LIMK1_RAT
ID LIMK1_RAT Reviewed; 647 AA.
AC P53669;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=LIM domain kinase 1;
DE Short=LIMK-1;
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:P53667};
GN Name=Limk1; Synonyms=Limk;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar; TISSUE=Brain;
RX PubMed=7651734;
RA Nunoue K., Ohashi K., Okano I., Mizuno K.;
RT "LIMK-1 and LIMK-2, two members of a LIM motif-containing protein kinase
RT family.";
RL Oncogene 11:701-710(1995).
RN [2]
RP INTERACTION WITH NRG1.
RX PubMed=9685409; DOI=10.1074/jbc.273.32.20525;
RA Wang J.Y., Frenzel K.E., Wen D., Falls D.L.;
RT "Transmembrane neuregulins interact with LIM kinase 1, a cytoplasmic
RT protein kinase implicated in development of visuospatial cognition.";
RL J. Biol. Chem. 273:20525-20534(1998).
RN [3]
RP SUBCELLULAR LOCATION.
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 [4]
RP INTERACTION WITH RLIM AND RNF6.
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).
CC -!- FUNCTION: Serine/threonine-protein kinase that plays an essential role
CC in the regulation of actin filament dynamics. Acts downstream of
CC several Rho family GTPase signal transduction pathways. Activated by
CC upstream kinases including ROCK1, PAK1 and PAK4, which phosphorylate
CC LIMK1 on a threonine residue located in its activation loop. LIMK1
CC subsequently phosphorylates and inactivates the actin
CC binding/depolymerizing factors cofilin-1/CFL1, cofilin-2/CFL2 and
CC destrin/DSTN, thereby preventing the cleavage of filamentous actin (F-
CC actin), and stabilizing the actin cytoskeleton. In this way LIMK1
CC regulates several actin-dependent biological processes including cell
CC motility, cell cycle progression, and differentiation. Phosphorylates
CC TPPP on serine residues, thereby promoting microtubule disassembly.
CC Stimulates axonal outgrowth and may be involved in brain development.
CC {ECO:0000250|UniProtKB:P53667}.
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: Interacts (via LIM domain) with the cytoplasmic domain of NRG1
CC (PubMed:9685409). Interacts with NISCH. Interacts with RLIM and RNF6.
CC Self-associates to form homodimers. Interacts with HSP90AA1; this
CC interaction promotes LIMK1 dimerization and subsequent
CC transphosphorylation. Interacts with CDKN1C. Interacts with SSH1.
CC Interacts with ROCK1. Interacts (via LIM zinc-binding domains) with
CC FAM89B/LRAP25 (via LRR repeat). Forms a tripartite complex with
CC CDC42BPA, CDC42BPB and FAM89B/LRAP25 (By similarity).
CC {ECO:0000250|UniProtKB:P53667, ECO:0000250|UniProtKB:P53668,
CC ECO:0000269|PubMed:9685409}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15660133}. Nucleus
CC {ECO:0000269|PubMed:15660133}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:P53667}. Cell projection, lamellipodium
CC {ECO:0000250|UniProtKB:P53668}. Note=Predominantly found in the
CC cytoplasm. Localizes in the lamellipodium in a CDC42BPA, CDC42BPB and
CC FAM89B/LRAP25-dependent manner. {ECO:0000250|UniProtKB:P53667,
CC ECO:0000250|UniProtKB:P53668}.
CC -!- PTM: Autophosphorylated (By similarity). Phosphorylated on Thr-508 by
CC ROCK1 and PAK1, resulting in activation. Phosphorylated by PAK4 which
CC increases the ability of LIMK1 to phosphorylate cofilin. Phosphorylated
CC at Ser-323 by MAPKAPK2 during activation of VEGFA-induced signaling,
CC which results in activation of LIMK1 and promotion of actin
CC reorganization, cell migration, and tubule formation of endothelial
CC cells. Dephosphorylated and inactivated by SSH1. Phosphorylated by
CC CDC42BP (By similarity). {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 (By similarity).
