2.
DR Pfam; PF00595; PDZ; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00132; LIM; 2.
DR SMART; SM00228; PDZ; 1.
DR SUPFAM; SSF50156; SSF50156; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00478; LIM_DOMAIN_1; 2.
DR PROSITE; PS50023; LIM_DOMAIN_2; 2.
DR PROSITE; PS50106; PDZ; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell projection; Cytoplasm; Cytoskeleton; Kinase; LIM domain;
KW Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase;
KW Ubl conjugation; Zinc.
FT CHAIN 1..647
FT /note="LIM domain kinase 1"
FT /id="PRO_0000075804"
FT DOMAIN 25..75
FT /note="LIM zinc-binding 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DOMAIN 84..137
FT /note="LIM zinc-binding 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DOMAIN 165..258
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 339..604
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 256..319
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 272..317
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 460
FT /evidence="ECO:0000305"
FT BINDING 345..353
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 368
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 210
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 229
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P53667"
FT MOD_RES 298
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 302
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P53667"
FT MOD_RES 307
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P53667"
FT MOD_RES 310
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 323
FT /note="Phosphoserine; by MAPKAPK2"
FT /evidence="ECO:0000250|UniProtKB:P53667"
FT MOD_RES 337
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P53667"
FT MOD_RES 508
FT /note="Phosphothreonine; by ROCK1"
FT /evidence="ECO:0000269|PubMed:25107909"
FT MUTAGEN 460
FT /note="D->G: Abrogates kinase activity."
FT /evidence="ECO:0000269|PubMed:15056216"
FT CONFLICT 200..201
FT /note="RV -> EC (in Ref. 2; AAC52254)"
FT /evidence="ECO:0000305"
FT CONFLICT 269..271
FT /note="DPS -> GSQ (in Ref. 2; AAC52254)"
FT /evidence="ECO:0000305"
FT CONFLICT 326..327
FT /note="VV -> C (in Ref. 2; AAC52254)"
FT /evidence="ECO:0000305"
FT CONFLICT 523
FT /note="G -> P (in Ref. 5; AAC52147)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 647 AA; 72793 MW; 46E8992425A77883 CRC64;
MRLTLLCCTW REERMGEEGS ELPVCASCGQ RIYDGQYLQA LNADWHADCF RCCECSVSLS
HQYYEKDGQL FCKKDYWARY GESCHGCSEH ITKGLVMVAG ELKYHPECFI CLACGNFIGD
GDTYTLVEHS KLYCGQCYYQ TVVTPVIEQI LPDSPGSHLP HTVTLVSIPA SAHGKRGLSV
SIDPPHGPPG CGTEHSHTVR VQGVDPGCMS PDVKNSIHVG DRILEINGTP IRNVPLDEID
LLIQETSRLL QLTLEHDPHD SLGHGPVSDP SPLSSPVHTP SGQAASSARQ KPVLRSCSID
TSPGTSSLAS PASQRKDLGR SESLRVVCRP HRIFRPSDLI HGEVLGKGCF GQAIKVTHRE
TGEVMVMKEL IRFDEETQRT FLKEVKVMRC LEHPNVLKFI GVLYKDKRLN FITEYIKGGT
LRGIIKNMDS QYPWSQRVSF AKDIASGMAY LHSMNIIHRD LNSHNCLVRE NRNVVVADFG
LARLMIDEKN QSEDLRSLKK PDRKKRYTVV GNPYWMAPEM INGRSYDEKV DVFSFGIVLC
EIIGRVNADP DYLPRTMDFG LNVRGFLDRY CPPNCPPSFF PITVRCCDLD PEKRPSFVKL
EQWLETLRMH LSGHLPLGPQ LEQLERGFWE TYRRGESSLP AHPEVPD
