Mitogen-activated protein kinase 7

Details

Name
Mitogen-activated protein kinase 7
Kind
protein
Synonyms
  • 2.7.11.24
  • Big MAP kinase 1
  • BMK-1
  • BMK1
  • ERK-5
  • ERK5
  • Extracellular signal-regulated kinase 5
  • MAP kinase 7
  • MAPK 7
  • PRKM7
Gene Name
MAPK7
UniProtKB Entry
Q13164Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0051832|Mitogen-activated protein kinase 7
MAEPLKEEDGEDGSAEPPGPVKAEPAHTAASVAAKNLALLKARSFDVTFDVGDEYEIIET
IGNGAYGVVSSARRRLTGQQVAIKKIPNAFDVVTNAKRTLRELKILKHFKHDNIIAIKDI
LRPTVPYGEFKSVYVVLDLMESDLHQIIHSSQPLTLEHVRYFLYQLLRGLKYMHSAQVIH
RDLKPSNLLVNENCELKIGDFGMARGLCTSPAEHQYFMTEYVATRWYRAPELMLSLHEYT
QAIDLWSVGCIFGEMLARRQLFPGKNYVHQLQLIMMVLGTPSPAVIQAVGAERVRAYIQS
LPPRQPVPWETVYPGADRQALSLLGRMLRFEPSARISAAAALRHPFLAKYHDPDDEPDCA
PPFDFAFDREALTRERIKEAIVAEIEDFHARREGIRQQIRFQPSLQPVASEPGCPDVEMP
SPWAPSGDCAMESPPPAPPPCPGPAPDTIDLTLQPPPPVSEPAPPKKDGAISDNTKAALK
AALLKSLRSRLRDGPSAPLEAPEPRKPVTAQERQREREEKRRRRQERAKEREKRRQERER
KERGAGASGGPSTDPLAGLVLSDNDRSLLERWTRMARPAAPALTSVPAPAPAPTPTPTPV
QPTSPPPGPVAQPTGPQPQSAGSTSGPVPQPACPPPGPAPHPTGPPGPIPVPAPPQIATS
TSLLAAQSLVPPPGLPGSSTPGVLPYFPPGLPPPDAGGAPQSSMSESPDVNLVTQQLSKS
QVEDPLPPVFSGTPKGSGAGYGVGFDLEEFLNQSFDMGVADGPQDGQADSASLSASLLAD
WLEGHGMNPADIESLQREIQMDSPMLLADLPDLQDP
Number of residues
816
Molecular Weight
88385.515
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / MAP kinase activity / mitogen-activated protein kinase binding / protein serine/threonine kinase activity
Processes
cellular response to growth factor stimulus / cellular response to hydrogen peroxide / cellular response to laminar fluid shear stress / cellular response to transforming growth factor beta stimulus / negative regulation of endothelial cell apoptotic process / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / negative regulation of heterotypic cell-cell adhesion / negative regulation of inflammatory response / negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / negative regulation of response to cytokine stimulus / positive regulation of protein metabolic process / positive regulation of transcription by RNA polymerase II / regulation of angiogenesis / signal transduction
Components
cytoplasm / cytosol / nucleoplasm / nucleus / PML body
General Function
Plays a role in various cellular processes such as proliferation, differentiation and cell survival. The upstream activator of MAPK7 is the MAPK kinase MAP2K5. Upon activation, it translocates to the nucleus and phosphorylates various downstream targets including MEF2C. EGF activates MAPK7 through a Ras-independent and MAP2K5-dependent pathway. As part of the MAPK/ERK signaling pathway, acts as a negative regulator of apoptosis in cardiomyocytes via interaction with STUB1/CHIP and promotion of STUB1-mediated ubiquitination and degradation of ICER-type isoforms of CREM (By similarity). May have a role in muscle cell differentiation. May be important for endothelial function and maintenance of blood vessel integrity. MAP2K5 and MAPK7 interact specifically with one another and not with MEK1/ERK1 or MEK2/ERK2 pathways. Phosphorylates SGK1 at Ser-78 and this is required for growth factor-induced cell cycle progression. Involved in the regulation of p53/TP53 by disrupting the PML-MDM2 interaction
