Mitogen-activated protein kinase 13

Details

Name
Mitogen-activated protein kinase 13
Synonyms
  • 2.7.11.24
  • MAP kinase 13
  • MAP kinase p38 delta
  • Mitogen-activated protein kinase p38 delta
  • PRKM13
  • SAPK4
  • Stress-activated protein kinase 4
Gene Name
MAPK13
Organism
Humans
Amino acid sequence
>lcl|BSEQ0006617|Mitogen-activated protein kinase 13
MSLIRKKGFYKQDVNKTAWELPKTYVSPTHVGSGAYGSVCSAIDKRSGEKVAIKKLSRPF
QSEIFAKRAYRELLLLKHMQHENVIGLLDVFTPASSLRNFYDFYLVMPFMQTDLQKIMGM
EFSEEKIQYLVYQMLKGLKYIHSAGVVHRDLKPGNLAVNEDCELKILDFGLARHADAEMT
GYVVTRWYRAPEVILSWMHYNQTVDIWSVGCIMAEMLTGKTLFKGKDYLDQLTQILKVTG
VPGTEFVQKLNDKAAKSYIQSLPQTPRKDFTQLFPRASPQAADLLEKMLELDVDKRLTAA
QALTHPFFEPFRDPEEETEAQQPFDDSLEHEKLTVDEWKQHIYKEIVNFSPIARKDSRRR
SGMKL
Number of residues
365
Molecular Weight
42089.28
Theoretical pI
8.66
GO Classification
Functions
ATP binding / MAP kinase activity / protein serine/threonine kinase activity
Processes
cell cycle / intracellular signal transduction / MAPK cascade / neurotrophin TRK receptor signaling pathway / peptidyl-serine phosphorylation / positive regulation of inflammatory response / positive regulation of interleukin-6 production / Ras protein signal transduction / regulation of transcription, DNA-templated / response to osmotic stress / response to stress / transcription, DNA-templated / vascular endothelial growth factor receptor signaling pathway
Components
cytosol
General Function
Protein serine/threonine kinase activity
Specific Function
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK13 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. MAPK13 is one of the less studied p38 MAPK isoforms. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in the regulation of protein translation by phosphorylating and inactivating EEF2K. Involved in cytoskeletal remodeling through phosphorylation of MAPT and STMN1. Mediates UV irradiation induced up-regulation of the gene expression of CXCL14. Plays an important role in the regulation of epidermal keratinocyte differentiation, apoptosis and skin tumor development. Phosphorylates the transcriptional activator MYB in response to stress which leads to rapid MYB degradation via a proteasome-dependent pathway. MAPK13 also phosphorylates and down-regulates PRKD1 during regulation of insulin secretion in pancreatic beta cells.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Not Available
Gene sequence
>lcl|BSEQ0012373|Mitogen-activated protein kinase 13 (MAPK13)
ATGAGCCTCATCCGGAAAAAGGGCTTCTACAAGCAGGACGTCAACAAGACAGCCTGGGAG
CTGCCCAAGACCTACGTGTCCCCGACGCACGTCGGCAGCGGGGCCTATGGCTCCGTGTGC
TCGGCCATCGACAAGCGGTCAGGGGAGAAGGTGGCCATCAAGAAGCTGAGCCGACCCTTT
CAGTCCGAGATCTTCGCCAAGCGCGCCTACCGGGAGCTGCTGCTGCTGAAGCACATGCAG
CATGAGAACGTCATTGGGCTCCTGGATGTCTTCACCCCAGCCTCCTCCCTGCGCAACTTC
TATGACTTCTACCTGGTGATGCCCTTCATGCAGACGGATCTGCAGAAGATCATGGGGATG
GAGTTCAGTGAGGAGAAGATCCAGTACCTGGTGTATCAGATGCTCAAAGGCCTTAAGTAC
ATCCACTCTGCTGGGGTCGTGCACAGGGACCTGAAGCCAGGCAACCTGGCTGTGAATGAG
GACTGTGAACTGAAGATTCTGGATTTTGGGCTGGCGCGACATGCAGACGCCGAGATGACT
GGCTACGTGGTGACCCGCTGGTACCGAGCCCCCGAGGTGATCCTCAGCTGGATGCACTAC
AACCAGACAGTGGACATCTGGTCTGTGGGCTGTATCATGGCAGAGATGCTGACAGGGAAA
ACTCTGTTCAAGGGGAAAGATTACCTGGACCAGCTGACCCAGATCCTGAAAGTGACCGGG
GTGCCTGGCACGGAGTTTGTGCAGAAGCTGAACGACAAAGCGGCCAAATCCTACATCCAG
TCCCTGCCACAGACCCCCAGGAAGGATTTCACTCAGCTGTTCCCACGGGCCAGCCCCCAG
GCTGCGGACCTGCTGGAGAAGATGCTGGAGCTAGACGTGGACAAGCGCCTGACGGCCGCG
CAGGCCCTCACCCATCCCTTCTTTGAACCCTTCCGGGACCCTGAGGAAGAGACGGAGGCC
CAGCAGCCGTTTGATGATTCCTTAGAACACGAGAAACTCACAGTGGATGAATGGAAGCAG
