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P53667 (LIMK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 155. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
LIM domain kinase 1

Short name=LIMK-1
EC=2.7.11.1
Gene names
Name:LIMK1
Synonyms:LIMK
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length647 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Required for atypical chemokine receptor ACKR2-induced phosphorylation of cofilin (CFL1). Ref.4 Ref.9 Ref.13 Ref.14 Ref.17 Ref.18 Ref.21 Ref.29

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Subunit structure

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. Ref.9 Ref.10 Ref.15 Ref.17 Ref.20

Subcellular location

Cytoplasm. Nucleus. Note: Predominantly found in the cytoplasm. Ref.4 Ref.18 Ref.28

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.

Post-translational modification

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. Ref.8 Ref.10 Ref.11 Ref.12 Ref.17 Ref.19 Ref.29

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.

Involvement in disease

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.

Sequence similarities

Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.

Contains 2 LIM zinc-binding domains.

Contains 1 PDZ (DHR) domain.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseWilliams-Beuren syndrome
   DomainLIM domain
Repeat
   LigandATP-binding
Metal-binding
Nucleotide-binding
Zinc
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processFc-gamma receptor signaling pathway involved in phagocytosis

Traceable author statement. Source: Reactome

Rho protein signal transduction

Traceable author statement Ref.9. Source: ProtInc

actin cytoskeleton organization

Traceable author statement PubMed 10428028. Source: ProtInc

axon guidance

Traceable author statement. Source: Reactome

innate immune response

Traceable author statement. Source: Reactome

negative regulation of ubiquitin-protein ligase activity

Inferred from direct assay PubMed 17512523. Source: BHF-UCL

nervous system development

Traceable author statement Ref.2. Source: ProtInc

positive regulation of actin filament bundle assembly

Inferred from direct assay PubMed 17512523. Source: BHF-UCL

positive regulation of axon extension

Inferred from sequence or structural similarity. Source: UniProtKB

protein phosphorylation

Inferred from mutant phenotype Ref.29. Source: UniProtKB

signal transduction

Traceable author statement PubMed 10428028Ref.9. Source: ProtInc

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 17512523. Source: BHF-UCL

cytosol

Traceable author statement. Source: Reactome

focal adhesion

Inferred from electronic annotation. Source: Ensembl

neuron projection

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from direct assay. Source: HPA

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

heat shock protein binding

Inferred from direct assay PubMed 17512523. Source: BHF-UCL

protein kinase activity

Non-traceable author statement PubMed 8537403. Source: ProtInc

protein serine/threonine kinase activity

Traceable author statement. Source: Reactome

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: 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.
Isoform 2 (identifier: P53667-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-14: Missing.
Isoform 3 (identifier: P53667-3)

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.
Isoform 4 (identifier: P53667-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-51: MRLTLLCCTWREERMGEEGSELPVCASCGQRIYDGQYLQALNADWHADCFR → MLLASAPRRRRFLQRAK
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 647647LIM domain kinase 1
PRO_0000075803

Regions

Domain25 – 7551LIM zinc-binding 1
Domain84 – 13754LIM zinc-binding 2
Domain165 – 25894PDZ
Domain339 – 604266Protein kinase
Nucleotide binding345 – 3539ATP By similarity

Sites

Active site4601 By similarity
Binding site3681ATP By similarity

Amino acid modifications

Modified residue2101Phosphoserine Ref.23 Ref.26
Modified residue2291Phosphothreonine Ref.23 Ref.26
Modified residue3021Phosphoserine Ref.26
Modified residue3071Phosphoserine Ref.24
Modified residue3101Phosphoserine Ref.23 Ref.24 Ref.26
Modified residue3231Phosphoserine; by MAPKAPK2 Ref.19
Modified residue3371Phosphoserine Ref.23
Modified residue5081Phosphothreonine; by ROCK1 and PAK1 Ref.8 Ref.10 Ref.17 Ref.29

Natural variations

Alternative sequence1 – 5151MRLTL…ADCFR → MLLASAPRRRRFLQRAK in isoform 4.
VSP_043331
Alternative sequence1 – 1414Missing in isoform 2.
VSP_003125
Alternative sequence294 – 30512LRSCS…RSPGA → FARTWVALSPSA in isoform 3.
VSP_003126
Alternative sequence306 – 647342Missing in isoform 3.
VSP_003127
Natural variant1901G → A. Ref.30
Corresponds to variant rs35827364 [ dbSNP | Ensembl ].
VAR_042246
Natural variant2471S → N. Ref.30
Corresponds to variant rs55661242 [ dbSNP | Ensembl ].
VAR_042247
Natural variant4221R → Q. Ref.30
Corresponds to variant rs55679316 [ dbSNP | Ensembl ].
VAR_042248
Natural variant5801F → Y. Ref.2 Ref.3
Corresponds to variant rs178412 [ dbSNP | Ensembl ].
VAR_050148

Experimental info

Mutagenesis841C → S: Enhances actin aggregation. Ref.4
Mutagenesis177 – 1782GL → EA: Enhances actin aggregation.
Mutagenesis4601D → N: Abrogates kinase activity. Ref.4
Mutagenesis496 – 50611Missing: Reduces actin aggregation. Ref.4
Mutagenesis503 – 5053RKK → GAA: Abolishes kinase activity. Ref.4
Mutagenesis5081T → A: Abolishes activation by ROCK1. Ref.4 Ref.10
Mutagenesis5081T → EE: Enhances kinase activity. Ref.4 Ref.10
Mutagenesis5081T → V or E: Reduces kinase activity. Ref.4 Ref.10

Secondary structure

............................................. 647
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 7, 2006. Version 3.
Checksum: 9838BEFBE7006447

FASTA64772,585
        10         20         30         40         50         60 
MRLTLLCCTW REERMGEEGS ELPVCASCGQ RIYDGQYLQA LNADWHADCF RCCDCSASLS 

        70         80         90        100        110        120 
HQYYEKDGQL FCKKDYWARY GESCHGCSEQ ITKGLVMVAG ELKYHPECFI CLTCGTFIGD 

       130        140        150        160        170        180 
GDTYTLVEHS KLYCGHCYYQ TVVTPVIEQI LPDSPGSHLP HTVTLVSIPA SSHGKRGLSV 

       190        200        210        220        230        240 
SIDPPHGPPG CGTEHSHTVR VQGVDPGCMS PDVKNSIHVG DRILEINGTP IRNVPLDEID 

       250        260        270        280        290        300 
LLIQETSRLL QLTLEHDPHD TLGHGLGPET SPLSSPAYTP SGEAGSSARQ KPVLRSCSID 

       310        320        330        340        350        360 
RSPGAGSLGS PASQRKDLGR SESLRVVCRP HRIFRPSDLI HGEVLGKGCF GQAIKVTHRE 

       370        380        390        400        410        420 
TGEVMVMKEL IRFDEETQRT FLKEVKVMRC LEHPNVLKFI GVLYKDKRLN FITEYIKGGT 

       430        440        450        460        470        480 
LRGIIKSMDS QYPWSQRVSF AKDIASGMAY LHSMNIIHRD LNSHNCLVRE NKNVVVADFG 

       490        500        510        520        530        540 
LARLMVDEKT QPEGLRSLKK PDRKKRYTVV GNPYWMAPEM INGRSYDEKV DVFSFGIVLC 

       550        560        570        580        590        600 
EIIGRVNADP DYLPRTMDFG LNVRGFLDRY CPPNCPPSFF PITVRCCDLD PEKRPSFVKL 

       610        620        630        640 
EHWLETLRMH LAGHLPLGPQ LEQLDRGFWE TYRRGESGLP AHPEVPD 

« Hide

Isoform 2 [UniParc].

Checksum: EAF0A3B93916D9FA
Show »

FASTA63370,793
Isoform 3 [UniParc].

Checksum: 65FEF49849CCA142
Show »

FASTA30533,373
Isoform 4 [UniParc].

Checksum: A78F41C1313E9CEE
Show »

