MAP kinase-interacting serine/threonine-protein kinase 2

Details

Name
MAP kinase-interacting serine/threonine-protein kinase 2
Synonyms
  • 2.7.11.1
  • GPRK7
  • MAP kinase signal-integrating kinase 2
  • MAPK signal-integrating kinase 2
  • MNK2
Gene Name
MKNK2
Organism
Humans
Amino acid sequence
>lcl|BSEQ0051856|MAP kinase-interacting serine/threonine-protein kinase 2
MVQKKPAELQGFHRSFKGQNPFELAFSLDQPDHGDSDFGLQCSARPDMPASQPIDIPDAK
KRGKKKKRGRATDSFSGRFEDVYQLQEDVLGEGAHARVQTCINLITSQEYAVKIIEKQPG
HIRSRVFREVEMLYQCQGHRNVLELIEFFEEEDRFYLVFEKMRGGSILSHIHKRRHFNEL
EASVVVQDVASALDFLHNKGIAHRDLKPENILCEHPNQVSPVKICDFDLGSGIKLNGDCS
PISTPELLTPCGSAEYMAPEVVEAFSEEASIYDKRCDLWSLGVILYILLSGYPPFVGRCG
SDCGWDRGEACPACQNMLFESIQEGKYEFPDKDWAHISCAAKDLISKLLVRDAKQRLSAA
QVLQHPWVQGCAPENTLPTPMVLQRNSCAKDLTSFAAEAIAMNRQLAQHDEDLAEEEAAG
QGQPVLVRATSRCLQLSPPSQSKLAQRRQRASLSSAPVVLVGDHA
Number of residues
465
Molecular Weight
51874.4
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / calcium-dependent protein serine/threonine kinase activity / calmodulin binding / calmodulin-dependent protein kinase activity / metal ion binding / protein serine/threonine kinase activity
Processes
cell surface receptor signaling pathway / cellular response to arsenic-containing substance / extrinsic apoptotic signaling pathway in absence of ligand / hemopoiesis / intracellular signal transduction / peptidyl-serine phosphorylation / protein autophosphorylation / protein phosphorylation / regulation of translation
Components
cytoplasm / nuclear body / nucleoplasm / nucleus / PML body
General Function
Serine/threonine-protein kinase that phosphorylates SFPQ/PSF, HNRNPA1 and EIF4E. May play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine-containing mRNA cap. Required for mediating PP2A-inhibition-induced EIF4E phosphorylation. Triggers EIF4E shuttling from cytoplasm to nucleus. Isoform 1 displays a high basal kinase activity, but isoform 2 exhibits a very low kinase activity. Acts as a mediator of the suppressive effects of IFNgamma on hematopoiesis. Negative regulator for signals that control generation of arsenic trioxide As(2)O(3)-dependent apoptosis and anti-leukemic responses. Involved in anti-apoptotic signaling in response to serum withdrawal.
Specific Function
Atp binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0051857|MAP kinase-interacting serine/threonine-protein kinase 2 (MKNK2)
ATGGTGCAGAAGAAACCAGCCGAACTTCAGGGTTTCCACCGTTCGTTCAAGGGGCAGAAC
CCCTTCGAGCTGGCCTTCTCCCTAGACCAGCCCGACCACGGAGACTCTGACTTTGGCCTG
CAGTGCTCAGCCCGCCCTGACATGCCCGCCAGCCAGCCCATTGACATCCCGGACGCCAAG
AAGAGGGGCAAGAAGAAGAAGCGCGGCCGGGCCACCGACAGCTTCTCGGGCAGGTTTGAA
GACGTCTACCAGCTGCAGGAAGATGTGCTGGGGGAGGGCGCTCATGCCCGAGTGCAGACC
TGCATCAACCTGATCACCAGCCAGGAGTACGCCGTCAAGATCATTGAGAAGCAGCCAGGC
CACATTCGGAGCAGGGTTTTCAGGGAGGTGGAGATGCTGTACCAGTGCCAGGGACACAGG
AACGTCCTAGAGCTGATTGAGTTCTTCGAGGAGGAGGACCGCTTCTACCTGGTGTTTGAG
AAGATGCGGGGAGGCTCCATCCTGAGCCACATCCACAAGCGCCGGCACTTCAACGAGCTG
GAGGCCAGCGTGGTGGTGCAGGACGTGGCCAGCGCCTTGGACTTTCTGCATAACAAAGGC
ATCGCCCACAGGGACCTAAAGCCGGAAAACATCCTCTGTGAGCACCCCAACCAGGTCTCC
CCCGTGAAGATCTGTGACTTCGACCTGGGCAGCGGCATCAAACTCAACGGGGACTGCTCC
CCTATCTCCACCCCGGAGCTGCTCACTCCGTGCGGCTCGGCGGAGTACATGGCCCCGGAG
GTAGTGGAGGCCTTCAGCGAGGAGGCTAGCATCTACGACAAGCGCTGCGACCTGTGGAGC
CTGGGCGTCATCTTGTATATCCTACTCAGCGGCTACCCGCCCTTCGTGGGCCGCTGTGGC
AGCGACTGCGGCTGGGACCGCGGCGAGGCCTGCCCTGCCTGCCAGAACATGCTGTTTGAG
AGCATCCAGGAGGGCAAGTACGAGTTCCCCGACAAGGACTGGGCCCACATCTCCTGCGCT
GCCAAAGACCTCATCTCCAAGCTGCTGGTCCGTGACGCCAAGCAGAGGCTGAGTGCCGCC
CAAGTCCTGCAGCACCCCTGGGTTCAGGGGTGCGCCCCGGAGAACACCTTGCCCACTCCC
ATGGTCCTGCAGAGGAACAGCTGTGCCAAAGACCTCACGTCCTTCGCGGCTGAGGCCATT
GCCATGAACCGGCAGCTGGCCCAGCACGACGAGGACCTGGCTGAGGAGGAGGCCGCGGGG
CAGGGCCAGCCCGTCCTGGTCCGAGCTACCTCACGCTGCCTGCAGCTGTCTCCACCCTCC
CAGTCCAAGCTGGCGCAGCGGCGGCAAAGGGCCAGTCTGTCCTCGGCCCCAGTGGTCCTG
GTGGGAGACCACGCCTGA
Chromosome Location
19
Locus
19p13.3
External Identifiers
ResourceLink
UniProtKB IDQ9HBH9
UniProtKB Entry NameMKNK2_HUMAN
HGNC IDHGNC:7111
General References
  1. Slentz-Kesler K, Moore JT, Lombard M, Zhang J, Hollingsworth R, Weiner MP: Identification of the human Mnk2 gene (MKNK2) through protein interaction with estrogen receptor beta. Genomics. 2000 Oct 1;69(1):63-71. [Article]
  2. Grimwood J, Gordon LA, Olsen A, Terry A, Schmutz J, Lamerdin J, Hellsten U, Goodstein D, Couronne O, Tran-Gyamfi M, Aerts A, Altherr M, Ashworth L, Bajorek E, Black S, Branscomb E, Caenepeel S, Carrano A, Caoile C, Chan YM, Christensen M, Cleland CA, Copeland A, Dalin E, Dehal P, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Garcia C, Georgescu AM, Glavina T, Gomez M, Gonzales E, Groza M, Hammon N, Hawkins T, Haydu L, Ho I, Huang W, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Larionov V, Leem SH, Lopez F, Lou Y, Lowry S, Malfatti S, Martinez D, McCready P, Medina C, Morgan J, Nelson K, Nolan M, Ovcharenko I, Pitluck S, Pollard M, Popkie AP, Predki P, Quan G, Ramirez L, Rash S, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, She X, Smith D, Slezak T, Solovyev V, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wagner M, Wheeler J, Wu K, Xie G, Yang J, Dubchak I, Furey TS, DeJong P, Dickson M, Gordon D, Eichler EE, Pennacchio LA, Richardson P, Stubbs L, Rokhsar DS, Myers RM, Rubin EM, Lucas SM: The DNA sequence and biology of human chromosome 19. Nature. 2004 Apr 1;428(6982):529-35. [Article]
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  4. Scheper GC, Morrice NA, Kleijn M, Proud CG: The mitogen-activated protein kinase signal-integrating kinase Mnk2 is a eukaryotic initiation factor 4E kinase with high levels of basal activity in mammalian cells. Mol Cell Biol. 2001 Feb;21(3):743-54. [Article]
  5. Knauf U, Tschopp C, Gram H: Negative regulation of protein translation by mitogen-activated protein kinase-interacting kinases 1 and 2. Mol Cell Biol. 2001 Aug;21(16):5500-11. [Article]
  6. Scheper GC, Parra JL, Wilson M, Van Kollenburg B, Vertegaal AC, Han ZG, Proud CG: The N and C termini of the splice variants of the human mitogen-activated protein kinase-interacting kinase Mnk2 determine activity and localization. Mol Cell Biol. 2003 Aug;23(16):5692-705. [Article]
  7. Buxade M, Parra JL, Rousseau S, Shpiro N, Marquez R, Morrice N, Bain J, Espel E, Proud CG: The Mnks are novel components in the control of TNF alpha biosynthesis and phosphorylate and regulate hnRNP A1. Immunity. 2005 Aug;23(2):177-89. [Article]
  8. Buxade M, Morrice N, Krebs DL, Proud CG: The PSF.p54nrb complex is a novel Mnk substrate that binds the mRNA for tumor necrosis factor alpha. J Biol Chem. 2008 Jan 4;283(1):57-65. Epub 2007 Oct 26. [Article]
  9. Dolniak B, Katsoulidis E, Carayol N, Altman JK, Redig AJ, Tallman MS, Ueda T, Watanabe-Fukunaga R, Fukunaga R, Platanias LC: Regulation of arsenic trioxide-induced cellular responses by Mnk1 and Mnk2. J Biol Chem. 2008 May 2;283(18):12034-42. doi: 10.1074/jbc.M708816200. Epub 2008 Feb 25. [Article]
  10. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [Article]
  11. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [Article]
  12. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [Article]
  13. Oyarzabal J, Zarich N, Albarran MI, Palacios I, Urbano-Cuadrado M, Mateos G, Reymundo I, Rabal O, Salgado A, Corrionero A, Fominaya J, Pastor J, Bischoff JR: Discovery of mitogen-activated protein kinase-interacting kinase 1 inhibitors by a comprehensive fragment-oriented virtual screening approach. J Med Chem. 2010 Sep 23;53(18):6618-28. doi: 10.1021/jm1005513. [Article]
  14. Shveygert M, Kaiser C, Bradrick SS, Gromeier M: Regulation of eukaryotic initiation factor 4E (eIF4E) phosphorylation by mitogen-activated protein kinase occurs through modulation of Mnk1-eIF4G interaction. Mol Cell Biol. 2010 Nov;30(21):5160-7. doi: 10.1128/MCB.00448-10. Epub 2010 Sep 7. [Article]
  15. Altman JK, Glaser H, Sassano A, Joshi S, Ueda T, Watanabe-Fukunaga R, Fukunaga R, Tallman MS, Platanias LC: Negative regulatory effects of Mnk kinases in the generation of chemotherapy-induced antileukemic responses. Mol Pharmacol. 2010 Oct;78(4):778-84. doi: 10.1124/mol.110.064642. Epub 2010 Jul 27. [Article]
  16. Li Y, Yue P, Deng X, Ueda T, Fukunaga R, Khuri FR, Sun SY: Protein phosphatase 2A negatively regulates eukaryotic initiation factor 4E phosphorylation and eIF4F assembly through direct dephosphorylation of Mnk and eIF4E. Neoplasia. 2010 Oct;12(10):848-55. [Article]
  17. Joshi S, Sharma B, Kaur S, Majchrzak B, Ueda T, Fukunaga R, Verma AK, Fish EN, Platanias LC: Essential role for Mnk kinases in type II interferon (IFNgamma) signaling and its suppressive effects on normal hematopoiesis. J Biol Chem. 2011 Feb 25;286(8):6017-26. doi: 10.1074/jbc.M110.197921. Epub 2010 Dec 13. [Article]
  18. Buxade M, Parra-Palau JL, Proud CG: The Mnks: MAP kinase-interacting kinases (MAP kinase signal-integrating kinases). Front Biosci. 2008 May 1;13:5359-73. [Article]
  19. Zhou H, Di Palma S, Preisinger C, Peng M, Polat AN, Heck AJ, Mohammed S: Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res. 2013 Jan 4;12(1):260-71. doi: 10.1021/pr300630k. Epub 2012 Dec 18. [Article]
  20. Jauch R, Jakel S, Netter C, Schreiter K, Aicher B, Jackle H, Wahl MC: Crystal structures of the Mnk2 kinase domain reveal an inhibitory conformation and a zinc binding site. Structure. 2005 Oct;13(10):1559-68. [Article]
  21. Jauch R, Cho MK, Jakel S, Netter C, Schreiter K, Aicher B, Zweckstetter M, Jackle H, Wahl MC: Mitogen-activated protein kinases interacting kinases are autoinhibited by a reprogrammed activation segment. EMBO J. 2006 Sep 6;25(17):4020-32. Epub 2006 Aug 17. [Article]
  22. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails