MAP kinase-activated protein kinase 5

NameMAP kinase-activated protein kinase 5
Synonyms
  • 2.7.11.1
  • MAPK-activated protein kinase 5
  • p38-regulated/activated protein kinase
  • PRAK
Gene NameMAPKAPK5
OrganismHuman
Amino acid sequence
>lcl|BSEQ0009231|MAP kinase-activated protein kinase 5
MSEESDMDKAIKETSILEEYSINWTQKLGAGISGPVRVCVKKSTQERFALKILLDRPKAR
NEVRLHMMCATHPNIVQIIEVFANSVQFPHESSPRARLLIVMEMMEGGELFHRISQHRHF
TEKQASQVTKQIALALRHCHLLNIAHRDLKPENLLFKDNSLDAPVKLCDFGFAKIDQGDL
MTPQFTPYYVAPQVLEAQRRHQKEKSGIIPTSPTPYTYNKSCDLWSLGVIIYVMLCGYPP
FYSKHHSRTIPKDMRRKIMTGSFEFPEEEWSQISEMAKDVVRKLLKVKPEERLTIEGVLD
HPWLNSTEALDNVLPSAQLMMDKAVVAGIQQAHAEQLANMRIQDLKVSLKPLHSVNNPIL
RKRKLLGTKPKDSVYIHDHENGAEDSNVALEKLRDVIAQCILPQAGKGENEDEKLNEVMQ
EAWKYNRECKLLRDTLQSFSWNGRGFTDKVDRLKLAEIVKQVIEEQTTSHESQ
Number of residues473
Molecular Weight54220.04
Theoretical pINot Available
GO Classification
Functions
  • MAP kinase kinase activity
  • calcium-dependent protein serine/threonine kinase activity
  • mitogen-activated protein kinase binding
  • calmodulin binding
  • calmodulin-dependent protein kinase activity
  • signal transducer activity
  • ATP binding
  • p53 binding
  • protein serine/threonine kinase activity
Processes
  • stress-induced premature senescence
  • MAPK cascade
  • Ras protein signal transduction
  • cell surface receptor signaling pathway
  • protein autophosphorylation
  • activation of MAPK activity
  • peptidyl-serine phosphorylation
  • negative regulation of TOR signaling
  • regulation of translation
  • positive regulation of telomerase activity
  • positive regulation of telomere capping
  • signal transduction
  • positive regulation of telomere maintenance via telomerase
Components
  • cytosol
  • nucleoplasm
  • cytoplasm
General FunctionSignal transducer activity
Specific FunctionTumor suppressor serine/threonine-protein kinase involved in mTORC1 signaling and post-transcriptional regulation. Phosphorylates FOXO3, ERK3/MAPK6, ERK4/MAPK4, HSP27/HSPB1, p53/TP53 and RHEB. Acts as a tumor suppressor by mediating Ras-induced senescence and phosphorylating p53/TP53. Involved in post-transcriptional regulation of MYC by mediating phosphorylation of FOXO3: phosphorylation of FOXO3 leads to promote nuclear localization of FOXO3, enabling expression of miR-34b and miR-34c, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent MYC translation. Acts as a negative regulator of mTORC1 signaling by mediating phosphorylation and inhibition of RHEB. Part of the atypical MAPK signaling via its interaction with ERK3/MAPK6 or ERK4/MAPK4: the precise role of the complex formed with ERK3/MAPK6 or ERK4/MAPK4 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPK (ERK3/MAPK6 or ERK4/MAPK4), ERK3/MAPK6 (or ERK4/MAPK4) is phosphorylated and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK3/MAPK6 (or ERK4/MAPK4). Mediates phosphorylation of HSP27/HSPB1 in response to PKA/PRKACA stimulation, inducing F-actin rearrangement.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDQ8IW41
UniProtKB Entry NameMAPK5_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0019743|MAP kinase-activated protein kinase 5 (MAPKAPK5)
ATGTCGGAGGAGAGCGACATGGACAAAGCCATCAAGGAAACTTCCATTTTAGAAGAATAC
AGTATCAATTGGACTCAGAAGCTGGGAGCTGGAATTAGTGGTCCAGTTAGAGTCTGTGTA
AAGAAATCTACTCAAGAACGGTTTGCGCTGAAAATTCTTCTTGATCGTCCAAAAGCTAGA
AATGAGGTACGTCTGCACATGATGTGTGCCACACACCCAAACATAGTTCAGATTATTGAA
GTGTTTGCTAACAGTGTCCAGTTTCCCCATGAGTCCAGCCCTAGGGCCCGACTCTTAATT
