LIMK2_HUMAN
ID LIMK2_HUMAN Reviewed; 638 AA.
AC P53671; A8K6H5; Q7KZ80; Q7L3H5; Q96E10; Q99464; Q9UFU0;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 212.
DE RecName: Full=LIM domain kinase 2;
DE Short=LIMK-2;
DE EC=2.7.11.1 {ECO:0000269|PubMed:22328514, ECO:0000269|PubMed:8537403};
GN Name=LIMK2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LIMK2A), FUNCTION, AND CATALYTIC
RP ACTIVITY.
RC TISSUE=Hepatoma;
RX PubMed=8537403; DOI=10.1074/jbc.270.52.31321;
RA Okano I., Hiraoka J., Otera H., Nunoue K., Ohashi K., Iwashita S.,
RA Hirai M., Mizuno K.;
RT "Identification and characterization of a novel family of serine/threonine
RT kinases containing two N-terminal LIM motifs.";
RL J. Biol. Chem. 270:31321-31330(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LIMK2A AND LIMK2B), SELF-INTERACTION,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Lung;
RX PubMed=8954941; DOI=10.1006/bbrc.1996.1847;
RA Osada H., Hasada K., Inazawa J., Uchida K., Ueda R., Takahashi T.,
RA Takahashi T.;
RT "Subcellular localization and protein interaction of the human LIMK2 gene
RT expressing alternative transcripts with tissue-specific regulation.";
RL Biochem. Biophys. Res. Commun. 229:582-589(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LIMK2B).
RC TISSUE=Uterus;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LIMK2A).
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LIMK2A).
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP INTERACTION WITH MARF1.
RA Miyamoto K., Nakamura T., Shirakawa K., Matsumoto K.;
RT "Molecular cloning and characterization of novel large protein, limkain b1,
RT which associates with the LIM-kinase 2.";
RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP FUNCTION, AND INTERACTION WITH ROCK1.
RX PubMed=10436159; DOI=10.1126/science.285.5429.895;
RA Maekawa M., Ishizaki T., Boku S., Watanabe N., Fujita A., Iwamatsu A.,
RA Obinata T., Ohashi K., Mizuno K., Narumiya S.;
RT "Signaling from Rho to the actin cytoskeleton through protein kinases ROCK
RT and LIM-kinase.";
RL Science 285:895-898(1999).
RN [11]
RP PHOSPHORYLATION AT THR-505, MUTAGENESIS OF THR-505, FUNCTION, AND
RP INTERACTION WITH ROCK1.
RX PubMed=11018042; DOI=10.1074/jbc.m007074200;
RA Sumi T., Matsumoto K., Nakamura T.;
RT "Specific activation of LIM kinase 2 via phosphorylation of threonine 505
RT by ROCK, a Rho-dependent protein kinase.";
RL J. Biol. Chem. 276:670-676(2001).
RN [12]
RP PHOSPHORYLATION AT THR-505 BY CDC42BP.
RX PubMed=11340065; DOI=10.1074/jbc.c100196200;
RA Sumi T., Matsumoto K., Shibuya A., Nakamura T.;
RT "Activation of LIM kinases by myotonic dystrophy kinase-related Cdc42-
RT binding kinase alpha.";
RL J. Biol. Chem. 276:23092-23096(2001).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-210 AND SER-293, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-293 AND SER-298, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [16]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-451
RP AND THR-505, AND ACTIVE SITE.
RX PubMed=22328514; DOI=10.1242/jcs.096818;
RA Heng Y.W., Lim H.H., Mina T., Utomo P., Zhong S., Lim C.T., Koh C.G.;
RT "TPPP acts downstream of RhoA-ROCK-LIMK2 to regulate astral microtubule
RT organization and spindle orientation.";
RL J. Cell Sci. 125:1579-1590(2012).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-298, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [18]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=25849865; DOI=10.1038/ncomms7781;
RA Kim J., Jo H., Hong H., Kim M.H., Kim J.M., Lee J.K., Heo W.D., Kim J.;
RT "Actin remodelling factors control ciliogenesis by regulating YAP/TAZ
RT activity and vesicle trafficking.";
RL Nat. Commun. 6:6781-6781(2015).
RN [19]
RP STRUCTURE BY NMR OF 62-129.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structures of the second LIM domain of human LIM-kinase 2
RT (LIMK2).";
RL Submitted (NOV-2005) to the PDB data bank.
RN [20]
RP VARIANTS [LARGE SCALE ANALYSIS] SER-35; ASN-45; CYS-213; ARG-296 AND
RP CYS-418.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Serine/threonine-protein kinase that plays an essential role
CC in the regulation of actin filament dynamics (PubMed:10436159,
CC PubMed:11018042). Acts downstream of several Rho family GTPase signal
CC transduction pathways (PubMed:10436159, PubMed:11018042). Involved in
CC astral microtubule organization and mitotic spindle orientation during
CC early stages of mitosis by mediating phosphorylation of TPPP
CC (PubMed:22328514). Displays serine/threonine-specific phosphorylation
CC of myelin basic protein and histone (MBP) in vitro (PubMed:8537403).
CC Suppresses ciliogenesis via multiple pathways; phosphorylation of CFL1,
CC suppression of directional trafficking of ciliary vesicles to the
CC ciliary base, and by facilitating YAP1 nuclear localization where it
CC acts as a transcriptional corepressor of the TEAD4 target genes AURKA
CC and PLK1 (PubMed:25849865). {ECO:0000269|PubMed:10436159,
CC ECO:0000269|PubMed:11018042, ECO:0000269|PubMed:22328514,
CC ECO:0000269|PubMed:25849865, ECO:0000269|PubMed:8537403}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:22328514, ECO:0000269|PubMed:8537403};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990;
CC Evidence={ECO:0000269|PubMed:22328514};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:22328514,
CC ECO:0000269|PubMed:8537403};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46609;
CC Evidence={ECO:0000269|PubMed:22328514};
CC -!- SUBUNIT: [Isoform LIMK2a]: Interacts with LIMK2b.
CC {ECO:0000269|PubMed:8954941}.
CC -!- SUBUNIT: [Isoform LIMK2b]: Interacts with LIMK2a.
CC {ECO:0000269|PubMed:8954941}.
CC -!- SUBUNIT: Binds ROCK1 and MARF1 (Ref.9, PubMed:11018042,
CC PubMed:10436159). Interacts with NISCH (By similarity).
CC {ECO:0000250|UniProtKB:Q8BJ34, ECO:0000269|PubMed:10436159,
CC ECO:0000269|PubMed:11018042, ECO:0000269|Ref.9}.
CC -!- INTERACTION:
CC P53671; Q16543: CDC37; NbExp=2; IntAct=EBI-1384350, EBI-295634;
CC P53671; P08238: HSP90AB1; NbExp=3; IntAct=EBI-1384350, EBI-352572;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, spindle
CC {ECO:0000269|PubMed:22328514}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000269|PubMed:25849865}.
CC -!- SUBCELLULAR LOCATION: [Isoform LIMK2a]: Cytoplasm
CC {ECO:0000269|PubMed:8954941}. Nucleus {ECO:0000269|PubMed:8954941}.
CC -!- SUBCELLULAR LOCATION: [Isoform LIMK2b]: Cytoplasm
CC {ECO:0000269|PubMed:8954941}. Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:8954941}. Nucleus {ECO:0000269|PubMed:8954941}.
CC Note=Mainly present in the cytoplasm and is scarcely translocated to
CC the nucleus. {ECO:0000269|PubMed:8954941}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=LIMK2a {ECO:0000303|PubMed:8954941};
CC IsoId=P53671-1; Sequence=Displayed;
CC Name=LIMK2b {ECO:0000303|PubMed:8954941};
CC IsoId=P53671-2; Sequence=VSP_012287;
CC Name=3;
CC IsoId=P53671-3; Sequence=VSP_012287, VSP_043332;
CC -!- PTM: Phosphorylated on serine and/or threonine residues by ROCK1.
CC {ECO:0000269|PubMed:11018042, ECO:0000269|PubMed:11340065}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
CC protein kinase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB54055.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; D45906; BAA08312.1; -; mRNA.
DR EMBL; D85527; BAA12827.1; -; mRNA.
DR EMBL; AL117466; CAB55941.1; -; mRNA.
DR EMBL; CR456513; CAG30399.1; -; mRNA.
DR EMBL; AK291640; BAF84329.1; -; mRNA.
DR EMBL; AC002073; AAB54055.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AC002073; AAB54056.1; -; Genomic_DNA.
DR EMBL; CH471095; EAW59954.1; -; Genomic_DNA.
DR EMBL; CH471095; EAW59956.1; -; Genomic_DNA.
DR EMBL; CH471095; EAW59958.1; -; Genomic_DNA.
DR EMBL; BC013051; AAH13051.1; -; mRNA.
DR CCDS; CCDS13891.1; -. [P53671-1]
DR CCDS; CCDS13892.1; -. [P53671-2]
DR CCDS; CCDS33637.1; -. [P53671-3]
DR PIR; A59196; A59196.
DR RefSeq; NP_001026971.1; NM_001031801.1. [P53671-3]
DR RefSeq; NP_005560.1; NM_005569.3. [P53671-1]
DR RefSeq; NP_057952.1; NM_016733.2. [P53671-2]
DR PDB; 1X6A; NMR; -; A=62-129.
DR PDB; 4TPT; X-ray; 2.60 A; A/B=330-632.
DR PDB; 5NXD; X-ray; 1.90 A; A/B=330-632.
DR PDB; 7QHG; X-ray; 1.45 A; A/B=330-632.
DR PDBsum; 1X6A; -.
DR PDBsum; 4TPT; -.
DR PDBsum; 5NXD; -.
DR PDBsum; 7QHG; -.
DR AlphaFoldDB; P53671; -.
DR SMR; P53671; -.
DR BioGRID; 110173; 53.
DR IntAct; P53671; 57.
DR MINT; P53671; -.
DR STRING; 9606.ENSP00000339916; -.
DR BindingDB; P53671; -.
DR ChEMBL; CHEMBL5932; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; P53671; -.
DR GuidetoPHARMACOLOGY; 2055; -.
DR GlyGen; P53671; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P53671; -.
DR PhosphoSitePlus; P53671; -.
DR BioMuta; LIMK2; -.
DR DMDM; 1708824; -.
DR EPD; P53671; -.
DR jPOST; P53671; -.
DR MassIVE; P53671; -.
DR MaxQB; P53671; -.
DR PaxDb; P53671; -.
DR PeptideAtlas; P53671; -.
DR PRIDE; P53671; -.
DR ProteomicsDB; 56602; -. [P53671-1]
DR ProteomicsDB; 56603; -. [P53671-2]
DR ProteomicsDB; 56604; -. [P53671-3]
DR Antibodypedia; 2106; 584 antibodies from 38 providers.
DR DNASU; 3985; -.
DR Ensembl; ENST00000331728.9; ENSP00000332687.4; ENSG00000182541.18. [P53671-1]
DR Ensembl; ENST00000333611.8; ENSP00000330470.4; ENSG00000182541.18. [P53671-2]
DR Ensembl; ENST00000340552.4; ENSP00000339916.4; ENSG00000182541.18. [P53671-3]
DR GeneID; 3985; -.
DR KEGG; hsa:3985; -.
DR MANE-Select; ENST00000331728.9; ENSP00000332687.4; NM_005569.4; NP_005560.1.
DR UCSC; uc003akh.4; human. [P53671-1]
DR CTD; 3985; -.
DR DisGeNET; 3985; -.
DR GeneCards; LIMK2; -.
DR HGNC; HGNC:6614; LIMK2.
DR HPA; ENSG00000182541; Low tissue specificity.
DR MIM; 601988; gene.
DR neXtProt; NX_P53671; -.
DR OpenTargets; ENSG00000182541; -.
DR PharmGKB; PA30387; -.
DR VEuPathDB; HostDB:ENSG00000182541; -.
DR eggNOG; KOG1187; Eukaryota.
DR GeneTree; ENSGT00940000159133; -.
DR HOGENOM; CLU_000288_7_23_1; -.
DR InParanoid; P53671; -.
DR OMA; NAGHSPT; -.
DR OrthoDB; 988822at2759; -.
DR PhylomeDB; P53671; -.
DR TreeFam; TF318014; -.
DR BRENDA; 2.7.10.2; 2681.
DR PathwayCommons; P53671; -.
DR Reactome; R-HSA-3928662; EPHB-mediated forward signaling.
DR Reactome; R-HSA-416572; Sema4D induced cell migration and growth-cone collapse.
DR Reactome; R-HSA-5627117; RHO GTPases Activate ROCKs.
DR SignaLink; P53671; -.
DR SIGNOR; P53671; -.
DR BioGRID-ORCS; 3985; 14 hits in 1114 CRISPR screens.
DR ChiTaRS; LIMK2; human.
DR EvolutionaryTrace; P53671; -.
DR GeneWiki; LIMK2; -.
DR GenomeRNAi; 3985; -.
DR Pharos; P53671; Tchem.
DR PRO; PR:P53671; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; P53671; protein.
DR Bgee; ENSG00000182541; Expressed in cervix squamous epithelium and 190 other tissues.
DR ExpressionAtlas; P53671; baseline and differential.
DR Genevisible; P53671; HS.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005801; C:cis-Golgi network; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0072686; C:mitotic spindle; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0030036; P:actin cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0030953; P:astral microtubule organization; IDA:UniProtKB.
DR GO; GO:0061303; P:cornea development in camera-type eye; IEA:Ensembl.
DR GO; GO:0051650; P:establishment of vesicle localization; IMP:UniProtKB.
DR GO; GO:0060322; P:head development; IEA:Ensembl.
DR GO; GO:1902018; P:negative regulation of cilium assembly; IMP:UniProtKB.
DR GO; GO:0016310; P:phosphorylation; TAS:UniProtKB.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; IMP:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
DR Gene3D; 2.30.42.10; -; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR036034; PDZ_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR001781; Znf_LIM.
DR Pfam; PF00412; LIM; 2.
DR Pfam; PF00595; PDZ; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR SMART; SM00132; LIM; 2.
DR SMART; SM00228; PDZ; 1.
DR SUPFAM; SSF50156; SSF50156; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00478; LIM_DOMAIN_1; 2.
DR PROSITE; PS50023; LIM_DOMAIN_2; 2.
DR PROSITE; PS50106; PDZ; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cytoplasm; Cytoskeleton;
KW Kinase; LIM domain; Metal-binding; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transferase; Zinc.
FT CHAIN 1..638
FT /note="LIM domain kinase 2"
FT /id="PRO_0000075809"
FT DOMAIN 12..63
FT /note="LIM zinc-binding 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DOMAIN 72..124
FT /note="LIM zinc-binding 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DOMAIN 152..239
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 331..608
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 279..304
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 451
FT /evidence="ECO:0000269|PubMed:22328514"
FT BINDING 337..345
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 360
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 210
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 293
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976"
FT MOD_RES 298
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 505
FT /note="Phosphothreonine; by ROCK1 and CDC42BP"
FT /evidence="ECO:0000269|PubMed:11018042,
FT ECO:0000269|PubMed:11340065"
FT VAR_SEQ 1..37
FT /note="MSALAGEDVWRCPGCGDHIAPSQIWYRTVNETWHGSC -> MGSYLSVPAYF
FT TSRDL (in isoform LIMK2b and isoform 3)"
FT /evidence="ECO:0000303|PubMed:11230166,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:8954941"
FT /id="VSP_012287"
FT VAR_SEQ 592..638
FT /note="PAFSKLEDSFEALSLYLGELGIPLPAELEELDHTVSMQYGLTRDSPP -> A
FT PPGAAGEGPGCADDEGPVRRQGKVTIKYDPKELRKHLNLEEWILEQLTRLYDCQEEEIS
FT ELEIDVDELLDMESDDAWASRVKELLVDCYKPTEAFISGLLDKIRAMQKLSTPQKK
FT (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_043332"
FT VARIANT 35
FT /note="G -> S (in dbSNP:rs5997917)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_034069"
FT VARIANT 45
FT /note="D -> N (in dbSNP:rs35923988)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042249"
FT VARIANT 213
FT /note="R -> C (in dbSNP:rs34930775)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042250"
FT VARIANT 296
FT /note="P -> R (in dbSNP:rs34875793)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042251"
FT VARIANT 381
FT /note="R -> H (in dbSNP:rs2229874)"
FT /id="VAR_050149"
FT VARIANT 418
FT /note="R -> C (in dbSNP:rs35422808)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042252"
FT MUTAGEN 451
FT /note="D->A: Abrogates kinase activity."
FT /evidence="ECO:0000269|PubMed:22328514"
FT MUTAGEN 505
FT /note="T->E: Phosphomimetic mutant; enhances kinase
FT activity."
FT /evidence="ECO:0000269|PubMed:11018042,
FT ECO:0000269|PubMed:22328514"
FT MUTAGEN 505
FT /note="T->V: Abolishes cofilin phosphorylation and
FT enhancement of stress fiber formation."
FT /evidence="ECO:0000269|PubMed:11018042"
FT TURN 73..75
FT /evidence="ECO:0007829|PDB:1X6A"
FT TURN 99..101
FT /evidence="ECO:0007829|PDB:1X6A"
FT STRAND 111..113
FT /evidence="ECO:0007829|PDB:1X6A"
FT STRAND 115..117
FT /evidence="ECO:0007829|PDB:1X6A"
FT STRAND 119..121
FT /evidence="ECO:0007829|PDB:1X6A"
FT HELIX 122..129
FT /evidence="ECO:0007829|PDB:1X6A"
FT STRAND 331..337
FT /evidence="ECO:0007829|PDB:7QHG"
FT HELIX 341..343
FT /evidence="ECO:0007829|PDB:7QHG"
FT STRAND 345..350
FT /evidence="ECO:0007829|PDB:7QHG"
FT TURN 351..353
FT /evidence="ECO:0007829|PDB:7QHG"
FT STRAND 356..361
FT /evidence="ECO:0007829|PDB:7QHG"
FT HELIX 367..375
FT /evidence="ECO:0007829|PDB:7QHG"
FT HELIX 377..382
FT /evidence="ECO:0007829|PDB:7QHG"
FT STRAND 391..397
FT /evidence="ECO:0007829|PDB:7QHG"
FT STRAND 400..406
FT /evidence="ECO:0007829|PDB:7QHG"
FT STRAND 410..412
FT /evidence="ECO:0007829|PDB:7QHG"
FT HELIX 413..418
FT /evidence="ECO:0007829|PDB:7QHG"
FT HELIX 425..444
FT /evidence="ECO:0007829|PDB:7QHG"
FT STRAND 456..460
FT /evidence="ECO:0007829|PDB:7QHG"
FT STRAND 465..467
FT /evidence="ECO:0007829|PDB:7QHG"
FT STRAND 506..508
FT /evidence="ECO:0007829|PDB:7QHG"
FT HELIX 510..512
FT /evidence="ECO:0007829|PDB:7QHG"
FT HELIX 515..518
FT /evidence="ECO:0007829|PDB:7QHG"
FT HELIX 527..541
FT /evidence="ECO:0007829|PDB:7QHG"
FT HELIX 547..549
FT /evidence="ECO:0007829|PDB:7QHG"
FT HELIX 560..567
FT /evidence="ECO:0007829|PDB:7QHG"
FT HELIX 576..583
FT /evidence="ECO:0007829|PDB:7QHG"
FT HELIX 588..590
FT /evidence="ECO:0007829|PDB:7QHG"
FT HELIX 594..608
FT /evidence="ECO:0007829|PDB:7QHG"
FT STRAND 609..611
FT /evidence="ECO:0007829|PDB:4TPT"
FT HELIX 617..630
FT /evidence="ECO:0007829|PDB:7QHG"
SQ SEQUENCE 638 AA; 72232 MW; FB51813D99AFAC18 CRC64;
MSALAGEDVW RCPGCGDHIA PSQIWYRTVN ETWHGSCFRC SECQDSLTNW YYEKDGKLYC
PKDYWGKFGE FCHGCSLLMT GPFMVAGEFK YHPECFACMS CKVIIEDGDA YALVQHATLY
CGKCHNEVVL APMFERLSTE SVQEQLPYSV TLISMPATTE GRRGFSVSVE SACSNYATTV
QVKEVNRMHI SPNNRNAIHP GDRILEINGT PVRTLRVEEV EDAISQTSQT LQLLIEHDPV
SQRLDQLRLE ARLAPHMQNA GHPHALSTLD TKENLEGTLR RRSLRRSNSI SKSPGPSSPK
EPLLFSRDIS RSESLRCSSS YSQQIFRPCD LIHGEVLGKG FFGQAIKVTH KATGKVMVMK
ELIRCDEETQ KTFLTEVKVM RSLDHPNVLK FIGVLYKDKK LNLLTEYIEG GTLKDFLRSM
DPFPWQQKVR FAKGIASGMA YLHSMCIIHR DLNSHNCLIK LDKTVVVADF GLSRLIVEER
KRAPMEKATT KKRTLRKNDR KKRYTVVGNP YWMAPEMLNG KSYDETVDIF SFGIVLCEII
GQVYADPDCL PRTLDFGLNV KLFWEKFVPT DCPPAFFPLA AICCRLEPES RPAFSKLEDS
FEALSLYLGE LGIPLPAELE ELDHTVSMQY GLTRDSPP
