P53667 · LIMK1_HUMAN
- ProteinLIM domain kinase 1
- GeneLIMK1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids647 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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).
Isoform 3
Catalytic activity
- ATP + L-seryl-[protein] = ADP + H+ + O-phospho-L-seryl-[protein]This reaction proceeds in the forward direction.
Features
Showing features for binding site, active site.
GO annotations
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameLIM domain kinase 1
- EC number
- Short namesLIMK-1
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP53667
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 84 | Enhances actin aggregation. | ||||
Sequence: C → S | ||||||
Mutagenesis | 177-178 | Enhances actin aggregation. | ||||
Sequence: GL → EA | ||||||
Natural variant | VAR_042246 | 190 | in dbSNP:rs35827364 | |||
Sequence: G → A | ||||||
Natural variant | VAR_042247 | 247 | in dbSNP:rs55661242 | |||
Sequence: S → N | ||||||
Natural variant | VAR_042248 | 422 | in dbSNP:rs55679316 | |||
Sequence: R → Q | ||||||
Mutagenesis | 460 | Abrogates kinase activity. | ||||
Sequence: D → N or A | ||||||
Mutagenesis | 496-506 | Reduces actin aggregation. | ||||
Sequence: Missing | ||||||
Mutagenesis | 503-505 | Abolishes kinase activity. | ||||
Sequence: RKK → GAA | ||||||
Mutagenesis | 508 | Abolishes activation by ROCK1. | ||||
Sequence: T → A | ||||||
Mutagenesis | 508 | Phosphomimetic mutant; enhances kinase activity. | ||||
Sequence: T → E | ||||||
Mutagenesis | 508 | Enhances kinase activity. | ||||
Sequence: T → EE | ||||||
Mutagenesis | 508 | Reduces kinase activity. | ||||
Sequence: T → V | ||||||
Natural variant | VAR_050148 | 580 | in dbSNP:rs178412 | |||
Sequence: F → Y |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 654 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000075803 | 1-647 | UniProt | LIM domain kinase 1 | |||
Sequence: MRLTLLCCTWREERMGEEGSELPVCASCGQRIYDGQYLQALNADWHADCFRCCDCSASLSHQYYEKDGQLFCKKDYWARYGESCHGCSEQITKGLVMVAGELKYHPECFICLTCGTFIGDGDTYTLVEHSKLYCGHCYYQTVVTPVIEQILPDSPGSHLPHTVTLVSIPASSHGKRGLSVSIDPPHGPPGCGTEHSHTVRVQGVDPGCMSPDVKNSIHVGDRILEINGTPIRNVPLDEIDLLIQETSRLLQLTLEHDPHDTLGHGLGPETSPLSSPAYTPSGEAGSSARQKPVLRSCSIDRSPGAGSLGSPASQRKDLGRSESLRVVCRPHRIFRPSDLIHGEVLGKGCFGQAIKVTHRETGEVMVMKELIRFDEETQRTFLKEVKVMRCLEHPNVLKFIGVLYKDKRLNFITEYIKGGTLRGIIKSMDSQYPWSQRVSFAKDIASGMAYLHSMNIIHRDLNSHNCLVRENKNVVVADFGLARLMVDEKTQPEGLRSLKKPDRKKRYTVVGNPYWMAPEMINGRSYDEKVDVFSFGIVLCEIIGRVNADPDYLPRTMDFGLNVRGFLDRYCPPNCPPSFFPITVRCCDLDPEKRPSFVKLEHWLETLRMHLAGHLPLGPQLEQLDRGFWETYRRGESGLPAHPEVPD | |||||||
Modified residue | 210 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 210 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 229 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 229 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 270 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 275 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 296 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 298 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 298 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 302 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 302 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 307 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 307 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 310 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 310 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 323 | UniProt | Phosphoserine; by MAPKAPK2 | ||||
Sequence: S | |||||||
Modified residue | 337 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 508 | UniProt | Phosphothreonine; by ROCK1 and PAK1 | ||||
Sequence: T |
Post-translational modification
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Gene expression databases
Organism-specific databases
Interaction
Subunit
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).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
XENO | P53667 | Arrb1 P29066 | 2 | EBI-444403, EBI-4303019 | |