GTAATGGAGATGATGGAAGGGGGAGAGCTATTTCACAGAATCAGCCAGCACCGGCACTTT
ACAGAGAAGCAAGCCAGCCAAGTAACAAAGCAGATAGCTTTGGCTCTGCGGCACTGTCAC
TTGTTAAACATTGCGCACAGAGACCTCAAGCCTGAAAATCTGCTTTTTAAGGATAACTCT
TTGGATGCCCCAGTGAAGTTGTGTGACTTTGGATTTGCCAAGATTGACCAAGGTGACTTG
ATGACACCCCAGTTCACCCCTTATTATGTAGCACCCCAGGTACTGGAGGCGCAAAGAAGG
CATCAGAAGGAGAAATCTGGCATCATACCTACCTCACCGACGCCCTACACTTACAACAAG
AGCTGTGACTTGTGGTCCCTAGGGGTGATTATCTATGTGATGCTGTGCGGATACCCTCCT
TTTTACTCCAAACACCACAGCCGGACTATCCCAAAGGATATGCGAAGAAAGATCATGACA
GGCAGTTTTGAGTTCCCAGAGGAAGAGTGGAGTCAGATCTCAGAGATGGCCAAAGATGTT
GTGAGGAAGCTCCTGAAGGTCAAACCGGAGGAGAGACTCACCATCGAGGGAGTGCTGGAC
CACCCCTGGCTCAATTCCACCGAGGCCCTGGATAATGTGCTGCCTTCTGCTCAGCTGATG
ATGGACAAGGCAGTGGTTGCAGGAATCCAGCAGGCTCACGCGGAACAGTTGGCCAACATG
AGAATCCAGGATCTGAAAGTCAGCCTCAAACCCCTGCACTCAGTGAACAACCCCATTCTG
CGGAAGAGGAAGTTACTTGGCACCAAGCCAAAGGACAGTGTCTATATCCACGACCATGAG
AATGGAGCCGAGGATTCCAATGTTGCCTTGGAAAAACTCCGAGATGTGATTGCTCAGTGT
ATTCTCCCCCAGGCTGGAGAGAATGAAGATGAGAAACTGAATGAAGTAATGCAGGAGGCT
TGGAAGTATAACCGGGAATGCAAACTCCTAAGAGATACTCTGCAGAGCTTCAGCTGGAAT
GGTCGTGGATTCACAGATAAAGTAGATCGACTAAAACTGGCAGAAATTGTGAAGCAGGTG
ATAGAAGAGCAAACCACGTCCCACGAATCCCAATAA
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:6889
Chromosome Location12
LocusNot Available
References
  1. New L, Jiang Y, Zhao M, Liu K, Zhu W, Flood LJ, Kato Y, Parry GC, Han J: PRAK, a novel protein kinase regulated by the p38 MAP kinase. EMBO J. 1998 Jun 15;17(12):3372-84. 9628874
  2. 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
  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. 15489334
  4. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. 17974005
  5. Sudo T, Maruyama M, Osada H: p62 functions as a p38 MAP kinase regulator. Biochem Biophys Res Commun. 2000 Mar 16;269(2):521-5. 10708586
  6. New L, Jiang Y, Han J: Regulation of PRAK subcellular location by p38 MAP kinases. Mol Biol Cell. 2003 Jun;14(6):2603-16. Epub 2003 Mar 20. 12808055
  7. Tak H, Jang E, Kim SB, Park J, Suk J, Yoon YS, Ahn JK, Lee JH, Joe CO: 14-3-3epsilon inhibits MK5-mediated cell migration by disrupting F-actin polymerization. Cell Signal. 2007 Nov;19(11):2379-87. Epub 2007 Jul 31. 17728103
  8. 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. 18669648
  9. 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
  10. Kostenko S, Johannessen M, Moens U: PKA-induced F-actin rearrangement requires phosphorylation of Hsp27 by the MAPKAP kinase MK5. Cell Signal. 2009 May;21(5):712-8. doi: 10.1016/j.cellsig.2009.01.009. Epub 2009 Jan 8. 19166925
  11. 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. 19690332
  12. 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
  13. Sun P, Yoshizuka N, New L, Moser BA, Li Y, Liao R, Xie C, Chen J, Deng Q, Yamout M, Dong MQ, Frangou CG, Yates JR 3rd, Wright PE, Han J: PRAK is essential for ras-induced senescence and tumor suppression. Cell. 2007 Jan 26;128(2):295-308. 17254968
  14. Kress TR, Cannell IG, Brenkman AB, Samans B, Gaestel M, Roepman P, Burgering BM, Bushell M, Rosenwald A, Eilers M: The MK5/PRAK kinase and Myc form a negative feedback loop that is disrupted during colorectal tumorigenesis. Mol Cell. 2011 Feb 18;41(4):445-57. doi: 10.1016/j.molcel.2011.01.023. 21329882
  15. Shiryaev A, Moens U: Mitogen-activated protein kinase p38 and MK2, MK3 and MK5: menage a trois or menage a quatre? Cell Signal. 2010 Aug;22(8):1185-92. doi: 10.1016/j.cellsig.2010.03.002. Epub 2010 Mar 11. 20227494