NameMitogen-activated protein kinase 10
Synonyms
  • 2.7.11.24
  • c-Jun N-terminal kinase 3
  • JNK3
  • JNK3A
  • MAP kinase 10
  • MAP kinase p49 3F12
  • PRKM10
  • SAPK1B
  • Stress-activated protein kinase 1b
  • Stress-activated protein kinase JNK3
Gene NameMAPK10
OrganismHuman
Amino acid sequence
>lcl|BSEQ0002183|Mitogen-activated protein kinase 10
MSLHFLYYCSEPTLDVKIAFCQGFDKQVDVSYIAKHYNMSKSKVDNQFYSVEVGDSTFTV
LKRYQNLKPIGSGAQGIVCAAYDAVLDRNVAIKKLSRPFQNQTHAKRAYRELVLMKCVNH
KNIISLLNVFTPQKTLEEFQDVYLVMELMDANLCQVIQMELDHERMSYLLYQMLCGIKHL
HSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTAGTSFMMTPYVVTRYYRAPEVILGMGY
KENVDIWSVGCIMGEMVRHKILFPGRDYIDQWNKVIEQLGTPCPEFMKKLQPTVRNYVEN
RPKYAGLTFPKLFPDSLFPADSEHNKLKASQARDLLSKMLVIDPAKRISVDDALQHPYIN
VWYDPAEVEAPPPQIYDKQLDEREHTIEEWKELIYKEVMNSEEKTKNGVVKGQPSPSGAA
VNSSESLPPSSSVNDISSMSTDQTLASDTDSSLEASAGPLGCCR
Number of residues464
Molecular Weight52585.015
Theoretical pI6.78
GO Classification
Functions
  • MAP kinase kinase activity
  • JUN kinase activity
  • ATP binding
Processes
  • rhythmic process
  • toll-like receptor 3 signaling pathway
  • toll-like receptor 4 signaling pathway
  • toll-like receptor 5 signaling pathway
  • toll-like receptor 9 signaling pathway
  • innate immune response
  • toll-like receptor signaling pathway
  • Fc-epsilon receptor signaling pathway
  • toll-like receptor TLR1
  • protein phosphorylation
  • toll-like receptor TLR6
  • TRIF-dependent toll-like receptor signaling pathway
  • activation of MAPK activity
  • JNK cascade
  • regulation of circadian rhythm
  • MyD88-dependent toll-like receptor signaling pathway
  • MyD88-independent toll-like receptor signaling pathway
  • signal transduction
  • regulation of sequence-specific DNA binding transcription factor activity
  • stress-activated MAPK cascade
  • toll-like receptor 10 signaling pathway
  • response to light stimulus
  • toll-like receptor 2 signaling pathway
Components
  • cytosol
  • nucleoplasm
  • neuronal postsynaptic density
  • cytoplasm
  • mitochondrion
  • plasma membrane
General FunctionMap kinase kinase activity
Specific FunctionSerine/threonine-protein kinase involved in various processes such as neuronal proliferation, differentiation, migration 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 MAPK10/JNK3. In turn, MAPK10/JNK3 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. Plays regulatory roles in the signaling pathways during neuronal apoptosis. Phosphorylates the neuronal microtubule regulator STMN2. Acts in the regulation of the beta-amyloid precursor protein/APP signaling during neuronal differentiation by phosphorylating APP. Participates also in neurite growth in spiral ganglion neurons. Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the photic regulation of the circadian clock (PubMed:22441692).
