RBCC Red Blood Cell Collection

MYLK (MLCK, MLCK1, MYLK1) [Confidence: low (only semi-automatic identification from reviews)]
Myosin light chain kinase, smooth muscle; MLCK; smMLCK; 2.7.11.18 (Kinase-related protein; KRP; Telokin; Myosin light chain kinase, smooth muscle, deglutamylated form)
Note: presumably soluble (membrane word is not in UniProt keywords or features)

UniProt Q15746
ID MYLK_HUMAN Reviewed; 1914 AA.
AC Q15746; O95796; O95797; O95798; O95799; Q14844; Q16794; Q3ZCP9;
read moreAC Q5MY99; Q5MYA0; Q7Z4J0; Q9C0L5; Q9UBG5; Q9UBY6; Q9UIT9;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 13-JUL-2010, sequence version 4.
DT 22-JAN-2014, entry version 154.
DE RecName: Full=Myosin light chain kinase, smooth muscle;
DE Short=MLCK;
DE Short=smMLCK;
DE EC=2.7.11.18;
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; Synonyms=MLCK, MLCK1, MYLK1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), 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; 3B AND 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, BIOPHYSICOCHEMICAL PROPERTIES, PHOSPHORYLATION AT
RP TYR-464 AND TYR-471, CALMODULIN-BINDING, AND ENZYME REGULATION.
RX PubMed=11113114; DOI=10.1074/jbc.M005270200;
RA Birukov K.G., Csortos C., Marzilli L., Dudek S., Ma S.-F.,
RA Bresnick A.R., Verin A.D., Cotter R.J., Garcia J.G.N.;
RT "Differential regulation of alternatively spliced endothelial cell
RT myosin 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
RP DNA / MRNA] OF 1614-1914 (ISOFORM 5), 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
RT 3q21 in a multi-gene cluster: organization, expression, alternative
RT splicing and 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
RT kinase, 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
RT spindle 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] (ISOFORM 6).
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA 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.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6).
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [13]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1456-1914.
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
RP 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
RT chain kinase.";
RL Biochem. Biophys. Res. Commun. 298:511-519(2002).
RN [15]
RP FUNCTION IN HYPOTONICITY RESPONSE, AND ENZYME 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
RT and Cl- channel activity in human cervical cancer cells.";
RL Pflugers Arch. 444:276-285(2002).
RN [16]
RP ENZYME 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
RT of 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.,
RA Gitter A.H., 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, AND TISSUE SPECIFICITY.
RX PubMed=16835238; DOI=10.1074/jbc.M602164200;
RA Graham W.V., Wang F., Clayburgh D.R., Cheng J.X., Yoon B., Wang Y.,
RA Lin A., Turner J.R.;
RT "Tumor necrosis factor-induced long myosin light chain kinase
RT transcription is regulated by differentiation-dependent signaling
RT events. Characterization of the human long myosin light chain kinase
RT promoter.";
RL J. Biol. Chem. 281:26205-26215(2006).
RN [19]
RP FUNCTION IN EPITHELIAL CELL SURVIVAL, AND ENZYME 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
RT epithelial cell survival.";
RL J. Cell Sci. 119:2269-2281(2006).
RN [20]
RP FUNCTION IN TRPC5 REGULATION, AND ENZYME REGULATION.
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
RT migration of breast cancer cells through cross-talk with activated
RT ERK1/2.";
RL Cancer Lett. 270:312-327(2008).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1438, AND MASS
RP SPECTROMETRY.
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
RT transmigration in sepsis-induced lung inflammation by activating beta2
RT integrins.";
RL Nat. Immunol. 9:880-886(2008).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1438, AND MASS
RP SPECTROMETRY.
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
RT enrichment and fractionation of phosphopeptides with strong anion
RT exchange 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.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a 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
RT cancer cells.";
RL J. Steroid Biochem. Mol. Biol. 114:174-179(2009).
RN [27]
RP FUNCTION IN TUMOR CELL MIGRATION, ACETYLATION AT LYS-608 BY
RP NAA10/ARD1, 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
RT ability of breast cancer cells via anti-apoptosis involving p38
RT 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
RT 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.,
RA Dudek S.M.;
RT "Quantitative distribution and colocalization of non-muscle myosin
RT light 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;
RP TYR-846; TYR-1449; TYR-1575 AND TYR-1635 BY ABL1, AND INTERACTION WITH
RP CTTN AND 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
RT kinase to 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
RT coupling 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.,
RA Turner J.R., Chiang E.T., Evenoski C., Wang T., Singleton P.A.,
RA Huang Y., Lussier Y.A., Watterson D.M., Dudek S.M., Garcia J.G.N.;
RT "Non-muscle myosin light chain kinase isoform is a viable molecular
RT target in acute inflammatory lung injury.";
RL Am. J. Respir. Cell Mol. Biol. 44:40-52(2011).
RN [34]
RP ENZYME 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
RT function in asthma.";
RL Am. J. Respir. Crit. Care Med. 179:194-204(2009).
RN [36]
RP IDENTIFICATION 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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [37]
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 [38]
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 [39]
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;
RP VAL-1527 AND LEU-1588.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C.,
RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
RN [40]
RP VARIANT AAT7 PRO-1759, VARIANTS VAL-128; HIS-133; ARG-160; CYS-656;
RP ALA-1085; MET-1213; LYS-1399 AND THR-1754, CHARACTERIZATION OF VARIANT
RP AAT7 PRO-1759, AND CHARACTERIZATION OF VARIANT THR-1754.
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.,
RA Elefteriades J., 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).
CC -!- FUNCTION: Calcium/calmodulin-dependent myosin light chain kinase
CC implicated in smooth muscle contraction via phosphorylation of
CC myosin light chains (MLC). Also regulates actin-myosin interaction
CC through a non-kinase activity. Phosphorylates PTK2B/PYK2 and
CC myosin light-chains. Involved in the inflammatory response (e.g.
CC apoptosis, vascular permeability, leukocyte diapedesis), cell
CC motility and morphology, airway hyperreactivity and other
CC activities relevant to asthma. Required for tonic airway smooth
CC muscle contraction that is necessary for physiological and
CC asthmatic airway resistance. Necessary for gastrointestinal
CC motility. Implicated in the regulation of endothelial as well as
CC vascular permeability, probably via the regulation of cytoskeletal
CC rearrangements. In the nervous system it has been shown to control
CC the growth initiation of astrocytic processes in culture and to
CC participate in transmitter release at synapses formed between
CC cultured sympathetic ganglion cells. Critical participant in
CC signaling sequences that result in fibroblast apoptosis. Plays a
CC role in the regulation of epithelial cell survival. Required for
CC epithelial wound healing, especially during actomyosin ring
CC contraction during purse-string wound closure. Mediates RhoA-
CC dependent membrane blebbing. Triggers TRPC5 channel activity in a
CC calcium-dependent signaling, by inducing its subcellular
CC localization at the plasma membrane. Promotes cell migration
CC (including tumor cells) and tumor metastasis. PTK2B/PYK2
CC activation by phosphorylation mediates ITGB2 activation and is
CC thus essential to trigger neutrophil transmigration during acute
CC lung injury (ALI). May regulate optic nerve head astrocyte
CC migration. Probably involved in mitotic cytoskeletal regulation.
CC Regulates tight junction probably by modulating ZO-1 exchange in
CC the perijunctional actomyosin ring. Mediates burn-induced
CC microvascular barrier injury; triggers endothelial contraction in
CC the development of microvascular hyperpermeability by
CC phosphorylating MLC. Essential for intestinal barrier dysfunction.
CC Mediates Giardia spp.-mediated reduced epithelial barrier function
CC during giardiasis intestinal infection via reorganization of
CC cytoskeletal F-actin and tight junctional ZO-1. Necessary for
CC hypotonicity-induced Ca(2+) entry and subsequent activation of
CC volume-sensitive organic osmolyte/anion channels (VSOAC) in
CC cervical cancer cells. Responsible for high proliferative ability
CC of breast cancer cells through anti-apoptosis.
CC -!- CATALYTIC ACTIVITY: ATP + [myosin light-chain] = ADP + [myosin
CC light-chain] phosphate.
CC -!- COFACTOR: Magnesium.
CC -!- COFACTOR: Calcium.
CC -!- ENZYME REGULATION: Isoform 1 is activated by phosphorylation on
CC Tyr-464 and Tyr-471. Isoforms which lack these tyrosine residues
CC are not regulated in this way. All catalytically active isoforms
CC require binding to calcium and calmodulin for activation.
CC Repressed by organometallic pyridylnaphthalimide complexes,
CC wortmannin, ML-7 (a synthetic naphthalenesulphonyl derivative that
CC inhibits the binding of ATP to MLCK) and ML-9.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=6.5 uM for MLC (isoform 1 at 22 degrees Celsius);
CC KM=7.2 uM for MLC (isoform 2 at 22 degrees Celsius);
CC Vmax=11.9 umol/min/mg enzyme (isoform 1 at 22 degrees Celsius);
CC Vmax=10.9 umol/min/mg enzyme (isoform 1 at 22 degrees Celsius);
CC -!- SUBUNIT: All isoforms including Telokin bind calmodulin. Interacts
CC with SVIL (By similarity). Interacts with CTTN; this interaction
CC is reduced during thrombin-induced endothelial cell (EC)