FASTA61368,729

References

« Hide 'large scale' references
[1]"Identification of a human cDNA encoding a novel protein kinase with two repeats of the LIM/double zinc finger motif."
Mizuno K., Okano I., Ohashi K., Nunoue K., Kuma K., Miyata T., Nakamura T.
Oncogene 9:1605-1612(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"LIM-kinase1 hemizygosity implicated in impaired visuospatial constructive cognition."
Frangiskakis J.M., Ewart A.K., Morris C.A., Mervis C.B., Bertrand J., Robinson B.F., Klein B.P., Ensing G.J., Everett L.A., Green E.D., Proeschel C., Gutowski N.J., Noble M., Atkinson D.L., Odelberg S.J., Keating M.T.
Cell 86:59-69(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2), VARIANT TYR-580.
Tissue: Hippocampus and Placenta.
[3]"Identification of genes from a 500-kb region at 7q11.23 that is commonly deleted in Williams syndrome patients."
Osborne L.R., Martindale D.W., Scherer S.W., Shi X.-M., Huizenga J., Heng H.H.Q., Costa T., Pober B., Lew L., Brinkman J., Rommens J., Koop B.F., Tsui L.-C.
Genomics 36:328-336(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT TYR-580, GENE DELETION IN WILLIAMS-BEUREN SYNDROME.
[4]"Structural features of LIM kinase that control effects on the actin cytoskeleton."
Edwards D.C., Gill G.N.
J. Biol. Chem. 274:11352-11361(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, SELF-ASSOCIATION, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-84; 177-GLY-LEU-178; ASP-460; 496-ARG--ARG-506; 503-ARG--GLY-505 AND THR-508.
Tissue: Epidermal carcinoma.
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
Tissue: Placenta.
[6]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics."
Edwards D.C., Sanders L.C., Bokoch G.M., Gill G.N.
Nat. Cell Biol. 1:253-259(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-508 BY PAK1.
[9]"Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase."
Maekawa M., Ishizaki T., Boku S., Watanabe N., Fujita A., Iwamatsu A., Obinata T., Ohashi K., Mizuno K., Narumiya S.
Science 285:895-898(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ROCK1.
[10]"Rho-associated kinase ROCK activates LIM-kinase 1 by phosphorylation at threonine 508 within the activation loop."
Ohashi K., Nagata K., Maekawa M., Ishizaki T., Narumiya S., Mizuno K.
J. Biol. Chem. 275:3577-3582(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-508, MUTAGENESIS OF THR-508, INTERACTION WITH ROCK1.
[11]"Activation of LIM kinases by myotonic dystrophy kinase-related Cdc42-binding kinase alpha."
Sumi T., Matsumoto K., Shibuya A., Nakamura T.
J. Biol. Chem. 276:23092-23096(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY CDC42BP.
[12]"Cytoskeletal changes regulated by the PAK4 serine/threonine kinase are mediated by LIM kinase 1 and cofilin."
Dan C., Kelly A., Bernard O., Minden A.
J. Biol. Chem. 276:32115-32121(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY PAK4.
[13]"Control of actin reorganization by Slingshot, a family of phosphatases that dephosphorylate ADF/cofilin."
Niwa R., Nagata-Ohashi K., Takeichi M., Mizuno K., Uemura T.
Cell 108:233-246(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[14]"Cell cycle-associated changes in Slingshot phosphatase activity and roles in cytokinesis in animal cells."
Kaji N., Ohashi K., Shuin M., Niwa R., Uemura T., Mizuno K.
J. Biol. Chem. 278:33450-33455(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[15]"p57Kip2 regulates actin dynamics by binding and translocating LIM-kinase 1 to the nucleus."
Yokoo T., Toyoshima H., Miura M., Wang Y., Iida K.T., Suzuki H., Sone H., Shimano H., Gotoda T., Nishimori S., Tanaka K., Yamada N.
J. Biol. Chem. 278:52919-52923(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CDKN1C.
[16]"An unappreciated role for RNA surveillance."
Hillman R.T., Green R.E., Brenner S.E.
Genome Biol. 5:R8.1-R8.16(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
[17]"Interplay between components of a novel LIM kinase-slingshot phosphatase complex regulates cofilin."
Soosairajah J., Maiti S., Wiggan O., Sarmiere P., Moussi N., Sarcevic B., Sampath R., Bamburg J.R., Bernard O.
EMBO J. 24:473-486(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH SSH1, PHOSPHORYLATION AT THR-508, DEPHOSPHORYLATION.
[18]"Spatial and temporal regulation of cofilin activity by LIM kinase and Slingshot is critical for directional cell migration."
Nishita M., Tomizawa C., Yamamoto M., Horita Y., Ohashi K., Mizuno K.
J. Cell Biol. 171:349-359(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[19]"MAPKAPK-2-mediated LIM-kinase activation is critical for VEGF-induced actin remodeling and cell migration."
Kobayashi M., Nishita M., Mishima T., Ohashi K., Mizuno K.
EMBO J. 25:713-726(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-323 BY MAPKAPK2.
[20]"Hsp90 increases LIM kinase activity by promoting its homo-dimerization."
Li R., Soosairajah J., Harari D., Citri A., Price J., Ng H.L., Morton C.J., Parker M.W., Yarden Y., Bernard O.
FASEB J. 20:1218-1220(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HSP90AA1.
[21]"The phosphorylation of p25/TPPP by LIM kinase 1 inhibits its ability to assemble microtubules."
Acevedo K., Li R., Soo P., Suryadinata R., Sarcevic B., Valova V.A., Graham M.E., Robinson P.J., Bernard O.
Exp. Cell Res. 313:4091-4106(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF TPPP.
[22]"Lim kinases, regulators of actin dynamics."
Bernard O.
Int. J. Biochem. Cell Biol. 39:1071-1076(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[23]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-210; THR-229; SER-310 AND SER-337, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[24]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-307 AND SER-310, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[25]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[26]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-210; THR-229; SER-302 AND SER-310, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[27]"LIM kinases are attractive targets with many macromolecular partners and only a few small molecule regulators."
Manetti F.
Med. Res. Rev. 0:0-0(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[28]"Nuclear and cytoplasmic LIMK1 enhances human breast cancer progression."
McConnell B.V., Koto K., Gutierrez-Hartmann A.
Mol. Cancer 10:75-75(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[29]"Beta-arrestin-dependent activation of the cofilin pathway is required for the scavenging activity of the atypical chemokine receptor D6."
Borroni E.M., Cancellieri C., Vacchini A., Benureau Y., Lagane B., Bachelerie F., Arenzana-Seisdedos F., Mizuno K., Mantovani A., Bonecchi R., Locati M.
Sci. Signal. 6:RA30-RA30(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION AT THR-508.
[30]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] ALA-190; ASN-247 AND GLN-422.
[31]"Crystal structure of the human limk1 kinase domain in complex with staurosporine."
Structural genomics consortium (SGC)
Submitted (JUL-2011) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 330-637.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRJP0078.
RefSeqNP_001191355.1. NM_001204426.1.
NP_002305.1. NM_002314.3.
UniGeneHs.647035.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3S95X-ray1.65A/B330-637[»]
ProteinModelPortalP53667.
SMRP53667. Positions 22-145, 158-258, 330-637.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110172. 24 interactions.
DIPDIP-31605N.
IntActP53667. 16 interactions.
MINTMINT-2833166.
STRING9606.ENSP00000336740.

