Mitogen-activated protein kinase 4

Details

Name
Mitogen-activated protein kinase 4
Synonyms
  • 2.7.11.24
  • ERK-4
  • ERK4
  • Extracellular signal-regulated kinase 4
  • MAP kinase 4
  • MAP kinase isoform p63
  • p63-MAPK
  • PRKM4
Gene Name
MAPK4
Organism
Humans
Amino acid sequence
>lcl|BSEQ0051830|Mitogen-activated protein kinase 4
MAEKGDCIASVYGYDLGGRFVDFQPLGFGVNGLVLSAVDSRACRKVAVKKIALSDARSMK
HALREIKIIRRLDHDNIVKVYEVLGPKGTDLQGELFKFSVAYIVQEYMETDLARLLEQGT
LAEEHAKLFMYQLLRGLKYIHSANVLHRDLKPANIFISTEDLVLKIGDFGLARIVDQHYS
HKGYLSEGLVTKWYRSPRLLLSPNNYTKAIDMWAAGCILAEMLTGRMLFAGAHELEQMQL
ILETIPVIREEDKDELLRVMPSFVSSTWEVKRPLRKLLPEVNSEAIDFLEKILTFNPMDR
LTAEMGLQHPYMSPYSCPEDEPTSQHPFRIEDEIDDIVLMAANQSQLSNWDTCSSRYPVS
LSSDLEWRPDRCQDASEVQRDPRAGSAPLAEDVQVDPRKDSHSSSERFLEQSHSSMERAF
EADYGRSCDYKVGSPSYLDKLLWRDNKPHHYSEPKLILDLSHWKQAAGAPPTATGLADTG
AREDEPASLFLEIAQWVKSTQGGPEHASPPADDPERRLSASPPGRPAPVDGGASPQFDLD
VFISRALKLCTKPEDLPDNKLGDLNGACIPEHPGDLVQTEAFSKERW
Number of residues
587
Molecular Weight
65921.01
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / MAP kinase activity / protein heterodimerization activity / protein homodimerization activity / protein kinase binding / protein serine/threonine kinase activity
Processes
cell cycle / cellular response to organic substance / protein phosphorylation / regulation of gene expression
Components
cytoplasm / cytosol / nucleoplasm / nucleus
General Function
Atypical MAPK protein. Phosphorylates microtubule-associated protein 2 (MAP2) and MAPKAPK5. The precise role of the complex formed with MAPKAPK5 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPKAPK5, ERK4/MAPK4 is phosphorylated at Ser-186 and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK4/MAPK4. May promote entry in the cell cycle (By similarity).
Specific Function
Atp binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0051831|Mitogen-activated protein kinase 4 (MAPK4)
ATGGCTGAGAAGGGTGACTGCATCGCCAGTGTCTATGGGTATGACCTCGGTGGGCGCTTT
GTTGACTTCCAACCCCTGGGCTTCGGTGTCAATGGTTTGGTGCTGTCGGCCGTGGACAGC
CGGGCCTGCCGGAAGGTCGCTGTGAAGAAGATTGCCCTGAGCGATGCCCGCAGCATGAAG
CACGCGCTCCGAGAGATCAAGATCATTCGGCGCCTGGACCACGACAACATCGTCAAAGTG
TACGAGGTGCTCGGTCCCAAGGGCACTGACCTGCAGGGTGAGCTGTTCAAGTTCAGCGTG
GCGTACATCGTCCAGGAGTACATGGAGACCGACCTGGCACGCCTGCTGGAGCAGGGCACG
CTGGCAGAAGAGCATGCCAAGCTGTTCATGTACCAGCTGCTCCGCGGGCTCAAGTACATC
CACTCCGCCAACGTGCTGCACAGGGACCTGAAGCCCGCCAACATCTTCATCAGCACAGAG
GACCTCGTGCTCAAGATTGGGGATTTCGGGTTGGCAAGGATCGTTGATCAGCATTACTCC
CACAAGGGTTATCTGTCAGAAGGGTTGGTAACAAAGTGGTACCGTTCCCCACGACTGCTC
CTTTCCCCCAATAACTACACCAAAGCCATCGACATGTGGGCCGCCGGCTGCATCCTGGCT
GAGATGCTTACGGGGAGAATGCTCTTTGCTGGGGCCCATGAGCTGGAGCAGATGCAACTC
ATCCTGGAGACCATCCCTGTAATCCGGGAGGAAGACAAGGACGAGCTGCTCAGGGTGATG
CCTTCCTTTGTCAGCAGCACCTGGGAGGTGAAGAGGCCTCTGCGCAAGCTGCTCCCTGAA
GTGAACAGTGAAGCCATCGACTTTCTGGAGAAGATCCTGACCTTTAACCCCATGGATCGC
CTAACAGCTGAGATGGGGCTGCAACACCCCTACATGAGCCCATACTCGTGCCCTGAGGAC
GAGCCCACCTCACAACACCCCTTCCGCATTGAGGATGAGATCGACGACATCGTGCTGATG
GCCGCTAACCAGAGCCAGCTGTCCAACTGGGACACGTGCAGTTCCAGGTACCCTGTGAGC
CTGTCGTCGGACCTGGAGTGGCGGCCTGACCGGTGCCAGGACGCCAGCGAGGTACAGCGC
GACCCGCGCGCGGGTTCGGCGCCACTGGCTGAGGACGTGCAGGTGGACCCGCGCAAGGAC
TCGCACAGCAGCTCCGAGCGCTTCCTAGAGCAGTCGCACTCGTCCATGGAGCGCGCCTTC
GAGGCCGACTACGGGCGCTCCTGCGACTACAAGGTGGGGTCGCCGTCCTACCTGGACAAG
CTGCTGTGGCGCGACAACAAGCCGCACCACTACTCGGAGCCCAAGCTCATCCTGGACCTG
TCGCACTGGAAGCAGGCGGCCGGCGCGCCCCCCACGGCCACGGGGCTGGCGGACACGGGG
GCGCGCGAGGACGAGCCGGCCAGCCTCTTCCTGGAGATCGCGCAGTGGGTCAAGAGCACG
CAGGGCGGCCCAGAGCACGCCAGCCCGCCCGCCGACGACCCCGAGCGCCGCTTGTCTGCC
TCGCCCCCCGGCCGCCCGGCCCCGGTGGACGGCGGCGCCAGCCCCCAGTTCGACCTGGAC
GTGTTCATCTCCCGCGCCCTGAAGCTCTGCACCAAGCCCGAGGACCTGCCGGACAATAAA
CTGGGCGACCTCAATGGTGCGTGCATCCCCGAGCACCCTGGCGACCTCGTGCAGACCGAG
GCCTTCTCCAAAGAAAGGTGGTGA
Chromosome Location
18
Locus
18q21.1-q21.2
External Identifiers
ResourceLink
UniProtKB IDP31152
UniProtKB Entry NameMK04_HUMAN
HGNC IDHGNC:6878
General References
  1. Gonzalez FA, Raden DL, Rigby MR, Davis RJ: Heterogeneous expression of four MAP kinase isoforms in human tissues. FEBS Lett. 1992 Jun 15;304(2-3):170-8. [PubMed:1319925]
  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. [PubMed:14702039]
  3. Nusbaum C, Zody MC, Borowsky ML, Kamal M, Kodira CD, Taylor TD, Whittaker CA, Chang JL, Cuomo CA, Dewar K, FitzGerald MG, Yang X, Abouelleil A, Allen NR, Anderson S, Bloom T, Bugalter B, Butler J, Cook A, DeCaprio D, Engels R, Garber M, Gnirke A, Hafez N, Hall JL, Norman CH, Itoh T, Jaffe DB, Kuroki Y, Lehoczky J, Lui A, Macdonald P, Mauceli E, Mikkelsen TS, Naylor JW, Nicol R, Nguyen C, Noguchi H, O'Leary SB, O'Neill K, Piqani B, Smith CL, Talamas JA, Topham K, Totoki Y, Toyoda A, Wain HM, Young SK, Zeng Q, Zimmer AR, Fujiyama A, Hattori M, Birren BW, Sakaki Y, Lander ES: DNA sequence and analysis of human chromosome 18. Nature. 2005 Sep 22;437(7058):551-5. [PubMed:16177791]
  4. 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. [PubMed:15489334]
  5. 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. [PubMed:18669648]
  6. Deleris P, Trost M, Topisirovic I, Tanguay PL, Borden KL, Thibault P, Meloche S: Activation loop phosphorylation of ERK3/ERK4 by group I p21-activated kinases (PAKs) defines a novel PAK-ERK3/4-MAPK-activated protein kinase 5 signaling pathway. J Biol Chem. 2011 Feb 25;286(8):6470-8. doi: 10.1074/jbc.M110.181529. Epub 2010 Dec 22. [PubMed:21177870]
  7. Zhou H, Di Palma S, Preisinger C, Peng M, Polat AN, Heck AJ, Mohammed S: Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res. 2013 Jan 4;12(1):260-71. doi: 10.1021/pr300630k. Epub 2012 Dec 18. [PubMed:23186163]
  8. 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. [PubMed:17344846]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails
DB00945Acetylsalicylic acidapproved, vet_approvedunknownDetails
DB01017Minocyclineapproved, investigationalunknowninhibitorDetails