Dual specificity mitogen-activated protein kinase kinase 7

NameDual specificity mitogen-activated protein kinase kinase 7
Synonyms
  • 2.7.12.2
  • c-Jun N-terminal kinase kinase 2
  • JNK kinase 2
  • JNK-activating kinase 2
  • JNKK 2
  • JNKK2
  • MAP kinase kinase 7
  • MAPK/ERK kinase 7
  • MEK 7
  • MEK7
  • MKK7
  • PRKMK7
  • SAPK kinase 4
  • SAPKK-4
  • SAPKK4
  • SKK4
  • Stress-activated protein kinase kinase 4
Gene NameMAP2K7
OrganismHuman
Amino acid sequence
>lcl|BSEQ0004335|Dual specificity mitogen-activated protein kinase kinase 7
MAASSLEQKLSRLEAKLKQENREARRRIDLNLDISPQRPRPTLQLPLANDGGSRSPSSES
SPQHPTPPARPRHMLGLPSTLFTPRSMESIEIDQKLQEIMKQTGYLTIGGQRYQAEINDL
ENLGEMGSGTCGQVWKMRFRKTGHVIAVKQMRRSGNKEENKRILMDLDVVLKSHDCPYIV
QCFGTFITNTDVFIAMELMGTCAEKLKKRMQGPIPERILGKMTVAIVKALYYLKEKHGVI
HRDVKPSNILLDERGQIKLCDFGISGRLVDSKAKTRSAGCAAYMAPERIDPPDPTKPDYD
IRADVWSLGISLVELATGQFPYKNCKTDFEVLTKVLQEEPPLLPGHMGFSGDFQSFVKDC
LTKDHRKRPKYNKLLEHSFIKRYETLEVDVASWFKDVMAKTESPRTSGVLSQPHLPFFR
Number of residues419
Molecular Weight47484.49
Theoretical pI9.62
GO Classification
Functions
  • protein serine/threonine kinase activity
  • MAP kinase kinase activity
  • magnesium ion binding
  • enzyme binding
  • protein tyrosine kinase activity
  • protein kinase binding
  • protein phosphatase binding
  • ATP binding
Processes
  • MyD88-dependent toll-like receptor signaling pathway
  • response to tumor necrosis factor
  • MyD88-independent toll-like receptor signaling pathway
  • positive regulation of telomerase activity
  • positive regulation of telomere capping
  • positive regulation of telomere maintenance via telomerase
  • stress-activated MAPK cascade
  • toll-like receptor 10 signaling pathway
  • innate immune response
  • toll-like receptor 2 signaling pathway
  • activation of JUN kinase activity
  • toll-like receptor 3 signaling pathway
  • Fc-epsilon receptor signaling pathway
  • toll-like receptor 4 signaling pathway
  • apoptotic process
  • toll-like receptor 5 signaling pathway
  • JNK cascade
  • toll-like receptor 9 signaling pathway
  • response to osmotic stress
  • toll-like receptor signaling pathway
  • toll-like receptor TLR1
  • response to heat
  • signal transduction
  • toll-like receptor TLR6
  • response to UV
  • TRIF-dependent toll-like receptor signaling pathway
Components
  • nucleus
  • cytosol
  • cytoplasm
General FunctionProtein tyrosine kinase activity
Specific FunctionDual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K4/MKK4, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4/MKK4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The monophosphorylation of JNKs on the Thr residue is sufficient to increase JNK activity indicating that MAP2K7/MKK7 is important to trigger JNK activity, while the additional phosphorylation of the Tyr residue by MAP2K4/MKK4 ensures optimal JNK activation. Has a specific role in JNK signal transduction pathway activated by proinflammatory cytokines. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID2318119
UniProtKB IDO14733
UniProtKB Entry NameMP2K7_HUMAN
Cellular LocationNucleus
Gene sequence
>lcl|BSEQ0011596|Dual specificity mitogen-activated protein kinase kinase 7 (MAP2K7)
ATGGCGGCGTCCTCCCTGGAACAGAAGCTGTCCCGCCTGGAAGCAAAGCTGAAGCAGGAG
AACCGGGAGGCCCGGCGGAGGATCGACCTCAACCTGGATATCAGCCCCCAGCGGCCCAGG
CCCATTATTGTGATCACTCTAAGCCCTGCTCCTGCCCCGTCCCAACGAGCAGCCCTGCAG
CTCCCGCTGGCCAACGATGGGGGCAGCCGCTCGCCATCCTCAGAGAGCTCCCCGCAGCAC
CCCACGCCCCCCGCCCGGCCCCGCCACATGCTGGGGCTCCCGTCAACCCTGTTCACACCC
CGCAGCATGGAGAGCATTGAGATTGACCAGAAGCTGCAGGAGATCATGAAGCAGACGGGC
TACCTGACCATCGGGGGCCAGCGCTACCAGGCAGAAATCAACGACCTGGAGAACTTGGGC
GAGATGGGCAGCGGCACCTGCGGCCAGGTGTGGAAGATGCGCTTCCGGAAGACCGGCCAC
GTCATTGCCGTTAAGCAAATGCGGCGCTCCGGGAACAAGGAGGAGAACAAGCGCATCCTC
ATGGACCTGGATGTGGTGCTGAAGAGCCACGACTGCCCCTACATCGTGCAGTGCTTTGGG
ACGTTCATCACCAACACGGACGTCTTCATCGCCATGGAGCTCATGGGCACCTGCGCTGAG
AAGCTCAAGAAGCGGATGCAGGGCCCCATCCCCGAGCGCATTCTGGGCAAGATGACAGTG
GCGATTGTGAAGGCGCTGTACTACCTGAAGGAGAAGCACGGTGTCATCCACCGCGACGTC
AAGCCCTCCAACATCCTGCTGGACGAGCGGGGCCAGATCAAGCTCTGCGACTTCGGCATC