CC contraction but is promoted by the barrier-protective agonist
CC sphingosine 1-phosphate (S1P) within lamellipodia. A complex made
CC of ABL1, CTTN and MYLK regulates cortical actin-based cytoskeletal
CC rearrangement critical to sphingosine 1-phosphate (S1P)-mediated
CC endothelial cell (EC) barrier enhancement. Binds to NAA10/ARD1 and
CC PTK2B/PYK2.
CC -!- INTERACTION:
CC P16333:NCK1; NbExp=2; IntAct=EBI-968482, EBI-389883;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell projection, lamellipodium.
CC Cleavage furrow. Cytoplasm, cytoskeleton. Note=Localized to stress
CC fibers during interphase and to the cleavage furrow during
CC mitosis.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=8;
CC Comment=Additional isoforms seem to exist;
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 Note=Ref.3 (AAD15922) sequence differs from that shown due to
CC frameshifts in positions 1433 and 1439;
CC Name=3B;
CC IsoId=Q15746-4; Sequence=VSP_004791, VSP_004794;
CC Note=Ref.3 (AAD15923) sequence differs from that shown due to
CC frameshifts in positions 1433 and 1439;
CC Name=4;
CC IsoId=Q15746-5; Sequence=VSP_004793;
CC Note=Ref.3 (AAD15924) sequence differs from that shown due to
CC frameshifts in positions 1433 and 1439;
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 Note=Produced by alternative initiation at Met-923 of isoform 1;
CC Name=6; Synonyms=Telokin;
CC IsoId=Q15746-8; Sequence=VSP_018846;
CC Note=Produced by alternative initiation at Met-1761 of isoform
CC 1. Has no catalytic activity;
CC -!- TISSUE SPECIFICITY: Smooth muscle and non-muscle isozymes are
CC expressed in a wide variety of adult and fetal tissues and in
CC cultured endothelium with qualitative expression appearing to be
CC neither tissue- nor development-specific. Non-muscle isoform 2 is
CC the dominant splice variant expressed in various tissues. Telokin
CC has been found in a wide variety of adult and fetal tissues.
CC Accumulates in well differentiated enterocytes of the intestinal
CC epithelium in response to tumor necrosis factor (TNF).
CC -!- INDUCTION: Accumulates in individuals with asthma (at protein
CC levels). Induced by tumor necrosis factor (TNF). Repressed by
CC androgens (e.g. R1881).
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-
CC 471 promotes CTTN binding.
CC -!- PTM: The C-terminus is deglutamylated by AGTPBP1/CCP1, AGBL1/CCP4
CC and AGBL4/CCP6, leading to the formation of Myosin light chain
CC kinase, smooth muscle, deglutamylated form. The consequences of C-
CC terminal deglutamylation are unknown (By similarity).
CC -!- PTM: Acetylated at Lys-608 by NAA10/ARD1 via a calcium-dependent
CC signaling; this acetylation represses kinase activity and reduces
CC tumor cell migration.
CC -!- DISEASE: Aortic aneurysm, familial thoracic 7 (AAT7) [MIM:613780]:
CC A disease characterized by permanent dilation of the thoracic
CC aorta usually due to degenerative changes in the aortic wall. It
CC is primarily associated with a characteristic histologic
CC appearance known as 'medial necrosis' or 'Erdheim cystic medial
CC necrosis' in which there is degeneration and fragmentation of
CC elastic fibers, loss of smooth muscle cells, and an accumulation
CC of basophilic ground substance. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: In asthmatic patients, overexpression promotes
CC actin filament propulsion, thus contributing to airway
CC hyperresponsiveness. Some MYLK variants may contribute to acute
CC lung injury (ALI) susceptibility. Potential therapeutic target in
CC the treatment of burn edema.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK
CC Ser/Thr protein kinase family.
CC -!- SIMILARITY: Contains 1 fibronectin type-III domain.
CC -!- SIMILARITY: Contains 9 Ig-like C2-type (immunoglobulin-like)
CC domains.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD15922.1; Type=Frameshift; Positions=1433;
CC Sequence=AAD15923.1; Type=Frameshift; Positions=1433;
CC Sequence=AAD15924.1; Type=Frameshift; Positions=1433;
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Myosin light-chain kinase
CC entry;
CC URL="http://en.wikipedia.org/wiki/Myosin_light-chain_kinase";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and 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; AK314443; BAG37052.1; -; mRNA.
DR EMBL; AC020634; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC023165; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471052; EAW79439.1; -; Genomic_DNA.
DR EMBL; BC100761; AAI00762.2; -; mRNA.
DR EMBL; BC100762; AAI00763.2; -; mRNA.
DR EMBL; X90870; CAA62378.1; -; mRNA.
DR RefSeq; NP_444253.3; NM_053025.3.
DR RefSeq; NP_444254.3; NM_053026.3.
DR RefSeq; NP_444255.3; NM_053027.3.
DR RefSeq; NP_444256.3; NM_053028.3.
DR RefSeq; NP_444259.1; NM_053031.2.
DR RefSeq; NP_444260.1; NM_053032.2.
DR RefSeq; XP_005247554.1; XM_005247497.1.
DR UniGene; Hs.477375; -.
DR PDB; 2CQV; NMR; -; A=1238-1338.
DR PDB; 2K0F; NMR; -; B=1742-1760.
DR PDB; 2YR3; NMR; -; A=510-601.
DR PDBsum; 2CQV; -.
DR PDBsum; 2K0F; -.
DR PDBsum; 2YR3; -.
