Tchem LIMK1 LIM domain kinase 1

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Tkl Group / Lisk Family / Limk Subfamily / Lim Domain Kinase 1

Protein Summary

Description

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). There are approximately 40 known eukaryotic LIM proteins, so named for the LIM domains they contain. LIM domains are highly conserved cysteine-rich structures containing 2 zinc fingers. Although zinc fingers usually function by binding to DNA or RNA, the LIM motif probably mediates protein-protein interactions. LIM kinase-1 and LIM kinase-2 belong to a small subfamily with a unique combination of 2 N-terminal LIM motifs and a C-terminal protein kinase domain. LIMK1 is a serine/threonine kinase that regulates actin polymerization via phosphorylation and inactivation of the actin binding factor cofilin. This protein is ubiquitously expressed during development and plays a role in many cellular processes associated with cytoskeletal structure. This protein also stimulates axon growth and may play a role in brain development. LIMK1 hemizygosity is implicated in the impaired visuospatial constructive cognition of Williams syndrome. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Feb 2011]

Uniprot Accession IDs

• P53667
• B7Z6I8
• D3DXF4
• D3DXF5
• O15283
• Q15820
• Q15821
• Q75MU3
• Q9Y5Q1
• LIMK-1

Gene Name

• LIMK1

Ensembl ID

• ENST00000336180
• ENSP00000336740
• ENSG00000106683
• ENST00000435201
• ENSP00000414606
• ENST00000538333
• ENSP00000444452

Symbol

• LIMK
• LIMK
• LIMK-1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	0.98
biological process	0.91
kinase	0.86
protein domain	0.85
transcription factor perturbation	0.84

Related Tools

ProKinO

The ProKinO is a protein kinase-specific ontology, which provides a controlled vocabulary of terms, their hierarchy, and relationships unifying sequence, structure, function, mutation and pathway information on kinases.

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Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 303.23   (req: < 5)

Gene RIFs: 77   (req: <= 3)

Antibodies: 887   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 303.23   (req: >= 5)

Gene RIFs: 77   (req: > 3)

Antibodies: 887   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 16

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 61

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 1

Approved Drugs (1)

Explore Approved Drugs

1 – 1 of 1

encorafenib

LIMK1Tchem Kinase

Kd : 7.58

Active Ligands (61)

Explore Active Ligands

1 – 10 of 61

staurosporine

LIMK1Tchem Kinase

IC50 : 8.61

CHEMBL4465866

LIMK1Tchem Kinase

Kd : 8.22

SID103904591

LIMK1Tchem Kinase

Ki : 7.7

SID103904402

LIMK1Tchem Kinase

Ki : 7.8

voruciclib

LIMK1Tchem Kinase

IC50 : 7.65999985

RKI-1447

LIMK1Tchem Kinase

IC50 : 8.76000023

SID103904404

LIMK1Tchem Kinase

Ki : 8

compound 30 [PMID: 22902653]

LIMK1Tchem Kinase

IC50 : 7.63999987

CHEMBL2070615

LIMK1Tchem Kinase

IC50 : 9

CHEMBL2070619

LIMK1Tchem Kinase

IC50 : 7.51999998

GWAS Traits (7)

• Explore on Target Illumination GWAS Analytics (TIGA)

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1 – 5 of 7

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
monocyte count	EFO_0005091	1	1	1		45.2
serum non-albumin protein measurement	EFO_0004568	1	1	1		40.7
systemic lupus erythematosus	EFO_0002690	2	2	0	1.6	32.8
pulse pressure measurement	EFO_0005763	1	1	1		8.9
systemic scleroderma	EFO_0000717	1	1	0	1.5	7.1

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
monocyte count	EFO_0005091	1		45.2
serum non-albumin protein measurement	EFO_0004568	1		40.7
systemic lupus erythematosus	EFO_0002690	0	1.6	32.8
pulse pressure measurement	EFO_0005763	1		8.9
systemic scleroderma	EFO_0000717	0	1.5	7.1

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Orthologs (13)

1 – 5 of 13

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	LIM domain kinase 1	VGNC:14036	463466
Macaque	LIM domain kinase 1		699494
Mouse	LIM-domain containing, protein kinase	MGI:104572	16885
Rat	LIM domain kinase 1	RGD:62055	65172
Dog	LIM domain kinase 1	VGNC:42681	489800

Species	Name	OMA	EggNOG	Inparanoid
Chimp	LIM domain kinase 1
Macaque	LIM domain kinase 1
Mouse	LIM-domain containing, protein kinase
Rat	LIM domain kinase 1
Dog	LIM domain kinase 1

Protein Structure (5 Structures, 1 AlphaFold Model)

tutorial

Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

Click on a row in the table to change the structure displayed.
More information can be found at RCSB PDB

AF-P53667-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 5 of 5

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (37)

Reactome (17)

KEGG (5)

PathwayCommons (7)

WikiPathways (8)

Axon guidance (R-HSA-422475)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Axon guidance	533 targets	R-HSA-422475
Reactome	Developmental Biology	1055 targets	R-HSA-1266738
Reactome	EPH-Ephrin signaling	92 targets	R-HSA-2682334
Reactome	EPHB-mediated forward signaling	34 targets	R-HSA-3928662
Reactome	Fcgamma receptor (FCGR) dependent phagocytosis	163 targets	R-HSA-2029480

Name	Explore in Pharos	Explore in Source
Axon guidance	533 targets	R-HSA-422475
Developmental Biology	1055 targets	R-HSA-1266738
EPH-Ephrin signaling	92 targets	R-HSA-2682334
EPHB-mediated forward signaling	34 targets	R-HSA-3928662
Fcgamma receptor (FCGR) dependent phagocytosis	163 targets	R-HSA-2029480

Gene Ontology Terms (24)

Functions (6)

Components (8)

Processes (10)

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1 – 6 of 6

GO Term	Evidence	Assigned by
heat shock protein binding	Inferred from Direct Assay (IDA)	BHF-UCL
protein serine/threonine kinase activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
protein kinase activity	Non-traceable Author Statement (NAS)	ProtInc
ATP binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW
metal ion binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW
protein heterodimerization activity	Inferred from Electronic Annotation (IEA)	Ensembl

Protein-Protein Interactions (141)

Explore Interacting Targets

1 – 10 of 141

• See Interactions on String-DB

CFL1

Tbio

Novelty:  0.00071544

Score:  0.997

Data Source:  Reactome,STRINGDB

RHOA

Tbio

Family:  Enzyme

Novelty:  0.00022204

Score:  0.979

Data Source:  Reactome,STRINGDB

CFL2

Tbio

Novelty:  0.01563343

Score:  0.977

Data Source:  STRINGDB

CDC42

Tchem

Family:  Enzyme

Novelty:  0.00032619

Score:  0.976

Data Source:  STRINGDB

RHOC

Tbio

Family:  Enzyme

Novelty:  0.00262213

Score:  0.967

Data Source:  Reactome,STRINGDB

PAK1

Tchem

Family:  Kinase

Novelty:  0.00411227

Score:  0.96

Data Source:  Reactome,STRINGDB

ROCK1

Tclin

Family:  Kinase

Novelty:  0.00156045

Score:  0.96

Data Source:  Reactome,STRINGDB

RAC1

Tbio

Family:  Enzyme

Novelty:  0.00365325

Score:  0.959

Data Source:  STRINGDB

RHOB

Tbio

Family:  Enzyme

Novelty:  0.0019205

Score:  0.958

Data Source:  Reactome,STRINGDB

HSP90AA1

Tchem

Novelty:  0.00016774

Score:  0.958

Data Source:  Reactome,STRINGDB

Publication Statistics

PubMed Score  303.23

PubMed score by year

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PubTator Score  170.13

PubTator score by year

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Patents

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Amino Acid Sequence

Residue Counts

Protein Sequence

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Ortholog Sequence Conservation

WebLogo Color Code

PolarG S T Y C

NeutralQ N

BasicK R H

AcidicD E

HydrophobicA V L I P W F M

Compare across kinases on ProKinO

Structural Annotations

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Alternative splicing
ATP-binding
Cell projection
Complete proteome
Cytoplasm
Kinase
LIM domain
Metal-binding
Nucleotide-binding

GWAS Trait Find Similar Targets

No Header	No Header
monocyte count
myositis
pulse pressure measurement
rheumatoid arthritis
serum non-albumin protein measurement
systemic lupus erythematosus
systemic scleroderma

MGI Phenotype Find Similar Targets

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behavior/neurological phenotype
cellular phenotype
nervous system phenotype