Myotonin-protein kinase

Details

Name
Myotonin-protein kinase
Synonyms
  • 2.7.11.1
  • DM-kinase
  • DM1 protein kinase
  • DM1PK
  • DMK
  • DMPK
  • MDPK
  • MT-PK
  • Myotonic dystrophy protein kinase
Gene Name
DMPK
Organism
Humans
Amino acid sequence
>lcl|BSEQ0037266|Myotonin-protein kinase
MSAEVRLRRLQQLVLDPGFLGLEPLLDLLLGVHQELGASELAQDKYVADFLQWAEPIVVR
LKEVRLQRDDFEILKVIGRGAFSEVAVVKMKQTGQVYAMKIMNKWDMLKRGEVSCFREER
DVLVNGDRRWITQLHFAFQDENYLYLVMEYYVGGDLLTLLSKFGERIPAEMARFYLAEIV
MAIDSVHRLGYVHRDIKPDNILLDRCGHIRLADFGSCLKLRADGTVRSLVAVGTPDYLSP
EILQAVGGGPGTGSYGPECDWWALGVFAYEMFYGQTPFYADSTAETYGKIVHYKEHLSLP
LVDEGVPEEARDFIQRLLCPPETRLGRGGAGDFRTHPFFFGLDWDGLRDSVPPFTPDFEG
ATDTCNFDLVEDGLTAMVSGGGETLSDIREGAPLGVHLPFVGYSYSCMALRDSEVPGPTP
MELEAEQLLEPHVQAPSLEPSVSPQDETAEVAVPAAVPAAEAEAEVTLRELQEALEEEVL
TRQSLSREMEAIRTDNQNFASQLREAEARNRDLEAHVRQLQERMELLQAEGATAVTGVPS
PRATDPPSHLDGPPAVAVGQCPLVGPGPMHRRHLLLPARVPRPGLSEALSLLLFAVVLSR
AAALGCIGLVAHAGQLTAVWRRPGAARAP
Number of residues
629
Molecular Weight
69384.5
Theoretical pI
4.83
GO Classification
Functions
ATP binding / metal ion binding / myosin phosphatase regulator activity / protein serine/threonine kinase activity
Processes
cellular calcium ion homeostasis / muscle cell apoptotic process / nuclear envelope organization / peptidyl-serine phosphorylation / protein phosphorylation / regulation of catalytic activity / regulation of excitatory postsynaptic membrane potential involved in skeletal muscle contraction / regulation of heart contraction / regulation of myotube differentiation / regulation of skeletal muscle contraction by calcium ion signaling / regulation of sodium ion transport / regulation of synapse structural plasticity
Components
cytosol / endoplasmic reticulum membrane / integral component of mitochondrial outer membrane / nuclear membrane / nuclear outer membrane / plasma membrane / sarcoplasmic reticulum membrane
General Function
Protein serine/threonine kinase activity
Specific Function
Non-receptor serine/threonine protein kinase which is necessary for the maintenance of skeletal muscle structure and function. May play a role in myocyte differentiation and survival by regulating the integrity of the nuclear envelope and the expression of muscle-specific genes. May also phosphorylate PPP1R12A and inhibit the myosin phosphatase activity to regulate myosin phosphorylation. Also critical to the modulation of cardiac contractility and to the maintenance of proper cardiac conduction activity probably through the regulation of cellular calcium homeostasis. Phosphorylates PLN, a regulator of calcium pumps and may regulate sarcoplasmic reticulum calcium uptake in myocytes. May also phosphorylate FXYD1/PLM which is able to induce chloride currents. May also play a role in synaptic plasticity.
