MYLK_HUMAN
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 03-AUG-2022, entry version 225.
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>3.0.co;2-5;
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 NOTICE 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="http://atlasgeneticsoncology.org/Genes/MYLKID43364ch3q21.html";
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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 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. [Q15746-11]
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; 28.
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 DrugCentral; Q15746; -.
DR GuidetoPHARMACOLOGY; 1552; -.
DR iPTMnet; Q15746; -.
DR MetOSite; Q15746; -.
DR PhosphoSitePlus; Q15746; -.
DR BioMuta; MYLK; -.
DR DMDM; 300669714; -.
DR EPD; Q15746; -.
DR jPOST; Q15746; -.
DR MassIVE; Q15746; -.
DR MaxQB; Q15746; -.
DR PaxDb; Q15746; -.
DR PeptideAtlas; Q15746; -.
DR PRIDE; 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 Antibodypedia; 4044; 392 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 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; MQVLEIQ; -.
DR OrthoDB; 330091at2759; -.
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; 9 hits in 1077 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 210 other tissues.
DR ExpressionAtlas; Q15746; baseline and differential.
DR Genevisible; Q15746; HS.
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:0004672; F:protein kinase activity; IBA:GO_Central.
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; cd14191; STKc_MLCK1; 1.
DR Gene3D; 2.60.40.10; -; 10.
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 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; SSF48726; SSF48726; 9.
DR SUPFAM; SSF49265; SSF49265; 1.
DR SUPFAM; SSF56112; SSF56112; 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.
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; unknown pathological 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; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:28401540"
FT /id="VAR_083423"
FT VARIANT 1487..1914
FT /note="Missing (in AAT7; unknown pathological
FT 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; AAD15921/
FT 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
