ID MYLK_HUMAN Reviewed; 1914 AA. AC Q15746; B4DUE3; D3DN97; O95796; O95797; O95798; O95799; Q14844; Q16794; AC Q17S15; Q3ZCP9; Q5MY99; Q5MYA0; Q6P2N0; Q7Z4J0; Q9C0L5; Q9UBG5; Q9UBY6; AC Q9UIT9; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 13-JUL-2010, sequence version 4. DT 27-MAR-2024, entry version 234. DE RecName: Full=Myosin light chain kinase, smooth muscle {ECO:0000305}; DE Short=MLCK; DE Short=smMLCK; DE EC=2.7.11.18 {ECO:0000269|PubMed:11113114}; DE AltName: Full=Kinase-related protein; DE Short=KRP; DE AltName: Full=Telokin; DE Contains: DE RecName: Full=Myosin light chain kinase, smooth muscle, deglutamylated form; GN Name=MYLK {ECO:0000312|HGNC:HGNC:7590}; Synonyms=MLCK, MLCK1, MYLK1; 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 9), AND TISSUE SPECIFICITY. RC TISSUE=Hippocampus; RX PubMed=8575746; DOI=10.1006/geno.1995.9965; RA Potier M.-C., Chelot E., Pekarsky Y., Gardiner K., Rossier J., RA Turnell W.G.; RT "The human myosin light chain kinase (MLCK) from hippocampus: cloning, RT sequencing, expression, and localization to 3qcen-q21."; RL Genomics 29:562-570(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Umbilical vein endothelial cell; RX PubMed=9160829; DOI=10.1165/ajrcmb.16.5.9160829; RA Garcia J.G.N., Lazar V.L., Gilbert-Mcclain L.I., Gallagher P.J., RA Verin A.D.; RT "Myosin light chain kinase in endothelium: molecular cloning and RT regulation."; RL Am. J. Respir. Cell Mol. Biol. 16:489-494(1997). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3A AND 3B), AND NUCLEOTIDE SEQUENCE RP [MRNA] OF 1281-1914 (ISOFORM 4). RC TISSUE=Umbilical vein; RX PubMed=10198165; DOI=10.1006/geno.1999.5774; RA Lazar V.L., Garcia J.G.N.; RT "A single human myosin light chain kinase gene (MLCK; MYLK)."; RL Genomics 57:256-267(1999). RN [4] RP SEQUENCE REVISION (ISOFORMS 1 AND 2), PROTEIN SEQUENCE OF 457-476 AND RP 968-985, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, RP PHOSPHORYLATION AT TYR-464 AND TYR-471, CALMODULIN-BINDING, AND ACTIVITY RP REGULATION. RX PubMed=11113114; DOI=10.1074/jbc.m005270200; RA Birukov K.G., Csortos C., Marzilli L., Dudek S., Ma S.-F., Bresnick A.R., RA Verin A.D., Cotter R.J., Garcia J.G.N.; RT "Differential regulation of alternatively spliced endothelial cell myosin RT light chain kinase isoforms by p60(Src)."; RL J. Biol. Chem. 276:8567-8573(2001). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6), NUCLEOTIDE SEQUENCE [GENOMIC DNA / RP MRNA] (ISOFORM 8), NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1614-1914 (ISOFORM RP 9/DEL-1790), AND TISSUE SPECIFICITY. RC TISSUE=Lung, and Placenta; RX PubMed=10536370; RX DOI=10.1002/(sici)1097-4644(19991201)75:3<481::aid-jcb12>3.3.co;2-x; RA Watterson D.M., Schavocky J.P., Guo L., Weiss C., Chlenski A., RA Shrinsky V.P., Van Eldik L.J., Haiech J.; RT "Analysis of the kinase-related protein gene found at human chromosome 3q21 RT in a multi-gene cluster: organization, expression, alternative splicing and RT polymorphic marker."; RL J. Cell. Biochem. 75:481-491(1999). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Intestinal epithelium; RX PubMed=15507455; DOI=10.1074/jbc.m408822200; RA Clayburgh D.R., Rosen S., Witkowski E.D., Wang F., Blair S., Dudek S., RA Garcia J.G., Alverdy J.C., Turner J.R.; RT "A differentiation-dependent splice variant of myosin light chain kinase, RT MLCK1, regulates epithelial tight junction permeability."; RL J. Biol. Chem. 279:55506-55513(2004). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION IN CELL CYCLE, AND RP SUBCELLULAR LOCATION. RC TISSUE=Cervix carcinoma; RX PubMed=15020676; DOI=10.1242/jcs.00993; RA Dulyaninova N.G., Patskovsky Y.V., Bresnick A.R.; RT "The N-terminus of the long MLCK induces a disruption in normal spindle RT morphology and metaphase arrest."; RL J. Cell Sci. 117:1481-1493(2004). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5). RC TISSUE=Cervix carcinoma; RA Kikuchi A., Murata-Hori M., Hosoya H.; RT "HeLa myosin light chain kinase."; RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 6; 7 AND 8). RC TISSUE=Testis; 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 [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton 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 [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 6 AND 8). 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 [13] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1456-1914 (ISOFORM 9/DEL-1790). RC TISSUE=Placenta; RA Watterson D.M.; RL Submitted (NOV-1995) to the EMBL/GenBank/DDBJ databases. RN [14] RP INTERACTION WITH CTTN, AND PHOSPHORYLATION AT TYR-464 AND TYR-471 BY SRC. RX PubMed=12408982; DOI=10.1016/s0006-291x(02)02492-0; RA Dudek S.M., Birukov K.G., Zhan X., Garcia J.G.N.; RT "Novel interaction of cortactin with endothelial cell myosin light chain RT kinase."; RL Biochem. Biophys. Res. Commun. 298:511-519(2002). RN [15] RP FUNCTION IN HYPOTONICITY RESPONSE, AND ACTIVITY REGULATION. RX PubMed=11976941; DOI=10.1007/s00424-002-0811-3; RA Shen M.-R., Furla P., Chou C.-Y., Ellory J.C.; RT "Myosin light chain kinase modulates hypotonicity-induced Ca2+ entry and RT Cl- channel activity in human cervical cancer cells."; RL Pflugers Arch. 444:276-285(2002). RN [16] RP ACTIVITY REGULATION BY CALCIUM. RX PubMed=14741352; DOI=10.1016/s0014-5793(03)01456-x; RA Geguchadze R., Zhi G., Lau K.S., Isotani E., Persechini A., Kamm K.E., RA Stull J.T.; RT "Quantitative measurements of Ca(2+)/calmodulin binding and activation of RT myosin light chain kinase in cells."; RL FEBS Lett. 557:121-124(2004). RN [17] RP FUNCTION IN WOUND HEALING. RX PubMed=15825080; DOI=10.1053/j.gastro.2005.01.004; RA Russo J.M., Florian P., Shen L., Graham W.V., Tretiakova M.S., Gitter A.H., RA Mrsny R.J., Turner J.R.; RT "Distinct temporal-spatial roles for rho kinase and myosin light chain RT kinase in epithelial purse-string wound closure."; RL Gastroenterology 128:987-1001(2005). RN [18] RP INDUCTION BY TNF, TISSUE SPECIFICITY, AND ALTERNATIVE PROMOTER USAGE RP (ISOFORMS 1/2/3A/3B/4/DEL-1790). RX PubMed=16835238; DOI=10.1074/jbc.m602164200; RA Graham W.V., Wang F., Clayburgh D.R., Cheng J.X., Yoon B., Wang Y., Lin A., RA Turner J.R.; RT "Tumor necrosis factor-induced long myosin light chain kinase transcription RT is regulated by differentiation-dependent signaling events. RT Characterization of the human long myosin light chain kinase promoter."; RL J. Biol. Chem. 281:26205-26215(2006). RN [19] RP FUNCTION IN EPITHELIAL CELL SURVIVAL, AND ACTIVITY REGULATION. RX PubMed=16723733; DOI=10.1242/jcs.02926; RA Connell L.E., Helfman D.M.; RT "Myosin light chain kinase plays a role in the regulation of epithelial RT cell survival."; RL J. Cell Sci. 119:2269-2281(2006). RN [20] RP FUNCTION IN TRPC5 REGULATION, ACTIVITY REGULATION, AND CATALYTIC ACTIVITY. RX PubMed=16284075; DOI=10.1113/jphysiol.2005.097998; RA Shimizu S., Yoshida T., Wakamori M., Ishii M., Okada T., Takahashi M., RA Seto M., Sakurada K., Kiuchi Y., Mori Y.; RT "Ca2+-calmodulin-dependent myosin light chain kinase is essential for RT activation of TRPC5 channels expressed in HEK293 cells."; RL J. Physiol. (Lond.) 570:219-235(2006). RN [21] RP FUNCTION IN CELL MIGRATION. RX PubMed=18710790; DOI=10.1016/j.canlet.2008.05.028; RA Zhou X., Liu Y., You J., Zhang H., Zhang X., Ye L.; RT "Myosin light-chain kinase contributes to the proliferation and migration RT of breast cancer cells through cross-talk with activated ERK1/2."; RL Cancer Lett. 270:312-327(2008). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1438, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Platelet; RX PubMed=18088087; DOI=10.1021/pr0704130; RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., RA Schuetz C., Walter U., Gambaryan S., Sickmann A.; RT "Phosphoproteome of resting human platelets."; RL J. Proteome Res. 7:526-534(2008). RN [23] RP FUNCTION AS PTK2B/PYK2 KINASE, AND INTERACTION WITH PTK2B/PYK2. RX PubMed=18587400; DOI=10.1038/ni.1628; RA Xu J., Gao X.-P., Ramchandran R., Zhao Y.-Y., Vogel S.M., Malik A.B.; RT "Nonmuscle myosin light-chain kinase mediates neutrophil transmigration in RT sepsis-induced lung inflammation by activating beta2 integrins."; RL Nat. Immunol. 9:880-886(2008). RN [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1438, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=18318008; DOI=10.1002/pmic.200700884; RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., RA Zou H., Gu J.; RT "Large-scale phosphoproteome analysis of human liver tissue by enrichment RT and fractionation of phosphopeptides with strong anion exchange RT chromatography."; RL Proteomics 8:1346-1361(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 INDUCTION BY ANDROGENS. RX PubMed=19429448; DOI=10.1016/j.jsbmb.2009.02.002; RA Leveille N., Fournier A., Labrie C.; RT "Androgens down-regulate myosin light chain kinase in human prostate cancer RT cells."; RL J. Steroid Biochem. Mol. Biol. 114:174-179(2009). RN [27] RP FUNCTION IN TUMOR CELL MIGRATION, ACETYLATION AT LYS-608 BY NAA10/ARD1, RP INTERACTION WITH NAA10/ARD1, AND MUTAGENESIS OF LYS-608. RX PubMed=19826488; DOI=10.1371/journal.pone.0007451; RA Shin D.H., Chun Y.-S., Lee K.-H., Shin H.-W., Park J.-W.; RT "Arrest defective-1 controls tumor cell behavior by acetylating myosin RT light chain kinase."; RL PLoS ONE 4:E7451-E7451(2009). RN [28] RP FUNCTION IN BREAST CANCER. RX PubMed=20453870; DOI=10.1038/aps.2010.56; RA Cui W.-J., Liu Y., Zhou X.-L., Wang F.-Z., Zhang X.-D., Ye L.-H.; RT "Myosin light chain kinase is responsible for high proliferative ability of RT breast cancer cells via anti-apoptosis involving p38 pathway."; RL Acta Pharmacol. Sin. 31:725-732(2010). RN [29] RP FUNCTION IN OPTIC NERVE HEAD ASTROCYTE MIGRATION. RX PubMed=20375339; DOI=10.1167/iovs.10-5177; RA Miao H., Crabb A.W., Hernandez M.R., Lukas T.J.; RT "Modulation of factors affecting optic nerve head astrocyte migration."; RL Invest. Ophthalmol. Vis. Sci. 51:4096-4103(2010). RN [30] RP TISSUE SPECIFICITY, INTERACTION WITH CTTN, AND SUBCELLULAR LOCATION. RX PubMed=20053363; DOI=10.1016/j.mvr.2009.12.010; RA Brown M., Adyshev D., Bindokas V., Moitra J., Garcia J.G.N., Dudek S.M.; RT "Quantitative distribution and colocalization of non-muscle myosin light RT chain kinase isoforms and cortactin in human lung endothelium."; RL Microvasc. Res. 80:75-88(2010). RN [31] RP PHOSPHORYLATION AT TYR-231; TYR-464; TYR-556; TYR-611; TYR-792; TYR-846; RP TYR-1449; TYR-1575 AND TYR-1635 BY ABL1, AND INTERACTION WITH CTTN AND RP ABL1. RX PubMed=20861316; DOI=10.1091/mbc.e09-10-0876; RA Dudek S.M., Chiang E.T., Camp S.M., Guo Y., Zhao J., Brown M.E., RA Singleton P.A., Wang L., Desai A., Arce F.T., Lal R., Van Eyk J.E., RA Imam S.Z., Garcia J.G.N.; RT "Abl tyrosine kinase phosphorylates nonmuscle Myosin light chain kinase to RT regulate endothelial barrier function."; RL Mol. Biol. Cell 21:4042-4056(2010). RN [32] RP FUNCTION IN MEMBRANE BLEBBING. RX PubMed=20181817; DOI=10.1124/mol.110.063859; RA Godin C.M., Ferguson S.S.G.; RT "The angiotensin II type 1 receptor induces membrane blebbing by coupling RT to Rho A, Rho kinase, and myosin light chain kinase."; RL Mol. Pharmacol. 77:903-911(2010). RN [33] RP FUNCTION IN INFLAMMATORY RESPONSE. RX PubMed=20139351; DOI=10.1165/rcmb.2009-0197oc; RA Mirzapoiazova T., Moitra J., Moreno-Vinasco L., Sammani S., Turner J.R., RA Chiang E.T., Evenoski C., Wang T., Singleton P.A., Huang Y., Lussier Y.A., RA Watterson D.M., Dudek S.M., Garcia J.G.N.; RT "Non-muscle myosin light chain kinase isoform is a viable molecular target RT in acute inflammatory lung injury."; RL Am. J. Respir. Cell Mol. Biol. 44:40-52(2011). RN [34] RP ACTIVITY REGULATION. RX PubMed=21918590; DOI=10.1021/om200366r; RA Blanck S., Cruchter T., Vultur A., Riedel R., Harms K., Herlyn M., RA Meggers E.; RT "Organometallic pyridylnaphthalimide complexes as protein kinase RT inhibitors."; RL Organometallics 30:4598-4606(2011). RN [35] RP REVIEW ON ASTHMA, AND INDUCTION BY ASTHMA. RX PubMed=19011151; DOI=10.1164/rccm.200609-1367oc; RA Leguillette R., Laviolette M., Bergeron C., Zitouni N., Kogut P., RA Solway J., Kachmar L., Hamid Q., Lauzon A.-M.; RT "Myosin, transgelin, and myosin light chain kinase: expression and function RT in asthma."; RL Am. J. Respir. Crit. Care Med. 179:194-204(2009). RN [36] RP ALTERNATIVE PROMOTER USAGE (ISOFORMS 5/9). RX PubMed=22015949; DOI=10.1007/s00109-011-0820-9; RA Han Y.J., Ma S.F., Wade M.S., Flores C., Garcia J.G.; RT "An intronic MYLK variant associated with inflammatory lung disease RT regulates promoter activity of the smooth muscle myosin light chain kinase RT isoform."; RL J. Mol. Med. 90:299-308(2012). RN [37] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2 (ISOFORMS 6 AND 8), CLEAVAGE OF RP INITIATOR METHIONINE [LARGE SCALE ANALYSIS] (ISOFORM 6), CLEAVAGE OF RP INITIATOR METHIONINE [LARGE SCALE ANALYSIS] (ISOFORM 8), AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [38] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-305; SER-1438; SER-1772; RP SER-1776 AND SER-1779, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [39] RP STRUCTURE BY NMR OF 1238-1338. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the eighth Ig-like domain of human myosin light RT chain kinase."; RL Submitted (NOV-2005) to the PDB data bank. RN [40] RP STRUCTURE BY NMR OF 1742-1760 IN COMPLEX WITH CALMODULIN. RX PubMed=18462678; DOI=10.1016/j.str.2008.02.017; RA Gsponer J., Christodoulou J., Cavalli A., Bui J.M., Richter B., RA Dobson C.M., Vendruscolo M.; RT "A coupled equilibrium shift mechanism in calmodulin-mediated signal RT transduction."; RL Structure 16:736-746(2008). RN [41] RP VARIANTS [LARGE SCALE ANALYSIS] ALA-261; ALA-276; HIS-378; VAL-405; RP SER-443; GLY-607; ALA-652; CYS-656; MET-692; THR-701; MET-709; VAL-1527 AND RP LEU-1588. 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 [42] RP VARIANTS AAT7 MET-1213; THR-1754 AND PRO-1759, VARIANTS VAL-128; HIS-133; RP ARG-160; CYS-656; ALA-1085 AND LYS-1399, AND CHARACTERIZATION OF VARIANTS RP AAT7 THR-1754 AND PRO-1759. RX PubMed=21055718; DOI=10.1016/j.ajhg.2010.10.006; RA Wang L., Guo D.C., Cao J., Gong L., Kamm K.E., Regalado E., Li L., RA Shete S., He W.Q., Zhu M.S., Offermanns S., Gilchrist D., Elefteriades J., RA Stull J.T., Milewicz D.M.; RT "Mutations in myosin light chain kinase cause familial aortic RT dissections."; RL Am. J. Hum. Genet. 87:701-707(2010). RN [43] RP VARIANTS AAT7 1458-GLN--GLU-1914 DEL AND 1487-ARG--GLU-1914 DEL. RX PubMed=28401540; DOI=10.1111/cge.13000; RA Luyckx I., Proost D., Hendriks J.M.H., Saenen J., Van Craenenbroeck E.M., RA Vermeulen T., Peeters N., Wuyts W., Rodrigus I., Verstraeten A., RA Van Laer L., Loeys B.L.; RT "Two novel MYLK nonsense mutations causing thoracic aortic RT aneurysms/dissections in patients without apparent family history."; RL Clin. Genet. 92:444-446(2017). RN [44] RP ERRATUM OF PUBMED:28401540. RX PubMed=29537095; DOI=10.1111/cge.13213; RA Luyckx I., Proost D., Hendriks J.M.H., Saenen J., Van Craenenbroeck E.M., RA Vermeulen T., Peeters N., Wuyts W., Rodrigus I., Verstraeten A., RA Van Laer L., Loeys B.L.; RL Clin. Genet. 93:938-938(2018). RN [45] RP VARIANT AAT7 SER-1491, CHARACTERIZATION OF VARIANT AAT7 SER-1491, AND RP BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=29544503; DOI=10.1186/s13023-018-0769-7; RA Shalata A., Mahroom M., Milewicz D.M., Limin G., Kassum F., Badarna K., RA Tarabeih N., Assy N., Fell R., Cohen H., Nashashibi M., Livoff A., Azab M., RA Habib G., Geiger D., Weissbrod O., Nseir W.; RT "Fatal thoracic aortic aneurysm and dissection in a large family with a RT novel MYLK gene mutation: delineation of the clinical phenotype."; RL Orphanet J. Rare Dis. 13:41-41(2018). RN [46] RP INVOLVEMENT IN MMIHS. RX PubMed=28602422; DOI=10.1016/j.ajhg.2017.05.011; RA Halim D., Brosens E., Muller F., Wangler M.F., Beaudet A.L., Lupski J.R., RA Akdemir Z.H.C., Doukas M., Stoop H.J., de Graaf B.M., Brouwer R.W.W., RA van Ijcken W.F.J., Oury J.F., Rosenblatt J., Burns A.J., Tibboel D., RA Hofstra R.M.W., Alves M.M.; RT "Loss-of-Function Variants in MYLK Cause Recessive Megacystis Microcolon RT Intestinal Hypoperistalsis Syndrome."; RL Am. J. Hum. Genet. 101:123-129(2017). CC -!- FUNCTION: Calcium/calmodulin-dependent myosin light chain kinase CC implicated in smooth muscle contraction via phosphorylation of myosin CC light chains (MLC). Also regulates actin-myosin interaction through a CC non-kinase activity. Phosphorylates PTK2B/PYK2 and myosin light-chains. CC Involved in the inflammatory response (e.g. apoptosis, vascular CC permeability, leukocyte diapedesis), cell motility and morphology, CC airway hyperreactivity and other activities relevant to asthma. CC Required for tonic airway smooth muscle contraction that is necessary CC for physiological and asthmatic airway resistance. Necessary for CC gastrointestinal motility. Implicated in the regulation of endothelial CC as well as vascular permeability, probably via the regulation of CC cytoskeletal rearrangements. In the nervous system it has been shown to CC control the growth initiation of astrocytic processes in culture and to CC participate in transmitter release at synapses formed between cultured CC sympathetic ganglion cells. Critical participant in signaling sequences CC that result in fibroblast apoptosis. Plays a role in the regulation of CC epithelial cell survival. Required for epithelial wound healing, CC especially during actomyosin ring contraction during purse-string wound CC closure. Mediates RhoA-dependent membrane blebbing. Triggers TRPC5 CC channel activity in a calcium-dependent signaling, by inducing its CC subcellular localization at the plasma membrane. Promotes cell CC migration (including tumor cells) and tumor metastasis. PTK2B/PYK2 CC activation by phosphorylation mediates ITGB2 activation and is thus CC essential to trigger neutrophil transmigration during acute lung injury CC (ALI). May regulate optic nerve head astrocyte migration. Probably CC involved in mitotic cytoskeletal regulation. Regulates tight junction CC probably by modulating ZO-1 exchange in the perijunctional actomyosin CC ring. Mediates burn-induced microvascular barrier injury; triggers CC endothelial contraction in the development of microvascular CC hyperpermeability by phosphorylating MLC. Essential for intestinal CC barrier dysfunction. Mediates Giardia spp.-mediated reduced epithelial CC barrier function during giardiasis intestinal infection via CC reorganization of cytoskeletal F-actin and tight junctional ZO-1. CC Necessary for hypotonicity-induced Ca(2+) entry and subsequent CC activation of volume-sensitive organic osmolyte/anion channels (VSOAC) CC in cervical cancer cells. Responsible for high proliferative ability of CC breast cancer cells through anti-apoptosis. CC {ECO:0000269|PubMed:11113114, ECO:0000269|PubMed:11976941, CC ECO:0000269|PubMed:15020676, ECO:0000269|PubMed:15825080, CC ECO:0000269|PubMed:16284075, ECO:0000269|PubMed:16723733, CC ECO:0000269|PubMed:18587400, ECO:0000269|PubMed:18710790, CC ECO:0000269|PubMed:19826488, ECO:0000269|PubMed:20139351, CC ECO:0000269|PubMed:20181817, ECO:0000269|PubMed:20375339, CC ECO:0000269|PubMed:20453870}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-seryl-[myosin light chain] = ADP + H(+) + O-phospho-L- CC seryl-[myosin light chain]; Xref=Rhea:RHEA:22004, Rhea:RHEA- CC COMP:13684, Rhea:RHEA-COMP:13685, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, CC ChEBI:CHEBI:456216; EC=2.7.11.18; CC Evidence={ECO:0000269|PubMed:11113114}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22005; CC Evidence={ECO:0000305|PubMed:11113114}; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-threonyl-[myosin light chain] = ADP + H(+) + O- CC phospho-L-threonyl-[myosin light chain]; Xref=Rhea:RHEA:53900, CC Rhea:RHEA-COMP:13686, Rhea:RHEA-COMP:13687, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, CC ChEBI:CHEBI:456216; EC=2.7.11.18; CC Evidence={ECO:0000269|PubMed:11113114}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53901; CC Evidence={ECO:0000305|PubMed:11113114}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC -!- ACTIVITY REGULATION: Isoform 1 is activated by phosphorylation on Tyr- CC 464 and Tyr-471. Isoforms which lack these tyrosine residues are not CC regulated in this way. All catalytically active isoforms require CC binding to calcium and calmodulin for activation. Repressed by CC organometallic pyridylnaphthalimide complexes, wortmannin, ML-7 (a CC synthetic naphthalenesulphonyl derivative that inhibits the binding of CC ATP to MLCK) and ML-9. {ECO:0000269|PubMed:11113114, CC ECO:0000269|PubMed:11976941, ECO:0000269|PubMed:14741352, CC ECO:0000269|PubMed:16284075, ECO:0000269|PubMed:16723733, CC ECO:0000269|PubMed:21918590}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=6.5 uM for MLC (isoform 1 at 22 degrees Celsius) CC {ECO:0000269|PubMed:11113114}; CC KM=7.2 uM for MLC (isoform 2 at 22 degrees Celsius) CC {ECO:0000269|PubMed:11113114}; CC KM=9.3 uM for MLC {ECO:0000269|PubMed:29544503}; CC Vmax=11.9 umol/min/mg enzyme (isoform 1 at 22 degrees Celsius) CC {ECO:0000269|PubMed:11113114}; CC Vmax=10.9 umol/min/mg enzyme (isoform 1 at 22 degrees Celsius) CC {ECO:0000269|PubMed:11113114}; CC -!- SUBUNIT: All isoforms including Telokin bind calmodulin. Interacts with CC SVIL (By similarity). Interacts with CTTN; this interaction is reduced CC during thrombin-induced endothelial cell (EC) contraction but is CC promoted by the barrier-protective agonist sphingosine 1-phosphate CC (S1P) within lamellipodia. A complex made of ABL1, CTTN and MYLK CC regulates cortical actin-based cytoskeletal rearrangement critical to CC sphingosine 1-phosphate (S1P)-mediated endothelial cell (EC) barrier CC enhancement. Binds to NAA10/ARD1 and PTK2B/PYK2. {ECO:0000250, CC ECO:0000269|PubMed:12408982, ECO:0000269|PubMed:18462678, CC ECO:0000269|PubMed:18587400, ECO:0000269|PubMed:19826488, CC ECO:0000269|PubMed:20053363, ECO:0000269|PubMed:20861316}. CC -!- INTERACTION: CC Q15746; Q9HD26: GOPC; NbExp=3; IntAct=EBI-968482, EBI-349832; CC Q15746; P16333: NCK1; NbExp=2; IntAct=EBI-968482, EBI-389883; CC Q15746-7; Q92624: APPBP2; NbExp=3; IntAct=EBI-12189939, EBI-743771; CC Q15746-7; Q9HD26-2: GOPC; NbExp=5; IntAct=EBI-12189939, EBI-11102276; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:20053363}. Cell CC projection, lamellipodium {ECO:0000269|PubMed:20053363}. Cleavage CC furrow {ECO:0000269|PubMed:15020676}. Cytoplasm, cytoskeleton, stress CC fiber {ECO:0000269|PubMed:15020676}. Note=Localized to stress fibers CC during interphase and to the cleavage furrow during mitosis. CC {ECO:0000269|PubMed:15020676}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=11; CC Name=1; Synonyms=Non-muscle isozyme; CC IsoId=Q15746-1; Sequence=Displayed; CC Name=2; CC IsoId=Q15746-2; Sequence=VSP_004791; CC Name=3A; CC IsoId=Q15746-3; Sequence=VSP_004794; CC Name=3B; CC IsoId=Q15746-4; Sequence=VSP_004791, VSP_004794; CC Name=4; CC IsoId=Q15746-5; Sequence=VSP_004793; CC Name=Del-1790; CC IsoId=Q15746-6; Sequence=VSP_004795; CC Name=5; Synonyms=Smooth-muscle isozyme; CC IsoId=Q15746-7; Sequence=VSP_018845; CC Name=6; Synonyms=Telokin; CC IsoId=Q15746-8; Sequence=VSP_018846; CC Name=7; CC IsoId=Q15746-9; Sequence=VSP_053791; CC Name=8; CC IsoId=Q15746-10; Sequence=VSP_018846, VSP_004795; CC Name=9; CC IsoId=Q15746-11; Sequence=VSP_018845, VSP_004795; CC -!- TISSUE SPECIFICITY: Smooth muscle and non-muscle isozymes are expressed CC in a wide variety of adult and fetal tissues and in cultured CC endothelium with qualitative expression appearing to be neither CC tissue- nor development-specific. Non-muscle isoform 2 is the dominant CC splice variant expressed in various tissues. Telokin has been found in CC a wide variety of adult and fetal tissues. Accumulates in well CC differentiated enterocytes of the intestinal epithelium in response to CC tumor necrosis factor (TNF). {ECO:0000269|PubMed:10536370, CC ECO:0000269|PubMed:16835238, ECO:0000269|PubMed:20053363, CC ECO:0000269|PubMed:8575746}. CC -!- INDUCTION: Accumulates in individuals with asthma (at protein levels). CC Induced by tumor necrosis factor (TNF). Repressed by androgens (e.g. CC R1881). {ECO:0000269|PubMed:16835238, ECO:0000269|PubMed:19011151, CC ECO:0000269|PubMed:19429448}. CC -!- PTM: Can probably be down-regulated by phosphorylation. Tyrosine CC phosphorylation by ABL1 increases kinase activity, reverses MLCK- CC mediated inhibition of Arp2/3-mediated actin polymerization, and CC enhances CTTN-binding. Phosphorylation by SRC at Tyr-464 and Tyr-471 CC promotes CTTN binding. {ECO:0000269|PubMed:11113114, CC ECO:0000269|PubMed:12408982, ECO:0000269|PubMed:20861316}. CC -!- PTM: The C-terminus is deglutamylated by AGTPBP1/CCP1, AGBL1/CCP4 and CC AGBL4/CCP6, leading to the formation of Myosin light chain kinase, CC smooth muscle, deglutamylated form. The consequences of C-terminal CC deglutamylation are unknown (By similarity). {ECO:0000250}. CC -!- PTM: Acetylated at Lys-608 by NAA10/ARD1 via a calcium-dependent CC signaling; this acetylation represses kinase activity and reduces tumor CC cell migration. {ECO:0000269|PubMed:19826488}. CC -!- DISEASE: Aortic aneurysm, familial thoracic 7 (AAT7) [MIM:613780]: A CC disease characterized by permanent dilation of the thoracic aorta CC usually due to degenerative changes in the aortic wall. It is primarily CC associated with a characteristic histologic appearance known as 'medial CC necrosis' or 'Erdheim cystic medial necrosis' in which there is CC degeneration and fragmentation of elastic fibers, loss of smooth muscle CC cells, and an accumulation of basophilic ground substance. CC {ECO:0000269|PubMed:21055718, ECO:0000269|PubMed:28401540, CC ECO:0000269|PubMed:29544503}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Megacystis-microcolon-intestinal hypoperistalsis syndrome CC (MMIHS) [MIM:249210]: A form of megacystis-microcolon-intestinal CC hypoperistalsis syndrome, a congenital visceral myopathy primarily CC affecting females, and characterized by loss of smooth muscle CC contraction in the bladder and intestine. Affected individuals present CC at birth with functional obstruction of intestine, microcolon, dilation CC of bladder, and secondary hydronephrosis. The majority of cases have a CC fatal outcome due to malnutrition and sepsis, followed by multiorgan CC failure. MMIHS inheritance is autosomal recessive. CC {ECO:0000269|PubMed:28602422}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: In asthmatic patients, overexpression promotes actin CC filament propulsion, thus contributing to airway hyperresponsiveness. CC Some MYLK variants may contribute to acute lung injury (ALI) CC susceptibility. Potential therapeutic target in the treatment of burn CC edema. {ECO:0000305|PubMed:19011151}. CC -!- MISCELLANEOUS: [Isoform 5]: Transcribed from an alternative promoter CC resulting in the usage of Met-923 as initiator codon. CC {ECO:0000269|PubMed:22015949}. CC -!- MISCELLANEOUS: [Isoform 6]: Transcribed from an alternative promoter CC resulting in the usage of Met-1761 as initiator codon. Has no catalytic CC activity. Initiator Met is removed. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 8]: Transcribed from an alternative promoter CC resulting in the usage of Met-1761 as initiator codon. Initiator Met is CC removed. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 9]: Transcribed from an alternative promoter CC resulting in the usage of Met-923 as initiator codon. CC {ECO:0000269|PubMed:22015949}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr CC protein kinase family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAD15922.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=AAD15923.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=AAD15924.1; Type=Frameshift; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Myosin light-chain kinase entry; CC URL="https://en.wikipedia.org/wiki/Myosin_light-chain_kinase"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/43364/MYLK"; 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; X85337; CAA59685.1; -; mRNA. DR EMBL; U48959; AAC18423.2; -; mRNA. DR EMBL; AF069601; AAD15921.2; -; mRNA. DR EMBL; AF069602; AAD15922.1; ALT_FRAME; mRNA. DR EMBL; AF069603; AAD15923.1; ALT_FRAME; mRNA. DR EMBL; AF069604; AAD15924.1; ALT_FRAME; mRNA. DR EMBL; AF096771; AAD51380.1; -; Genomic_DNA. DR EMBL; AF096766; AAD51380.1; JOINED; Genomic_DNA. DR EMBL; AF096767; AAD51380.1; JOINED; Genomic_DNA. DR EMBL; AF096768; AAD51380.1; JOINED; Genomic_DNA. DR EMBL; AF096769; AAD51380.1; JOINED; Genomic_DNA. DR EMBL; AF096770; AAD51380.1; JOINED; Genomic_DNA. DR EMBL; AF096771; AAD51381.1; -; Genomic_DNA. DR EMBL; AF096769; AAD51381.1; JOINED; Genomic_DNA. DR EMBL; AF096770; AAD51381.1; JOINED; Genomic_DNA. DR EMBL; AF096773; AAD54017.1; -; mRNA. DR EMBL; AF096774; AAD54018.1; -; mRNA. DR EMBL; AF096775; AAD54019.1; -; mRNA. DR EMBL; AY424269; AAR29061.1; -; mRNA. DR EMBL; AY424270; AAR29062.1; -; mRNA. DR EMBL; AY339601; AAQ02673.1; -; mRNA. DR EMBL; AB037663; BAB21504.1; -; mRNA. DR EMBL; AK300610; BAG62305.1; -; mRNA. DR EMBL; AK314412; BAG37033.1; -; mRNA. DR EMBL; AK314443; BAG37052.1; -; mRNA. DR EMBL; AC020634; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC023165; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471052; EAW79438.1; -; Genomic_DNA. DR EMBL; CH471052; EAW79439.1; -; Genomic_DNA. DR EMBL; CH471052; EAW79440.1; -; Genomic_DNA. DR EMBL; CH471052; EAW79441.1; -; Genomic_DNA. DR EMBL; BC100761; AAI00762.2; -; mRNA. DR EMBL; BC100762; AAI00763.2; -; mRNA. DR EMBL; BC100763; AAI00764.2; -; mRNA. DR EMBL; BC064420; AAH64420.2; -; mRNA. DR EMBL; X90870; CAA62378.1; -; mRNA. DR CCDS; CCDS3023.1; -. [Q15746-3] DR CCDS; CCDS43141.1; -. [Q15746-2] DR CCDS; CCDS46896.1; -. [Q15746-1] DR CCDS; CCDS46897.1; -. [Q15746-8] DR CCDS; CCDS58849.1; -. [Q15746-10] DR CCDS; CCDS93356.1; -. [Q15746-4] DR RefSeq; NP_001308238.1; NM_001321309.1. DR RefSeq; NP_444253.3; NM_053025.3. [Q15746-1] DR RefSeq; NP_444254.3; NM_053026.3. [Q15746-2] DR RefSeq; NP_444255.3; NM_053027.3. [Q15746-3] DR RefSeq; NP_444256.3; NM_053028.3. [Q15746-4] DR RefSeq; NP_444259.1; NM_053031.3. [Q15746-10] DR RefSeq; NP_444260.1; NM_053032.3. [Q15746-8] DR RefSeq; XP_011511162.1; XM_011512860.2. DR RefSeq; XP_016861958.1; XM_017006469.1. DR RefSeq; XP_016861960.1; XM_017006471.1. [Q15746-9] DR RefSeq; XP_016861961.1; XM_017006472.1. [Q15746-8] DR RefSeq; XP_016861962.1; XM_017006473.1. [Q15746-10] DR PDB; 2CQV; NMR; -; A=1238-1338. DR PDB; 2K0F; NMR; -; B=1742-1760. DR PDB; 2YR3; NMR; -; A=510-601. DR PDB; 5JQA; X-ray; 1.80 A; B=1742-1761. DR PDB; 5JTH; X-ray; 1.84 A; B=1742-1761. DR PDB; 6C6M; X-ray; 2.50 A; A/B/C=405-507. DR PDBsum; 2CQV; -. DR PDBsum; 2K0F; -. DR PDBsum; 2YR3; -. DR PDBsum; 5JQA; -. DR PDBsum; 5JTH; -. DR PDBsum; 6C6M; -. DR AlphaFoldDB; Q15746; -. DR SMR; Q15746; -. DR BioGRID; 110722; 94. DR CORUM; Q15746; -. DR IntAct; Q15746; 86. DR MINT; Q15746; -. DR STRING; 9606.ENSP00000353452; -. DR BindingDB; Q15746; -. DR ChEMBL; CHEMBL2428; -. DR DrugBank; DB12010; Fostamatinib. DR DrugBank; DB00867; Ritodrine. DR DrugCentral; Q15746; -. DR GuidetoPHARMACOLOGY; 1552; -. DR GlyGen; Q15746; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q15746; -. DR MetOSite; Q15746; -. DR PhosphoSitePlus; Q15746; -. DR BioMuta; MYLK; -. DR DMDM; 300669714; -. DR CPTAC; CPTAC-2997; -. DR EPD; Q15746; -. DR jPOST; Q15746; -. DR MassIVE; Q15746; -. DR MaxQB; Q15746; -. DR PaxDb; 9606-ENSP00000353452; -. DR PeptideAtlas; Q15746; -. DR ProteomicsDB; 5180; -. DR ProteomicsDB; 60733; -. [Q15746-1] DR ProteomicsDB; 60734; -. [Q15746-2] DR ProteomicsDB; 60735; -. [Q15746-3] DR ProteomicsDB; 60736; -. [Q15746-4] DR ProteomicsDB; 60737; -. [Q15746-5] DR ProteomicsDB; 60738; -. [Q15746-6] DR ProteomicsDB; 60739; -. [Q15746-7] DR ProteomicsDB; 60740; -. [Q15746-8] DR Pumba; Q15746; -. DR Antibodypedia; 4044; 450 antibodies from 37 providers. DR DNASU; 4638; -. DR Ensembl; ENST00000346322.10; ENSP00000320622.6; ENSG00000065534.20. [Q15746-4] DR Ensembl; ENST00000360304.8; ENSP00000353452.3; ENSG00000065534.20. [Q15746-1] DR Ensembl; ENST00000360772.7; ENSP00000354004.3; ENSG00000065534.20. [Q15746-3] DR Ensembl; ENST00000418370.6; ENSP00000428967.1; ENSG00000065534.20. [Q15746-8] DR Ensembl; ENST00000508240.2; ENSP00000422984.2; ENSG00000065534.20. [Q15746-9] DR Ensembl; ENST00000583087.6; ENSP00000462118.1; ENSG00000065534.20. [Q15746-8] DR Ensembl; ENST00000685021.1; ENSP00000508447.1; ENSG00000065534.20. [Q15746-7] DR Ensembl; ENST00000685744.1; ENSP00000510047.1; ENSG00000065534.20. [Q15746-10] DR Ensembl; ENST00000686406.1; ENSP00000509044.1; ENSG00000065534.20. [Q15746-6] DR Ensembl; ENST00000686761.1; ENSP00000508758.1; ENSG00000065534.20. [Q15746-1] DR Ensembl; ENST00000687375.1; ENSP00000509867.1; ENSG00000065534.20. [Q15746-10] DR Ensembl; ENST00000688024.1; ENSP00000509803.1; ENSG00000065534.20. [Q15746-11] DR Ensembl; ENST00000693689.1; ENSP00000510503.1; ENSG00000065534.20. [Q15746-2] DR GeneID; 4638; -. DR KEGG; hsa:4638; -. DR MANE-Select; ENST00000360304.8; ENSP00000353452.3; NM_053025.4; NP_444253.3. DR UCSC; uc003egl.4; human. [Q15746-1] DR AGR; HGNC:7590; -. DR CTD; 4638; -. DR DisGeNET; 4638; -. DR GeneCards; MYLK; -. DR GeneReviews; MYLK; -. DR HGNC; HGNC:7590; MYLK. DR HPA; ENSG00000065534; Tissue enhanced (seminal vesicle, smooth muscle). DR MalaCards; MYLK; -. DR MIM; 249210; phenotype. DR MIM; 600922; gene. DR MIM; 613780; phenotype. DR neXtProt; NX_Q15746; -. DR OpenTargets; ENSG00000065534; -. DR Orphanet; 91387; Familial thoracic aortic aneurysm and aortic dissection. DR Orphanet; 2241; Megacystis-microcolon-intestinal hypoperistalsis syndrome. DR PharmGKB; PA31388; -. DR VEuPathDB; HostDB:ENSG00000065534; -. DR eggNOG; KOG0613; Eukaryota. DR GeneTree; ENSGT00940000157879; -. DR HOGENOM; CLU_000288_76_2_1; -. DR InParanoid; Q15746; -. DR OMA; GAPIKTG; -. DR OrthoDB; 4215065at2759; -. DR PhylomeDB; Q15746; -. DR TreeFam; TF314166; -. DR BRENDA; 2.7.11.18; 2681. DR PathwayCommons; Q15746; -. DR Reactome; R-HSA-445355; Smooth Muscle Contraction. DR Reactome; R-HSA-5627123; RHO GTPases activate PAKs. DR SABIO-RK; Q15746; -. DR SignaLink; Q15746; -. DR SIGNOR; Q15746; -. DR BioGRID-ORCS; 4638; 12 hits in 1156 CRISPR screens. DR ChiTaRS; MYLK; human. DR EvolutionaryTrace; Q15746; -. DR GeneWiki; MYLK; -. DR GenomeRNAi; 4638; -. DR Pharos; Q15746; Tchem. DR PRO; PR:Q15746; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; Q15746; Protein. DR Bgee; ENSG00000065534; Expressed in cauda epididymis and 212 other cell types or tissues. DR ExpressionAtlas; Q15746; baseline and differential. DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA. DR GO; GO:0032154; C:cleavage furrow; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0001725; C:stress fiber; IDA:UniProtKB. DR GO; GO:0003779; F:actin binding; IEA:UniProtKB-KW. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004687; F:myosin light chain kinase activity; IDA:UniProtKB. DR GO; GO:0060414; P:aorta smooth muscle tissue morphogenesis; IMP:BHF-UCL. DR GO; GO:0032060; P:bleb assembly; IMP:UniProtKB. DR GO; GO:0071476; P:cellular hypotonic response; IDA:UniProtKB. DR GO; GO:0051928; P:positive regulation of calcium ion transport; IDA:UniProtKB. DR GO; GO:0030335; P:positive regulation of cell migration; IDA:UniProtKB. DR GO; GO:0090303; P:positive regulation of wound healing; IDA:UniProtKB. DR GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc. DR GO; GO:0006939; P:smooth muscle contraction; ISS:UniProtKB. DR GO; GO:0014820; P:tonic smooth muscle contraction; ISS:UniProtKB. DR CDD; cd00063; FN3; 1. DR CDD; cd20978; IgI_4_hemolin-like; 1. DR CDD; cd20976; IgI_4_MYLK-like; 1. DR CDD; cd05762; IgI_8_hMLCK_like; 1. DR CDD; cd20973; IgI_telokin-like; 1. DR CDD; cd14191; STKc_MLCK1; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 10. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR003961; FN3_dom. DR InterPro; IPR036116; FN3_sf. DR InterPro; IPR007110; Ig-like_dom. DR InterPro; IPR036179; Ig-like_dom_sf. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR013098; Ig_I-set. DR InterPro; IPR003599; Ig_sub. DR InterPro; IPR003598; Ig_sub2. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR015725; MLCK1_kinase_dom. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR PANTHER; PTHR47633:SF7; IG-LIKE DOMAIN-CONTAINING PROTEIN; 1. DR PANTHER; PTHR47633; IMMUNOGLOBULIN; 1. DR Pfam; PF16620; 23ISL; 1. DR Pfam; PF00041; fn3; 1. DR Pfam; PF07679; I-set; 9. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00060; FN3; 1. DR SMART; SM00409; IG; 9. DR SMART; SM00408; IGc2; 9. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF49265; Fibronectin type III; 1. DR SUPFAM; SSF48726; Immunoglobulin; 9. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS50853; FN3; 1. DR PROSITE; PS50835; IG_LIKE; 9. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR Genevisible; Q15746; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Actin-binding; Alternative promoter usage; KW Alternative splicing; Aortic aneurysm; ATP-binding; Calcium; KW Calmodulin-binding; Cell projection; Cytoplasm; Cytoskeleton; KW Direct protein sequencing; Disease variant; Disulfide bond; KW Immunoglobulin domain; Kinase; Magnesium; Metal-binding; KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat; KW Serine/threonine-protein kinase; Transferase. FT CHAIN 1..1914 FT /note="Myosin light chain kinase, smooth muscle" FT /id="PRO_0000024354" FT CHAIN 1..1910 FT /note="Myosin light chain kinase, smooth muscle, FT deglutamylated form" FT /evidence="ECO:0000250" FT /id="PRO_0000403731" FT DOMAIN 33..122 FT /note="Ig-like C2-type 1" FT DOMAIN 161..249 FT /note="Ig-like C2-type 2" FT DOMAIN 414..503 FT /note="Ig-like C2-type 3" FT DOMAIN 514..599 FT /note="Ig-like C2-type 4" FT DOMAIN 620..711 FT /note="Ig-like C2-type 5" FT DOMAIN 721..821 FT /note="Ig-like C2-type 6" FT REPEAT 868..895 FT /note="1-1" FT REPEAT 896..923 FT /note="1-2" FT REPEAT 924..951 FT /note="1-3" FT REPEAT 952..979 FT /note="1-4" FT REPEAT 980..998 FT /note="1-5; truncated" FT REPEAT 999..1003 FT /note="2-1; truncated" FT REPEAT 1004..1015 FT /note="2-2" FT REPEAT 1016..1027 FT /note="2-3" FT REPEAT 1028..1039 FT /note="2-4" FT REPEAT 1040..1051 FT /note="2-5" FT REPEAT 1052..1063 FT /note="2-6" FT DOMAIN 1098..1186 FT /note="Ig-like C2-type 7" FT DOMAIN 1238..1326 FT /note="Ig-like C2-type 8" FT DOMAIN 1334..1426 FT /note="Fibronectin type-III" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 1464..1719 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT DOMAIN 1809..1898 FT /note="Ig-like C2-type 9" FT REGION 286..393 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 868..998 FT /note="5 X 28 AA approximate tandem repeats" FT REGION 923..963 FT /note="Actin-binding (calcium/calmodulin-sensitive)" FT /evidence="ECO:0000250" FT REGION 932..1098 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 948..963 FT /note="Calmodulin-binding" FT /evidence="ECO:0000250" FT REGION 999..1063 FT /note="6 X 12 AA approximate tandem repeats" FT REGION 1061..1460 FT /note="Actin-binding (calcium/calmodulin-insensitive)" FT /evidence="ECO:0000250" FT REGION 1192..1237 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1413..1446 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1711..1774 FT /note="Calmodulin-binding" FT REGION 1767..1787 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 292..319 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 327..350 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 935..949 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 995..1022 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1058..1088 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1767..1783 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 1585 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 1470..1478 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 1493 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 231 FT /note="Phosphotyrosine; by ABL1" FT /evidence="ECO:0000269|PubMed:20861316" FT MOD_RES 305 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 343 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6PDN3" FT MOD_RES 365 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6PDN3" FT MOD_RES 464 FT /note="Phosphotyrosine; by ABL1 and SRC" FT /evidence="ECO:0000269|PubMed:11113114, FT ECO:0000269|PubMed:12408982, ECO:0000269|PubMed:20861316" FT MOD_RES 471 FT /note="Phosphotyrosine; by SRC" FT /evidence="ECO:0000269|PubMed:11113114, FT ECO:0000269|PubMed:12408982" FT MOD_RES 556 FT /note="Phosphotyrosine; by ABL1" FT /evidence="ECO:0000269|PubMed:20861316" FT MOD_RES 608 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:19826488" FT MOD_RES 611 FT /note="Phosphotyrosine; by ABL1" FT /evidence="ECO:0000269|PubMed:20861316" FT MOD_RES 792 FT /note="Phosphotyrosine; by ABL1" FT /evidence="ECO:0000269|PubMed:20861316" FT MOD_RES 846 FT /note="Phosphotyrosine; by ABL1" FT /evidence="ECO:0000269|PubMed:20861316" FT MOD_RES 947 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6PDN3" FT MOD_RES 1438 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18088087, FT ECO:0007744|PubMed:18318008, ECO:0007744|PubMed:24275569" FT MOD_RES 1449 FT /note="Phosphotyrosine; by ABL1" FT /evidence="ECO:0000269|PubMed:20861316" FT MOD_RES 1575 FT /note="Phosphotyrosine; by ABL1" FT /evidence="ECO:0000269|PubMed:20861316" FT MOD_RES 1635 FT /note="Phosphotyrosine; by ABL1" FT /evidence="ECO:0000269|PubMed:20861316" FT MOD_RES 1759 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6PDN3" FT MOD_RES 1760 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6PDN3" FT MOD_RES 1772 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 1773 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6PDN3" FT MOD_RES 1776 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 1778 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q6PDN3" FT MOD_RES 1779 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT DISULFID 182..233 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT DISULFID 435..487 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT DISULFID 535..583 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT DISULFID 742..805 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT DISULFID 1119..1170 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT DISULFID 1830..1882 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT VAR_SEQ 1..1760 FT /note="Missing (in isoform 6 and isoform 8)" FT /evidence="ECO:0000303|PubMed:10536370, FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334" FT /id="VSP_018846" FT VAR_SEQ 1..1200 FT /note="Missing (in isoform 7)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_053791" FT VAR_SEQ 1..922 FT /note="Missing (in isoform 5 and isoform 9)" FT /evidence="ECO:0000303|PubMed:8575746, ECO:0000303|Ref.8" FT /id="VSP_018845" FT VAR_SEQ 437..506 FT /note="VSGIPKPEVAWFLEGTPVRRQEGSIEVYEDAGSHYLCLLKARTRDSGTYSCT FT ASNAQGQLSCSWTLQVER -> G (in isoform 2 and isoform 3B)" FT /evidence="ECO:0000303|PubMed:10198165, FT ECO:0000303|PubMed:15507455" FT /id="VSP_004791" FT VAR_SEQ 1473..1545 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:10198165" FT /id="VSP_004793" FT VAR_SEQ 1655..1705 FT /note="Missing (in isoform 3A and isoform 3B)" FT /evidence="ECO:0000303|PubMed:10198165" FT /id="VSP_004794" FT VAR_SEQ 1790 FT /note="Missing (in isoform Del-1790, isoform 8 and isoform FT 9)" FT /evidence="ECO:0000303|PubMed:10536370, FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:8575746" FT /id="VSP_004795" FT VARIANT 21 FT /note="P -> H (in dbSNP:rs28497577)" FT /id="VAR_057106" FT VARIANT 128 FT /note="A -> V (in dbSNP:rs143896146)" FT /evidence="ECO:0000269|PubMed:21055718" FT /id="VAR_065570" FT VARIANT 133 FT /note="Q -> H (in dbSNP:rs140148380)" FT /evidence="ECO:0000269|PubMed:21055718" FT /id="VAR_065571" FT VARIANT 160 FT /note="P -> R (in dbSNP:rs111256888)" FT /evidence="ECO:0000269|PubMed:21055718" FT /id="VAR_065572" FT VARIANT 261 FT /note="V -> A (in dbSNP:rs3796164)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040847" FT VARIANT 276 FT /note="T -> A (in dbSNP:rs55846245)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040848" FT VARIANT 336 FT /note="P -> L (in dbSNP:rs35912339)" FT /id="VAR_057107" FT VARIANT 378 FT /note="R -> H (in dbSNP:rs56378658)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040849" FT VARIANT 405 FT /note="M -> V (in dbSNP:rs35436690)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040850" FT VARIANT 443 FT /note="P -> S (in dbSNP:rs35156360)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040851" FT VARIANT 607 FT /note="R -> G" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040852" FT VARIANT 652 FT /note="P -> A (in dbSNP:rs750686734)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040853" FT VARIANT 656 FT /note="W -> C (in dbSNP:rs138172035)" FT /evidence="ECO:0000269|PubMed:17344846, FT ECO:0000269|PubMed:21055718" FT /id="VAR_040854" FT VARIANT 692 FT /note="T -> M (in dbSNP:rs776858093)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040855" FT VARIANT 701 FT /note="A -> T (in dbSNP:rs142835596)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040856" FT VARIANT 709 FT /note="V -> M (in dbSNP:rs112537316)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040857" FT VARIANT 845 FT /note="R -> C (in dbSNP:rs3732485)" FT /id="VAR_057108" FT VARIANT 861 FT /note="L -> P (in dbSNP:rs3732486)" FT /id="VAR_019986" FT VARIANT 877 FT /note="V -> M (in dbSNP:rs34542174)" FT /id="VAR_057109" FT VARIANT 914 FT /note="D -> E (in dbSNP:rs3732487)" FT /id="VAR_019987" FT VARIANT 1085 FT /note="T -> A (in dbSNP:rs75370906)" FT /evidence="ECO:0000269|PubMed:21055718" FT /id="VAR_065573" FT VARIANT 1213 FT /note="V -> M (in AAT7; uncertain significance; FT dbSNP:rs368390254)" FT /evidence="ECO:0000269|PubMed:21055718" FT /id="VAR_065574" FT VARIANT 1399 FT /note="E -> K (in dbSNP:rs181663420)" FT /evidence="ECO:0000269|PubMed:21055718" FT /id="VAR_065575" FT VARIANT 1458..1914 FT /note="Missing (in AAT7; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28401540" FT /id="VAR_083423" FT VARIANT 1487..1914 FT /note="Missing (in AAT7; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28401540" FT /id="VAR_083424" FT VARIANT 1491 FT /note="A -> S (in AAT7; decreases kinase activity; FT dbSNP:rs1576422965)" FT /evidence="ECO:0000269|PubMed:29544503" FT /id="VAR_083425" FT VARIANT 1527 FT /note="A -> V (in dbSNP:rs34982967)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040858" FT VARIANT 1588 FT /note="P -> L (in an ovarian mucinous carcinoma sample; FT somatic mutation; dbSNP:rs1576401641)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040859" FT VARIANT 1754 FT /note="A -> T (in AAT7; 4-fold reduced affinity for FT calmodulin; decreased kinase activity compared to wild-type FT protein)" FT /evidence="ECO:0000269|PubMed:21055718" FT /id="VAR_065576" FT VARIANT 1759 FT /note="S -> P (in AAT7; 7-fold reduced affinity for FT calmodulin; 6-fold decreased Vmax; dbSNP:rs387906781)" FT /evidence="ECO:0000269|PubMed:21055718" FT /id="VAR_065577" FT MUTAGEN 608 FT /note="K->A: Loss of acetylation and no kinase activity FT repression by NAA10/ARD1." FT /evidence="ECO:0000269|PubMed:19826488" FT CONFLICT 147 FT /note="P -> S (in Ref. 2; AAC18423, 3; AAD15922/AAD15923, FT 6; AAR29062, 7; AAQ02673 and 11; EAW79438/EAW79440)" FT /evidence="ECO:0000305" FT CONFLICT 466 FT /note="D -> N (in Ref. 6; AAR29062)" FT /evidence="ECO:0000305" FT CONFLICT 496 FT /note="L -> V (in Ref. 2; AAC18423, 3; AAD15922, 6; FT AAR29062 and 7; AAQ02673)" FT /evidence="ECO:0000305" FT CONFLICT 681 FT /note="C -> W (in Ref. 2; AAC18423 and 3; FT AAD15921/AAD15922/AAD15923)" FT /evidence="ECO:0000305" FT CONFLICT 933 FT /note="V -> M (in Ref. 1; CAA59685)" FT /evidence="ECO:0000305" FT CONFLICT 963 FT /note="S -> P (in Ref. 3; AAD15922)" FT /evidence="ECO:0000305" FT CONFLICT 1022 FT /note="P -> A (in Ref. 1; CAA59685)" FT /evidence="ECO:0000305" FT CONFLICT 1048..1050 FT /note="KPM -> EAH (in Ref. 1; CAA59685 and 8; BAB21504)" FT /evidence="ECO:0000305" FT CONFLICT 1162 FT /note="P -> L (in Ref. 3; AAD15922/AAD15923)" FT /evidence="ECO:0000305" FT CONFLICT 1210 FT /note="L -> P (in Ref. 1; CAA59685)" FT /evidence="ECO:0000305" FT CONFLICT 1280 FT /note="E -> D (in Ref. 3; AAD15922/AAD15923)" FT /evidence="ECO:0000305" FT CONFLICT 1284 FT /note="M -> I (in Ref. 3; AAD15922/AAD15923/AAD15924)" FT /evidence="ECO:0000305" FT CONFLICT 1300 FT /note="A -> G (in Ref. 1; CAA59685)" FT /evidence="ECO:0000305" FT CONFLICT 1316 FT /note="L -> S (in Ref. 1; CAA59685)" FT /evidence="ECO:0000305" FT CONFLICT 1326 FT /note="T -> S (in Ref. 1; CAA59685)" FT /evidence="ECO:0000305" FT CONFLICT 1478 FT /note="V -> C (in Ref. 1; CAA59685)" FT /evidence="ECO:0000305" FT CONFLICT 1511 FT /note="S -> T (in Ref. 3; AAD15922/AAD15923)" FT /evidence="ECO:0000305" FT CONFLICT 1518 FT /note="H -> P (in Ref. 6; AAR29061/AAR29062)" FT /evidence="ECO:0000305" FT CONFLICT 1563 FT /note="I -> T (in Ref. 1; CAA59685)" FT /evidence="ECO:0000305" FT CONFLICT 1609 FT /note="A -> P (in Ref. 1; CAA59685)" FT /evidence="ECO:0000305" FT CONFLICT 1634 FT /note="N -> I (in Ref. 6; AAR29061/AAR29062)" FT /evidence="ECO:0000305" FT CONFLICT 1639..1640 FT /note="GY -> D (in Ref. 3; AAD15922/AAD15923/AAD15924)" FT /evidence="ECO:0000305" FT CONFLICT 1639 FT /note="G -> R (in Ref. 1; CAA59685)" FT /evidence="ECO:0000305" FT CONFLICT 1648 FT /note="G -> R (in Ref. 1; CAA59685)" FT /evidence="ECO:0000305" FT CONFLICT 1658..1659 FT /note="LS -> PF (in Ref. 1; CAA59685)" FT /evidence="ECO:0000305" FT CONFLICT 1676 FT /note="A -> P (in Ref. 6; AAR29061/AAR29062)" FT /evidence="ECO:0000305" FT CONFLICT 1710..1711 FT /note="CT -> LA (in Ref. 1; CAA59685)" FT /evidence="ECO:0000305" FT CONFLICT 1897 FT /note="L -> H (in Ref. 3; AAD15922/AAD15923/AAD15924)" FT /evidence="ECO:0000305" FT STRAND 415..418 FT /evidence="ECO:0007829|PDB:6C6M" FT STRAND 423..425 FT /evidence="ECO:0007829|PDB:6C6M" FT STRAND 431..438 FT /evidence="ECO:0007829|PDB:6C6M" FT STRAND 444..449 FT /evidence="ECO:0007829|PDB:6C6M" FT STRAND 458..466 FT /evidence="ECO:0007829|PDB:6C6M" FT STRAND 469..476 FT /evidence="ECO:0007829|PDB:6C6M" FT HELIX 479..481 FT /evidence="ECO:0007829|PDB:6C6M" FT STRAND 483..491 FT /evidence="ECO:0007829|PDB:6C6M" FT STRAND 494..504 FT /evidence="ECO:0007829|PDB:6C6M" FT STRAND 512..518 FT /evidence="ECO:0007829|PDB:2YR3" FT STRAND 523..526 FT /evidence="ECO:0007829|PDB:2YR3" FT STRAND 531..534 FT /evidence="ECO:0007829|PDB:2YR3" FT STRAND 536..541 FT /evidence="ECO:0007829|PDB:2YR3" FT STRAND 546..553 FT /evidence="ECO:0007829|PDB:2YR3" FT STRAND 560..562 FT /evidence="ECO:0007829|PDB:2YR3" FT STRAND 565..570 FT /evidence="ECO:0007829|PDB:2YR3" FT STRAND 581..586 FT /evidence="ECO:0007829|PDB:2YR3" FT STRAND 591..595 FT /evidence="ECO:0007829|PDB:2YR3" FT STRAND 598..601 FT /evidence="ECO:0007829|PDB:2YR3" FT STRAND 1239..1241 FT /evidence="ECO:0007829|PDB:2CQV" FT STRAND 1246..1250 FT /evidence="ECO:0007829|PDB:2CQV" FT STRAND 1255..1266 FT /evidence="ECO:0007829|PDB:2CQV" FT STRAND 1268..1277 FT /evidence="ECO:0007829|PDB:2CQV" FT STRAND 1281..1288 FT /evidence="ECO:0007829|PDB:2CQV" FT STRAND 1290..1297 FT /evidence="ECO:0007829|PDB:2CQV" FT TURN 1302..1304 FT /evidence="ECO:0007829|PDB:2CQV" FT STRAND 1306..1313 FT /evidence="ECO:0007829|PDB:2CQV" FT STRAND 1318..1320 FT /evidence="ECO:0007829|PDB:2CQV" FT STRAND 1323..1328 FT /evidence="ECO:0007829|PDB:2CQV" FT HELIX 1743..1760 FT /evidence="ECO:0007829|PDB:5JQA" FT INIT_MET Q15746-8:1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:22814378" FT MOD_RES Q15746-8:2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:22814378" FT INIT_MET Q15746-10:1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:22814378" FT MOD_RES Q15746-10:2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:22814378" SQ SEQUENCE 1914 AA; 210715 MW; 2D094E161CE2D4BA CRC64; MGDVKLVASS HISKTSLSVD PSRVDSMPLT EAPAFILPPR NLCIKEGATA KFEGRVRGYP EPQVTWHRNG QPITSGGRFL LDCGIRGTFS LVIHAVHEED RGKYTCEATN GSGARQVTVE LTVEGSFAKQ LGQPVVSKTL GDRFSAPAVE TRPSIWGECP PKFATKLGRV VVKEGQMGRF SCKITGRPQP QVTWLKGNVP LQPSARVSVS EKNGMQVLEI HGVNQDDVGV YTCLVVNGSG KASMSAELSI QGLDSANRSF VRETKATNSD VRKEVTNVIS KESKLDSLEA AAKSKNCSSP QRGGSPPWAA NSQPQPPRES KLESCKDSPR TAPQTPVLQK TSSSITLQAA RVQPEPRAPG LGVLSPSGEE RKRPAPPRPA TFPTRQPGLG SQDVVSKAAN RRIPMEGQRD SAFPKFESKP QSQEVKENQT VKFRCEVSGI PKPEVAWFLE GTPVRRQEGS IEVYEDAGSH YLCLLKARTR DSGTYSCTAS NAQGQLSCSW TLQVERLAVM EVAPSFSSVL KDCAVIEGQD FVLQCSVRGT PVPRITWLLN GQPIQYARST CEAGVAELHI QDALPEDHGT YTCLAENALG QVSCSAWVTV HEKKSSRKSE YLLPVAPSKP TAPIFLQGLS DLKVMDGSQV TMTVQVSGNP PPEVIWLHNG NEIQESEDFH FEQRGTQHSL CIQEVFPEDT GTYTCEAWNS AGEVRTQAVL TVQEPHDGTQ PWFISKPRSV TASLGQSVLI SCAIAGDPFP TVHWLRDGKA LCKDTGHFEV LQNEDVFTLV LKKVQPWHAG QYEILLKNRV GECSCQVSLM LQNSSARALP RGREPASCED LCGGGVGADG GGSDRYGSLR PGWPARGQGW LEEEDGEDVR GVLKRRVETR QHTEEAIRQQ EVEQLDFRDL LGKKVSTKTL SEDDLKEIPA EQMDFRANLQ RQVKPKTVSE EERKVHSPQQ VDFRSVLAKK GTSKTPVPEK VPPPKPATPD FRSVLGGKKK LPAENGSSSA ETLNAKAVES SKPLSNAQPS GPLKPVGNAK PAETLKPMGN AKPAETLKPM GNAKPDENLK SASKEELKKD VKNDVNCKRG HAGTTDNEKR SESQGTAPAF KQKLQDVHVA EGKKLLLQCQ VSSDPPATII WTLNGKTLKT TKFIILSQEG SLCSVSIEKA LPEDRGLYKC VAKNDAGQAE CSCQVTVDDA PASENTKAPE MKSRRPKSSL PPVLGTESDA TVKKKPAPKT PPKAAMPPQI IQFPEDQKVR AGESVELFGK VTGTQPITCT WMKFRKQIQE SEHMKVENSE NGSKLTILAA RQEHCGCYTL LVENKLGSRQ AQVNLTVVDK PDPPAGTPCA SDIRSSSLTL SWYGSSYDGG SAVQSYSIEI WDSANKTWKE LATCRSTSFN VQDLLPDHEY KFRVRAINVY GTSEPSQESE LTTVGEKPEE PKDEVEVSDD DEKEPEVDYR TVTINTEQKV SDFYDIEERL GSGKFGQVFR LVEKKTRKVW AGKFFKAYSA KEKENIRQEI SIMNCLHHPK LVQCVDAFEE KANIVMVLEI VSGGELFERI IDEDFELTER ECIKYMRQIS EGVEYIHKQG IVHLDLKPEN IMCVNKTGTR IKLIDFGLAR RLENAGSLKV LFGTPEFVAP EVINYEPIGY ATDMWSIGVI CYILVSGLSP FMGDNDNETL ANVTSATWDF DDEAFDEISD DAKDFISNLL KKDMKNRLDC TQCLQHPWLM KDTKNMEAKK LSKDRMKKYM ARRKWQKTGN AVRAIGRLSS MAMISGLSGR KSSTGSPTSP LNAEKLESEE DVSQAFLEAV AEEKPHVKPY FSKTIRDLEV VEGSAARFDC KIEGYPDPEV VWFKDDQSIR ESRHFQIDYD EDGNCSLIIS DVCGDDDAKY TCKAVNSLGE ATCTAELIVE TMEEGEGEGE EEEE //