AGCGGCCGCCTGGTGGACTCCAAAGCCAAGACGCGGAGCGCCGGCTGTGCCGCCTACATG
GCACCCGAGCGCATTGACCCCCCAGACCCCACCAAGCCGGACTATGACATCCGGGCCGAC
GTATGGAGCCTGGGCATCTCGTTGGTGGAGCTGGCAACAGGACAGTTTCCCTACAAGAAC
TGCAAGACGGACTTTGAGGTCCTCACCAAAGTCCTACAGGAAGAGCCCCCGCTTCTGCCC
GGACACATGGGCTTCTCGGGGGACTTCCAGTCCTTCGTCAAAGACTGCCTTACTAAAGAT
CACAGGAAGAGACCAAAGTATAATAAGCTACTTGAACACAGCTTCATCAAGCGCTACGAG
ACGCTGGAGGTGGACGTGGCGTCCTGGTTCAAGGATGTCATGGCGAAGACTGAGTCACCG
CGGACTAGCGGCGTCCTGAGCCAGCCCCACCTGCCCTTCTTCAGGTAG
GenBank Gene IDAF014401
GeneCard IDNot Available
GenAtlas IDMAP2K7
HGNC IDHGNC:6847
Chromosome Location19
Locus19p13.3-p13.2
References
  1. Wu Z, Wu J, Jacinto E, Karin M: Molecular cloning and characterization of human JNKK2, a novel Jun NH2-terminal kinase-specific kinase. Mol Cell Biol. 1997 Dec;17(12):7407-16. 9372971
  2. Lu X, Nemoto S, Lin A: Identification of c-Jun NH2-terminal protein kinase (JNK)-activating kinase 2 as an activator of JNK but not p38. J Biol Chem. 1997 Oct 3;272(40):24751-4. 9312068
  3. Foltz IN, Gerl RE, Wieler JS, Luckach M, Salmon RA, Schrader JW: Human mitogen-activated protein kinase kinase 7 (MKK7) is a highly conserved c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) activated by environmental stresses and physiological stimuli. J Biol Chem. 1998 Apr 10;273(15):9344-51. 9535930
  4. Michael L, Swantek J, Robinson MJ: Cloning and expression of human mitogen-activated protein kinase kinase 7gamma1. Biochem Biophys Res Commun. 2006 Mar 17;341(3):679-83. Epub 2006 Jan 18. 16442502
  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. 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
  7. Tournier C, Whitmarsh AJ, Cavanagh J, Barrett T, Davis RJ: Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase. Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7337-42. 9207092
  8. Yasuda J, Whitmarsh AJ, Cavanagh J, Sharma M, Davis RJ: The JIP group of mitogen-activated protein kinase scaffold proteins. Mol Cell Biol. 1999 Oct;19(10):7245-54. 10490659
  9. Vitale G, Bernardi L, Napolitani G, Mock M, Montecucco C: Susceptibility of mitogen-activated protein kinase kinase family members to proteolysis by anthrax lethal factor. Biochem J. 2000 Dec 15;352 Pt 3:739-45. 11104681
  10. Matsuura H, Nishitoh H, Takeda K, Matsuzawa A, Amagasa T, Ito M, Yoshioka K, Ichijo H: Phosphorylation-dependent scaffolding role of JSAP1/JIP3 in the ASK1-JNK signaling pathway. A new mode of regulation of the MAP kinase cascade. J Biol Chem. 2002 Oct 25;277(43):40703-9. Epub 2002 Aug 19. 12189133
  11. Takekawa M, Tatebayashi K, Saito H: Conserved docking site is essential for activation of mammalian MAP kinase kinases by specific MAP kinase kinase kinases. Mol Cell. 2005 Apr 29;18(3):295-306. 15866172
  12. Blanco S, Sanz-Garcia M, Santos CR, Lazo PA: Modulation of interleukin-1 transcriptional response by the interaction between VRK2 and the JIP1 scaffold protein. PLoS One. 2008 Feb 20;3(2):e1660. doi: 10.1371/journal.pone.0001660. 18286207
  13. Raman M, Chen W, Cobb MH: Differential regulation and properties of MAPKs. Oncogene. 2007 May 14;26(22):3100-12. 17496909
  14. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. 19413330
  15. Asaoka Y, Nishina H: Diverse physiological functions of MKK4 and MKK7 during early embryogenesis. J Biochem. 2010 Oct;148(4):393-401. doi: 10.1093/jb/mvq098. Epub 2010 Aug 27. 20801953
  16. Takahashi S, Ebihara A, Kajiho H, Kontani K, Nishina H, Katada T: RASSF7 negatively regulates pro-apoptotic JNK signaling by inhibiting the activity of phosphorylated-MKK7. Cell Death Differ. 2011 Apr;18(4):645-55. doi: 10.1038/cdd.2010.137. Epub 2010 Nov 19. 21278800
  17. Haeusgen W, Herdegen T, Waetzig V: The bottleneck of JNK signaling: molecular and functional characteristics of MKK4 and MKK7. Eur J Cell Biol. 2011 Jun-Jul;90(6-7):536-44. doi: 10.1016/j.ejcb.2010.11.008. Epub 2011 Feb 18. 21333379
  18. Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54. doi: 10.1073/pnas.1210303109. Epub 2012 Jul 18. 22814378
  19. 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