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID468151
UniProtKB IDP53779
UniProtKB Entry NameMK10_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0019059|Mitogen-activated protein kinase 10 (MAPK10)
ATGAGCCTCCATTTCTTATACTACTGCAGTGAACCAACATTGGATGTGAAAATTGCCTTT
TGTCAGGGATTCGATAAACAAGTGGATGTGTCATATATTGCCAAACATTACAACATGAGC
AAAAGCAAAGTTGACAACCAGTTCTACAGTGTGGAAGTGGGAGACTCAACCTTCACAGTT
CTCAAGCGCTACCAGAATCTAAAGCCTATTGGCTCTGGGGCTCAGGGCATAGTTTGTGCC
GCGTATGATGCTGTCCTTGACAGAAATGTGGCCATTAAGAAGCTCAGCAGACCCTTTCAG
AACCAAACACATGCCAAGAGAGCGTACCGGGAGCTGGTCCTCATGAAGTGTGTGAACCAT
AAAAACATTATTAGTTTATTAAATGTCTTCACACCCCAGAAAACGCTGGAGGAGTTCCAA
GATGTTTACTTAGTAATGGAACTGATGGATGCCAACTTATGTCAAGTGATTCAGATGGAA
TTAGACCATGAGCGAATGTCTTACCTGCTGTACCAAATGTTGTGTGGCATTAAGCACCTC
CATTCTGCTGGAATTATTCACAGGGATTTAAAACCAAGTAACATTGTAGTCAAGTCTGAT
TGCACATTGAAAATCCTGGACTTTGGACTGGCCAGGACAGCAGGCACAAGCTTCATGATG
ACTCCATATGTGGTGACACGTTATTACAGAGCCCCTGAGGTCATCCTGGGGATGGGCTAC
AAGGAGAACGTGGATATATGGTCTGTGGGATGCATTATGGGAGAAATGGTTCGCCACAAA
ATCCTCTTTCCAGGAAGGGACTATATTGACCAGTGGAATAAGGTAATTGAACAACTAGGA
ACACCATGTCCAGAATTCATGAAGAAATTGCAACCCACAGTAAGAAACTATGTGGAGAAT
CGGCCCAAGTATGCGGGACTCACCTTCCCCAAACTCTTCCCAGATTCCCTCTTCCCAGCG
GACTCCGAGCACAATAAACTCAAAGCCAGCCAAGCCAGGGACTTGTTGTCAAAGATGCTA
GTGATTGACCCAGCAAAAAGAATATCAGTGGACGACGCCTTACAGCATCCCTACATCAAC
GTCTGGTATGACCCAGCCGAAGTGGAGGCGCCTCCACCTCAGATATATGACAAGCAGTTG
GATGAAAGAGAACACACAATTGAAGAATGGAAAGAACTTATCTACAAGGAAGTAATGAAT
TCAGAAGAAAAGACTAAAAATGGTGTAGTAAAAGGACAGCCTTCTCCTTCAGCACAGGTG
CAGCAGTGA
GenBank Gene IDU07620
GeneCard IDNot Available
GenAtlas IDMAPK10
HGNC IDHGNC:6872
Chromosome Location4
Locus4q22.1-q23
References
  1. Mohit AA, Martin JH, Miller CA: p493F12 kinase: a novel MAP kinase expressed in a subset of neurons in the human nervous system. Neuron. 1995 Jan;14(1):67-78. 7826642
  2. 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
  3. 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
  4. Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. 15815621
  5. 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
  6. Lisnock J, Griffin P, Calaycay J, Frantz B, Parsons J, O'Keefe SJ, LoGrasso P: Activation of JNK3 alpha 1 requires both MKK4 and MKK7: kinetic characterization of in vitro phosphorylated JNK3 alpha 1. Biochemistry. 2000 Mar 21;39(11):3141-8. 10715136
  7. 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
  8. Neidhart S, Antonsson B, Gillieron C, Vilbois F, Grenningloh G, Arkinstall S: c-Jun N-terminal kinase-3 (JNK3)/stress-activated protein kinase-beta (SAPKbeta) binds and phosphorylates the neuronal microtubule regulator SCG10. FEBS Lett. 2001 Nov 16;508(2):259-64. 11718727
  9. 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
  10. Shoichet SA, Duprez L, Hagens O, Waetzig V, Menzel C, Herdegen T, Schweiger S, Dan B, Vamos E, Ropers HH, Kalscheuer VM: Truncation of the CNS-expressed JNK3 in a patient with a severe developmental epileptic encephalopathy. Hum Genet. 2006 Jan;118(5):559-67. Epub 2005 Oct 25. 16249883
  11. Song X, Raman D, Gurevich EV, Vishnivetskiy SA, Gurevich VV: Visual and both non-visual arrestins in their "inactive" conformation bind JNK3 and Mdm2 and relocalize them from the nucleus to the cytoplasm. J Biol Chem. 2006 Jul 28;281(30):21491-9. Epub 2006 May 31. 16737965
  12. Morrison BE, Majdzadeh N, Zhang X, Lyles A, Bassel-Duby R, Olson EN, D'Mello SR: Neuroprotection by histone deacetylase-related protein. Mol Cell Biol. 2006 May;26(9):3550-64. 16611996
  13. Xu TR, Baillie GS, Bhari N, Houslay TM, Pitt AM, Adams DR, Kolch W, Houslay MD, Milligan G: Mutations of beta-arrestin 2 that limit self-association also interfere with interactions with the beta2-adrenoceptor and the ERK1/2 MAPKs: implications for beta2-adrenoceptor signalling via the ERK1/2 MAPKs. Biochem J. 2008 Jul 1;413(1):51-60. doi: 10.1042/BJ20080685. 18435604
  14. Yang G, Liu Y, Yang K, Liu R, Zhu S, Coquinco A, Wen W, Kojic L, Jia W, Cynader M: Isoform-specific palmitoylation of JNK regulates axonal development. Cell Death Differ. 2012 Apr;19(4):553-61. doi: 10.1038/cdd.2011.124. Epub 2011 Sep 23. 21941371
  15. 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
  16. Xie X, Gu Y, Fox T, Coll JT, Fleming MA, Markland W, Caron PR, Wilson KP, Su MS: Crystal structure of JNK3: a kinase implicated in neuronal apoptosis. Structure. 1998 Aug 15;6(8):983-91. 9739089