CACATCTACAAGGAGATTGTGAACTTCAGCCCCATTGCCCGGAAGGACTCACGGCGCCGG
AGTGGCATGAAGCTGTAG
Chromosome Location
6
Locus
6p21.31
External Identifiers
ResourceLink
UniProtKB IDO15264
UniProtKB Entry NameMK13_HUMAN
GenBank Gene IDY10488
GenAtlas IDMAPK13
HGNC IDHGNC:6875
General References
  1. Goedert M, Cuenda A, Craxton M, Jakes R, Cohen P: Activation of the novel stress-activated protein kinase SAPK4 by cytokines and cellular stresses is mediated by SKK3 (MKK6); comparison of its substrate specificity with that of other SAP kinases. EMBO J. 1997 Jun 16;16(12):3563-71. [Article]
  2. Jiang Y, Gram H, Zhao M, New L, Gu J, Feng L, Di Padova F, Ulevitch RJ, Han J: Characterization of the structure and function of the fourth member of p38 group mitogen-activated protein kinases, p38delta. J Biol Chem. 1997 Nov 28;272(48):30122-8. [Article]
  3. Wang XS, Diener K, Manthey CL, Wang S, Rosenzweig B, Bray J, Delaney J, Cole CN, Chan-Hui PY, Mantlo N, Lichenstein HS, Zukowski M, Yao Z: Molecular cloning and characterization of a novel p38 mitogen-activated protein kinase. J Biol Chem. 1997 Sep 19;272(38):23668-74. [Article]
  4. Kumar S, McDonnell PC, Gum RJ, Hand AT, Lee JC, Young PR: Novel homologues of CSBP/p38 MAP kinase: activation, substrate specificity and sensitivity to inhibition by pyridinyl imidazoles. Biochem Biophys Res Commun. 1997 Jun 27;235(3):533-8. [Article]
  5. Hu MC, Wang YP, Mikhail A, Qiu WR, Tan TH: Murine p38-delta mitogen-activated protein kinase, a developmentally regulated protein kinase that is activated by stress and proinflammatory cytokines. J Biol Chem. 1999 Mar 12;274(11):7095-102. [Article]
  6. Herbison CE, Sayer DC, Bellgard M, Allcock RJ, Christiansen FT, Price P: Structure and polymorphism of two stress-activated protein kinase genes centromeric of the MHC: SAPK2a and SAPK4. DNA Seq. 1999;10(4-5):229-43. [Article]
  7. Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, Horton R, Hunt SE, Scott CE, Gilbert JG, Clamp ME, Bethel G, Milne S, Ainscough R, Almeida JP, Ambrose KD, Andrews TD, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beare DM, Beasley H, Beasley O, Bird CP, Blakey S, Bray-Allen S, Brook J, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Clark SY, Clark G, Clee CM, Clegg S, Cobley V, Collier RE, Collins JE, Colman LK, Corby NR, Coville GJ, Culley KM, Dhami P, Davies J, Dunn M, Earthrowl ME, Ellington AE, Evans KA, Faulkner L, Francis MD, Frankish A, Frankland J, French L, Garner P, Garnett J, Ghori MJ, Gilby LM, Gillson CJ, Glithero RJ, Grafham DV, Grant M, Gribble S, Griffiths C, Griffiths M, Hall R, Halls KS, Hammond S, Harley JL, Hart EA, Heath PD, Heathcott R, Holmes SJ, Howden PJ, Howe KL, Howell GR, Huckle E, Humphray SJ, Humphries MD, Hunt AR, Johnson CM, Joy AA, Kay M, Keenan SJ, Kimberley AM, King A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd CR, Lloyd DM, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, Maslen GL, Matthews L, McCann OT, McLaren SJ, McLay K, McMurray A, Moore MJ, Mullikin JC, Niblett D, Nickerson T, Novik KL, Oliver K, Overton-Larty EK, Parker A, Patel R, Pearce AV, Peck AI, Phillimore B, Phillips S, Plumb RW, Porter KM, Ramsey Y, Ranby SA, Rice CM, Ross MT, Searle SM, Sehra HK, Sheridan E, Skuce CD, Smith S, Smith M, Spraggon L, Squares SL, Steward CA, Sycamore N, Tamlyn-Hall G, Tester J, Theaker AJ, Thomas DW, Thorpe A, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, White SS, Whitehead SL, Whittaker H, Wild A, Willey DJ, Wilmer TE, Wood JM, Wray PW, Wyatt JC, Young L, Younger RM, Bentley DR, Coulson A, Durbin R, Hubbard T, Sulston JE, Dunham I, Rogers J, Beck S: The DNA sequence and analysis of human chromosome 6. Nature. 2003 Oct 23;425(6960):805-11. [Article]