Chemistry

BindingDBP53667.
ChEMBLCHEMBL3836.
GuidetoPHARMACOLOGY2054.

PTM databases

PhosphoSiteP53667.

Polymorphism databases

DMDM90185240.

Proteomic databases

PaxDbP53667.
PRIDEP53667.

Protocols and materials databases

DNASU3984.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000336180; ENSP00000336740; ENSG00000106683. [P53667-1]
ENST00000435201; ENSP00000414606; ENSG00000106683. [P53667-3]
ENST00000538333; ENSP00000444452; ENSG00000106683. [P53667-4]
ENST00000570926; ENSP00000460109; ENSG00000262063. [P53667-3]
ENST00000571928; ENSP00000460552; ENSG00000262063. [P53667-1]
ENST00000572388; ENSP00000461249; ENSG00000262063. [P53667-4]
GeneID3984.
KEGGhsa:3984.
UCSCuc003uaa.2. human. [P53667-1]
uc003uab.3. human. [P53667-4]

Organism-specific databases

CTD3984.
GeneCardsGC07P073497.
HGNCHGNC:6613. LIMK1.
HPAHPA028064.
HPA028516.
MIM601329. gene.
neXtProtNX_P53667.
Orphanet904. Williams syndrome.
PharmGKBPA30386.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000013121.
HOVERGENHBG052328.
InParanoidP53667.
KOK05743.
PhylomeDBP53667.
TreeFamTF318014.

Enzyme and pathway databases

BRENDA2.7.11.1. 2681.
ReactomeREACT_111045. Developmental Biology.
REACT_6900. Immune System.
SignaLinkP53667.

Gene expression databases

ArrayExpressP53667.
BgeeP53667.
CleanExHS_LIMK1.
GenevestigatorP53667.

Family and domain databases

Gene3D2.10.110.10. 2 hits.
2.30.42.10. 1 hit.
InterProIPR011009. Kinase-like_dom.
IPR001478. PDZ.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR001781. Znf_LIM.
[Graphical view]
PfamPF00412. LIM. 2 hits.
PF00595. PDZ. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSPR00109. TYRKINASE.
SMARTSM00132. LIM. 2 hits.
SM00228. PDZ. 1 hit.
[Graphical view]
SUPFAMSSF50156. SSF50156. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS00478. 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.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP53667.
GeneWikiLIMK1.
GenomeRNAi3984.
NextBio15626.
PROP53667.
SOURCESearch...

Entry information

Entry nameLIMK1_HUMAN
AccessionPrimary (citable) accession number: P53667
Secondary accession number(s): B7Z6I8 expand/collapse secondary AC list , D3DXF4, D3DXF5, O15283, Q15820, Q15821, Q75MU3, Q9Y5Q1
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: March 7, 2006
Last modified: April 16, 2014
This is version 155 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM