UniProtKB - P53667 (LIMK1_HUMAN)
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Protein
LIM domain kinase 1
Gene
LIMK1
Organism
Homo sapiens (Human)
Status
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 368 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 460 | By similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 345 – 353 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- heat shock protein binding Source: BHF-UCL
- metal ion binding Source: UniProtKB-KW
- protein heterodimerization activity Source: Ensembl
- protein kinase activity Source: ProtInc
- protein serine/threonine kinase activity Source: GO_Central
- signal transducer activity Source: GO_Central
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
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Ligand | ATP-binding, Metal-binding, Nucleotide-binding, Zinc |
Enzyme and pathway databases
BRENDAi | 2.7.11.1. 2681. |
Reactomei | R-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. |
SignaLinki | P53667. |
SIGNORi | P53667. |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:LIMK1 Synonyms:LIMK |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000106683.14. |
HGNCi | HGNC:6613. LIMK1. |
MIMi | 601329. gene. |
neXtProti | NX_P53667. |
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 84 | C → S: Enhances actin aggregation. 1 Publication | 1 | |
Mutagenesisi | 177 – 178 | GL → EA: Enhances actin aggregation. 1 Publication | 2 | |
Mutagenesisi | 460 | D → N: Abrogates kinase activity. 1 Publication | 1 | |
Mutagenesisi | 496 – 506 | Missing : Reduces actin aggregation. 1 PublicationAdd BLAST | 11 | |
Mutagenesisi | 503 – 505 | RKK → GAA: Abolishes kinase activity. 1 Publication | 3 | |
Mutagenesisi | 508 | T → A: Abolishes activation by ROCK1. 2 Publications | 1 | |
Mutagenesisi | 508 | T → EE: Enhances kinase activity. 2 Publications | 1 | |
Mutagenesisi | 508 | T → V or E: Reduces kinase activity. 2 Publications | 1 |
Keywords - Diseasei
Williams-Beuren syndromeOrganism-specific databases
DisGeNETi | 3984. |
MalaCardsi | LIMK1. |
OpenTargetsi | ENSG00000106683. |
Orphaneti | 904. Williams syndrome. |
PharmGKBi | PA30386. |
Chemistry databases
ChEMBLi | CHEMBL3836. |
DrugBanki | DB08912. Dabrafenib. |
GuidetoPHARMACOLOGYi | 2054. |
Polymorphism and mutation databases
BioMutai | LIMK1. |
DMDMi | 90185240. |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000075803 | 1 – 647 | LIM domain kinase 1Add BLAST | 647 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 210 | PhosphoserineCombined sources | 1 | |
Modified residuei | 229 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 298 | PhosphoserineCombined sources | 1 | |
Modified residuei | 302 | PhosphoserineCombined sources | 1 | |
Modified residuei | 307 | PhosphoserineCombined sources | 1 | |
Modified residuei | 310 | PhosphoserineCombined sources | 1 | |
Modified residuei | 323 | Phosphoserine; by MAPKAPK21 Publication | 1 | |
Modified residuei | 337 | PhosphoserineCombined sources | 1 | |
Modified residuei | 508 | Phosphothreonine; by ROCK1 and PAK14 Publications | 1 |
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 conjugationProteomic databases
MaxQBi | P53667. |
PaxDbi | P53667. |
PeptideAtlasi | P53667. |
PRIDEi | P53667. |
PTM databases
iPTMneti | P53667. |
PhosphoSitePlusi | P53667. |
SwissPalmi | P53667. |
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
Bgeei | ENSG00000106683. |
CleanExi | HS_LIMK1. |
ExpressionAtlasi | P53667. baseline and differential. |
Genevisiblei | P53667. HS. |
Organism-specific databases
HPAi | HPA028064. HPA028516. |
Interactioni
Subunit structurei
Interacts (via LIM domain) with the cytoplasmic domain of NRG1. Interacts with NISCH. Interacts with RLIM and RNF6 (By similarity). Self-associates to form homodimers (PubMed:10196227). Interacts with HSP90AA1; this interaction promotes LIMK1 dimerization and subsequent transphosphorylation (PubMed:16641196). Interacts with CDKN1C (PubMed:14530263). Interacts with SSH1 (PubMed:15660133). Interacts with ROCK1 (PubMed:10436159, PubMed:10652353). Interacts (via LIM zinc-binding domains) with FAM89B/LRAP25 (via LRR repeat). Forms a tripartite complex with CDC42BPA, CDC42BPB and FAM89B/LRAP25 (By similarity).By similarity6 Publications
Binary interactionsi
GO - Molecular functioni
- heat shock protein binding Source: BHF-UCL
- protein heterodimerization activity Source: Ensembl
Protein-protein interaction databases
BioGridi | 110172. 40 interactors. |
DIPi | DIP-31605N. |
IntActi | P53667. 38 interactors. |
MINTi | P53667. |
STRINGi | 9606.ENSP00000336740. |
Chemistry databases
BindingDBi | P53667. |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more detailsFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Beta strandi | 332 – 334 | Combined sources | 3 | |
Helixi | 336 – 338 | Combined sources | 3 | |
Beta strandi | 339 – 346 | Combined sources | 8 | |
Beta strandi | 349 – 358 | Combined sources | 10 | |
Turni | 359 – 361 | Combined sources | 3 | |
Beta strandi | 364 – 371 | Combined sources | 8 | |
Helixi | 375 – 388 | Combined sources | 14 | |
Beta strandi | 399 – 405 | Combined sources | 7 | |
Beta strandi | 408 – 414 | Combined sources | 7 | |
Helixi | 421 – 427 | Combined sources | 7 | |
Helixi | 434 – 453 | Combined sources | 20 | |
Beta strandi | 465 – 468 | Combined sources | 4 | |
Beta strandi | 474 – 476 | Combined sources | 3 | |
Helixi | 513 – 515 | Combined sources | 3 | |
Helixi | 518 – 521 | Combined sources | 4 | |
Helixi | 529 – 544 | Combined sources | 16 | |
Turni | 550 – 552 | Combined sources | 3 | |
Beta strandi | 559 – 561 | Combined sources | 3 | |
Helixi | 563 – 569 | Combined sources | 7 | |
Helixi | 579 – 586 | Combined sources | 8 | |
Helixi | 591 – 593 | Combined sources | 3 | |
Helixi | 597 – 613 | Combined sources | 17 | |
Helixi | 618 – 634 | Combined sources | 17 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3S95 | X-ray | 1.65 | A/B | 330-637 | [»] | |
5HVJ | X-ray | 2.20 | A/B | 329-638 | [»] | |
5HVK | X-ray | 3.50 | A/C | 329-638 | [»] | |
5L6W | X-ray | 2.53 | L | 330-637 | [»] | |
5NXC | X-ray | 2.25 | L | 330-637 | [»] | |
ProteinModelPortali | P53667. | |||||
SMRi | P53667. | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P53667. |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 25 – 75 | LIM zinc-binding 1PROSITE-ProRule annotationAdd BLAST | 51 | |
Domaini | 84 – 137 | LIM zinc-binding 2PROSITE-ProRule annotationAdd BLAST | 54 | |
Domaini | 165 – 258 | PDZPROSITE-ProRule annotationAdd BLAST | 94 | |
Domaini | 339 – 604 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 266 |
Sequence similaritiesi
Keywords - Domaini
LIM domain, RepeatPhylogenomic databases
eggNOGi | ENOG410IEZ9. Eukaryota. COG0515. LUCA. |
GeneTreei | ENSGT00530000063025. |
HOGENOMi | HOG000013121. |
HOVERGENi | HBG052328. |
InParanoidi | P53667. |
KOi | K05743. |
PhylomeDBi | P53667. |
TreeFami | TF318014. |
Family and domain databases
InterProi | View protein in InterPro IPR011009. Kinase-like_dom_sf. IPR001478. PDZ. IPR036034. PDZ_sf. IPR000719. Prot_kinase_dom. IPR017441. Protein_kinase_ATP_BS. IPR001245. Ser-Thr/Tyr_kinase_cat_dom. IPR001781. Znf_LIM. |
Pfami | View protein in Pfam PF00412. LIM. 2 hits. PF00595. PDZ. 1 hit. PF07714. Pkinase_Tyr. 1 hit. |
PRINTSi | PR00109. TYRKINASE. |
SMARTi | View protein in SMART SM00132. LIM. 2 hits. SM00228. PDZ. 1 hit. |
SUPFAMi | SSF50156. SSF50156. 1 hit. SSF56112. SSF56112. 1 hit. |
PROSITEi | View 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. |
s (4)i Sequence
Sequence statusi: Complete.
This entry describes 4 produced by isoformsialternative 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.
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
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 »Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_042246 | 190 | G → A1 PublicationCorresponds to variant dbSNP:rs35827364Ensembl. | 1 | |
Natural variantiVAR_042247 | 247 | S → N1 PublicationCorresponds to variant dbSNP:rs55661242Ensembl. | 1 | |
Natural variantiVAR_042248 | 422 | R → Q1 PublicationCorresponds to variant dbSNP:rs55679316Ensembl. | 1 | |
Natural variantiVAR_050148 | 580 | F → Y2 PublicationsCorresponds to variant dbSNP:rs178412Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_043331 | 1 – 51 | MRLTL…ADCFR → MLLASAPRRRRFLQRAK in isoform 4. 1 PublicationAdd BLAST | 51 | |
Alternative sequenceiVSP_003125 | 1 – 14 | Missing in isoform 2. CuratedAdd BLAST | 14 | |
Alternative sequenceiVSP_003126 | 294 – 305 | LRSCS…RSPGA → FARTWVALSPSA in isoform 3. 1 PublicationAdd BLAST | 12 | |
Alternative sequenceiVSP_003127 | 306 – 647 | Missing in isoform 3. 1 PublicationAdd BLAST | 342 |
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. |
CCDSi | CCDS5563.1. [P53667-1] CCDS56491.1. [P53667-4] |
PIRi | JP0078. |
RefSeqi | NP_001191355.1. NM_001204426.1. [P53667-4] NP_002305.1. NM_002314.3. [P53667-1] |
UniGenei | Hs.647035. |
Genome annotation databases
Ensembli | ENST00000336180; ENSP00000336740; ENSG00000106683. [P53667-1] ENST00000435201; ENSP00000414606; ENSG00000106683. [P53667-3] ENST00000538333; ENSP00000444452; ENSG00000106683. [P53667-4] |
GeneIDi | 3984. |
KEGGi | hsa:3984. |
UCSCi | uc003uaa.3. human. [P53667-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Entry informationi
Entry namei | LIMK1_HUMAN | |
Accessioni | P53667Primary (citable) accession number: P53667 Secondary accession number(s): B7Z6I8 Q9Y5Q1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 1, 1996 |
Last sequence update: | March 7, 2006 | |
Last modified: | March 28, 2018 | |
This is version 195 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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. |