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UniProtKB - P53667 (LIMK1_HUMAN)

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Protein

LIM domain kinase 1

Gene

LIMK1

Organism
Homo sapiens (Human)
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. Isoform 3 has a dominant negative effect on actin cytoskeletal changes. Required for atypical chemokine receptor ACKR2-induced phosphorylation of cofilin (CFL1).8 Publications

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

Complete GO annotation...

GO - Biological processi

  • actin cytoskeleton organization Source: ProtInc
  • Fc-gamma receptor signaling pathway involved in phagocytosis Source: Reactome
  • negative regulation of ubiquitin-protein transferase activity Source: BHF-UCL
  • nervous system development Source: ProtInc
  • positive regulation of actin filament bundle assembly Source: BHF-UCL
  • positive regulation of axon extension Source: UniProtKB
  • positive regulation of stress fiber assembly Source: GO_Central
  • protein phosphorylation Source: BHF-UCL
  • Rho protein signal transduction Source: ProtInc
  • signal transduction Source: ProtInc
Complete GO annotation...

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BRENDAi2.7.11.1. 2681.
ReactomeiR-HSA-2029482. Regulation of actin dynamics for phagocytic cup formation.
R-HSA-3928662. EPHB-mediated forward signaling.
R-HSA-399954. Sema3A PAK dependent Axon repulsion.
R-HSA-416572. Sema4D induced cell migration and growth-cone collapse.
R-HSA-5627117. RHO GTPases Activate ROCKs.
R-HSA-5627123. RHO GTPases activate PAKs.
SignaLinkiP53667.
SIGNORiP53667.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:6613. LIMK1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: BHF-UCL
  • cytosol Source: HPA
  • focal adhesion Source: Ensembl
  • Golgi apparatus Source: GO_Central
  • membrane Source: Ensembl
  • neuron projection Source: UniProtKB
  • nuclear speck Source: HPA
  • nucleus Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

LIMK1 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region.

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi84C → S: Enhances actin aggregation. 1 Publication1
Mutagenesisi177 – 178GL → EA: Enhances actin aggregation. 1 Publication2
Mutagenesisi460D → N: Abrogates kinase activity. 1 Publication1
Mutagenesisi496 – 506Missing : Reduces actin aggregation. 1 PublicationAdd BLAST11
Mutagenesisi503 – 505RKK → GAA: Abolishes kinase activity. 1 Publication3
Mutagenesisi508T → A: Abolishes activation by ROCK1. 2 Publications1
Mutagenesisi508T → EE: Enhances kinase activity. 2 Publications1
Mutagenesisi508T → V or E: Reduces kinase activity. 2 Publications1

Keywords - Diseasei

Williams-Beuren syndrome

Organism-specific databases

DisGeNETi3984.
MalaCardsiLIMK1.
OpenTargetsiENSG00000106683.
Orphaneti904. Williams syndrome.
PharmGKBiPA30386.

Chemistry databases

ChEMBLiCHEMBL3836.
DrugBankiDB08912. Dabrafenib.
GuidetoPHARMACOLOGYi2054.

Polymorphism and mutation databases

BioMutaiLIMK1.
DMDMi90185240.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000758031 – 647LIM domain kinase 1Add BLAST647

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei210PhosphoserineCombined sources1
Modified residuei229PhosphothreonineCombined sources1
Modified residuei298PhosphoserineCombined sources1
Modified residuei302PhosphoserineCombined sources1
Modified residuei307PhosphoserineCombined sources1
Modified residuei310PhosphoserineCombined sources1
Modified residuei323Phosphoserine; by MAPKAPK21 Publication1
Modified residuei337PhosphoserineCombined sources1
Modified residuei508Phosphothreonine; by ROCK1 and PAK14 Publications1

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 similarity7 Publications
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

EPDiP53667.
MaxQBiP53667.
PaxDbiP53667.
PeptideAtlasiP53667.
PRIDEiP53667.

PTM databases

iPTMnetiP53667.
PhosphoSitePlusiP53667.
SwissPalmiP53667.