CC {ECO:0000250|UniProtKB:P53668}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
CC protein kinase family. {ECO:0000305}.
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DR EMBL; D31873; BAA06672.1; -; mRNA.
DR PIR; I58353; I58353.
DR AlphaFoldDB; P53669; -.
DR SMR; P53669; -.
DR IntAct; P53669; 1.
DR STRING; 10116.ENSRNOP00000001996; -.
DR BindingDB; P53669; -.
DR ChEMBL; CHEMBL3407314; -.
DR iPTMnet; P53669; -.
DR PhosphoSitePlus; P53669; -.
DR PaxDb; P53669; -.
DR UCSC; RGD:62055; rat.
DR RGD; 62055; Limk1.
DR eggNOG; KOG1187; Eukaryota.
DR InParanoid; P53669; -.
DR PhylomeDB; P53669; -.
DR BRENDA; 2.7.11.1; 5301.
DR Reactome; R-RNO-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-RNO-399954; Sema3A PAK dependent Axon repulsion.
DR Reactome; R-RNO-5627123; RHO GTPases activate PAKs.
DR PRO; PR:P53669; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0044295; C:axonal growth cone; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005925; C:focal adhesion; ISO:RGD.
DR GO; GO:0005794; C:Golgi apparatus; IDA:RGD.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0043005; C:neuron projection; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0031072; F:heat shock protein binding; ISO:RGD.
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:0051444; P:negative regulation of ubiquitin-protein transferase activity; ISO:RGD.
DR GO; GO:0032233; P:positive regulation of actin filament bundle assembly; ISO:RGD.
DR GO; GO:0045773; P:positive regulation of axon extension; ISS:UniProtKB.
DR GO; GO:0051496; P:positive regulation of stress fiber assembly; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
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_0000075805"
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..316
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 274..316
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 460
FT /evidence="ECO:0000250"
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:0000250|UniProtKB:P53667"
FT MOD_RES 229
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P53667"
FT MOD_RES 298
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P53667"
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:0000250|UniProtKB:P53667"
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 and PAK1"
FT /evidence="ECO:0000250|UniProtKB:P53667"
SQ SEQUENCE 647 AA; 72594 MW; 51099F87703BB051 CRC64;
MRLTLLCCTW REERMGEEGS ELPVCASCSQ SIYDGQYLQA LNADWHADCF RCCECSTSLS
HQYYEKDGQL FCKKDYWARY GESCHGCSEH ITKGLVMVGG ELKYHPECFI CLACGNFIGD
GDTYTLVEHS KLYCGQCYYQ TVVTPVIEQI LPDSPGSHLP HTVTLVSIPA SAHGKRGLSV
SIDPPHGPPG CGTEHSHTVR VQGVDPGCMS PDVKNSIHIG DRILEINGTP IRNVPLDEID
LLIQETSRLL QLTLEHDPHD SLGHGPVSDP SPLASPVHTP SGQAGSSARQ KPVLRSCSID
TSPGAGSLVS PASQRKDLGR SESLRVVCRP HRIFRPSDLI HGEVLGKGCF GQAIKVTHRE
TGEVMVMKEL IRFDEETQRT FLKEVKVMRC LEHPNVLKFI GVLYKDKRLN FITEYIKGGT
LRGIIKSMDS QYPWSQRVSF AKDIASGMAY LHSMNIIHRD LNSHNCLVRE NRNVVVADFG
LARLMIDEKG QSEDLRSLKK PDRKKRYTVV GNPYWMAPEM INGRSYDEKV DVFSFGIVLC
EIIGRVNADP DYLPRTMDFG LNVRGFLDRY CPPNCPPSFF PITVRCCDLD PEKRPSFVKL
EQWLETLRMH LAGHLPLGPQ LEQLERGFWE TYRRGESSLP AHPEVPD