DR ProteinModelPortal; Q15746; -.
DR SMR; Q15746; 510-601, 1238-1338, 1801-1902.
DR IntAct; Q15746; 10.
DR MINT; MINT-2807402; -.
DR BindingDB; Q15746; -.
DR ChEMBL; CHEMBL2428; -.
DR GuidetoPHARMACOLOGY; 1552; -.
DR MEROPS; I43.001; -.
DR PhosphoSite; Q15746; -.
DR DMDM; 300669714; -.
DR PaxDb; Q15746; -.
DR PRIDE; Q15746; -.
DR DNASU; 4638; -.
DR Ensembl; ENST00000346322; ENSP00000320622; ENSG00000065534.
DR Ensembl; ENST00000359169; ENSP00000352088; ENSG00000065534.
DR Ensembl; ENST00000360304; ENSP00000353452; ENSG00000065534.
DR Ensembl; ENST00000360772; ENSP00000354004; ENSG00000065534.
DR Ensembl; ENST00000418370; ENSP00000428967; ENSG00000065534.
DR Ensembl; ENST00000475616; ENSP00000418335; ENSG00000065534.
DR Ensembl; ENST00000583087; ENSP00000462118; ENSG00000065534.
DR GeneID; 4638; -.
DR KEGG; hsa:4638; -.
DR UCSC; uc003ego.3; human.
DR CTD; 4638; -.
DR GeneCards; GC03M123281; -.
DR HGNC; HGNC:7590; MYLK.
DR HPA; CAB009628; -.
DR HPA; CAB020789; -.
DR HPA; HPA031677; -.
DR MIM; 600922; gene.
DR MIM; 613780; phenotype.
DR neXtProt; NX_Q15746; -.
DR Orphanet; 91387; Familial thoracic aortic aneurysm and aortic dissection.
DR PharmGKB; PA31388; -.
DR eggNOG; COG0515; -.
DR HOVERGEN; HBG052551; -.
DR InParanoid; Q15746; -.
DR KO; K00907; -.
DR OMA; KFIILSQ; -.
DR OrthoDB; EOG7WQ7RC; -.
DR BRENDA; 2.7.11.18; 2681.
DR Reactome; REACT_17044; Muscle contraction.
DR SignaLink; Q15746; -.
DR ChiTaRS; MYLK; human.
DR EvolutionaryTrace; Q15746; -.
DR GeneWiki; MYLK; -.
DR GenomeRNAi; 4638; -.
DR NextBio; 17860; -.
DR PRO; PR:Q15746; -.
DR ArrayExpress; Q15746; -.
DR Bgee; Q15746; -.
DR Genevestigator; Q15746; -.
DR GO; GO:0032154; C:cleavage furrow; 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:0005524; F:ATP 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:0014820; P:tonic smooth muscle contraction; ISS:UniProtKB.
DR Gene3D; 2.60.40.10; -; 10.
DR InterPro; IPR003961; Fibronectin_type3.
DR InterPro; IPR007110; Ig-like_dom.
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.
DR InterPro; IPR020675; Myosin_light_ch_kinase-rel.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR22964; PTHR22964; 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; 1.
DR SMART; SM00408; IGc2; 8.
DR SMART; SM00220; S_TKc; 1.
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 initiation;
KW Alternative splicing; Aortic aneurysm; ATP-binding; Calcium;
KW Calmodulin-binding; Cell projection; Complete proteome; Cytoplasm;
KW Cytoskeleton; Direct protein sequencing; Disease mutation;
KW Disulfide bond; Immunoglobulin domain; Kinase; Magnesium;
KW Metal-binding; Nucleotide-binding; Phosphoprotein; Polymorphism;
KW Reference proteome; Repeat; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1 1914 Myosin light chain kinase, smooth muscle.
FT /FTId=PRO_0000024354.
FT CHAIN 1 1910 Myosin light chain kinase, smooth muscle,
FT deglutamylated form (By similarity).
FT /FTId=PRO_0000403731.
FT DOMAIN 33 122 Ig-like C2-type 1.
FT DOMAIN 161 249 Ig-like C2-type 2.
FT DOMAIN 414 503 Ig-like C2-type 3.
FT DOMAIN 514 599 Ig-like C2-type 4.
FT DOMAIN 620 711 Ig-like C2-type 5.
FT DOMAIN 721 821 Ig-like C2-type 6.
FT REPEAT 868 895 1-1.
FT REPEAT 896 923 1-2.
FT REPEAT 924 951 1-3.
FT REPEAT 952 979 1-4.
FT REPEAT 980 998 1-5; truncated.
FT REPEAT 999 1003 2-1; truncated.
FT REPEAT 1004 1015 2-2.
FT REPEAT 1016 1027 2-3.
FT REPEAT 1028 1039 2-4.
FT REPEAT 1040 1051 2-5.
FT REPEAT 1052 1063 2-6.
FT DOMAIN 1098 1186 Ig-like C2-type 7.
FT DOMAIN 1238 1326 Ig-like C2-type 8.
FT DOMAIN 1334 1426 Fibronectin type-III.
FT DOMAIN 1464 1719 Protein kinase.
FT DOMAIN 1809 1898 Ig-like C2-type 9.
FT NP_BIND 1470 1478 ATP (By similarity).
FT REGION 868 998 5 X 28 AA approximate tandem repeats.
FT REGION 923 963 Actin-binding (calcium/calmodulin-
FT sensitive) (By similarity).
FT REGION 948 963 Calmodulin-binding (By similarity).
FT REGION 999 1063 6 X 12 AA approximate tandem repeats.
FT REGION 1061 1460 Actin-binding (calcium/calmodulin-
FT insensitive) (By similarity).
FT REGION 1711 1774 Calmodulin-binding.
FT COMPBIAS 1906 1914 Poly-Glu.
FT ACT_SITE 1585 1585 Proton acceptor (By similarity).
FT BINDING 1493 1493 ATP (By similarity).
FT MOD_RES 231 231 Phosphotyrosine; by ABL1.
FT MOD_RES 365 365 Phosphoserine (By similarity).
FT MOD_RES 464 464 Phosphotyrosine; by ABL1 and SRC.
FT MOD_RES 471 471 Phosphotyrosine; by SRC.
FT MOD_RES 556 556 Phosphotyrosine; by ABL1.
FT MOD_RES 608 608 N6-acetyllysine.
FT MOD_RES 611 611 Phosphotyrosine; by ABL1.
FT MOD_RES 792 792 Phosphotyrosine; by ABL1.
FT MOD_RES 846 846 Phosphotyrosine; by ABL1.
FT MOD_RES 1438 1438 Phosphoserine.
FT MOD_RES 1449 1449 Phosphotyrosine; by ABL1.
FT MOD_RES 1575 1575 Phosphotyrosine; by ABL1.
FT MOD_RES 1635 1635 Phosphotyrosine; by ABL1.
FT MOD_RES 1760 1760 Phosphoserine (By similarity).
FT MOD_RES 1776 1776 Phosphoserine (By similarity).
FT DISULFID 182 233 By similarity.
FT DISULFID 435 487 By similarity.
FT DISULFID 535 583 By similarity.
FT DISULFID 742 805 By similarity.