Pfam Domain Function
Transmembrane Regions
591-611
Cellular Location
Endoplasmic reticulum membrane
Gene sequence
>lcl|BSEQ0012712|Myotonin-protein kinase (DMPK)
ATGTCAGCCGAGGTGCGGCTGAGGCGGCTCCAGCAGCTGGTGTTGGACCCGGGCTTCCTG
GGGCTGGAGCCCCTGCTCGACCTTCTCCTGGGCGTCCACCAGGAGCTGGGCGCCTCCGAA
CTGGCCCAGGACAAGTACGTGGCCGACTTCTTGCAGTGGGCGGAGCCCATCGTGGTGAGG
CTTAAGGAGGTCCGACTGCAGAGGGACGACTTCGAGATTCTGAAGGTGATCGGACGCGGG
GCGTTCAGCGAGGTAGCGGTAGTGAAGATGAAGCAGACGGGCCAGGTGTATGCCATGAAG
ATCATGAACAAGTGGGACATGCTGAAGAGGGGCGAGGTGTCGTGCTTCCGTGAGGAGAGG
GACGTGTTGGTGAATGGGGACCGGCGGTGGATCACGCAGCTGCACTTCGCCTTCCAGGAT
GAGAACTACCTGTACCTGGTCATGGAGTATTACGTGGGCGGGGACCTGCTGACACTGCTG
AGCAAGTTTGGGGAGCGGATTCCGGCCGAGATGGCGCGCTTCTACCTGGCGGAGATTGTC
ATGGCCATAGACTCGGTGCACCGGCTTGGCTACGTGCACAGGGACATCAAACCCGACAAC
ATCCTGCTGGACCGCTGTGGCCACATCCGCCTGGCCGACTTCGGCTCTTGCCTCAAGCTG
CGGGCAGATGGAACGGTGCGGTCGCTGGTGGCTGTGGGCACCCCAGACTACCTGTCCCCC
GAGATCCTGCAGGCTGTGGGCGGTGGGCCTGGGACAGGCAGCTACGGGCCCGAGTGTGAC
TGGTGGGCGCTGGGTGTATTCGCCTATGAAATGTTCTATGGGCAGACGCCCTTCTACGCG
GATTCCACGGCGGAGACCTATGGCAAGATCGTCCACTACAAGGAGCACCTCTCTCTGCCG
CTGGTGGACGAAGGGGTCCCTGAGGAGGCTCGAGACTTCATTCAGCGGTTGCTGTGTCCC
CCGGAGACACGGCTGGGCCGGGGTGGAGCAGGCGACTTCCGGACACATCCCTTCTTCTTT
GGCCTCGACTGGGATGGTCTCCGGGACAGCGTGCCCCCCTTTACACCGGATTTCGAAGGT
GCCACCGACACATGCAACTTCGACTTGGTGGAGGACGGGCTCACTGCCATGGAGACACTG
TCGGACATTCGGGAAGGTGCGCCGCTAGGGGTCCACCTGCCTTTTGTGGGCTACTCCTAC
TCCTGCATGGCCCTCAGGGACAGTGAGGTCCCAGGCCCCACACCCATGGAACTGGAGGCC
GAGCAGCTGCTTGAGCCACACGTGCAAGCGCCCAGCCTGGAGCCCTCGGTGTCCCCACAG
GATGAAACAGCTGAAGTGGCAGTTCCAGCGGCTGTCCCTGCGGCAGAGGCTGAGGCCGAG
GTGACGCTGCGGGAGCTCCAGGAAGCCCTGGAGGAGGAGGTGCTCACCCGGCAGAGCCTG
AGCCGGGAGATGGAGGCCATCCGCACGGACAACCAGAACTTCGCCAGTCAACTACGCGAG
GCAGAGGCTCGGAACCGGGACCTAGAGGCACACGTCCGGCAGTTGCAGGAGCGGATGGAG
TTGCTGCAGGCAGAGGGAGCCACAGCTGTCACGGGGGTCCCCAGTCCCCGGGCCACGGAT
CCACCTTCCCATCTAGATGGCCCCCCGGCCGTGGCTGTGGGCCAGTGCCCGCTGGTGGGG
CCAGGCCCCATGCACCGCCGCCACCTGCTGCTCCCTGCCAGGGTCCCTAGGCCTGGCCTA
TCGGAGGCGCTTTCCCTGCTCCTGTTCGCCGTTGTTCTGTCTCGTGCCGCCGCCCTGGGC
TGCATTGGGTTGGTGGCCCACGCCGGCCAACTCACCGCAGTCTGGCGCCGCCCAGGAGCC
GCCCGCGCTCCCTGA
Chromosome Location
19
Locus
19q13.3
External Identifiers
ResourceLink
UniProtKB IDQ09013
UniProtKB Entry NameDMPK_HUMAN
GenBank Gene IDM87312
HGNC IDHGNC:2933
General References
  1. Fu YH, Pizzuti A, Fenwick RG Jr, King J, Rajnarayan S, Dunne PW, Dubel J, Nasser GA, Ashizawa T, de Jong P, et al.: An unstable triplet repeat in a gene related to myotonic muscular dystrophy. Science. 1992 Mar 6;255(5049):1256-8. [Article]
  2. Shaw DJ, McCurrach M, Rundle SA, Harley HG, Crow SR, Sohn R, Thirion JP, Hamshere MG, Buckler AJ, Harper PS, et al.: Genomic organization and transcriptional units at the myotonic dystrophy locus. Genomics. 1993 Dec;18(3):673-9. [Article]
  3. Mahadevan MS, Amemiya C, Jansen G, Sabourin L, Baird S, Neville CE, Wormskamp N, Segers B, Batzer M, Lamerdin J, et al.: Structure and genomic sequence of the myotonic dystrophy (DM kinase) gene. Hum Mol Genet. 1993 Mar;2(3):299-304. [Article]
  4. Fu YH, Friedman DL, Richards S, Pearlman JA, Gibbs RA, Pizzuti A, Ashizawa T, Perryman MB, Scarlato G, Fenwick RG Jr, et al.: Decreased expression of myotonin-protein kinase messenger RNA and protein in adult form of myotonic dystrophy. Science. 1993 Apr 9;260(5105):235-8. [Article]
  5. Sasagawa N, Sorimachi H, Maruyama K, Arahata K, Ishiura S, Suzuki K: Expression of a novel human myotonin protein kinase (MtPK) cDNA clone which encodes a protein with a thymopoietin-like domain in COS cells. FEBS Lett. 1994 Aug 29;351(1):22-6. [Article]
  6. Wang W, Shen P, Thiyagarajan S, Lin S, Palm C, Horvath R, Klopstock T, Cutler D, Pique L, Schrijver I, Davis RW, Mindrinos M, Speed TP, Scharfe C: Identification of rare DNA variants in mitochondrial disorders with improved array-based sequencing. Nucleic Acids Res. 2011 Jan;39(1):44-58. doi: 10.1093/nar/gkq750. Epub 2010 Sep 15. [Article]
  7. Corominas R, Yang X, Lin GN, Kang S, Shen Y, Ghamsari L, Broly M, Rodriguez M, Tam S, Trigg SA, Fan C, Yi S, Tasan M, Lemmens I, Kuang X, Zhao N, Malhotra D, Michaelson JJ, Vacic V, Calderwood MA, Roth FP, Tavernier J, Horvath S, Salehi-Ashtiani K, Korkin D, Sebat J, Hill DE, Hao T, Vidal M, Iakoucheva LM: Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism. Nat Commun. 2014 Apr 11;5:3650. doi: 10.1038/ncomms4650. [Article]
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  9. Brook JD, McCurrach ME, Harley HG, Buckler AJ, Church D, Aburatani H, Hunter K, Stanton VP, Thirion JP, Hudson T, et al.: Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3' end of a transcript encoding a protein kinase family member. Cell. 1992 Feb 21;68(4):799-808. [Article]
  10. Gennarelli M, Lucarelli M, Zelano G, Pizzuti A, Novelli G, Dallapiccola B: Different expression of the myotonin protein kinase gene in discrete areas of human brain. Biochem Biophys Res Commun. 1995 Nov 13;216(2):489-94. [Article]
  11. Jansen G, Mahadevan M, Amemiya C, Wormskamp N, Segers B, Hendriks W, O'Hoy K, Baird S, Sabourin L, Lennon G, et al.: Characterization of the myotonic dystrophy region predicts multiple protein isoform-encoding mRNAs. Nat Genet. 1992 Jul;1(4):261-6. [Article]
  12. Suzuki A, Sugiyama Y, Hayashi Y, Nyu-i N, Yoshida M, Nonaka I, Ishiura S, Arahata K, Ohno S: MKBP, a novel member of the small heat shock protein family, binds and activates the myotonic dystrophy protein kinase. J Cell Biol. 1998 Mar 9;140(5):1113-24. [Article]
  13. Bush EW, Helmke SM, Birnbaum RA, Perryman MB: Myotonic dystrophy protein kinase domains mediate localization, oligomerization, novel catalytic activity, and autoinhibition. Biochemistry. 2000 Jul 25;39(29):8480-90. [Article]
  14. Shimizu M, Wang W, Walch ET, Dunne PW, Epstein HF: Rac-1 and Raf-1 kinases, components of distinct signaling pathways, activate myotonic dystrophy protein kinase. FEBS Lett. 2000 Jun 23;475(3):273-7. [Article]
  15. Groenen PJ, Wansink DG, Coerwinkel M, van den Broek W, Jansen G, Wieringa B: Constitutive and regulated modes of splicing produce six major myotonic dystrophy protein kinase (DMPK) isoforms with distinct properties. Hum Mol Genet. 2000 Mar 1;9(4):605-16. [Article]
  16. Mounsey JP, John JE 3rd, Helmke SM, Bush EW, Gilbert J, Roses AD, Perryman MB, Jones LR, Moorman JR: Phospholemman is a substrate for myotonic dystrophy protein kinase. J Biol Chem. 2000 Jul 28;275(30):23362-7. [Article]
  17. Muranyi A, Zhang R, Liu F, Hirano K, Ito M, Epstein HF, Hartshorne DJ: Myotonic dystrophy protein kinase phosphorylates the myosin phosphatase targeting subunit and inhibits myosin phosphatase activity. FEBS Lett. 2001 Mar 30;493(2-3):80-4. [Article]
  18. Zhang R, Epstein HF: Homodimerization through coiled-coil regions enhances activity of the myotonic dystrophy protein kinase. FEBS Lett. 2003 Jul 10;546(2-3):281-7. [Article]
  19. Kaliman P, Catalucci D, Lam JT, Kondo R, Gutierrez JC, Reddy S, Palacin M, Zorzano A, Chien KR, Ruiz-Lozano P: Myotonic dystrophy protein kinase phosphorylates phospholamban and regulates calcium uptake in cardiomyocyte sarcoplasmic reticulum. J Biol Chem. 2005 Mar 4;280(9):8016-21. Epub 2004 Dec 13. [Article]
  20. van Herpen RE, Oude Ophuis RJ, Wijers M, Bennink MB, van de Loo FA, Fransen J, Wieringa B, Wansink DG: Divergent mitochondrial and endoplasmic reticulum association of DMPK splice isoforms depends on unique sequence arrangements in tail anchors. Mol Cell Biol. 2005 Feb;25(4):1402-14. [Article]
  21. Musova Z, Mazanec R, Krepelova A, Ehler E, Vales J, Jaklova R, Prochazka T, Koukal P, Marikova T, Kraus J, Havlovicova M, Sedlacek Z: Highly unstable sequence interruptions of the CTG repeat in the myotonic dystrophy gene. Am J Med Genet A. 2009 Jul;149A(7):1365-74. doi: 10.1002/ajmg.a.32987. [Article]
  22. Tan I, Lai J, Yong J, Li SF, Leung T: Chelerythrine perturbs lamellar actomyosin filaments by selective inhibition of myotonic dystrophy kinase-related Cdc42-binding kinase. FEBS Lett. 2011 May 6;585(9):1260-8. doi: 10.1016/j.febslet.2011.03.054. Epub 2011 Mar 30. [Article]
  23. Harmon EB, Harmon ML, Larsen TD, Yang J, Glasford JW, Perryman MB: Myotonic dystrophy protein kinase is critical for nuclear envelope integrity. J Biol Chem. 2011 Nov 18;286(46):40296-306. doi: 10.1074/jbc.M111.241455. Epub 2011 Sep 26. [Article]
  24. Garcia P, Marino M, Mayans O: Crystallization and preliminary X-ray analysis of the coiled-coil domain of dystrophia myotonica kinase. Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 2):2336-9. Epub 2004 Nov 26. [Article]
  25. Garcia P, Ucurum Z, Bucher R, Svergun DI, Huber T, Lustig A, Konarev PV, Marino M, Mayans O: Molecular insights into the self-assembly mechanism of dystrophia myotonica kinase. FASEB J. 2006 Jun;20(8):1142-51. [Article]
  26. Elkins JM, Amos A, Niesen FH, Pike AC, Fedorov O, Knapp S: Structure of dystrophia myotonica protein kinase. Protein Sci. 2009 Apr;18(4):782-91. doi: 10.1002/pro.82. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01946Bisindolylmaleimide VIIIexperimentalunknownDetails