  8. 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]
  9. Parker CG, Hunt J, Diener K, McGinley M, Soriano B, Keesler GA, Bray J, Yao Z, Wang XS, Kohno T, Lichenstein HS: Identification of stathmin as a novel substrate for p38 delta. Biochem Biophys Res Commun. 1998 Aug 28;249(3):791-6. [Article]
  10. Hale KK, Trollinger D, Rihanek M, Manthey CL: Differential expression and activation of p38 mitogen-activated protein kinase alpha, beta, gamma, and delta in inflammatory cell lineages. J Immunol. 1999 Apr 1;162(7):4246-52. [Article]
  11. Schoorlemmer J, Goldfarb M: Fibroblast growth factor homologous factors are intracellular signaling proteins. Curr Biol. 2001 May 15;11(10):793-7. [Article]
  12. Knebel A, Morrice N, Cohen P: A novel method to identify protein kinase substrates: eEF2 kinase is phosphorylated and inhibited by SAPK4/p38delta. EMBO J. 2001 Aug 15;20(16):4360-9. [Article]
  13. Buee-Scherrer V, Goedert M: Phosphorylation of microtubule-associated protein tau by stress-activated protein kinases in intact cells. FEBS Lett. 2002 Mar 27;515(1-3):151-4. [Article]
  14. Feijoo C, Campbell DG, Jakes R, Goedert M, Cuenda A: Evidence that phosphorylation of the microtubule-associated protein Tau by SAPK4/p38delta at Thr50 promotes microtubule assembly. J Cell Sci. 2005 Jan 15;118(Pt 2):397-408. Epub 2005 Jan 4. [Article]
  15. Kraft CA, Efimova T, Eckert RL: Activation of PKCdelta and p38delta MAPK during okadaic acid dependent keratinocyte apoptosis. Arch Dermatol Res. 2007 May;299(2):71-83. Epub 2007 Jan 26. [Article]
  16. Pani E, Ferrari S: p38MAPK delta controls c-Myb degradation in response to stress. Blood Cells Mol Dis. 2008 May-Jun;40(3):388-94. Epub 2007 Nov 19. [Article]
  17. Zahedi RP, Lewandrowski U, Wiesner J, Wortelkamp S, Moebius J, Schutz C, Walter U, Gambaryan S, Sickmann A: Phosphoproteome of resting human platelets. J Proteome Res. 2008 Feb;7(2):526-34. Epub 2007 Dec 19. [Article]
  18. Zhou X, Ferraris JD, Dmitrieva NI, Liu Y, Burg MB: MKP-1 inhibits high NaCl-induced activation of p38 but does not inhibit the activation of TonEBP/OREBP: opposite roles of p38alpha and p38delta. Proc Natl Acad Sci U S A. 2008 Apr 8;105(14):5620-5. doi: 10.1073/pnas.0801453105. Epub 2008 Mar 26. [Article]
  19. 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]
  20. Ozawa S, Ito S, Kato Y, Kubota E, Hata R: Human p38 delta MAP kinase mediates UV irradiation induced up-regulation of the gene expression of chemokine BRAK/CXCL14. Biochem Biophys Res Commun. 2010 Jun 11;396(4):1060-4. doi: 10.1016/j.bbrc.2010.05.072. Epub 2010 May 15. [Article]
  21. Efimova T: p38delta mitogen-activated protein kinase regulates skin homeostasis and tumorigenesis. Cell Cycle. 2010 Feb 1;9(3):498-05. [Article]
  22. Cuadrado A, Nebreda AR: Mechanisms and functions of p38 MAPK signalling. Biochem J. 2010 Aug 1;429(3):403-17. doi: 10.1042/BJ20100323. [Article]
  23. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  24. 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]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB05157KC706investigationalunknownDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails
DB01017Minocyclineapproved, investigationalunknowninhibitorDetails