FT DISULFID 1119 1170 By similarity.
FT DISULFID 1830 1882 By similarity.
FT VAR_SEQ 1 1760 Missing (in isoform 6).
FT /FTId=VSP_018846.
FT VAR_SEQ 1 922 Missing (in isoform 5).
FT /FTId=VSP_018845.
FT VAR_SEQ 437 506 VSGIPKPEVAWFLEGTPVRRQEGSIEVYEDAGSHYLCLLKA
FT RTRDSGTYSCTASNAQGQLSCSWTLQVER -> G (in
FT isoform 2 and isoform 3B).
FT /FTId=VSP_004791.
FT VAR_SEQ 1473 1545 Missing (in isoform 4).
FT /FTId=VSP_004793.
FT VAR_SEQ 1655 1705 Missing (in isoform 3A and isoform 3B).
FT /FTId=VSP_004794.
FT VAR_SEQ 1790 1790 Missing (in isoform Del-1790).
FT /FTId=VSP_004795.
FT VARIANT 21 21 P -> H (in dbSNP:rs28497577).
FT /FTId=VAR_057106.
FT VARIANT 128 128 A -> V (in dbSNP:rs143896146).
FT /FTId=VAR_065570.
FT VARIANT 133 133 Q -> H (in dbSNP:rs140148380).
FT /FTId=VAR_065571.
FT VARIANT 160 160 P -> R (in dbSNP:rs111256888).
FT /FTId=VAR_065572.
FT VARIANT 261 261 V -> A (in dbSNP:rs3796164).
FT /FTId=VAR_040847.
FT VARIANT 276 276 T -> A.
FT /FTId=VAR_040848.
FT VARIANT 336 336 P -> L (in dbSNP:rs35912339).
FT /FTId=VAR_057107.
FT VARIANT 378 378 R -> H.
FT /FTId=VAR_040849.
FT VARIANT 405 405 M -> V (in dbSNP:rs35436690).
FT /FTId=VAR_040850.
FT VARIANT 443 443 P -> S (in dbSNP:rs35156360).
FT /FTId=VAR_040851.
FT VARIANT 607 607 R -> G.
FT /FTId=VAR_040852.
FT VARIANT 652 652 P -> A.
FT /FTId=VAR_040853.
FT VARIANT 656 656 W -> C (in dbSNP:rs138172035).
FT /FTId=VAR_040854.
FT VARIANT 692 692 T -> M.
FT /FTId=VAR_040855.
FT VARIANT 701 701 A -> T (in dbSNP:rs142835596).
FT /FTId=VAR_040856.
FT VARIANT 709 709 V -> M.
FT /FTId=VAR_040857.
FT VARIANT 845 845 R -> C (in dbSNP:rs3732485).
FT /FTId=VAR_057108.
FT VARIANT 861 861 L -> P (in dbSNP:rs3732486).
FT /FTId=VAR_019986.
FT VARIANT 877 877 V -> M (in dbSNP:rs34542174).
FT /FTId=VAR_057109.
FT VARIANT 914 914 D -> E (in dbSNP:rs3732487).
FT /FTId=VAR_019987.
FT VARIANT 1085 1085 T -> A (in dbSNP:rs75370906).
FT /FTId=VAR_065573.
FT VARIANT 1213 1213 V -> M (found in a patient with familial
FT aortic dissections).
FT /FTId=VAR_065574.
FT VARIANT 1399 1399 E -> K (found in a patient with familial
FT aortic dissections; dbSNP:rs181663420).
FT /FTId=VAR_065575.
FT VARIANT 1527 1527 A -> V.
FT /FTId=VAR_040858.
FT VARIANT 1588 1588 P -> L (in an ovarian mucinous carcinoma
FT sample; somatic mutation).
FT /FTId=VAR_040859.
FT VARIANT 1754 1754 A -> T (found in a patient with familial
FT aortic dissections; binding to calmodulin
FT is reduced; significant reduction in
FT kinase activity compared to wild-type
FT protein).
FT /FTId=VAR_065576.
FT VARIANT 1759 1759 S -> P (in AAT7; shows minimal cells
FT endogenous expression; binding to
FT calmodulin is abolished; 6-fold reduction
FT in kinase activity compared to wild-type
FT protein).
FT /FTId=VAR_065577.
FT MUTAGEN 608 608 K->A: Loss of acetylation and no kinase
FT activity repression by NAA10/ARD1.
FT CONFLICT 147 147 P -> S (in Ref. 2; AAC18423, 3; AAD15922/
FT AAD15923, 6; AAR29062 and 7; AAQ02673).
FT CONFLICT 466 466 D -> N (in Ref. 6; AAR29062).
FT CONFLICT 496 496 L -> V (in Ref. 2; AAC18423, 3; AAD15922,
FT 6; AAR29062 and 7; AAQ02673).
FT CONFLICT 681 681 C -> W (in Ref. 2; AAC18423 and 3;
FT AAD15921/AAD15922/AAD15923).
FT CONFLICT 933 933 V -> M (in Ref. 1; CAA59685).
FT CONFLICT 963 963 S -> P (in Ref. 3; AAD15922).
FT CONFLICT 1022 1022 P -> A (in Ref. 1; CAA59685).
FT CONFLICT 1048 1050 KPM -> EAH (in Ref. 1 and 8).
FT CONFLICT 1162 1162 P -> L (in Ref. 3; AAD15922/AAD15923).
FT CONFLICT 1210 1210 L -> P (in Ref. 1; CAA59685).
FT CONFLICT 1280 1280 E -> D (in Ref. 3; AAD15922/AAD15923).
FT CONFLICT 1284 1284 M -> I (in Ref. 3; AAD15922/AAD15923/
FT AAD15924).
FT CONFLICT 1300 1300 A -> G (in Ref. 1; CAA59685).
FT CONFLICT 1316 1316 L -> S (in Ref. 1; CAA59685).
FT CONFLICT 1326 1326 T -> S (in Ref. 1; CAA59685).
FT CONFLICT 1478 1478 V -> C (in Ref. 1; CAA59685).
FT CONFLICT 1511 1511 S -> T (in Ref. 3; AAD15922/AAD15923).
FT CONFLICT 1518 1518 H -> P (in Ref. 6; AAR29061/AAR29062).
FT CONFLICT 1563 1563 I -> T (in Ref. 1; CAA59685).
FT CONFLICT 1609 1609 A -> P (in Ref. 1; CAA59685).
FT CONFLICT 1634 1634 N -> I (in Ref. 6; AAR29061/AAR29062).
FT CONFLICT 1639 1640 GY -> D (in Ref. 3; AAD15922/AAD15923/
FT AAD15924).
FT CONFLICT 1639 1639 G -> R (in Ref. 1; CAA59685).
FT CONFLICT 1648 1648 G -> R (in Ref. 1; CAA59685).
FT CONFLICT 1658 1659 LS -> PF (in Ref. 1; CAA59685).
FT CONFLICT 1676 1676 A -> P (in Ref. 6; AAR29061/AAR29062).
FT CONFLICT 1710 1711 CT -> LA (in Ref. 1; CAA59685).
FT CONFLICT 1897 1897 L -> H (in Ref. 3; AAD15922/AAD15923/
FT AAD15924).
FT STRAND 512 518
FT STRAND 523 526
FT STRAND 531 534
FT STRAND 536 541
FT STRAND 546 553
FT STRAND 560 562
FT STRAND 565 570
FT STRAND 581 586
FT STRAND 591 595
FT STRAND 598 601
FT STRAND 1239 1241
FT STRAND 1246 1250
FT STRAND 1255 1266
FT STRAND 1268 1277
FT STRAND 1281 1288
FT STRAND 1290 1297
FT TURN 1302 1304
FT STRAND 1306 1313
FT STRAND 1318 1320
FT STRAND 1323 1328
FT HELIX 1743 1759
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
//

