Human Gene LIMK1 (ENST00000336180.7_4) from GENCODE V47lift37
  Description: LIM domain kinase 1, transcript variant 1 (from RefSeq NM_002314.4)
Gencode Transcript: ENST00000336180.7_4
Gencode Gene: ENSG00000106683.15_7
Transcript (Including UTRs)
   Position: hg19 chr7:73,498,134-73,536,855 Size: 38,722 Total Exon Count: 16 Strand: +
Coding Region
   Position: hg19 chr7:73,498,321-73,535,631 Size: 37,311 Coding Exon Count: 16 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviewsModel Information
Methods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr7:73,498,134-73,536,855)mRNA (may differ from genome)Protein (647 aa)
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-  Comments and Description Text from UniProtKB
  ID: LIMK1_HUMAN
DESCRIPTION: RecName: Full=LIM domain kinase 1; Short=LIMK-1; EC=2.7.11.1;
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. 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.
CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
SUBUNIT: 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.
INTERACTION: P29066:Arrb1 (xeno); NbExp=2; IntAct=EBI-444403, EBI-4303019; P29067:Arrb2 (xeno); NbExp=2; IntAct=EBI-444403, EBI-1636616; O95835:LATS1; NbExp=5; IntAct=EBI-444403, EBI-444209; P50281:MMP14; NbExp=4; IntAct=EBI-444403, EBI-992788; Q13153:PAK1; NbExp=5; IntAct=EBI-444403, EBI-1307; Q13177:PAK2; NbExp=2; IntAct=EBI-444403, EBI-1045887;
SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Predominantly found in the cytoplasm.
TISSUE SPECIFICITY: 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.
PTM: 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.
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).
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.
SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.
SIMILARITY: Contains 2 LIM zinc-binding domains.
SIMILARITY: Contains 1 PDZ (DHR) domain.
SIMILARITY: Contains 1 protein kinase domain.

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: LIMK1
Diseases sorted by gene-association score: williams-beuren syndrome* (25), supravalvar aortic stenosis (14), intracranial aneurysm (11)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 52.35 RPKM in Brain - Frontal Cortex (BA9)
Total median expression: 643.98 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -102.80187-0.550 Picture PostScript Text
3' UTR -493.901224-0.404 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR011009 - Kinase-like_dom
IPR001478 - PDZ
IPR000719 - Prot_kinase_cat_dom
IPR017441 - Protein_kinase_ATP_BS
IPR001245 - Ser-Thr/Tyr_kinase_cat_dom
IPR001781 - Znf_LIM

Pfam Domains:
PF00069 - Protein kinase domain
PF00412 - LIM domain
PF00595 - PDZ domain
PF06293 - Lipopolysaccharide kinase (Kdo/WaaP) family
PF07714 - Protein tyrosine and serine/threonine kinase

SCOP Domains:
50156 - PDZ domain-like
52833 - Thioredoxin-like
56112 - Protein kinase-like (PK-like)
57716 - Glucocorticoid receptor-like (DNA-binding domain)

Protein Data Bank (PDB) 3-D Structure
MuPIT help
3S95 - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P53667
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
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-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0004871 signal transducer activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016740 transferase activity
GO:0031072 heat shock protein binding
GO:0046872 metal ion binding
GO:0046982 protein heterodimerization activity

Biological Process:
GO:0006468 protein phosphorylation
GO:0007165 signal transduction
GO:0007266 Rho protein signal transduction
GO:0007399 nervous system development
GO:0016310 phosphorylation
GO:0030036 actin cytoskeleton organization
GO:0032233 positive regulation of actin filament bundle assembly
GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis
GO:0045773 positive regulation of axon extension
GO:0051444 negative regulation of ubiquitin-protein transferase activity
GO:0051496 positive regulation of stress fiber assembly

Cellular Component:
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005794 Golgi apparatus
GO:0005829 cytosol
GO:0005925 focal adhesion
GO:0016020 membrane
GO:0016607 nuclear speck
GO:0030027 lamellipodium
GO:0042995 cell projection
GO:0043005 neuron projection