XENO | P53667 | Arrb2 P29067 | 2 | EBI-444403, EBI-1636616 | |
BINARY | P53667 | C22orf15 Q8WYQ4-2 | 3 | EBI-444403, EBI-12030460 | |
BINARY | P53667 | CFL1 P23528 | 3 | EBI-444403, EBI-352733 | |
BINARY | P53667 | HUNK P57058 | 2 | EBI-444403, EBI-3959804 | |
BINARY | P53667 | LATS1 O95835 | 5 | EBI-444403, EBI-444209 | |
BINARY | P53667 | MMP14 P50281 | 4 | EBI-444403, EBI-992788 | |
BINARY | P53667 | PAK1 Q13153 | 5 | EBI-444403, EBI-1307 | |
BINARY | P53667 | PAK2 Q13177 | 2 | EBI-444403, EBI-1045887 | |
XENO | P53667 | Prkcg P63319 | 3 | EBI-444403, EBI-12598030 | |
BINARY | P53667 | SSH1 Q8WYL5 | 6 | EBI-444403, EBI-1222387 | |
BINARY | P53667 | YWHAE P62258 | 2 | EBI-444403, EBI-356498 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 25-75 | LIM zinc-binding 1 | ||||
Sequence: CASCGQRIYDGQYLQALNADWHADCFRCCDCSASLSHQYYEKDGQLFCKKD | ||||||
Domain | 84-137 | LIM zinc-binding 2 | ||||
Sequence: CHGCSEQITKGLVMVAGELKYHPECFICLTCGTFIGDGDTYTLVEHSKLYCGHC | ||||||
Domain | 165-258 | PDZ | ||||
Sequence: LVSIPASSHGKRGLSVSIDPPHGPPGCGTEHSHTVRVQGVDPGCMSPDVKNSIHVGDRILEINGTPIRNVPLDEIDLLIQETSRLLQLTLEHDP | ||||||
Region | 260-319 | Disordered | ||||
Sequence: DTLGHGLGPETSPLSSPAYTPSGEAGSSARQKPVLRSCSIDRSPGAGSLGSPASQRKDLG | ||||||
Compositional bias | 272-286 | Polar residues | ||||
Sequence: PLSSPAYTPSGEAGS | ||||||
Domain | 339-604 | Protein kinase | ||||
Sequence: LIHGEVLGKGCFGQAIKVTHRETGEVMVMKELIRFDEETQRTFLKEVKVMRCLEHPNVLKFIGVLYKDKRLNFITEYIKGGTLRGIIKSMDSQYPWSQRVSFAKDIASGMAYLHSMNIIHRDLNSHNCLVRENKNVVVADFGLARLMVDEKTQPEGLRSLKKPDRKKRYTVVGNPYWMAPEMINGRSYDEKVDVFSFGIVLCEIIGRVNADPDYLPRTMDFGLNVRGFLDRYCPPNCPPSFFPITVRCCDLDPEKRPSFVKLEHWL |
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 4 isoforms produced by Alternative splicing.
P53667-1
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.
- Name1
- Length647
- Mass (Da)72,585
- Last updated2006-03-07 v3
- Checksum9838BEFBE7006447
P53667-2
- Name2
- Differences from canonical
- 1-14: Missing
P53667-3
- Name3
- NoteMay be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
P53667-4
- Name4
- Differences from canonical
- 1-51: MRLTLLCCTWREERMGEEGSELPVCASCGQRIYDGQYLQALNADWHADCFR → MLLASAPRRRRFLQRAK
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
E9PC47 | E9PC47_HUMAN | LIMK1 | 677 |
Features
Showing features for alternative sequence, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_003125 | 1-14 | in isoform 2 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_043331 | 1-51 | in isoform 4 | |||
Sequence: MRLTLLCCTWREERMGEEGSELPVCASCGQRIYDGQYLQALNADWHADCFR → MLLASAPRRRRFLQRAK | ||||||
Compositional bias | 272-286 | Polar residues | ||||
Sequence: PLSSPAYTPSGEAGS | ||||||
Alternative sequence | VSP_003126 | 294-305 | in isoform 3 | |||
Sequence: LRSCSIDRSPGA → FARTWVALSPSA | ||||||
Alternative sequence | VSP_003127 | 306-647 | in isoform 3 | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
D26309 EMBL· GenBank· DDBJ | BAA05371.1 EMBL· GenBank· DDBJ | mRNA | ||
U62293 EMBL· GenBank· DDBJ | AAB17545.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U62293 EMBL· GenBank· DDBJ | AAB17546.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U63721 EMBL· GenBank· DDBJ | AAC13885.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U63721 EMBL· GenBank· DDBJ | AAC13886.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF134379 EMBL· GenBank· DDBJ | AAD25742.1 EMBL· GenBank· DDBJ | mRNA | ||
AK300382 EMBL· GenBank· DDBJ | BAH13274.1 EMBL· GenBank· DDBJ | mRNA | ||
AC005056 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC005057 EMBL· GenBank· DDBJ | AAS07438.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471200 EMBL· GenBank· DDBJ | EAW69620.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471200 EMBL· GenBank· DDBJ | EAW69621.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471200 EMBL· GenBank· DDBJ | EAW69622.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471200 EMBL· GenBank· DDBJ | EAW69623.1 EMBL· GenBank· DDBJ | Genomic DNA |