Mitogen-activated protein kinase 9

Details

Name
Mitogen-activated protein kinase 9
Synonyms
  • 2.7.11.24
  • c-Jun N-terminal kinase 2
  • JNK-55
  • JNK2
  • MAP kinase 9
  • PRKM9
  • SAPK1A
  • Stress-activated protein kinase 1a
  • Stress-activated protein kinase JNK2
Gene Name
MAPK9
Organism
Humans
Amino acid sequence
>lcl|BSEQ0007238|Mitogen-activated protein kinase 9
MSDSKCDSQFYSVQVADSTFTVLKRYQQLKPIGSGAQGIVCAAFDTVLGINVAVKKLSRP
FQNQTHAKRAYRELVLLKCVNHKNIISLLNVFTPQKTLEEFQDVYLVMELMDANLCQVIH
MELDHERMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTACTNF
MMTPYVVTRYYRAPEVILGMGYKENVDIWSVGCIMGELVKGCVIFQGTDHIDQWNKVIEQ
LGTPSAEFMKKLQPTVRNYVENRPKYPGIKFEELFPDWIFPSESERDKIKTSQARDLLSK
MLVIDPDKRISVDEALRHPYITVWYDPAEAEAPPPQIYDAQLEEREHAIEEWKELIYKEV
MDWEERSKNGVVKDQPSDAAVSSNATPSQSSSINDISSMSTEQTLASDTDSSLDASTGPL
EGCR
Number of residues
424
Molecular Weight
48138.655
Theoretical pI
5.34
GO Classification
Functions
ATP binding / cysteine-type endopeptidase activator activity involved in apoptotic process / JUN kinase activity / transcription factor binding
Processes
cellular response to growth factor stimulus / cellular response to interleukin-1 / cellular response to lipopolysaccharide / cellular response to tumor necrosis factor / cellular response to UV / central nervous system development / Fc-epsilon receptor signaling pathway / innate immune response / JNK cascade / MyD88-dependent toll-like receptor signaling pathway / MyD88-independent toll-like receptor signaling pathway / neuron projection development / positive regulation of apoptotic signaling pathway / positive regulation of cell morphogenesis involved in differentiation / positive regulation of chemokine production / positive regulation of gene expression / positive regulation of macrophage derived foam cell differentiation / positive regulation of nitric oxide biosynthetic process / positive regulation of nitric-oxide synthase biosynthetic process / positive regulation of prostaglandin biosynthetic process / positive regulation of prostaglandin secretion / positive regulation of protein phosphorylation / positive regulation of transcription, DNA-templated / protein phosphorylation / protein targeting to mitochondrion / regulation of circadian rhythm / regulation of JNK cascade / regulation of protein ubiquitination / regulation of sequence-specific DNA binding transcription factor activity / release of cytochrome c from mitochondria / response to amine / response to cadmium ion / response to drug / response to mechanical stimulus / response to stress / response to toxic substance / rhythmic process / stress-activated MAPK cascade / toll-like receptor 10 signaling pathway / toll-like receptor 2 signaling pathway / toll-like receptor 3 signaling pathway / toll-like receptor 4 signaling pathway / toll-like receptor 5 signaling pathway / toll-like receptor 9 signaling pathway / toll-like receptor signaling pathway / toll-like receptor TLR1 / toll-like receptor TLR6 / TRIF-dependent toll-like receptor signaling pathway
Components
cytosol / mitochondrion / nucleoplasm
General Function
Transcription factor binding
Specific Function
Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK9/JNK2. In turn, MAPK9/JNK2 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. In response to oxidative or ribotoxic stresses, inhibits rRNA synthesis by phosphorylating and inactivating the RNA polymerase 1-specific transcription initiation factor RRN3. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including TP53 and YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Upon T-cell receptor (TCR) stimulation, is activated by CARMA1, BCL10, MAP2K7 and MAP3K7/TAK1 to regulate JUN protein levels. Plays an important role in the osmotic stress-induced epithelial tight-junctions disruption. When activated, promotes beta-catenin/CTNNB1 degradation and inhibits the canonical Wnt signaling pathway. Participates also in neurite growth in spiral ganglion neurons. Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the regulation of the circadian clock (PubMed:22441692).MAPK9 isoforms display different binding patterns: alpha-1 and alpha-2 preferentially bind to JUN, whereas beta-1 and beta-2 bind to ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms. JUNB is not a substrate for JNK2 alpha-2, and JUND binds only weakly to it.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0021865|Mitogen-activated protein kinase 9 (MAPK9)
ATGAGCGACAGTAAATGTGACAGTCAGTTTTATAGTGTGCAAGTGGCAGACTCAACCTTC
ACTGTCCTAAAACGTTACCAGCAGCTGAAACCAATTGGCTCTGGGGCCCAAGGGATTGTT
TGTGCTGCATTTGATACAGTTCTTGGGATAAATGTTGCAGTCAAGAAACTAAGCCGTCCT
TTTCAGAACCAAACTCATGCAAAGAGAGCTTATCGTGAACTTGTCCTCTTAAAATGTGTC
AATCATAAAAATATAATTAGTTTGTTAAATGTGTTTACACCACAAAAAACTCTAGAAGAA
TTTCAAGATGTGTATTTGGTTATGGAATTAATGGATGCTAACTTATGTCAGGTTATTCAC
ATGGAGCTGGATCATGAAAGAATGTCCTACCTTCTTTACCAGATGCTTTGTGGTATTAAA
CATCTGCATTCAGCTGGTATAATTCATAGAGATTTGAAGCCTAGCAACATTGTTGTGAAA
TCAGACTGCACCCTGAAGATCCTTGACTTTGGCCTGGCCCGGACAGCGTGCACTAACTTC
ATGATGACCCCTTACGTGGTGACACGGTACTACCGGGCGCCCGAAGTCATCCTGGGTATG
GGCTACAAAGAGAACGTTGATATCTGGTCAGTGGGTTGCATCATGGGAGAGCTGGTGAAA
GGTTGTGTGATATTCCAAGGCACTGACCGTATCCTTCCCCGCGACCTTGGCCCCGCCATG
CTTTCTTAA
Chromosome Location
5
Locus
5q35
External Identifiers
ResourceLink
UniProtKB IDP45984
UniProtKB Entry NameMK09_HUMAN
GenBank Protein ID598183
GenBank Gene IDL31951
HGNC IDHGNC:6886
General References
  1. Sluss HK, Barrett T, Derijard B, Davis RJ: Signal transduction by tumor necrosis factor mediated by JNK protein kinases. Mol Cell Biol. 1994 Dec;14(12):8376-84. [Article]
  2. Kallunki T, Su B, Tsigelny I, Sluss HK, Derijard B, Moore G, Davis R, Karin M: JNK2 contains a specificity-determining region responsible for efficient c-Jun binding and phosphorylation. Genes Dev. 1994 Dec 15;8(24):2996-3007. [Article]
  3. Gupta S, Barrett T, Whitmarsh AJ, Cavanagh J, Sluss HK, Derijard B, Davis RJ: Selective interaction of JNK protein kinase isoforms with transcription factors. EMBO J. 1996 Jun 3;15(11):2760-70. [Article]
  4. Wang P, Xiong Y, Ma C, Shi T, Ma D: Molecular cloning and characterization of novel human JNK2 (MAPK9) transcript variants that show different stimulation activities on AP-1. BMB Rep. 2010 Nov;43(11):738-43. doi: 10.5483/BMBRep.2010.43.11.738. [Article]
  5. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  6. Goshima N, Kawamura Y, Fukumoto A, Miura A, Honma R, Satoh R, Wakamatsu A, Yamamoto J, Kimura K, Nishikawa T, Andoh T, Iida Y, Ishikawa K, Ito E, Kagawa N, Kaminaga C, Kanehori K, Kawakami B, Kenmochi K, Kimura R, Kobayashi M, Kuroita T, Kuwayama H, Maruyama Y, Matsuo K, Minami K, Mitsubori M, Mori M, Morishita R, Murase A, Nishikawa A, Nishikawa S, Okamoto T, Sakagami N, Sakamoto Y, Sasaki Y, Seki T, Sono S, Sugiyama A, Sumiya T, Takayama T, Takayama Y, Takeda H, Togashi T, Yahata K, Yamada H, Yanagisawa Y, Endo Y, Imamoto F, Kisu Y, Tanaka S, Isogai T, Imai J, Watanabe S, Nomura N: Human protein factory for converting the transcriptome into an in vitro-expressed proteome,. Nat Methods. 2008 Dec;5(12):1011-7. [Article]
  7. Schmutz J, Martin J, Terry A, Couronne O, Grimwood J, Lowry S, Gordon LA, Scott D, Xie G, Huang W, Hellsten U, Tran-Gyamfi M, She X, Prabhakar S, Aerts A, Altherr M, Bajorek E, Black S, Branscomb E, Caoile C, Challacombe JF, Chan YM, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Glavina T, Gomez M, Gonzales E, Goodstein D, Grigoriev I, Groza M, Hammon N, Hawkins T, Haydu L, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Lopez F, Lou Y, Martinez D, Medina C, Morgan J, Nandkeshwar R, Noonan JP, Pitluck S, Pollard M, Predki P, Priest J, Ramirez L, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wheeler J, Wu K, Yang J, Dickson M, Cheng JF, Eichler EE, Olsen A, Pennacchio LA, Rokhsar DS, Richardson P, Lucas SM, Myers RM, Rubin EM: The DNA sequence and comparative analysis of human chromosome 5. Nature. 2004 Sep 16;431(7006):268-74. [Article]
  8. 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]
  9. De Graeve F, Bahr A, Sabapathy KT, Hauss C, Wagner EF, Kedinger C, Chatton B: Role of the ATFa/JNK2 complex in Jun activation. Oncogene. 1999 Jun 10;18(23):3491-500. [Article]
  10. Fleming Y, Armstrong CG, Morrice N, Paterson A, Goedert M, Cohen P: Synergistic activation of stress-activated protein kinase 1/c-Jun N-terminal kinase (SAPK1/JNK) isoforms by mitogen-activated protein kinase kinase 4 (MKK4) and MKK7. Biochem J. 2000 Nov 15;352 Pt 1:145-54. [Article]
  11. Jagadish N, Rana R, Selvi R, Mishra D, Garg M, Yadav S, Herr JC, Okumura K, Hasegawa A, Koyama K, Suri A: Characterization of a novel human sperm-associated antigen 9 (SPAG9) having structural homology with c-Jun N-terminal kinase-interacting protein. Biochem J. 2005 Jul 1;389(Pt 1):73-82. [Article]
  12. Mayer C, Bierhoff H, Grummt I: The nucleolus as a stress sensor: JNK2 inactivates the transcription factor TIF-IA and down-regulates rRNA synthesis. Genes Dev. 2005 Apr 15;19(8):933-41. Epub 2005 Apr 1. [Article]
  13. Yao K, Cho YY, Bergen HR 3rd, Madden BJ, Choi BY, Ma WY, Bode AM, Dong Z: Nuclear factor of activated T3 is a negative regulator of Ras-JNK1/2-AP-1 induced cell transformation. Cancer Res. 2007 Sep 15;67(18):8725-35. [Article]
  14. Blonska M, Pappu BP, Matsumoto R, Li H, Su B, Wang D, Lin X: The CARMA1-Bcl10 signaling complex selectively regulates JNK2 kinase in the T cell receptor-signaling pathway. Immunity. 2007 Jan;26(1):55-66. Epub 2006 Dec 28. [Article]
  15. Oleinik NV, Krupenko NI, Krupenko SA: Cooperation between JNK1 and JNK2 in activation of p53 apoptotic pathway. Oncogene. 2007 Nov 8;26(51):7222-30. Epub 2007 May 21. [Article]
  16. Blonska M, Lin X: CARMA1-mediated NF-kappaB and JNK activation in lymphocytes. Immunol Rev. 2009 Mar;228(1):199-211. doi: 10.1111/j.1600-065X.2008.00749.x. [Article]
  17. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [Article]
  18. Hu D, Bi X, Fang W, Han A, Yang W: GSK3beta is involved in JNK2-mediated beta-catenin inhibition. PLoS One. 2009 Aug 13;4(8):e6640. doi: 10.1371/journal.pone.0006640. [Article]
  19. Samak G, Suzuki T, Bhargava A, Rao RK: c-Jun NH2-terminal kinase-2 mediates osmotic stress-induced tight junction disruption in the intestinal epithelium. Am J Physiol Gastrointest Liver Physiol. 2010 Sep;299(3):G572-84. doi: 10.1152/ajpgi.00265.2010. Epub 2010 Jul 1. [Article]
  20. Tomlinson V, Gudmundsdottir K, Luong P, Leung KY, Knebel A, Basu S: JNK phosphorylates Yes-associated protein (YAP) to regulate apoptosis. Cell Death Dis. 2010;1:e29. doi: 10.1038/cddis.2010.7. [Article]
  21. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  22. Yoshitane H, Honma S, Imamura K, Nakajima H, Nishide SY, Ono D, Kiyota H, Shinozaki N, Matsuki H, Wada N, Doi H, Hamada T, Honma K, Fukada Y: JNK regulates the photic response of the mammalian circadian clock. EMBO Rep. 2012 May 1;13(5):455-61. doi: 10.1038/embor.2012.37. [Article]
  23. Shaw D, Wang SM, Villasenor AG, Tsing S, Walter D, Browner MF, Barnett J, Kuglstatter A: The crystal structure of JNK2 reveals conformational flexibility in the MAP kinase insert and indicates its involvement in the regulation of catalytic activity. J Mol Biol. 2008 Nov 21;383(4):885-93. doi: 10.1016/j.jmb.2008.08.086. Epub 2008 Sep 10. [Article]
  24. 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
DB07020N-{3-[5-(1H-1,2,4-triazol-3-yl)-1H-indazol-3-yl]phenyl}furan-2-carboxamideexperimentalunknownDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails
DB11718Encorafenibapproved, investigationalyesinhibitorDetails
DB01017Minocyclineapproved, investigationalunknowninhibitorDetails
DB15624HalicinexperimentalunknowninhibitorDetails