LIMK1
entrez
3984
canonical
uniprot
P53667
canonical
ensembl
ENSG00000106683
resolver
ensp
ENSP00000336740
resolver
ensp
ENSP00000444452
resolver
genesymbol
LIMK1
resolver
genesymbol_syn
LIMK
resolver
hgnc
HGNC:6613
resolver
uniprot
B7Z6I8
resolver
uniprot
D3DXF4
resolver
uniprot
D3DXF5
resolver
uniprot
O15283
resolver
uniprot
Q15820
resolver
uniprot
Q15821
resolver
uniprot
Q75MU3
resolver
uniprot
Q9Y5Q1
resolver
uniprot_entry
LIMK1_HUMAN
resolver
uniprot_sec
B7Z6I8
resolver
uniprot_sec
D3DXF4
resolver
uniprot_sec
D3DXF5
resolver
uniprot_sec
O15283
resolver
uniprot_sec
Q15820
resolver
uniprot_sec
Q15821
resolver
uniprot_sec
Q75MU3
resolver
uniprot_sec
Q9Y5Q1
resolver
amino_acid_sequence
MRLTLLCCTWREERMGEEGSELPVCASCGQRIYDGQYLQALNADWHADCFRCCDCSASLSHQYYEKDGQLFCKKDYWARYGESCHGCSEQITKGLVMVAGELKYHPECFICLTCGTFIGDGDTYTLVEHSKLYCGHCYYQTVVTPVIEQILPDSPGSHLPHTVTLVSIPASSHGKRGLSVSIDPPHGPPGCGTEHSHTVRVQGVDPGCMSPDVKNSIHVGDRILEINGTPIRNVPLDEIDLLIQETSRLLQLTLEHDPHDTLGHGLGPETSPLSSPAYTPSGEAGSSARQKPVLRSCSIDRSPGAGSLGSPASQRKDLGRSESLRVVCRPHRIFRPSDLIHGEVLGKGCFGQAIKVTHRETGEVMVMKELIRFDEETQRTFLKEVKVMRCLEHPNVLKFIGVLYKDKRLNFITEYIKGGTLRGIIKSMDSQYPWSQRVSFAKDIASGMAYLHSMNIIHRDLNSHNCLVRENKNVVVADFGLARLMVDEKTQPEGLRSLKKPDRKKRYTVVGNPYWMAPEMINGRSYDEKVDVFSFGIVLCEIIGRVNADPDYLPRTMDFGLNVRGFLDRYCPPNCPPSFFPITVRCCDLDPEKRPSFVKLEHWLETLRMHLAGHLPLGPQLEQLDRGFWETYRRGESGLPAHPEVPD
uniprot
proteins
disease_involvement
DISEASE: Note=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.
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
function
FUNCTION: 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 (PubMed:10436159, PubMed:11832213, PubMed:12807904, PubMed:15660133, PubMed:16230460, PubMed:18028908, PubMed:22328514, PubMed:23633677). Activated by upstream kinases including ROCK1, PAK1 and PAK4, which phosphorylate LIMK1 on a threonine residue located in its activation loop (PubMed:10436159). 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 (PubMed:11832213, PubMed:15660133, PubMed:16230460, PubMed:23633677). In this way LIMK1 regulates several actin-dependent biological processes including cell motility, cell cycle progression, and differentiation (PubMed:11832213, PubMed:15660133, PubMed:16230460, PubMed:23633677). Phosphorylates TPPP on serine residues, thereby promoting microtubule disassembly (PubMed:18028908). Stimulates axonal outgrowth and may be involved in brain development (PubMed:18028908). {ECO:0000269|PubMed:10436159, ECO:0000269|PubMed:11832213, ECO:0000269|PubMed:12807904, ECO:0000269|PubMed:15660133, ECO:0000269|PubMed:16230460, ECO:0000269|PubMed:18028908, ECO:0000269|PubMed:22328514, ECO:0000269|PubMed:23633677}.; FUNCTION: [Isoform 3]: Has a dominant negative effect on actin cytoskeletal changes. Required for atypical chemokine receptor ACKR2-induced phosphorylation of cofilin (CFL1). {ECO:0000269|PubMed:10196227}.
uniprot
proteins
mass_dalton
72585
uniprot
proteins
mutagenesis
MUTAGEN 84; /note="C->S: Enhances actin aggregation."; /evidence="ECO:0000269|PubMed:10196227"; MUTAGEN 177..178; /note="GL->EA: Enhances actin aggregation."; /evidence="ECO:0000269|PubMed:10196227"; MUTAGEN 460; /note="D->N,A: Abrogates kinase activity."; /evidence="ECO:0000269|PubMed:10196227, ECO:0000269|PubMed:22328514"; MUTAGEN 496..506; /note="Missing: Reduces actin aggregation."; /evidence="ECO:0000269|PubMed:10196227"; MUTAGEN 503..505; /note="RKK->GAA: Abolishes kinase activity."; /evidence="ECO:0000269|PubMed:10196227"; MUTAGEN 508; /note="T->A: Abolishes activation by ROCK1."; /evidence="ECO:0000269|PubMed:10196227, ECO:0000269|PubMed:10652353"; MUTAGEN 508; /note="T->E: Phosphomimetic mutant; enhances kinase activity."; /evidence="ECO:0000269|PubMed:22328514"; MUTAGEN 508; /note="T->EE: Enhances kinase activity."; /evidence="ECO:0000269|PubMed:10196227, ECO:0000269|PubMed:10652353"; MUTAGEN 508; /note="T->V: Reduces kinase activity."; /evidence="ECO:0000269|PubMed:10196227, ECO:0000269|PubMed:10652353
uniprot
proteins
post_translational_modification
PTM: Autophosphorylated. 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. {ECO:0000269|PubMed:10559936, ECO:0000269|PubMed:10652353, ECO:0000269|PubMed:11340065, ECO:0000269|PubMed:11413130, ECO:0000269|PubMed:15660133, ECO:0000269|PubMed:16456544, ECO:0000269|PubMed:23633677}.; PTM: 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). {ECO:0000250|UniProtKB:P53668}.
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
TKL Ser/Thr protein kinase family
uniprot
proteins
pubmed
10196227
uniprot
proteins
pubmed
10436159
uniprot
proteins
pubmed
10559936
uniprot
proteins
pubmed
10652353
uniprot
proteins
pubmed
11340065
uniprot
proteins
pubmed
11413130
uniprot
proteins
pubmed
11832213
uniprot
proteins
pubmed
12807904
uniprot
proteins
pubmed
12853948
uniprot
proteins
pubmed
14530263
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14759258
uniprot
proteins
pubmed
15660133
uniprot
proteins
pubmed
16230460
uniprot
proteins
pubmed
16456544
uniprot
proteins
pubmed
16641196
uniprot
proteins
pubmed
17188549
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
18028908
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
21682918
uniprot
proteins
pubmed
22328514
uniprot
proteins
pubmed
22886629
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23633677
uniprot
proteins
pubmed
8183554
uniprot
proteins
pubmed
8689688
uniprot
proteins
pubmed
8812460
uniprot
proteins
sequence_length
647
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21682918}. Nucleus {ECO:0000269|PubMed:21682918}. Cytoplasm, cytoskeleton {ECO:0000269|PubMed:10196227, ECO:0000269|PubMed:16230460}. Cell projection, lamellipodium {ECO:0000250|UniProtKB:P53668}. Note=Predominantly found in the cytoplasm. Localizes in the lamellipodium in a CDC42BPA, CDC42BPB and FAM89B/LRAP25-dependent manner. {ECO:0000250|UniProtKB:P53668}.
uniprot
proteins