LIMK1_HUMAN
ID LIMK1_HUMAN Reviewed; 647 AA.
AC P53667; B7Z6I8; D3DXF4; D3DXF5; O15283; Q15820; Q15821; Q75MU3; Q9Y5Q1;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 3.
DT 03-AUG-2022, entry version 221.
DE RecName: Full=LIM domain kinase 1;
DE Short=LIMK-1;
DE EC=2.7.11.1 {ECO:0000269|PubMed:22328514};
GN Name=LIMK1; Synonyms=LIMK;
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 1).
RX PubMed=8183554;
RA Mizuno K., Okano I., Ohashi K., Nunoue K., Kuma K., Miyata T., Nakamura T.;
RT "Identification of a human cDNA encoding a novel protein kinase with two
RT repeats of the LIM/double zinc finger motif.";
RL Oncogene 9:1605-1612(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2), AND VARIANT TYR-580.
RC TISSUE=Hippocampus, and Placenta;
RX PubMed=8689688; DOI=10.1016/s0092-8674(00)80077-x;
RA Frangiskakis J.M., Ewart A.K., Morris C.A., Mervis C.B., Bertrand J.,
RA Robinson B.F., Klein B.P., Ensing G.J., Everett L.A., Green E.D.,
RA Proeschel C., Gutowski N.J., Noble M., Atkinson D.L., Odelberg S.J.,
RA Keating M.T.;
RT "LIM-kinase1 hemizygosity implicated in impaired visuospatial constructive
RT cognition.";
RL Cell 86:59-69(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT TYR-580, AND GENE DELETION IN
RP WILLIAMS-BEUREN SYNDROME.
RX PubMed=8812460; DOI=10.1006/geno.1996.0469;
RA Osborne L.R., Martindale D.W., Scherer S.W., Shi X.-M., Huizenga J.,
RA Heng H.H.Q., Costa T., Pober B., Lew L., Brinkman J., Rommens J.,
RA Koop B.F., Tsui L.-C.;
RT "Identification of genes from a 500-kb region at 7q11.23 that is commonly
RT deleted in Williams syndrome patients.";
RL Genomics 36:328-336(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, SELF-ASSOCIATION,
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-84; 177-GLY-LEU-178; ASP-460;
RP 496-ARG--ARG-506; 503-ARG--GLY-505 AND THR-508.
RC TISSUE=Epidermal carcinoma;
RX PubMed=10196227; DOI=10.1074/jbc.274.16.11352;
RA Edwards D.C., Gill G.N.;
RT "Structural features of LIM kinase that control effects on the actin
RT cytoskeleton.";
RL J. Biol. Chem. 274:11352-11361(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
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=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP PHOSPHORYLATION AT THR-508 BY PAK1.
RX PubMed=10559936; DOI=10.1038/12963;
RA Edwards D.C., Sanders L.C., Bokoch G.M., Gill G.N.;
RT "Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to
RT actin cytoskeletal dynamics.";
RL Nat. Cell Biol. 1:253-259(1999).
RN [9]
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 [10]
RP PHOSPHORYLATION AT THR-508, MUTAGENESIS OF THR-508, AND INTERACTION WITH
RP ROCK1.
RX PubMed=10652353; DOI=10.1074/jbc.275.5.3577;
RA Ohashi K., Nagata K., Maekawa M., Ishizaki T., Narumiya S., Mizuno K.;
RT "Rho-associated kinase ROCK activates LIM-kinase 1 by phosphorylation at
RT threonine 508 within the activation loop.";
RL J. Biol. Chem. 275:3577-3582(2000).
RN [11]
RP PHOSPHORYLATION 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 [12]
RP PHOSPHORYLATION BY PAK4.
RX PubMed=11413130; DOI=10.1074/jbc.m100871200;
RA Dan C., Kelly A., Bernard O., Minden A.;
RT "Cytoskeletal changes regulated by the PAK4 serine/threonine kinase are
RT mediated by LIM kinase 1 and cofilin.";
RL J. Biol. Chem. 276:32115-32121(2001).
RN [13]
RP FUNCTION.
