P53667 (LIMK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
LIM domain kinase 1
Short name=LIMK-1
EC=2.7.11.1

Gene names

Name:	LIMK1
Synonyms:	LIMK

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	647 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Ref.4 Ref.9 Ref.13 Ref.14 Ref.17 Ref.18 Ref.21
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.27
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 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 component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Williams-Beuren syndrome
Domain	LIM domain Repeat
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	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 negative regulation of ubiquitin-protein ligase activity Inferred from direct assay PubMed 17512523. Source: BHF-UCL 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
Cellular_component	cytosol Traceable author statement. Source: Reactome focal adhesion Inferred from electronic annotation. Source: Compara neuron projection Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from direct assay. Source: HPA
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW heat shock protein binding Inferred from direct assay PubMed 17512523. Source: BHF-UCL protein serine/threonine kinase activity Traceable author statement. Source: Reactome zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Arrb1	P29066	2	EBI-444403,EBI-4303019	From a different organism.
Arrb2	P29067	2	EBI-444403,EBI-1636616	From a different organism.
LATS1	O95835	5	EBI-444403,EBI-444209
MMP14	P50281	4	EBI-444403,EBI-992788
PAK1	Q13153	5	EBI-444403,EBI-1307
PAK2	Q13177	2	EBI-444403,EBI-1045887

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 647

647

LIM domain kinase 1

PRO_0000075803

Regions

Domain

25 – 75

51

LIM zinc-binding 1

Domain

84 – 137

54

LIM zinc-binding 2

Domain

165 – 258

94

PDZ

Domain

339 – 604

266

Protein kinase

Nucleotide binding

345 – 353

9

ATP By similarity

Sites

Active site

460

1

By similarity

Binding site

368

1

ATP By similarity

Amino acid modifications

Modified residue

210

1

Phosphoserine Ref.23 Ref.25

Modified residue

229

1

Phosphothreonine Ref.23 Ref.25

Modified residue

302

1

Phosphoserine Ref.25

Modified residue

307

1

Phosphoserine Ref.24

Modified residue

310

1

Phosphoserine Ref.23 Ref.24 Ref.25

Modified residue

323

1

Phosphoserine; by MAPKAPK2 Ref.19

Modified residue

337

1

Phosphoserine Ref.23

Modified residue

508

1

Phosphothreonine; by ROCK1 and PAK1 Ref.8 Ref.10 Ref.17

Natural variations

Alternative sequence

1 – 51

51

MRLTL…ADCFR → MLLASAPRRRRFLQRAK in isoform 4.

VSP_043331

Alternative sequence

1 – 14

14

Missing in isoform 2.

VSP_003125

Alternative sequence

294 – 305

12

LRSCS…RSPGA → FARTWVALSPSA in isoform 3.

VSP_003126

Alternative sequence

306 – 647

342

Missing in isoform 3.

VSP_003127

Natural variant

190

1

G → A. Ref.28
Corresponds to variant rs35827364 [ dbSNP | Ensembl ].

VAR_042246

Natural variant

247

1

S → N. Ref.28
Corresponds to variant rs55661242 [ dbSNP | Ensembl ].

VAR_042247

Natural variant

422

1

R → Q. Ref.28
Corresponds to variant rs55679316 [ dbSNP | Ensembl ].

VAR_042248

Natural variant

580

1

F → Y. Ref.2 Ref.3
Corresponds to variant rs178412 [ dbSNP | Ensembl ].

VAR_050148

Experimental info

Mutagenesis

84

1

C → S: Enhances actin aggregation. Ref.4

Mutagenesis

177 – 178

2

GL → EA: Enhances actin aggregation.

Mutagenesis

460

1

D → N: Abrogates kinase activity. Ref.4

Mutagenesis

496 – 506

11

Missing: Reduces actin aggregation. Ref.4

Mutagenesis

503 – 505

3

RKK → GAA: Abolishes kinase activity. Ref.4

Mutagenesis

508

1

T → A: Abolishes activation by ROCK1. Ref.4 Ref.10

Mutagenesis

508

1

T → EE: Enhances kinase activity. Ref.4 Ref.10

Mutagenesis

508

1

T → V or E: Reduces kinase activity. Ref.4 Ref.10

Secondary structure

1

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647

Helix Strand Turn

Details...

Beta strand

332 – 334

3

Helix

336 – 338

3

Beta strand

339 – 346

8

Beta strand

349 – 358

10

Turn

359 – 361

3

Beta strand

364 – 371

8

Helix

375 – 388

14

Beta strand

399 – 405

7

Beta strand

408 – 414

7

Helix

421 – 427

7

Helix

434 – 453

20

Beta strand

465 – 468

4

Beta strand

474 – 476

3

Helix

513 – 515

3

Helix

518 – 521

4

Helix

529 – 544

16

Turn

550 – 552

3

Beta strand

559 – 561

3

Helix

563 – 569

7

Helix

579 – 586

8

Helix

591 – 593

3

Helix

597 – 613

17

Helix

618 – 634

17

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 7, 2006. Version 3. Checksum: 9838BEFBE7006447	FASTA	647	72,585
	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
	Isoform 2 [UniParc]. Checksum: EAF0A3B93916D9FA	FASTA	633	70,793
	10 20 30 40 50 60 MGEEGSELPV CASCGQRIYD GQYLQALNAD WHADCFRCCD CSASLSHQYY EKDGQLFCKK 70 80 90 100 110 120 DYWARYGESC HGCSEQITKG LVMVAGELKY HPECFICLTC GTFIGDGDTY TLVEHSKLYC 130 140 150 160 170 180 GHCYYQTVVT PVIEQILPDS PGSHLPHTVT LVSIPASSHG KRGLSVSIDP PHGPPGCGTE 190 200 210 220 230 240 HSHTVRVQGV DPGCMSPDVK NSIHVGDRIL EINGTPIRNV PLDEIDLLIQ ETSRLLQLTL 250 260 270 280 290 300 EHDPHDTLGH GLGPETSPLS SPAYTPSGEA GSSARQKPVL RSCSIDRSPG AGSLGSPASQ 310 320 330 340 350 360 RKDLGRSESL RVVCRPHRIF RPSDLIHGEV LGKGCFGQAI KVTHRETGEV MVMKELIRFD 370 380 390 400 410 420 EETQRTFLKE VKVMRCLEHP NVLKFIGVLY KDKRLNFITE YIKGGTLRGI IKSMDSQYPW 430 440 450 460 470 480 SQRVSFAKDI ASGMAYLHSM NIIHRDLNSH NCLVRENKNV VVADFGLARL MVDEKTQPEG 490 500 510 520 530 540 LRSLKKPDRK KRYTVVGNPY WMAPEMINGR SYDEKVDVFS FGIVLCEIIG RVNADPDYLP 550 560 570 580 590 600 RTMDFGLNVR GFLDRYCPPN CPPSFFPITV RCCDLDPEKR PSFVKLEHWL ETLRMHLAGH 610 620 630 LPLGPQLEQL DRGFWETYRR GESGLPAHPE VPD
	Isoform 3 [UniParc]. Checksum: 65FEF49849CCA142	FASTA	305	33,373
	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 KPVFARTWVA LSPSA
	Isoform 4 [UniParc]. Checksum: A78F41C1313E9CEE	FASTA	613	68,729
	10 20 30 40 50 60 MLLASAPRRR RFLQRAKCCD CSASLSHQYY EKDGQLFCKK DYWARYGESC HGCSEQITKG 70 80 90 100 110 120 LVMVAGELKY HPECFICLTC GTFIGDGDTY TLVEHSKLYC GHCYYQTVVT PVIEQILPDS 130 140 150 160 170 180 PGSHLPHTVT LVSIPASSHG KRGLSVSIDP PHGPPGCGTE HSHTVRVQGV DPGCMSPDVK 190 200 210 220 230 240 NSIHVGDRIL EINGTPIRNV PLDEIDLLIQ ETSRLLQLTL EHDPHDTLGH GLGPETSPLS 250 260 270 280 290 300 SPAYTPSGEA GSSARQKPVL RSCSIDRSPG AGSLGSPASQ RKDLGRSESL RVVCRPHRIF 310 320 330 340 350 360 RPSDLIHGEV LGKGCFGQAI KVTHRETGEV MVMKELIRFD EETQRTFLKE VKVMRCLEHP 370 380 390 400 410 420 NVLKFIGVLY KDKRLNFITE YIKGGTLRGI IKSMDSQYPW SQRVSFAKDI ASGMAYLHSM 430 440 450 460 470 480 NIIHRDLNSH NCLVRENKNV VVADFGLARL MVDEKTQPEG LRSLKKPDRK KRYTVVGNPY 490 500 510 520 530 540 WMAPEMINGR SYDEKVDVFS FGIVLCEIIG RVNADPDYLP RTMDFGLNVR GFLDRYCPPN 550 560 570 580 590 600 CPPSFFPITV RCCDLDPEKR PSFVKLEHWL ETLRMHLAGH LPLGPQLEQL DRGFWETYRR 610 GESGLPAHPE VPD

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[25]	"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, MASS SPECTROMETRY.
[26]	"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.
[27]	"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.
[28]	"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. , 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.
[29]	"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.

IPI

IPI00216433.
IPI00216434.
IPI00291702.

PIR

JP0078.

RefSeq

NP_001191355.1. NM_001204426.1.
NP_002305.1. NM_002314.3.

UniGene

Hs.647035.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3S95	X-ray	1.65	A/B	330-637	[»]

ProteinModelPortal

P53667.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31605N.

IntAct

P53667. 9 interactions.

MINT

MINT-2833166.

STRING

9606.ENSP00000336740.

PTM databases

PhosphoSite

P53667.

Polymorphism databases

DMDM

90185240.

Proteomic databases

PaxDb

P53667.

PRIDE

P53667.

Protocols and materials databases

DNASU

3984.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000336180; ENSP00000336740; ENSG00000106683.
ENST00000419043; ENSP00000394098; ENSG00000106683.
ENST00000435201; ENSP00000414606; ENSG00000106683.
ENST00000538333; ENSP00000444452; ENSG00000106683.
ENST00000570926; ENSP00000460109; ENSG00000262063.
ENST00000571928; ENSP00000460552; ENSG00000262063.
ENST00000572388; ENSP00000461249; ENSG00000262063.
ENST00000576167; ENSP00000460019; ENSG00000262063.

GeneID

3984.

KEGG

hsa:3984.

UCSC

uc003uaa.2. human.

Organism-specific databases

CTD

3984.

GeneCards

GC07P073497.

HGNC

HGNC:6613. LIMK1.

HPA

HPA028064.
HPA028516.

MIM

601329. gene.

neXtProt

NX_P53667.

Orphanet

904. Williams syndrome.

PharmGKB

PA30386.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000013121.

HOVERGEN

HBG052328.

InParanoid

P53667.

KO

K05743.

PhylomeDB

P53667.

Enzyme and pathway databases

BRENDA

2.7.11.1. 2681.

Pathway_Interaction_DB

caspase_pathway. Caspase cascade in apoptosis.

Reactome

REACT_111045. Developmental Biology.
REACT_127416. Developmental Biology.

Gene expression databases

ArrayExpress

P53667.

Bgee

P53667.

CleanEx

HS_LIMK1.

Genevestigator

P53667.

GermOnline

ENSG00000106683. Homo sapiens.

Family and domain databases

Gene3D

2.10.110.10. 2 hits.

InterPro

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.
[Graphical view]

Pfam

PF00412. LIM. 2 hits.
PF00595. PDZ. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]

PRINTS

PR00109. TYRKINASE.

SMART

SM00132. LIM. 2 hits.
SM00228. PDZ. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.
SSF50156. PDZ. 1 hit.

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.
PS00108. PROTEIN_KINASE_ST. False negative.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P53667.

ChEMBL

CHEMBL3836.

EvolutionaryTrace

P53667.

GenomeRNAi

3984.

NextBio

15626.

SOURCE

Search...

Entry information

Entry name

LIMK1_HUMAN

Accession

Primary (citable) accession number: P53667
Secondary accession number(s): B7Z6I8 , 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:	May 1, 2013
This is version 144 of the entry and version 3 of the sequence. [Complete history]

Entry status

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.