Mitogen-activated protein kinase 9

NameMitogen-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 NameMAPK9
OrganismHuman
Amino acid sequence
>lcl|BSEQ0007238|Mitogen-activated protein kinase 9
MSDSKCDSQFYSVQVADSTFTVLKRYQQLKPIGSGAQGIVCAAFDTVLGINVAVKKLSRP
FQNQTHAKRAYRELVLLKCVNHKNIISLLNVFTPQKTLEEFQDVYLVMELMDANLCQVIH
MELDHERMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTACTNF
MMTPYVVTRYYRAPEVILGMGYKENVDIWSVGCIMGELVKGCVIFQGTDHIDQWNKVIEQ
LGTPSAEFMKKLQPTVRNYVENRPKYPGIKFEELFPDWIFPSESERDKIKTSQARDLLSK
MLVIDPDKRISVDEALRHPYITVWYDPAEAEAPPPQIYDAQLEEREHAIEEWKELIYKEV
MDWEERSKNGVVKDQPSDAAVSSNATPSQSSSINDISSMSTEQTLASDTDSSLDASTGPL
EGCR
Number of residues424
Molecular Weight48138.655
Theoretical pI5.34
GO Classification
Functions
  • transcription factor binding
  • JUN kinase activity
  • cysteine-type endopeptidase activator activity involved in apoptotic process
  • ATP binding
Processes
  • MyD88-independent toll-like receptor signaling pathway
  • positive regulation of prostaglandin biosynthetic process
  • regulation of JNK cascade
  • response to drug
  • regulation of sequence-specific DNA binding transcription factor activity
  • response to mechanical stimulus
  • cellular response to UV
  • rhythmic process
  • stress-activated MAPK cascade
  • JNK cascade
  • regulation of protein ubiquitination
  • response to stress
  • toll-like receptor 10 signaling pathway
  • positive regulation of chemokine production
  • toll-like receptor 2 signaling pathway
  • positive regulation of gene expression
  • positive regulation of cell morphogenesis involved in differentiation
  • toll-like receptor 3 signaling pathway
  • response to amine
  • innate immune response
  • toll-like receptor 4 signaling pathway
  • response to cadmium ion
  • positive regulation of protein phosphorylation
  • toll-like receptor 5 signaling pathway
  • Fc-epsilon receptor signaling pathway
  • toll-like receptor 9 signaling pathway
  • positive regulation of apoptotic signaling pathway
  • cellular response to tumor necrosis factor
  • toll-like receptor signaling pathway
  • positive regulation of prostaglandin secretion
  • positive regulation of transcription, DNA-templated
  • toll-like receptor TLR1
  • regulation of circadian rhythm
  • protein phosphorylation
  • toll-like receptor TLR6
  • cellular response to growth factor stimulus
  • positive regulation of macrophage derived foam cell differentiation
  • TRIF-dependent toll-like receptor signaling pathway
  • central nervous system development
  • response to toxic substance
  • cellular response to interleukin-1
  • protein targeting to mitochondrion
  • positive regulation of nitric oxide biosynthetic process
  • cellular response to lipopolysaccharide
  • positive regulation of nitric-oxide synthase biosynthetic process
  • MyD88-dependent toll-like receptor signaling pathway
  • neuron projection development
  • release of cytochrome c from mitochondria
Components
  • cytosol
  • nucleoplasm
  • mitochondrion
General FunctionTranscription factor binding
Specific FunctionSerine/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 RegionsNot Available
GenBank Protein ID598183
UniProtKB IDP45984
UniProtKB Entry NameMK09_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0021865|Mitogen-activated protein kinase 9 (MAPK9)
ATGAGCGACAGTAAATGTGACAGTCAGTTTTATAGTGTGCAAGTGGCAGACTCAACCTTC
ACTGTCCTAAAACGTTACCAGCAGCTGAAACCAATTGGCTCTGGGGCCCAAGGGATTGTT
TGTGCTGCATTTGATACAGTTCTTGGGATAAATGTTGCAGTCAAGAAACTAAGCCGTCCT
TTTCAGAACCAAACTCATGCAAAGAGAGCTTATCGTGAACTTGTCCTCTTAAAATGTGTC
AATCATAAAAATATAATTAGTTTGTTAAATGTGTTTACACCACAAAAAACTCTAGAAGAA
TTTCAAGATGTGTATTTGGTTATGGAATTAATGGATGCTAACTTATGTCAGGTTATTCAC
ATGGAGCTGGATCATGAAAGAATGTCCTACCTTCTTTACCAGATGCTTTGTGGTATTAAA
CATCTGCATTCAGCTGGTATAATTCATAGAGATTTGAAGCCTAGCAACATTGTTGTGAAA
TCAGACTGCACCCTGAAGATCCTTGACTTTGGCCTGGCCCGGACAGCGTGCACTAACTTC
ATGATGACCCCTTACGTGGTGACACGGTACTACCGGGCGCCCGAAGTCATCCTGGGTATG
GGCTACAAAGAGAACGTTGATATCTGGTCAGTGGGTTGCATCATGGGAGAGCTGGTGAAA
GGTTGTGTGATATTCCAAGGCACTGACCGTATCCTTCCCCGCGACCTTGGCCCCGCCATG
CTTTCTTAA
GenBank Gene IDL31951
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:6886
Chromosome Location5
Locus5q35
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. 7969172
  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. 8001819
  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. 8654373
  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. 21110917
  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. 14702039
  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. 19054851
  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. 15372022
  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. 15489334
  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. 10376527
  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. 11062067
  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. 15693750
  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. 15805466
  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. 17875713
  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. 17189706
  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. 17525747
  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. 19290929
  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. 19369195
  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. 19675674
  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. 20595622
  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. 21364637
  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. 21269460
  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. 22441692
  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. 18801372
  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. 17344846