RX PubMed=11832213; DOI=10.1016/s0092-8674(01)00638-9;
RA Niwa R., Nagata-Ohashi K., Takeichi M., Mizuno K., Uemura T.;
RT "Control of actin reorganization by Slingshot, a family of phosphatases
RT that dephosphorylate ADF/cofilin.";
RL Cell 108:233-246(2002).
RN [14]
RP FUNCTION.
RX PubMed=12807904; DOI=10.1074/jbc.m305802200;
RA Kaji N., Ohashi K., Shuin M., Niwa R., Uemura T., Mizuno K.;
RT "Cell cycle-associated changes in Slingshot phosphatase activity and roles
RT in cytokinesis in animal cells.";
RL J. Biol. Chem. 278:33450-33455(2003).
RN [15]
RP INTERACTION WITH CDKN1C.
RX PubMed=14530263; DOI=10.1074/jbc.m309334200;
RA Yokoo T., Toyoshima H., Miura M., Wang Y., Iida K.T., Suzuki H., Sone H.,
RA Shimano H., Gotoda T., Nishimori S., Tanaka K., Yamada N.;
RT "p57Kip2 regulates actin dynamics by binding and translocating LIM-kinase 1
RT to the nucleus.";
RL J. Biol. Chem. 278:52919-52923(2003).
RN [16]
RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8;
RA Hillman R.T., Green R.E., Brenner S.E.;
RT "An unappreciated role for RNA surveillance.";
RL Genome Biol. 5:R8.1-R8.16(2004).
RN [17]
RP FUNCTION, INTERACTION WITH SSH1, PHOSPHORYLATION AT THR-508, AND
RP DEPHOSPHORYLATION.
RX PubMed=15660133; DOI=10.1038/sj.emboj.7600543;
RA Soosairajah J., Maiti S., Wiggan O., Sarmiere P., Moussi N., Sarcevic B.,
RA Sampath R., Bamburg J.R., Bernard O.;
RT "Interplay between components of a novel LIM kinase-slingshot phosphatase
RT complex regulates cofilin.";
RL EMBO J. 24:473-486(2005).
RN [18]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16230460; DOI=10.1083/jcb.200504029;
RA Nishita M., Tomizawa C., Yamamoto M., Horita Y., Ohashi K., Mizuno K.;
RT "Spatial and temporal regulation of cofilin activity by LIM kinase and
RT Slingshot is critical for directional cell migration.";
RL J. Cell Biol. 171:349-359(2005).
RN [19]
RP PHOSPHORYLATION AT SER-323 BY MAPKAPK2.
RX PubMed=16456544; DOI=10.1038/sj.emboj.7600973;
RA Kobayashi M., Nishita M., Mishima T., Ohashi K., Mizuno K.;
RT "MAPKAPK-2-mediated LIM-kinase activation is critical for VEGF-induced
RT actin remodeling and cell migration.";
RL EMBO J. 25:713-726(2006).
RN [20]
RP INTERACTION WITH HSP90AA1.
RX PubMed=16641196; DOI=10.1096/fj.05-5258fje;
RA Li R., Soosairajah J., Harari D., Citri A., Price J., Ng H.L., Morton C.J.,
RA Parker M.W., Yarden Y., Bernard O.;
RT "Hsp90 increases LIM kinase activity by promoting its homo-dimerization.";
RL FASEB J. 20:1218-1220(2006).
RN [21]
RP FUNCTION IN PHOSPHORYLATION OF TPPP.
RX PubMed=18028908; DOI=10.1016/j.yexcr.2007.08.012;
RA Acevedo K., Li R., Soo P., Suryadinata R., Sarcevic B., Valova V.A.,
RA Graham M.E., Robinson P.J., Bernard O.;
RT "The phosphorylation of p25/TPPP by LIM kinase 1 inhibits its ability to
RT assemble microtubules.";
RL Exp. Cell Res. 313:4091-4106(2007).
RN [22]
RP REVIEW ON FUNCTION.
RX PubMed=17188549; DOI=10.1016/j.biocel.2006.11.011;
RA Bernard O.;
RT "Lim kinases, regulators of actin dynamics.";
RL Int. J. Biochem. Cell Biol. 39:1071-1076(2007).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-210; THR-229; SER-310 AND
RP SER-337, AND 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 [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-307 AND SER-310, 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 [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-210; THR-229; SER-302 AND
RP SER-310, AND 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 [27]
RP REVIEW ON FUNCTION.
RX PubMed=22886629; DOI=10.1002/med.20230;
RA Manetti F.;
RT "LIM kinases are attractive targets with many macromolecular partners and
RT only a few small molecule regulators.";
RL Med. Res. Rev. 32:968-998(2012).
RN [28]
RP SUBCELLULAR LOCATION.
RX PubMed=21682918; DOI=10.1186/1476-4598-10-75;
RA McConnell B.V., Koto K., Gutierrez-Hartmann A.;
RT "Nuclear and cytoplasmic LIMK1 enhances human breast cancer progression.";
RL Mol. Cancer 10:75-75(2011).
RN [29]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ASP-460 AND THR-508.
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 [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-298 AND SER-310, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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 [31]
RP FUNCTION, AND PHOSPHORYLATION AT THR-508.
RX PubMed=23633677; DOI=10.1126/scisignal.2003627;
RA Borroni E.M., Cancellieri C., Vacchini A., Benureau Y., Lagane B.,
RA Bachelerie F., Arenzana-Seisdedos F., Mizuno K., Mantovani A., Bonecchi R.,
RA Locati M.;
RT "Beta-arrestin-dependent activation of the cofilin pathway is required for
RT the scavenging activity of the atypical chemokine receptor D6.";
RL Sci. Signal. 6:RA30-RA30(2013).
RN [32]
RP VARIANTS [LARGE SCALE ANALYSIS] ALA-190; ASN-247 AND GLN-422.
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).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 330-637.
RG Structural genomics consortium (SGC);
RT "Crystal structure of the human limk1 kinase domain in complex with
RT staurosporine.";
RL Submitted (JUL-2011) to the PDB data bank.
CC -!- FUNCTION: Serine/threonine-protein kinase that plays an essential role
CC in the regulation of actin filament dynamics. Acts downstream of
CC several Rho family GTPase signal transduction pathways
CC (PubMed:10436159, PubMed:11832213, PubMed:12807904, PubMed:15660133,
CC PubMed:16230460, PubMed:18028908, PubMed:22328514, PubMed:23633677).
CC Activated by upstream kinases including ROCK1, PAK1 and PAK4, which
CC phosphorylate LIMK1 on a threonine residue located in its activation
CC loop (PubMed:10436159). LIMK1 subsequently phosphorylates and
CC inactivates the actin binding/depolymerizing factors cofilin-1/CFL1,
CC cofilin-2/CFL2 and destrin/DSTN, thereby preventing the cleavage of
CC filamentous actin (F-actin), and stabilizing the actin cytoskeleton
CC (PubMed:11832213, PubMed:15660133, PubMed:16230460, PubMed:23633677).
CC In this way LIMK1 regulates several actin-dependent biological
CC processes including cell motility, cell cycle progression, and
CC differentiation (PubMed:11832213, PubMed:15660133, PubMed:16230460,
CC PubMed:23633677). Phosphorylates TPPP on serine residues, thereby
CC promoting microtubule disassembly (PubMed:18028908). Stimulates axonal
CC outgrowth and may be involved in brain development (PubMed:18028908).
CC {ECO:0000269|PubMed:10436159, ECO:0000269|PubMed:11832213,
CC ECO:0000269|PubMed:12807904, ECO:0000269|PubMed:15660133,
CC ECO:0000269|PubMed:16230460, ECO:0000269|PubMed:18028908,
CC ECO:0000269|PubMed:22328514, ECO:0000269|PubMed:23633677}.
CC -!- FUNCTION: [Isoform 3]: Has a dominant negative effect on actin
CC cytoskeletal changes. Required for atypical chemokine receptor ACKR2-
CC induced phosphorylation of cofilin (CFL1).
CC {ECO:0000269|PubMed:10196227}.
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};
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 PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46609;
CC Evidence={ECO:0000269|PubMed:22328514};
CC -!- SUBUNIT: Interacts (via LIM domain) with the cytoplasmic domain of
CC NRG1. Interacts with NISCH. Interacts with RLIM and RNF6 (By
CC similarity). Self-associates to form homodimers (PubMed:10196227).
CC Interacts with HSP90AA1; this interaction promotes LIMK1 dimerization
CC and subsequent transphosphorylation (PubMed:16641196). Interacts with
CC CDKN1C (PubMed:14530263). Interacts with SSH1 (PubMed:15660133).
CC Interacts with ROCK1 (PubMed:10436159, PubMed:10652353). Interacts (via
CC LIM zinc-binding domains) with FAM89B/LRAP25 (via LRR repeat). Forms a
CC tripartite complex with CDC42BPA, CDC42BPB and FAM89B/LRAP25 (By
CC similarity). {ECO:0000250|UniProtKB:P53668,
CC ECO:0000269|PubMed:10196227, ECO:0000269|PubMed:10436159,
CC ECO:0000269|PubMed:10652353, ECO:0000269|PubMed:14530263,
CC ECO:0000269|PubMed:15660133, ECO:0000269|PubMed:16641196}.
CC -!- INTERACTION:
CC P53667; Q8WYQ4-2: C22orf15; NbExp=3; IntAct=EBI-444403, EBI-12030460;
CC P53667; P23528: CFL1; NbExp=3; IntAct=EBI-444403, EBI-352733;
CC P53667; O95835: LATS1; NbExp=5; IntAct=EBI-444403, EBI-444209;
CC P53667; P50281: MMP14; NbExp=4; IntAct=EBI-444403, EBI-992788;
CC P53667; Q13153: PAK1; NbExp=5; IntAct=EBI-444403, EBI-1307;
CC P53667; Q13177: PAK2; NbExp=2; IntAct=EBI-444403, EBI-1045887;
CC P53667; Q8WYL5: SSH1; NbExp=6; IntAct=EBI-444403, EBI-1222387;
CC P53667; P29066: Arrb1; Xeno; NbExp=2; IntAct=EBI-444403, EBI-4303019;
CC P53667; P29067: Arrb2; Xeno; NbExp=2; IntAct=EBI-444403, EBI-1636616;
CC P53667; P63319: Prkcg; Xeno; NbExp=3; IntAct=EBI-444403, EBI-12598030;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21682918}. Nucleus
CC {ECO:0000269|PubMed:21682918}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:10196227, ECO:0000269|PubMed:16230460}. Cell
CC projection, lamellipodium {ECO:0000250|UniProtKB:P53668}.
CC Note=Predominantly found in the cytoplasm. Localizes in the
CC lamellipodium in a CDC42BPA, CDC42BPB and FAM89B/LRAP25-dependent
CC manner. {ECO:0000250|UniProtKB:P53668}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=P53667-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P53667-2; Sequence=VSP_003125;
CC Name=3;
CC IsoId=P53667-3; Sequence=VSP_003126, VSP_003127;
CC Name=4;
CC IsoId=P53667-4; Sequence=VSP_043331;
CC -!- TISSUE SPECIFICITY: Highest expression in both adult and fetal nervous
CC system. Detected ubiquitously throughout the different regions of adult
CC brain, with highest levels in the cerebral cortex. Expressed to a
CC lesser extent in heart and skeletal muscle.
CC -!- PTM: Autophosphorylated. Phosphorylated on Thr-508 by ROCK1 and PAK1,
CC resulting in activation. Phosphorylated by PAK4 which increases the
CC ability of LIMK1 to phosphorylate cofilin. Phosphorylated at Ser-323 by
CC MAPKAPK2 during activation of VEGFA-induced signaling, which results in
CC activation of LIMK1 and promotion of actin reorganization, cell
CC migration, and tubule formation of endothelial cells. Dephosphorylated
CC and inactivated by SSH1. Phosphorylated by CDC42BP.
CC {ECO:0000269|PubMed:10559936, ECO:0000269|PubMed:10652353,
CC ECO:0000269|PubMed:11340065, ECO:0000269|PubMed:11413130,
CC ECO:0000269|PubMed:15660133, ECO:0000269|PubMed:16456544,
CC ECO:0000269|PubMed:23633677}.
CC -!- PTM: Ubiquitinated. 'Lys-48'-linked polyubiquitination by RNF6 leads to
CC proteasomal degradation through the 26S proteasome, modulating LIMK1
CC levels in the growth cone and its effect on axonal outgrowth. Also
CC polyubiquitinated by RLIM (By similarity).
CC {ECO:0000250|UniProtKB:P53668}.
CC -!- DISEASE: Note=LIMK1 is located in the Williams-Beuren syndrome (WBS)
CC critical region. WBS results from a hemizygous deletion of several
CC genes on chromosome 7q11.23, thought to arise as a consequence of
CC unequal crossing over between highly homologous low-copy repeat
CC sequences flanking the deleted region.
CC -!- MISCELLANEOUS: [Isoform 3]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
CC protein kinase family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/LIMK1ID41159ch7q11.html";
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DR EMBL; D26309; BAA05371.1; -; mRNA.
DR EMBL; U62293; AAB17545.1; -; Genomic_DNA.
DR EMBL; U62293; AAB17546.1; -; Genomic_DNA.
DR EMBL; U63721; AAC13885.1; -; Genomic_DNA.
DR EMBL; U63721; AAC13886.1; -; Genomic_DNA.
DR EMBL; AF134379; AAD25742.1; -; mRNA.
DR EMBL; AK300382; BAH13274.1; -; mRNA.
DR EMBL; AC005056; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC005057; AAS07438.1; -; Genomic_DNA.
DR EMBL; CH471200; EAW69620.1; -; Genomic_DNA.
DR EMBL; CH471200; EAW69621.1; -; Genomic_DNA.
DR EMBL; CH471200; EAW69622.1; -; Genomic_DNA.
DR EMBL; CH471200; EAW69623.1; -; Genomic_DNA.
DR CCDS; CCDS5563.1; -. [P53667-1]
DR CCDS; CCDS56491.1; -. [P53667-4]
DR PIR; JP0078; JP0078.
DR RefSeq; NP_001191355.1; NM_001204426.1. [P53667-4]
DR RefSeq; NP_002305.1; NM_002314.3. [P53667-1]
DR PDB; 3S95; X-ray; 1.65 A; A/B=330-637.
DR PDB; 5HVJ; X-ray; 2.20 A; A/B=329-638.
DR PDB; 5HVK; X-ray; 3.50 A; A/C=329-638.
DR PDB; 5L6W; X-ray; 2.53 A; L=330-637.
DR PDB; 5NXC; X-ray; 2.25 A; L=330-637.
DR PDB; 6WLY; X-ray; 1.90 A; B=503-512.
DR PDB; 7ATS; X-ray; 2.80 A; A=330-637.
DR PDB; 7ATU; X-ray; 2.80 A; A/B/C/D=330-637.
DR PDB; 7B8W; X-ray; 2.80 A; A/B/C/D=330-637.
DR PDBsum; 3S95; -.
DR PDBsum; 5HVJ; -.
DR PDBsum; 5HVK; -.
DR PDBsum; 5L6W; -.
DR PDBsum; 5NXC; -.
DR PDBsum; 6WLY; -.
DR PDBsum; 7ATS; -.
DR PDBsum; 7ATU; -.
DR PDBsum; 7B8W; -.
DR AlphaFoldDB; P53667; -.
DR SMR; P53667; -.
DR BioGRID; 110172; 56.
DR DIP; DIP-31605N; -.
DR IntAct; P53667; 65.
DR MINT; P53667; -.
DR STRING; 9606.ENSP00000336740; -.
DR BindingDB; P53667; -.
DR ChEMBL; CHEMBL3836; -.
DR DrugBank; DB08912; Dabrafenib.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; P53667; -.
DR GuidetoPHARMACOLOGY; 2054; -.
DR iPTMnet; P53667; -.
DR PhosphoSitePlus; P53667; -.
DR SwissPalm; P53667; -.
DR BioMuta; LIMK1; -.
DR DMDM; 90185240; -.
DR EPD; P53667; -.
DR jPOST; P53667; -.
DR MassIVE; P53667; -.
DR MaxQB; P53667; -.
DR PaxDb; P53667; -.
DR PeptideAtlas; P53667; -.
DR PRIDE; P53667; -.
DR ProteomicsDB; 56598; -. [P53667-1]
DR ProteomicsDB; 56599; -. [P53667-2]
DR ProteomicsDB; 56600; -. [P53667-3]
DR ProteomicsDB; 56601; -. [P53667-4]
DR Antibodypedia; 14576; 1025 antibodies from 42 providers.
DR DNASU; 3984; -.
DR Ensembl; ENST00000336180.7; ENSP00000336740.2; ENSG00000106683.15. [P53667-1]
DR Ensembl; ENST00000435201.5; ENSP00000414606.1; ENSG00000106683.15. [P53667-3]
DR Ensembl; ENST00000538333.3; ENSP00000444452.1; ENSG00000106683.15. [P53667-4]
DR GeneID; 3984; -.
DR KEGG; hsa:3984; -.
DR MANE-Select; ENST00000336180.7; ENSP00000336740.2; NM_002314.4; NP_002305.1.
DR UCSC; uc003uaa.3; human. [P53667-1]
DR CTD; 3984; -.
DR DisGeNET; 3984; -.
DR GeneCards; LIMK1; -.
DR HGNC; HGNC:6613; LIMK1.
DR HPA; ENSG00000106683; Tissue enhanced (brain).
DR MalaCards; LIMK1; -.
DR MIM; 601329; gene.
DR neXtProt; NX_P53667; -.
DR OpenTargets; ENSG00000106683; -.
DR Orphanet; 904; Williams syndrome.
DR PharmGKB; PA30386; -.
DR VEuPathDB; HostDB:ENSG00000106683; -.
DR eggNOG; KOG1187; Eukaryota.
DR GeneTree; ENSGT00940000156345; -.
DR HOGENOM; CLU_000288_7_23_1; -.
DR InParanoid; P53667; -.
DR OMA; FDGQYLQ; -.
DR OrthoDB; 988822at2759; -.
DR PhylomeDB; P53667; -.
DR TreeFam; TF318014; -.
DR BRENDA; 2.7.11.1; 2681.
DR PathwayCommons; P53667; -.
DR Reactome; R-HSA-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-HSA-3928662; EPHB-mediated forward signaling.
DR Reactome; R-HSA-399954; Sema3A PAK dependent Axon repulsion.
DR Reactome; R-HSA-416572; Sema4D induced cell migration and growth-cone collapse.
DR Reactome; R-HSA-5627117; RHO GTPases Activate ROCKs.
DR Reactome; R-HSA-5627123; RHO GTPases activate PAKs.
DR SignaLink; P53667; -.
DR SIGNOR; P53667; -.
DR BioGRID-ORCS; 3984; 9 hits in 1108 CRISPR screens.
DR ChiTaRS; LIMK1; human.
DR EvolutionaryTrace; P53667; -.
DR GeneWiki; LIMK1; -.
DR GenomeRNAi; 3984; -.
DR Pharos; P53667; Tchem.
DR PRO; PR:P53667; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; P53667; protein.
DR Bgee; ENSG00000106683; Expressed in stromal cell of endometrium and 106 other tissues.
DR ExpressionAtlas; P53667; baseline and differential.
DR Genevisible; P53667; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005925; C:focal adhesion; IEA:Ensembl.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0001673; C:male germ cell nucleus; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; IEA:Ensembl.
DR GO; GO:0043005; C:neuron projection; ISS:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0031072; F:heat shock protein binding; IDA:BHF-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; NAS:ProtInc.
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:0048675; P:axon extension; IEA:Ensembl.
DR GO; GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
DR GO; GO:0051444; P:negative regulation of ubiquitin-protein transferase activity; IDA:BHF-UCL.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:0032233; P:positive regulation of actin filament bundle assembly; IDA:BHF-UCL.
DR GO; GO:0045773; P:positive regulation of axon extension; ISS:UniProtKB.
DR GO; GO:0051496; P:positive regulation of stress fiber assembly; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0007266; P:Rho protein signal transduction; TAS:ProtInc.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0043149; P:stress fiber assembly; 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 PRINTS; PR00109; TYRKINASE.
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; Cell projection;
KW Cytoplasm; Cytoskeleton; Kinase; LIM domain; Metal-binding;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transferase; Ubl conjugation;
KW Williams-Beuren syndrome; Zinc.
FT CHAIN 1..647
FT /note="LIM domain kinase 1"
FT /id="PRO_0000075803"
FT DOMAIN 25..75
FT /note="LIM zinc-binding 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DOMAIN 84..137
FT /note="LIM zinc-binding 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DOMAIN 165..258
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 339..604
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 260..319
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 272..286
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 460
FT /evidence="ECO:0000250"
FT BINDING 345..353
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 368
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 210
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 229
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 298
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 302
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 307
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 310
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 323
FT /note="Phosphoserine; by MAPKAPK2"
FT /evidence="ECO:0000269|PubMed:16456544"
FT MOD_RES 337
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 508
FT /note="Phosphothreonine; by ROCK1 and PAK1"
FT /evidence="ECO:0000269|PubMed:10559936,
FT ECO:0000269|PubMed:10652353, ECO:0000269|PubMed:15660133,
FT ECO:0000269|PubMed:23633677"
FT VAR_SEQ 1..51
FT /note="MRLTLLCCTWREERMGEEGSELPVCASCGQRIYDGQYLQALNADWHADCFR
FT -> MLLASAPRRRRFLQRAK (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043331"
FT VAR_SEQ 1..14
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_003125"
FT VAR_SEQ 294..305
FT /note="LRSCSIDRSPGA -> FARTWVALSPSA (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10196227"
FT /id="VSP_003126"
FT VAR_SEQ 306..647
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10196227"
FT /id="VSP_003127"
FT VARIANT 190
FT /note="G -> A (in dbSNP:rs35827364)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042246"
FT VARIANT 247
FT /note="S -> N (in dbSNP:rs55661242)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042247"
FT VARIANT 422
FT /note="R -> Q (in dbSNP:rs55679316)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042248"
FT VARIANT 580
FT /note="F -> Y (in dbSNP:rs178412)"
FT /evidence="ECO:0000269|PubMed:8689688,
FT ECO:0000269|PubMed:8812460"
FT /id="VAR_050148"
FT MUTAGEN 84
FT /note="C->S: Enhances actin aggregation."
FT /evidence="ECO:0000269|PubMed:10196227"
FT MUTAGEN 177..178
FT /note="GL->EA: Enhances actin aggregation."
FT /evidence="ECO:0000269|PubMed:10196227"
FT MUTAGEN 460
FT /note="D->N,A: Abrogates kinase activity."
FT /evidence="ECO:0000269|PubMed:10196227,
FT ECO:0000269|PubMed:22328514"
FT MUTAGEN 496..506
FT /note="Missing: Reduces actin aggregation."
FT /evidence="ECO:0000269|PubMed:10196227"
FT MUTAGEN 503..505
FT /note="RKK->GAA: Abolishes kinase activity."
FT /evidence="ECO:0000269|PubMed:10196227"
FT MUTAGEN 508
FT /note="T->A: Abolishes activation by ROCK1."
FT /evidence="ECO:0000269|PubMed:10196227,
FT ECO:0000269|PubMed:10652353"
FT MUTAGEN 508
FT /note="T->E: Phosphomimetic mutant; enhances kinase
FT activity."
FT /evidence="ECO:0000269|PubMed:22328514"
FT MUTAGEN 508
FT /note="T->EE: Enhances kinase activity."
FT /evidence="ECO:0000269|PubMed:10196227,
FT ECO:0000269|PubMed:10652353"
FT MUTAGEN 508
FT /note="T->V: Reduces kinase activity."
FT /evidence="ECO:0000269|PubMed:10196227,
FT ECO:0000269|PubMed:10652353"
FT STRAND 332..334
FT /evidence="ECO:0007829|PDB:3S95"
FT HELIX 336..338
FT /evidence="ECO:0007829|PDB:3S95"
FT STRAND 339..346
FT /evidence="ECO:0007829|PDB:3S95"
FT STRAND 349..358
FT /evidence="ECO:0007829|PDB:3S95"
FT TURN 359..361
FT /evidence="ECO:0007829|PDB:3S95"
FT STRAND 364..371
FT /evidence="ECO:0007829|PDB:3S95"
FT HELIX 375..388
FT /evidence="ECO:0007829|PDB:3S95"
FT STRAND 399..405
FT /evidence="ECO:0007829|PDB:3S95"
FT STRAND 408..414
FT /evidence="ECO:0007829|PDB:3S95"
FT STRAND 417..420
FT /evidence="ECO:0007829|PDB:7ATU"
FT HELIX 421..427
FT /evidence="ECO:0007829|PDB:3S95"
FT HELIX 434..453
FT /evidence="ECO:0007829|PDB:3S95"
FT STRAND 465..468
FT /evidence="ECO:0007829|PDB:3S95"
FT STRAND 470..472
FT /evidence="ECO:0007829|PDB:7ATS"
FT STRAND 474..476
FT /evidence="ECO:0007829|PDB:3S95"
FT HELIX 513..515
FT /evidence="ECO:0007829|PDB:3S95"
FT HELIX 518..521
FT /evidence="ECO:0007829|PDB:3S95"
FT HELIX 529..544
FT /evidence="ECO:0007829|PDB:3S95"
FT TURN 550..552
FT /evidence="ECO:0007829|PDB:3S95"
FT STRAND 559..561
FT /evidence="ECO:0007829|PDB:3S95"
FT HELIX 563..569
FT /evidence="ECO:0007829|PDB:3S95"
FT HELIX 579..586
FT /evidence="ECO:0007829|PDB:3S95"
FT HELIX 591..593
FT /evidence="ECO:0007829|PDB:3S95"
FT HELIX 597..613
FT /evidence="ECO:0007829|PDB:3S95"
FT HELIX 618..634
FT /evidence="ECO:0007829|PDB:3S95"
SQ SEQUENCE 647 AA; 72585 MW; 9838BEFBE7006447 CRC64;
MRLTLLCCTW REERMGEEGS ELPVCASCGQ RIYDGQYLQA LNADWHADCF RCCDCSASLS
HQYYEKDGQL FCKKDYWARY GESCHGCSEQ ITKGLVMVAG ELKYHPECFI CLTCGTFIGD
GDTYTLVEHS KLYCGHCYYQ TVVTPVIEQI LPDSPGSHLP HTVTLVSIPA SSHGKRGLSV
SIDPPHGPPG CGTEHSHTVR VQGVDPGCMS PDVKNSIHVG DRILEINGTP IRNVPLDEID
LLIQETSRLL QLTLEHDPHD TLGHGLGPET SPLSSPAYTP SGEAGSSARQ KPVLRSCSID
RSPGAGSLGS PASQRKDLGR SESLRVVCRP HRIFRPSDLI HGEVLGKGCF GQAIKVTHRE
TGEVMVMKEL IRFDEETQRT FLKEVKVMRC LEHPNVLKFI GVLYKDKRLN FITEYIKGGT
LRGIIKSMDS QYPWSQRVSF AKDIASGMAY LHSMNIIHRD LNSHNCLVRE NKNVVVADFG
LARLMVDEKT QPEGLRSLKK PDRKKRYTVV GNPYWMAPEM INGRSYDEKV DVFSFGIVLC
EIIGRVNADP DYLPRTMDFG LNVRGFLDRY CPPNCPPSFF PITVRCCDLD PEKRPSFVKL
EHWLETLRMH LAGHLPLGPQ LEQLDRGFWE TYRRGESGLP AHPEVPD
