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 27-MAR-2024, entry version 221. 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 P53671; P62258: YWHAE; NbExp=2; IntAct=EBI-1384350, EBI-356498; 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 8GI4; X-ray; 2.06 A; A/B/C/D/E/F/G/H=130-250. DR PDB; 8WSW; X-ray; 2.50 A; A/B/C/D=330-632. DR PDBsum; 1X6A; -. DR PDBsum; 4TPT; -. DR PDBsum; 5NXD; -. DR PDBsum; 7QHG; -. DR PDBsum; 8GI4; -. DR PDBsum; 8WSW; -. DR AlphaFoldDB; P53671; -. DR SMR; P53671; -. DR BioGRID; 110173; 84. DR IntAct; P53671; 59. DR MINT; P53671; -. DR STRING; 9606.ENSP00000339916; -. DR BindingDB; P53671; -. DR ChEMBL; CHEMBL5932; -. DR DrugBank; DB12010; Fostamatinib. DR DrugCentral; P53671; -. DR GuidetoPHARMACOLOGY; 2055; -. DR GlyCosmos; P53671; 1 site, 1 glycan. DR GlyGen; P53671; 2 sites, 2 O-linked glycans (2 sites). 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; 9606-ENSP00000339916; -. DR PeptideAtlas; P53671; -. DR ProteomicsDB; 56602; -. [P53671-1] DR ProteomicsDB; 56603; -. [P53671-2] DR ProteomicsDB; 56604; -. [P53671-3] DR Pumba; P53671; -. DR Antibodypedia; 2106; 682 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 AGR; HGNC:6614; -. 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; RMHISSN; -. DR OrthoDB; 5474815at2759; -. 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; 15 hits in 1192 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 192 other cell types or tissues. DR ExpressionAtlas; P53671; baseline and differential. 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 CDD; cd09463; LIM1_LIMK2; 1. DR CDD; cd09465; LIM2_LIMK2; 1. DR CDD; cd00992; PDZ_signaling; 1. DR CDD; cd14222; STKc_LIMK2; 1. DR Gene3D; 2.30.42.10; -; 1. DR Gene3D; 2.10.110.10; Cysteine Rich Protein; 2. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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 PANTHER; PTHR46485; LIM DOMAIN KINASE 1; 1. DR PANTHER; PTHR46485:SF1; LIM DOMAIN KINASE 2; 1. 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; SSF57716; Glucocorticoid receptor-like (DNA-binding domain); 2. DR SUPFAM; SSF50156; PDZ domain-like; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 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. DR Genevisible; P53671; HS. 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 //