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Protein

LIM domain kinase 1

Gene

Limk1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: 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. Stimulates axonal outgrowth and may be involved in brain development. Required for atypical chemokine receptor ACKR2-induced phosphorylation of cofilin (CFL1) (By similarity).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei368ATPPROSITE-ProRule annotation1
Active sitei460By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi345 – 353ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

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. 5301.

Names & Taxonomyi

Protein namesi
Recommended name:
LIM domain kinase 1 (EC:2.7.11.1)
Short name:
LIMK-1
Gene namesi
Name:Limk1
Synonyms:Limk
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi62055. Limk1.

Subcellular locationi

GO - Cellular componenti

  • axonal growth cone Source: RGD
  • cytoplasm Source: UniProtKB
  • Golgi apparatus Source: RGD
  • neuron projection Source: UniProtKB
  • nucleus Source: RGD
  • perinuclear region of cytoplasm Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3407314.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000758051 – 647LIM domain kinase 1Add BLAST647

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei210PhosphoserineBy similarity1
Modified residuei229PhosphothreonineBy similarity1
Modified residuei298PhosphoserineBy similarity1
Modified residuei302PhosphoserineBy similarity1
Modified residuei307PhosphoserineBy similarity1
Modified residuei310PhosphoserineBy similarity1
Modified residuei323Phosphoserine; by MAPKAPK2By similarity1
Modified residuei337PhosphoserineBy similarity1
Modified residuei508Phosphothreonine; by ROCK1 and PAK1By similarity1

Post-translational modificationi

Autophosphorylated (By similarity). 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 (By similarity).By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP53669.

PTM databases

iPTMnetiP53669.
PhosphoSitePlusiP53669.

Interactioni

Subunit structurei

Interacts (via LIM domain) with the cytoplasmic domain of NRG1. Interacts with NISCH. Interacts with RLIM and RNF6. Self-associates to form homodimers. Interacts with HSP90AA1; this interaction promotes LIMK1 dimerization and subsequent transphosphorylation. Interacts with CDN1C. Interacts with SSH1. Interacts with ROCK1 (By similarity).By similarity

Protein-protein interaction databases

IntActiP53669. 1 interactor.
STRINGi10116.ENSRNOP00000001996.

Chemistry databases

BindingDBiP53669.

Structurei

3D structure databases

ProteinModelPortaliP53669.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini25 – 75LIM zinc-binding 1PROSITE-ProRule annotationAdd BLAST51
Domaini84 – 137LIM zinc-binding 2PROSITE-ProRule annotationAdd BLAST54
Domaini165 – 258PDZPROSITE-ProRule annotationAdd BLAST94
Domaini339 – 604Protein kinasePROSITE-ProRule annotationAdd BLAST266

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

eggNOGiENOG410IEZ9. Eukaryota.
COG0515. LUCA.
HOGENOMiHOG000013121.
HOVERGENiHBG052328.
InParanoidiP53669.
PhylomeDBiP53669.

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.

P53669-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRLTLLCCTW REERMGEEGS ELPVCASCSQ SIYDGQYLQA LNADWHADCF
60 70 80 90 100
RCCECSTSLS HQYYEKDGQL FCKKDYWARY GESCHGCSEH ITKGLVMVGG
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 PDVKNSIHIG DRILEINGTP IRNVPLDEID LLIQETSRLL
260 270 280 290 300
QLTLEHDPHD SLGHGPVSDP SPLASPVHTP SGQAGSSARQ KPVLRSCSID
310 320 330 340 350
TSPGAGSLVS PASQRKDLGR SESLRVVCRP HRIFRPSDLI HGEVLGKGCF
360 370 380 390 400
GQAIKVTHRE TGEVMVMKEL IRFDEETQRT FLKEVKVMRC LEHPNVLKFI
410 420 430 440 450
GVLYKDKRLN FITEYIKGGT LRGIIKSMDS QYPWSQRVSF AKDIASGMAY
460 470 480 490 500
LHSMNIIHRD LNSHNCLVRE NRNVVVADFG LARLMIDEKG 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 LAGHLPLGPQ LEQLERGFWE TYRRGESSLP AHPEVPD
Length:647
Mass (Da):72,594
Last modified:October 1, 1996 - v1
Checksum:i51099F87703BB051
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D31873 mRNA. Translation: BAA06672.1.
PIRiI58353.
UniGeneiRn.11250.

Genome annotation databases

UCSCiRGD:62055. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D31873 mRNA. Translation: BAA06672.1.
PIRiI58353.
UniGeneiRn.11250.

3D structure databases

ProteinModelPortaliP53669.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP53669. 1 interactor.
STRINGi10116.ENSRNOP00000001996.

Chemistry databases

BindingDBiP53669.
ChEMBLiCHEMBL3407314.

PTM databases

iPTMnetiP53669.
PhosphoSitePlusiP53669.

Proteomic databases

PaxDbiP53669.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

UCSCiRGD:62055. rat.

Organism-specific databases

RGDi62055. Limk1.

Phylogenomic databases

eggNOGiENOG410IEZ9. Eukaryota.
COG0515. LUCA.
HOGENOMiHOG000013121.
HOVERGENiHBG052328.
InParanoidiP53669.
PhylomeDBiP53669.

Enzyme and pathway databases

BRENDAi2.7.11.1. 5301.

Miscellaneous databases

PROiP53669.

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]
ProtoNetiSearch...

Entry informationi

Entry nameiLIMK1_RAT
AccessioniPrimary (citable) accession number: P53669
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 2, 2016
This is version 140 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. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.