-  Descriptions from all associated GenBank mRNAs
  AK125156 - Homo sapiens cDNA FLJ43166 fis, clone FCBBF3003373, moderately similar to LIM DOMAIN KINASE 1 (EC 2.7.1.-).
AK290162 - Homo sapiens cDNA FLJ75611 complete cds, highly similar to Homo sapiens LIM domain kinase 1 (LIMK1), transcript variant 1, mRNA.
D26309 - Homo sapiens LIMK mRNA for LIM kinase, complete cds.
JA482219 - Sequence 202 from Patent WO2011072091.
JE980511 - Sequence 202 from Patent EP2862929.
AB385563 - Synthetic construct DNA, clone: pF1KB8017, Homo sapiens LIMK1 gene for LIM domain kinase 1, complete cds, without stop codon, in Flexi system.
BC148340 - Synthetic construct Homo sapiens clone IMAGE:100015326, MGC:182989 LIM domain kinase 1 (LIMK1) mRNA, encodes complete protein.
BC152982 - Synthetic construct Homo sapiens clone IMAGE:100016262, MGC:184237 LIM domain kinase 1 (LIMK1) mRNA, encodes complete protein.
AF134379 - Homo sapiens LIM domain kinase 1 splice variant (LIMK1) mRNA, complete cds.
AK300382 - Homo sapiens cDNA FLJ55661 complete cds, highly similar to LIM domain kinase 1 (EC 2.7.11.1).
AK026544 - Homo sapiens cDNA: FLJ22891 fis, clone KAT04587, highly similar to HUMLIMKA Human mRNA for LIMK (LIM kinase).
JD128744 - Sequence 109768 from Patent EP1572962.
JD104446 - Sequence 85470 from Patent EP1572962.
AB209557 - Homo sapiens mRNA for LIM domain kinase 1 isoform 1 variant protein.
JD446679 - Sequence 427703 from Patent EP1572962.
JD339277 - Sequence 320301 from Patent EP1572962.
JD555428 - Sequence 536452 from Patent EP1572962.
JD521214 - Sequence 502238 from Patent EP1572962.
JD495093 - Sequence 476117 from Patent EP1572962.
JD354334 - Sequence 335358 from Patent EP1572962.
JD197621 - Sequence 178645 from Patent EP1572962.
JD180895 - Sequence 161919 from Patent EP1572962.
JD477360 - Sequence 458384 from Patent EP1572962.
JD139980 - Sequence 121004 from Patent EP1572962.
JD246372 - Sequence 227396 from Patent EP1572962.
JD439638 - Sequence 420662 from Patent EP1572962.
JD543783 - Sequence 524807 from Patent EP1572962.
JD520308 - Sequence 501332 from Patent EP1572962.
JD404952 - Sequence 385976 from Patent EP1572962.
JD476255 - Sequence 457279 from Patent EP1572962.
JD157681 - Sequence 138705 from Patent EP1572962.
JD138098 - Sequence 119122 from Patent EP1572962.
JD141487 - Sequence 122511 from Patent EP1572962.
JD487562 - Sequence 468586 from Patent EP1572962.
JD371831 - Sequence 352855 from Patent EP1572962.
JD191692 - Sequence 172716 from Patent EP1572962.
JD526555 - Sequence 507579 from Patent EP1572962.
JD446746 - Sequence 427770 from Patent EP1572962.
JD151799 - Sequence 132823 from Patent EP1572962.
JD405945 - Sequence 386969 from Patent EP1572962.
JD192748 - Sequence 173772 from Patent EP1572962.
JD560453 - Sequence 541477 from Patent EP1572962.
JD191773 - Sequence 172797 from Patent EP1572962.
JD251225 - Sequence 232249 from Patent EP1572962.
JD464513 - Sequence 445537 from Patent EP1572962.
JD188936 - Sequence 169960 from Patent EP1572962.
JD518667 - Sequence 499691 from Patent EP1572962.
JD067133 - Sequence 48157 from Patent EP1572962.
JD351502 - Sequence 332526 from Patent EP1572962.
JD203994 - Sequence 185018 from Patent EP1572962.
JD148655 - Sequence 129679 from Patent EP1572962.
JD267485 - Sequence 248509 from Patent EP1572962.
JD531900 - Sequence 512924 from Patent EP1572962.
JD262837 - Sequence 243861 from Patent EP1572962.
JD144263 - Sequence 125287 from Patent EP1572962.
JD103973 - Sequence 84997 from Patent EP1572962.
JD362070 - Sequence 343094 from Patent EP1572962.
JD240402 - Sequence 221426 from Patent EP1572962.
JD156128 - Sequence 137152 from Patent EP1572962.
JD195754 - Sequence 176778 from Patent EP1572962.
JD223027 - Sequence 204051 from Patent EP1572962.
JD498151 - Sequence 479175 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  BioCarta from NCI Cancer Genome Anatomy Project
h_rhoPathway - Rho cell motility signaling pathway
h_rac1Pathway - Rac 1 cell motility signaling pathway
h_CCR3Pathway - CCR3 signaling in Eosinophils
h_malPathway - Role of MAL in Rho-Mediated Activation of SRF

Reactome (by CSHL, EBI, and GO)

Protein P53667 (Reactome details) participates in the following event(s):

R-HSA-399952 Phosphorylation of LIMK-1 by PAK
R-HSA-2029460 PAK1 phosphorylates LIMK1
R-HSA-419645 Dimerization of LIMK1 by Hsp90
R-NUL-421139 Limk1 phosphorylates Cfl1, inactivating it
R-HSA-419087 LIM kinase phosphorylation by ROCK
R-HSA-3928577 ROCK phosphorylates LIMK1,2
R-HSA-399950 Phosphorylation of cofilin by LIMK-1
R-HSA-3928608 LIMK phosphorylates CFL1, inactivating it
R-HSA-399954 Sema3A PAK dependent Axon repulsion
R-HSA-2029482 Regulation of actin dynamics for phagocytic cup formation
R-HSA-5627123 RHO GTPases activate PAKs
R-HSA-416572 Sema4D induced cell migration and growth-cone collapse
R-HSA-5627117 RHO GTPases Activate ROCKs
R-HSA-3928662 EPHB-mediated forward signaling
R-HSA-373755 Semaphorin interactions
R-HSA-2029480 Fcgamma receptor (FCGR) dependent phagocytosis
R-HSA-195258 RHO GTPase Effectors
R-HSA-400685 Sema4D in semaphorin signaling
R-HSA-2682334 EPH-Ephrin signaling
R-HSA-422475 Axon guidance
R-HSA-168249 Innate Immune System
R-HSA-194315 Signaling by Rho GTPases
R-HSA-1266738 Developmental Biology
R-HSA-168256 Immune System
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: B7Z6I8, D3DXF4, D3DXF5, ENST00000336180.1, ENST00000336180.2, ENST00000336180.3, ENST00000336180.4, ENST00000336180.5, ENST00000336180.6, LIMK, LIMK1_HUMAN, NM_002314, O15283, P53667, Q15820, Q15821, Q75MU3, Q9Y5Q1, uc317ulu.1, uc317ulu.2
UCSC ID: ENST00000336180.7_4
RefSeq Accession: NM_002314.4
Protein: P53667 (aka LIMK1_HUMAN or LIK1_HUMAN)

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene LIMK1:
williams (Williams Syndrome)

-  Gene Model Information
  Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.