Expressioni

Tissue specificityi

Highest expression in both adult and fetal nervous system. Detected ubiquitously throughout the different regions of adult brain, with highest levels in the cerebral cortex. Expressed to a lesser extent in heart and skeletal muscle.

Gene expression databases

BgeeiENSG00000106683.
CleanExiHS_LIMK1.
ExpressionAtlasiP53667. baseline and differential.
GenevisibleiP53667. HS.

Organism-specific databases

HPAiHPA028064.
HPA028516.

Interactioni

Subunit structurei

Interacts (via LIM domain) with the cytoplasmic domain of NRG1 (By similarity). Interacts with NISCH (By similarity). Interacts with RLIM and RNF6 (By similarity). 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 similarity5 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • heat shock protein binding Source: BHF-UCL
  • protein heterodimerization activity Source: Ensembl
Complete GO annotation...

Protein-protein interaction databases

BioGridi110172. 40 interactors.
DIPiDIP-31605N.
IntActiP53667. 37 interactors.
MINTiMINT-2833166.
STRINGi9606.ENSP00000336740.

Chemistry databases

BindingDBiP53667.

Structurei

Secondary structure

1647
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi332 – 334Combined sources3
Helixi336 – 338Combined sources3
Beta strandi339 – 346Combined sources8
Beta strandi349 – 358Combined sources10
Turni359 – 361Combined sources3
Beta strandi364 – 371Combined sources8
Helixi375 – 388Combined sources14
Beta strandi399 – 405Combined sources7
Beta strandi408 – 414Combined sources7
Helixi421 – 427Combined sources7
Helixi434 – 453Combined sources20
Beta strandi465 – 468Combined sources4
Beta strandi474 – 476Combined sources3
Helixi513 – 515Combined sources3
Helixi518 – 521Combined sources4
Helixi529 – 544Combined sources16
Turni550 – 552Combined sources3
Beta strandi559 – 561Combined sources3
Helixi563 – 569Combined sources7
Helixi579 – 586Combined sources8
Helixi591 – 593Combined sources3
Helixi597 – 613Combined sources17
Helixi618 – 634Combined sources17

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3S95X-ray1.65A/B330-637[»]
5HVJX-ray2.20A/B329-638[»]
5HVKX-ray3.50A/C329-638[»]
5L6WX-ray2.53L330-637[»]
ProteinModelPortaliP53667.
SMRiP53667.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP53667.

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

Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.Curated

Keywords - Domaini

LIM domain, Repeat

Phylogenomic databases

eggNOGiENOG410IEZ9. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00530000063025.
HOGENOMiHOG000013121.
HOVERGENiHBG052328.
InParanoidiP53667.
KOiK05743.
PhylomeDBiP53667.
TreeFamiTF318014.

Family and domain databases

InterProiView protein in InterPro
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.
PfamiView protein in Pfam
PF00412. LIM. 2 hits.
PF00595. PDZ. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiView protein in SMART
SM00132. LIM. 2 hits.
SM00228. PDZ. 1 hit.
SUPFAMiSSF50156. SSF50156. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiView protein in PROSITE
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.

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P53667-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MRLTLLCCTW REERMGEEGS ELPVCASCGQ RIYDGQYLQA LNADWHADCF 
        60         70         80         90        100
RCCDCSASLS HQYYEKDGQL FCKKDYWARY GESCHGCSEQ ITKGLVMVAG 
       110        120        130        140        150
ELKYHPECFI CLTCGTFIGD GDTYTLVEHS KLYCGHCYYQ TVVTPVIEQI 
       160        170        180        190        200
LPDSPGSHLP HTVTLVSIPA SSHGKRGLSV SIDPPHGPPG CGTEHSHTVR 
       210        220        230        240        250
VQGVDPGCMS PDVKNSIHVG DRILEINGTP IRNVPLDEID LLIQETSRLL 
       260        270        280        290        300
QLTLEHDPHD TLGHGLGPET SPLSSPAYTP SGEAGSSARQ KPVLRSCSID 
       310        320        330        340        350
RSPGAGSLGS 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 NKNVVVADFG LARLMVDEKT QPEGLRSLKK 
       510        520        530        540        550
PDRKKRYTVV GNPYWMAPEM INGRSYDEKV DVFSFGIVLC EIIGRVNADP 
       560        570        580        590        600
DYLPRTMDFG LNVRGFLDRY CPPNCPPSFF PITVRCCDLD PEKRPSFVKL 
       610        620        630        640 
EHWLETLRMH LAGHLPLGPQ LEQLDRGFWE TYRRGESGLP AHPEVPD
Length:647
Mass (Da):72,585
Last modified:March 7, 2006 - v3
Checksum:i9838BEFBE7006447
GO
Isoform 2 (identifier: P53667-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-14: Missing.

Show »
Length:633
Mass (Da):70,793
Checksum:iEAF0A3B93916D9FA
GO
Isoform 3 (identifier: P53667-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     294-305: LRSCSIDRSPGA → FARTWVALSPSA
     306-647: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:305
Mass (Da):33,373
Checksum:i65FEF49849CCA142
GO
Isoform 4 (identifier: P53667-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-51: MRLTLLCCTWREERMGEEGSELPVCASCGQRIYDGQYLQALNADWHADCFR → MLLASAPRRRRFLQRAK

Note: No experimental confirmation available.
Show »
Length:613
Mass (Da):68,729
Checksum:iA78F41C1313E9CEE
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_042246190G → A1 PublicationCorresponds to variant dbSNP:rs35827364Ensembl.1
Natural variantiVAR_042247247S → N1 PublicationCorresponds to variant dbSNP:rs55661242Ensembl.1
Natural variantiVAR_042248422R → Q1 PublicationCorresponds to variant dbSNP:rs55679316Ensembl.1
Natural variantiVAR_050148580F → Y2 PublicationsCorresponds to variant dbSNP:rs178412Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0433311 – 51MRLTL…ADCFR → MLLASAPRRRRFLQRAK in isoform 4. 1 PublicationAdd BLAST51
Alternative sequenceiVSP_0031251 – 14Missing in isoform 2. CuratedAdd BLAST14
Alternative sequenceiVSP_003126294 – 305LRSCS…RSPGA → FARTWVALSPSA in isoform 3. 1 PublicationAdd BLAST12
Alternative sequenceiVSP_003127306 – 647Missing in isoform 3. 1 PublicationAdd BLAST342

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D26309 mRNA. Translation: BAA05371.1.
U62293 Genomic DNA. Translation: AAB17545.1.
U62293 Genomic DNA. Translation: AAB17546.1.
U63721 Genomic DNA. Translation: AAC13885.1.
U63721 Genomic DNA. Translation: AAC13886.1.
AF134379 mRNA. Translation: AAD25742.1.
AK300382 mRNA. Translation: BAH13274.1.
AC005056 Genomic DNA. No translation available.
AC005057 Genomic DNA. Translation: AAS07438.1.
CH471200 Genomic DNA. Translation: EAW69620.1.
CH471200 Genomic DNA. Translation: EAW69621.1.
CH471200 Genomic DNA. Translation: EAW69622.1.
CH471200 Genomic DNA. Translation: EAW69623.1.
CCDSiCCDS5563.1. [P53667-1]
CCDS56491.1. [P53667-4]
PIRiJP0078.
RefSeqiNP_001191355.1. NM_001204426.1. [P53667-4]
NP_002305.1. NM_002314.3. [P53667-1]
UniGeneiHs.647035.

Genome annotation databases

EnsembliENST00000336180; ENSP00000336740; ENSG00000106683. [P53667-1]
ENST00000435201; ENSP00000414606; ENSG00000106683. [P53667-3]
ENST00000538333; ENSP00000444452; ENSG00000106683. [P53667-4]
GeneIDi3984.
KEGGihsa:3984.
UCSCiuc003uaa.3. human. [P53667-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

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.

Entry informationi

Entry nameiLIMK1_HUMAN
AccessioniPrimary (citable) accession number: P53667
Secondary accession number(s): B7Z6I8
, D3DXF4, D3DXF5, O15283, Q15820, Q15821, Q75MU3, Q9Y5Q1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: March 7, 2006
Last modified: July 5, 2017
This is version 188 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families