Specific Function
ATP binding
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0051833|Mitogen-activated protein kinase 7 (MAPK7)
ATGGCCGAGCCTCTGAAGGAGGAAGACGGCGAGGACGGCTCTGCGGAGCCCCCCGGGCCC
GTGAAGGCCGAACCCGCCCACACCGCTGCCTCTGTAGCGGCCAAGAACCTGGCCCTGCTT
AAAGCCCGCTCCTTCGATGTGACCTTTGACGTGGGCGACGAGTACGAGATCATCGAGACC
ATAGGCAACGGGGCCTATGGAGTGGTGTCCTCCGCCCGCCGCCGCCTCACCGGCCAGCAG
GTGGCCATCAAGAAGATCCCTAATGCTTTCGATGTGGTGACCAATGCCAAGCGGACCCTC
AGGGAGCTGAAGATCCTCAAGCACTTTAAACACGACAACATCATCGCCATCAAGGACATC
CTGAGGCCCACCGTGCCCTATGGCGAATTCAAATCTGTCTACGTGGTCCTGGACCTGATG
GAAAGCGACCTGCACCAGATCATCCACTCCTCACAGCCCCTCACACTGGAACACGTGCGC
TACTTCCTGTACCAACTGCTGCGGGGCCTGAAGTACATGCACTCGGCTCAGGTCATCCAC
CGTGACCTGAAGCCCTCCAACCTATTGGTGAATGAGAACTGTGAGCTCAAGATTGGTGAC
TTTGGTATGGCTCGTGGCCTGTGCACCTCGCCCGCTGAACATCAGTACTTCATGACTGAG
TATGTGGCCACGCGCTGGTACCGTGCGCCCGAGCTCATGCTCTCTTTGCATGAGTATACA
CAGGCTATTGACCTCTGGTCTGTGGGCTGCATCTTTGGTGAGATGCTGGCCCGGCGCCAG
CTCTTCCCAGGCAAAAACTATGTACACCAGCTACAGCTCATCATGATGGTGCTGGGTACC
CCATCACCAGCCGTGATTCAGGCTGTGGGGGCTGAGAGGGTGCGGGCCTATATCCAGAGC
TTGCCACCACGCCAGCCTGTGCCCTGGGAGACAGTGTACCCAGGTGCCGACCGCCAGGCC
CTATCACTGCTGGGTCGCATGCTGCGTTTTGAGCCCAGCGCTCGCATCTCAGCAGCTGCT
GCCCTTCGCCACCCTTTCCTGGCCAAGTACCATGATCCTGATGATGAGCCTGACTGTGCC
CCGCCCTTTGACTTTGCCTTTGACCGCGAAGCCCTCACTCGGGAGCGCATTAAGGAGGCC
ATTGTGGCTGAAATTGAGGACTTCCATGCAAGGCGTGAGGGCATCCGCCAACAGATCCGC
TTCCAGCCTTCTCTACAGCCTGTGGCTAGTGAGCCTGGCTGTCCAGATGTTGAAATGCCC
AGTCCCTGGGCTCCCAGTGGGGACTGTGCCATGGAGTCTCCACCACCAGCCCCGCCACCA
TGCCCCGGCCCTGCACCTGACACCATTGATCTGACCCTGCAGCCACCTCCACCAGTCAGT
GAGCCTGCCCCACCAAAGAAAGATGGTGCCATCTCAGACAATACTAAGGCTGCCCTTAAA
GCTGCCCTGCTCAAGTCTTTGAGGAGCCGGCTCAGAGATGGCCCCAGCGCACCCCTGGAG
GCTCCTGAGCCTCGGAAGCCGGTGACAGCCCAGGAGCGCCAGCGGGAGCGGGAGGAGAAG
CGGCGGAGGCGGCAAGAACGAGCCAAGGAGCGGGAGAAACGGCGGCAGGAGCGGGAGCGA
AAGGAACGGGGGGCTGGGGCCTCTGGGGGCCCCTCCACTGACCCCTTGGCTGGACTAGTG
CTCAGTGACAATGACAGAAGCCTGTTGGAACGCTGGACTCGAATGGCCCGGCCCGCAGCC
CCAGCCCTCACCTCTGTGCCGGCCCCTGCCCCAGCGCCAACGCCAACCCCAACCCCAGTC
CAACCTACCAGTCCTCCTCCTGGCCCTGTAGCCCAGCCCACTGGCCCGCAACCACAATCT
GCGGGCTCTACCTCTGGCCCTGTACCCCAGCCTGCCTGCCCACCCCCTGGCCCTGCACCC
CACCCCACTGGCCCTCCTGGGCCCATCCCTGTCCCCGCGCCACCCCAGATTGCCACCTCC
ACCAGCCTCCTGGCTGCCCAGTCACTTGTGCCACCCCCTGGGCTGCCTGGCTCCAGCACC
CCAGGAGTTTTGCCTTACTTCCCACCTGGCCTGCCGCCCCCAGACGCCGGGGGAGCCCCT
CAGTCTTCCATGTCAGAGTCACCTGATGTCAACCTTGTGACCCAGCAGCTATCTAAGTCA
CAGGTGGAGGACCCCCTGCCCCCTGTGTTCTCAGGCACACCAAAGGGCAGTGGGGCTGGC
TACGGTGTTGGCTTTGACCTGGAGGAATTCTTAAACCAGTCTTTCGACATGGGCGTGGCT
GATGGGCCACAGGATGGCCAGGCAGATTCAGCCTCTCTCTCAGCCTCCCTGCTTGCTGAC
TGGCTCGAAGGCCATGGCATGAACCCTGCCGATATTGAGTCCCTGCAGCGTGAGATCCAG
ATGGACTCCCCAATGCTGCTGGCTGACCTGCCTGACCTCCAGGACCCCTGA
Chromosome Location
17
Locus
17p11.2
External Identifiers
ResourceLink
UniProtKB IDQ13164
UniProtKB Entry NameMK07_HUMAN
GeneCard IDMAPK7
HGNC IDHGNC:6880
PDB ID(s)2Q8Y, 4B99, 4IC7, 4IC8, 4ZSG, 4ZSJ, 4ZSL, 5BYY, 5BYZ, 5O7I, 6HKM, 6HKN, 7PUS
KEGG IDhsa:5598
IUPHAR/Guide To Pharmacology ID2093
NCBI Gene ID5598
General References
  1. Lee JD, Ulevitch RJ, Han J: Primary structure of BMK1: a new mammalian map kinase. Biochem Biophys Res Commun. 1995 Aug 15;213(2):715-24. [Article]
  2. Zhou G, Bao ZQ, Dixon JE: Components of a new human protein kinase signal transduction pathway. J Biol Chem. 1995 May 26;270(21):12665-9. [Article]
  3. McCaw BJ, Chow SY, Wong ES, Tan KL, Guo H, Guy GR: Identification and characterization of mErk5-T, a novel Erk5/Bmk1 splice variant. Gene. 2005 Jan 31;345(2):183-90. Epub 2005 Jan 4. [Article]
  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. [Article]
  5. Kato Y, Kravchenko VV, Tapping RI, Han J, Ulevitch RJ, Lee JD: BMK1/ERK5 regulates serum-induced early gene expression through transcription factor MEF2C. EMBO J. 1997 Dec 1;16(23):7054-66. [Article]
  6. Kato Y, Tapping RI, Huang S, Watson MH, Ulevitch RJ, Lee JD: Bmk1/Erk5 is required for cell proliferation induced by epidermal growth factor. Nature. 1998 Oct 15;395(6703):713-6. [Article]
  7. Hayashi M, Tapping RI, Chao TH, Lo JF, King CC, Yang Y, Lee JD: BMK1 mediates growth factor-induced cell proliferation through direct cellular activation of serum and glucocorticoid-inducible kinase. J Biol Chem. 2001 Mar 23;276(12):8631-4. Epub 2001 Jan 31. [Article]
  8. Dong F, Gutkind JS, Larner AC: Granulocyte colony-stimulating factor induces ERK5 activation, which is differentially regulated by protein-tyrosine kinases and protein kinase C. Regulation of cell proliferation and survival. J Biol Chem. 2001 Apr 6;276(14):10811-6. Epub 2001 Jan 17. [Article]
  9. 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. [Article]
  10. 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. [Article]
  11. Erazo T, Moreno A, Ruiz-Babot G, Rodriguez-Asiain A, Morrice NA, Espadamala J, Bayascas JR, Gomez N, Lizcano JM: Canonical and kinase activity-independent mechanisms for extracellular signal-regulated kinase 5 (ERK5) nuclear translocation require dissociation of Hsp90 from the ERK5-Cdc37 complex. Mol Cell Biol. 2013 Apr;33(8):1671-86. doi: 10.1128/MCB.01246-12. Epub 2013 Feb 19. [Article]
  12. Yang Q, Liao L, Deng X, Chen R, Gray NS, Yates JR 3rd, Lee JD: BMK1 is involved in the regulation of p53 through disrupting the PML-MDM2 interaction. Oncogene. 2013 Jun 27;32(26):3156-64. doi: 10.1038/onc.2012.332. Epub 2012 Aug 6. [Article]
  13. 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. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Fostamatinibapproved, investigationalunknowntargetinhibitorDetails