MIM 600922
*RECORD*
*FIELD* NO
600922
*FIELD* TI
*600922 MYOSIN LIGHT CHAIN KINASE; MYLK
;;MYOSIN LIGHT POLYPEPTIDE KINASE; MLCK
KINASE-RELATED PROTEIN, INCLUDED; KRP, INCLUDED;;
read moreTELOKIN, INCLUDED
*FIELD* TX

DESCRIPTION

The contraction of smooth muscle begins with the phosphorylation of the
light chain of myosin (e.g., 160781), a reaction catalyzed by myosin
light chain kinase that is itself activated by the binding of
calcium-calmodulin (see 114180). This key enzyme in muscle contraction,
which exists in both nonmuscle and smooth muscle isoforms, has been
shown by immunohistology to be present in neurons and glia.

CLONING

Potier et al. (1995) cloned the cDNA for human myosin light chain
kinase, which they symbolized MLCK, from hippocampus and showed that it
encodes a protein sequence 95% similar to smooth muscle MLCKs but less
than 60% similar to skeletal muscle MLCKs. The cDNA clone detected 2 RNA
transcripts in human frontal and entorhinal cortex, in hippocampus, and
in jejunum, one corresponding to MLCK and the other probably to telokin
(kinase-related protein), the carboxy-terminal 154 codons of MLCK
expressed as an independent protein in smooth muscle. The authors found
that levels of expression were lower in brain than in smooth muscle.
Potier et al. (1995) showed that the protein sequence contains a motif
of 28 or 24 residues repeated 5 times, the second repeat ending with the
putative methionine start codon. These repeats overlap with the second
previously reported module of 12 residues repeated 5 times in the human
sequence. In addition, the acidic C terminus of all MLCKs from both
brain and smooth muscle resembles the C terminus of tubulins.

Garcia et al. (1997) cloned a human endothelial nonmuscle MLCK cDNA
encoding a deduced 1,914-amino acid protein with a calculated molecular
mass of 210 kD. The protein contains 9 C2-type immunoglobulin-like
homology domains, an SH2-binding domain, and a single tyrosine
phosphorylation site in the CaM-binding region.

Lazar and Garcia (1999) reported the cloning of several additional
nonmuscle variants of MLCK by RT-PCR from umbilical vein endothelial
cell RNA. They noted that the full-length MLCK gene contains at least 2
additional promoters that initiate transcription of 2 shorter isoforms.
The shorter isoforms include smooth muscle (SM) MLCK, a 5.8-kb
transcript that encodes a deduced 130-kD protein, and a 2.6-kb
transcript that encodes the deduced kinase-related protein. KRP contains
only the final C2 immunoglobulin-like domain. Northern blot analysis
detected the full-length, 8.1-kb nonmuscle MLCK isoform in all tissues
examined except skeletal muscle, with highest expression in lung,
placenta, liver, and kidney, and intermediate expression in heart,
brain, and pancreas. The transcript was also detected in fetal lung and
kidney, with lower expression in fetal brain and liver. The 5.8-kb
SM-MLCK transcript was detected in all adult tissues except liver, and
in fetal lung and kidney, with weaker expression in fetal brain and
liver. Lazar and Garcia (1999) also identified several isoforms that
resulted from in-frame internal deletions and were widely expressed in
adult and fetal tissues. The dominant isoform, which they designated
MLCK2, contains a deletion of residues 437-505, causing loss of the
tyrosine phosphorylation site and the SH2 binding site.

Watterson et al. (1999) cloned kinase-related protein from a genomic DNA
library by PCR using primers based on a previously isolated human
placenta KRP sequence. They noted that the human and chicken KRP
proteins share 80% sequence identity. Northern blot analysis detected a
2.7-kb KRP transcript in all adult and fetal tissues examined, with
highest expression in placenta, brain, heart, colon, small intestine,
and fetal small intestine. Probing with a sequence common to the 3 main
start site variants, Watterson et al. (1999) identified transcripts of
2.7 and 5.5 kb in heart, and of 2.7, 5.5, and 9.0 kb in placenta. By
immunohistochemical analysis of adult and fetal heart sections, they
found both full-length MLCK and the shorter KRP in cardiac muscle and in
the smooth muscle layer of major blood vessels.

GENE STRUCTURE

Watterson et al. (1999) noted that the various isoforms of MLCK are
encoded by differential use of 31 coding exons. They also noted that KRP
is derived from the last 3 exons spanning approximately 6.0 kb of the
MLCK gene, and that the transcription initiation site for KRP lies
within the intron preceding exon 29.

MAPPING

By PCR and Southern blotting using 2 somatic cell hybrid panels, Potier
et al. (1995) localized the MLCK gene to chromosome 3cen-q21.

By analysis of YAC clones, Giorgi et al. (2001) colocalized the MYLK
gene with D3S3552 in a greater than 5-Mb region of chromosome 3q21. They
confirmed the location of a pseudogene, MYLKP, to chromosome 3p13.

GENE FUNCTION

Walker et al. (2001) studied the KRP variant in the rabbit and
demonstrated that recombinant rabbit telokin could relax
telokin-depleted rabbit ileal smooth muscle in a dose-dependent manner.
Mutation analysis revealed that ser13 is the phosphorylation site
associated with cyclic nucleotide-induced Ca(2+)-independent relaxation
of smooth muscle.

MOLECULAR GENETICS

Wang et al. (2010) analyzed the MYLK gene in 193 probands from unrelated
families in which 2 or more members had thoracic aortic aneurysms or
dissections. They identified 2 heterozygous variants (600922.0001 and
600922.0002) that segregated with aortic dissections (AAT7; 613780) in 2
families, respectively, and were not found in 188 ethnically matched
controls. Three additional MYLK variants were identified in 3 unrelated
probands that were not detected in controls, but family members were not
available for segregation analysis.

ANIMAL MODEL

Wang et al. (2010) studied mice with smooth muscle cell-specific
knockdown of Mylk and observed increased pools of proteoglycans in the
aortic media compared to controls, along with increased expression of
lumican (600616) and decorin (125255). Increased collagen staining in
the adventitial layer and increased type III collagen (COL3A1; 120180)
expression were also identified. In addition, expression of the
elastin-degrading metalloproteinase MMP2 (120360) was also increased in
the aortas of the mice, although elastic fibers were not degraded in the
aortic media.

*FIELD* AV
.0001
AORTIC ANEURYSM, FAMILIAL THORACIC 7
MYLK, SER1759PRO

In 3 affected members of a family with aortic aneurysm and dissection
(AAT7; 613780), Wang et al. (2010) identified heterozygosity for a
5275T-C transition in the MYLK gene, resulting in a ser1759-to-pro
(S1759P) substitution in the alpha-helix of the calmodulin-binding
sequence that was predicted to cause loss of MLCK function by altering
calmodulin binding. The mutation segregated with disease in the family
and was not found in 188 ethnically matched controls. Transfection
studies in COS-7 cells showed minimal endogenous expression of MLCK, and
immunoprecipitation studies revealed that binding to calmodulin was
abolished with the S1759P mutant. Analysis of kinase activity showed a
6-fold reduction for S1759P compared to wildtype. Wang et al. (2010)
noted that affected individuals had acute aortic dissections with little
to no aortic enlargement. Examination of ascending aortic tissue from 2
family members showed medial degeneration of the aorta and a significant
increase in small arteries in the medial layer.

.0002
AORTIC ANEURYSM, FAMILIAL THORACIC 7
MYLK, ARG1480TER

In a 51-year-old father and his 18-year-old son with aortic aneurysm and
dissection (AAT7; 613780), Wang et al. (2010) identified heterozygosity
for a 4438C-T transition in the MYLK gene, resulting in an
arg1480-to-ter (R1480X) substitution that would lead to either
nonsense-mediated decay or a truncated protein missing the kinase and
calmodulin-binding domains, and was therefore predicted to disrupt
kinase activity but not to disturb telokin expression. The father had
undergone a type A dissection at 37 years of age, and the son had a type
B dissection at 16 years of age. The R1480X mutation was also detected
in 5 asymptomatic family members, with ages ranging from 59 years to 76
years. The mutation was not found in 188 ethnically matched controls.

*FIELD* RF
1. Garcia, J. G.; Lazar, V.; Gilbert-McClain, L. I.; Gallagher, P.
J.; Verin, A. D.: Myosin light chain kinase in endothelium: molecular
cloning and regulation. Am. J. Resp. Cell Molec. Biol. 16: 489-494,
1997.

2. Giorgi, D.; Brand-Arpon, V.; Rouquier, S.: The functional myosin
light chain kinase (MYLK) gene localizes with marker D3S3552 on human
chromosome 3q21 in a greater than 5-Mb yeast artificial chromosome
region and is not linked to olfactory receptor genes. Cytogenet.
Cell Genet. 92: 85-88, 2001.

3. Lazar, V.; Garcia, J. G. N.: A single human myosin light chain
kinase gene (MLCK; MYLK) transcribes multiple nonmuscle isoforms. Genomics 57:
256-267, 1999.

4. Potier, M.-C.; Chelot, E.; Pekarsky, Y.; Gardiner, K.; Rossier,
J.; Turnell, W. G.: The human myosin light chain kinase (MLCK) from
hippocampus: cloning, sequencing, expression, and localization to
3cen-q21. Genomics 29: 562-570, 1995.

5. Walker, L. A.; MacDonald, J. A.; Liu, X.; Nakamoto, R. K.; Haystead,
T. A. J.; Somlyo, A. V.; Somlyo, A. P.: Site-specific phosphorylation
and point mutations of telokin modulate its Ca(2+)-desensitizing effect
in smooth muscle. J. Biol. Chem. 276: 24519-24524, 2001.

6. Wang, L.; Guo, D.; Cao, J.; Gong, L.; Kamm, K. E.; Regalado, E.;
Li, L.; Shete, S.; He, W.-Q.; Zhu, M.-S.; Offermanns, S.; Gilchrist,
D.; Elefteriades, J.; Stull, J. T.; Milewicz, D. M.: Mutations in
myosin light chain kinase cause familial aortic dissections. Am.
J. Hum. Genet. 87: 701-707, 2010. Note: Erratum: Am. J. Hum. Genet.
88: 516 only, 2011.

7. Watterson, D. M.; Schavocky, J. P.; Guo, L.; Weiss, C.; Chlenski,
A.; Shirinsky, V. P.; Van Eldik, L. J.; Haiech, J.: Analysis of the
kinase-related protein gene found at human chromosome 3q21 in a multi-gene
cluster: organization, expression, alternative splicing, and polymorphic
marker. J. Cell. Biochem. 75: 481-491, 1999.

*FIELD* CN
Marla J. F. O'Neill - updated: 2/24/2011
Patricia A. Hartz - updated: 5/24/2002
Joanna S. Amberger - updated: 6/22/2001

*FIELD* CD
Victor A. McKusick: 11/7/1995

*FIELD* ED
carol: 12/19/2013
wwang: 4/28/2011
wwang: 2/28/2011
terry: 2/24/2011
wwang: 12/20/2005
carol: 5/30/2002
carol: 5/29/2002
terry: 5/24/2002
mcapotos: 6/25/2001
joanna: 6/22/2001
alopez: 4/30/1999
alopez: 3/26/1999
jenny: 4/4/1997
mark: 11/9/1995
terry: 11/7/1995

MIM 613780
*RECORD*
*FIELD* NO
613780
*FIELD* TI
#613780 AORTIC ANEURYSM, FAMILIAL THORACIC 7; AAT7
;;AORTIC DISSECTION, FAMILIAL, WITH OR WITHOUT AORTIC ANEURYSM
read more*FIELD* TX
A number sign (#) is used with this entry because of evidence that
aortic dissection with or without aortic aneurysm can be caused by
heterozygous mutation in the MYLK gene (600922).

For a general phenotypic description and discussion of genetic
heterogeneity of thoracic aortic aneurysm, see AAT1 (607086).

MOLECULAR GENETICS

Wang et al. (2010) analyzed the MYLK gene in 193 probands from unrelated
families in which 2 or more members had thoracic aortic aneurysms or
dissections. They identified 2 heterozygous variants (600922.0001 and
600922.0002) that segregated with aortic dissections in 2 families,
respectively, and were not found in 188 ethnically matched controls.
Three additional MYLK variants were identified in 3 unrelated probands
that were not detected in controls, but family members were not
available for segregation analysis. Wang et al. (2010) noted that acute
aortic dissections in the 2 mutation-positive families occurred with
little to no aortic enlargement, suggesting that there were likely other
family members with the defective gene who appeared phenotypically
normal. Examination of ascending aortic tissue from 2 affected members
of 1 family indicated medial degeneration of the aorta, characterized by
increased proteoglycan deposition and mild elastic fiber thinning and
fragmentation, along with a significant increase in the presence of
small arteries in the medial layer of the aorta. Wang et al. (2010)
noted that a similar increase of arteries in the medial layer had been
described in patients with mutations in the MYH11 gene (160745) (see
Pannu et al. (2007) and AAT4, 132900).

*FIELD* RF
1. Pannu, H.; Tran-Fadulu, V.; Papke, C. L.; Scherer, S.; Liu, Y.;
Presley, C.; Guo, D.; Estrera, A. L.; Safi, H. J.; Brasier, A. R.;
Vick, G. W.; Marian, A. J.; Raman, C. S.; Buja, L. M.; Milewicz, D.
M.: MYH11 mutations result in a distinct vascular pathology driven
by insulin-like growth factor 1 and angiotensin II. Hum. Molec. Genet. 16:
2453-2462, 2007. Note: Erratum: Hum. Molec. Genet. 17: 158 only, 2008.

2. Wang, L.; Guo, D.; Cao, J.; Gong, L.; Kamm, K. E.; Regalado, E.;
Li, L.; Shete, S.; He, W.-Q.; Zhu, M.-S.; Offermanns, S.; Gilchrist,
D.; Elefteriades, J.; Stull, J. T.; Milewicz, D. M.: Mutations in
myosin light chain kinase cause familial aortic dissections. Am.
J. Hum. Genet. 87: 701-707, 2010. Note: Erratum: Am. J. Hum. Genet.
88: 516 only, 2011.

*FIELD* CS
INHERITANCE:
Autosomal dominant

CARDIOVASCULAR:
[Vascular];
Aortic dissection;
Aortic aneurysm

MISCELLANEOUS:
Patients develop aortic dissection with little or no aortic enlargement

MOLECULAR BASIS:
Caused by mutation in the myosin light chain kinase gene (MYLK, 600922.0001)

*FIELD* CD
Marla J. F. O'Neill: 2/7/2012

*FIELD* ED
joanna: 02/07/2012

*FIELD* CD
Marla J. F. O'Neill: 2/28/2011

*FIELD* ED
carol: 04/12/2013
wwang: 4/28/2011
wwang: 2/28/2011