MAP2K5

MAP2K5
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2NPT, 2O2V, 4IC7
Identifiers
Aliases	MAP2K5, HsT17454, MAPKK5, MEK5, PRKMK5, mitogen-activated protein kinase kinase 5
External IDs	OMIM: 602520 MGI: 1346345 HomoloGene: 115933 GeneCards: MAP2K5
Gene location (Human)
Chr.	Chromosome 15 (human)[1]
End	67,807,117 bp[1]
Gene location (Mouse)
Chr.	Chromosome 9 (mouse)[2]
End	63,377,902 bp[2]
RNA expression pattern
	; ; ; ;
	More reference expression data
Gene ontology
Molecular function	• transferase activity; • protein kinase activity; • nucleotide binding; • metal ion binding; • kinase activity; • GO:0001948 protein binding; • protein tyrosine kinase activity; • ATP binding; • protein serine/threonine kinase activity; • MAP kinase kinase activity;
Cellular component	• cytoplasm; • cytosol; • spindle; • cell nucleus; • intracellular;
Biological process	• negative regulation of chemokine (C-X-C motif) ligand 2 production; • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; • phosphorylation; • positive regulation of epithelial cell proliferation; • cellular response to laminar fluid shear stress; • cellular response to growth factor stimulus; • negative regulation of transcription from RNA polymerase II promoter; • negative regulation of interleukin-8 biosynthetic process; • positive regulation of protein metabolic process; • negative regulation of response to cytokine stimulus; • MAPK cascade; • ERK5 cascade; • negative regulation of cell migration involved in sprouting angiogenesis; • protein phosphorylation; • heart development; • positive regulation of cell growth; • activation of MAPK activity; • peptidyl-tyrosine phosphorylation; • negative regulation of heterotypic cell-cell adhesion; • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; • negative regulation of NF-kappaB transcription factor activity; • signal transduction; • positive regulation of transcription from RNA polymerase II promoter; • regulation of mitotic cell cycle; • signal transduction by protein phosphorylation; • stress-activated protein kinase signaling cascade; • activation of protein kinase activity; • regulation of apoptotic process;
	Sources:Amigo / QuickGO
Orthologs
	5607
	23938
	ENSG00000137764
	ENSMUSG00000058444
	Q13163
	Q9WVS7
	NM_001206804; NM_002757; NM_145160; NM_145161; NM_145162
	NM_011840; NM_001364492; NM_001364493; NM_001364494
	NP_001193733; NP_002748; NP_660143
	NP_035970; NP_001351421; NP_001351422; NP_001351423
	Wikidata
View/Edit Human	View/Edit Mouse

Dual specificity mitogen-activated protein kinase kinase 5 is an enzyme that in humans is encoded by the MAP2K5 gene.[5][6]

Function

The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase specifically interacts with and activates MAPK7/ERK5. This kinase itself can be phosphorylated and activated by MAP3K3/MEKK3, as well as by atypical protein kinase C isoforms (aPKCs). The signal cascade mediated by this kinase is involved in growth factor stimulated cell proliferation and muscle cell differentiation. Four alternatively spliced transcript variants of this gene encoding distinct isoforms have been described.[6]

Upstream

This kinase itself can be phosphorylated and activated by MAP3K3/MEKK3, as well as by atypical protein kinase C isoforms (aPKCs).

Downstream

This kinase specifically interacts with and activates MAPK7/ERK5.

Interactions

MAP2K5 has been shown to interact with MAPK7,[5] MAP3K2,[7] Protein kinase Mζ[8] and MAP3K3.[7][9]

gollark: Draggable points are quite easy. At the extreme end you could just use a canvas or something.

gollark: Oh, these aren't *smooth* curves, oh bee oh apioform.

gollark: Simply allow dragging points around.

gollark: Update: it is degree n - 1 you need, as I just determined via methods.

gollark: No, it's probably not a mere Lagrange interpolation limitation, that would make no sense.

References

GRCh38: Ensembl release 89: ENSG00000137764 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000058444 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
Zhou G, Bao ZQ, Dixon JE (May 1995). "Components of a new human protein kinase signal transduction pathway". The Journal of Biological Chemistry. 270 (21): 12665–9. doi:10.1074/jbc.270.21.12665. PMID 7759517.
"Entrez Gene: MAP2K5 mitogen-activated protein kinase kinase 5".
Sun W, Kesavan K, Schaefer BC, Garrington TP, Ware M, Johnson NL, Gelfand EW, Johnson GL (Feb 2001). "MEKK2 associates with the adapter protein Lad/RIBP and regulates the MEK5-BMK1/ERK5 pathway". The Journal of Biological Chemistry. 276 (7): 5093–100. doi:10.1074/jbc.M003719200. PMID 11073940.
Diaz-Meco MT, Moscat J (Feb 2001). "MEK5, a new target of the atypical protein kinase C isoforms in mitogenic signaling". Molecular and Cellular Biology. 21 (4): 1218–27. doi:10.1128/MCB.21.4.1218-1227.2001. PMC 99575. PMID 11158308.
Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G (Feb 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nature Cell Biology. 6 (2): 97–105. doi:10.1038/ncb1086. PMID 14743216.

English JM, Vanderbilt CA, Xu S, Marcus S, Cobb MH (Dec 1995). "Isolation of MEK5 and differential expression of alternatively spliced forms". The Journal of Biological Chemistry. 270 (48): 28897–902. doi:10.1074/jbc.270.48.28897. PMID 7499418.
Kato Y, Kravchenko VV, Tapping RI, Han J, Ulevitch RJ, Lee JD (Dec 1997). "BMK1/ERK5 regulates serum-induced early gene expression through transcription factor MEF2C". The EMBO Journal. 16 (23): 7054–66. doi:10.1093/emboj/16.23.7054. PMC 1170308. PMID 9384584.
Kato Y, Tapping RI, Huang S, Watson MH, Ulevitch RJ, Lee JD (Oct 1998). "Bmk1/Erk5 is required for cell proliferation induced by epidermal growth factor". Nature. 395 (6703): 713–6. doi:10.1038/27234. PMID 9790194.
English JM, Pearson G, Hockenberry T, Shivakumar L, White MA, Cobb MH (Oct 1999). "Contribution of the ERK5/MEK5 pathway to Ras/Raf signaling and growth control". The Journal of Biological Chemistry. 274 (44): 31588–92. doi:10.1074/jbc.274.44.31588. PMID 10531364.
Chao TH, Hayashi M, Tapping RI, Kato Y, Lee JD (Dec 1999). "MEKK3 directly regulates MEK5 activity as part of the big mitogen-activated protein kinase 1 (BMK1) signaling pathway". The Journal of Biological Chemistry. 274 (51): 36035–8. doi:10.1074/jbc.274.51.36035. PMID 10593883.
Sun W, Kesavan K, Schaefer BC, Garrington TP, Ware M, Johnson NL, Gelfand EW, Johnson GL (Feb 2001). "MEKK2 associates with the adapter protein Lad/RIBP and regulates the MEK5-BMK1/ERK5 pathway". The Journal of Biological Chemistry. 276 (7): 5093–100. doi:10.1074/jbc.M003719200. PMID 11073940.
Diaz-Meco MT, Moscat J (Feb 2001). "MEK5, a new target of the atypical protein kinase C isoforms in mitogenic signaling". Molecular and Cellular Biology. 21 (4): 1218–27. doi:10.1128/MCB.21.4.1218-1227.2001. PMC 99575. PMID 11158308.
Nicol RL, Frey N, Pearson G, Cobb M, Richardson J, Olson EN (Jun 2001). "Activated MEK5 induces serial assembly of sarcomeres and eccentric cardiac hypertrophy". The EMBO Journal. 20 (11): 2757–67. doi:10.1093/emboj/20.11.2757. PMC 125475. PMID 11387209.
Dinev D, Jordan BW, Neufeld B, Lee JD, Lindemann D, Rapp UR, Ludwig S (Sep 2001). "Extracellular signal regulated kinase 5 (ERK5) is required for the differentiation of muscle cells". EMBO Reports. 2 (9): 829–34. doi:10.1093/embo-reports/kve177. PMC 1084032. PMID 11520859.
Weldon CB, Scandurro AB, Rolfe KW, Clayton JL, Elliott S, Butler NN, Melnik LI, Alam J, McLachlan JA, Jaffe BM, Beckman BS, Burow ME (Aug 2002). "Identification of mitogen-activated protein kinase kinase as a chemoresistant pathway in MCF-7 cells by using gene expression microarray". Surgery. 132 (2): 293–301. doi:10.1067/msy.2002.125389. PMID 12219026.
Mehta PB, Jenkins BL, McCarthy L, Thilak L, Robson CN, Neal DE, Leung HY (Mar 2003). "MEK5 overexpression is associated with metastatic prostate cancer, and stimulates proliferation, MMP-9 expression and invasion". Oncogene. 22 (9): 1381–9. doi:10.1038/sj.onc.1206154. PMID 12618764.
Mody N, Campbell DG, Morrice N, Peggie M, Cohen P (Jun 2003). "An analysis of the phosphorylation and activation of extracellular-signal-regulated protein kinase 5 (ERK5) by mitogen-activated protein kinase kinase 5 (MKK5) in vitro". The Biochemical Journal. 372 (Pt 2): 567–75. doi:10.1042/BJ20030193. PMC 1223423. PMID 12628002.
Huang J, Tu Z, Lee FS (Apr 2003). "Mutations in protein kinase subdomain X differentially affect MEKK2 and MEKK1 activity". Biochemical and Biophysical Research Communications. 303 (2): 532–40. doi:10.1016/S0006-291X(03)00387-5. PMID 12659851.
Lamark T, Perander M, Outzen H, Kristiansen K, Øvervatn A, Michaelsen E, Bjørkøy G, Johansen T (Sep 2003). "Interaction codes within the family of mammalian Phox and Bem1p domain-containing proteins". The Journal of Biological Chemistry. 278 (36): 34568–81. doi:10.1074/jbc.M303221200. PMID 12813044.
Cameron SJ, Abe J, Malik S, Che W, Yang J (Jan 2004). "Differential role of MEK5alpha and MEK5beta in BMK1/ERK5 activation". The Journal of Biological Chemistry. 279 (2): 1506–12. doi:10.1074/jbc.M308755200. PMID 14583600.
Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G (Feb 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nature Cell Biology. 6 (2): 97–105. doi:10.1038/ncb1086. PMID 14743216.
Raviv Z, Kalie E, Seger R (Apr 2004). "MEK5 and ERK5 are localized in the nuclei of resting as well as stimulated cells, while MEKK2 translocates from the cytosol to the nucleus upon stimulation". Journal of Cell Science. 117 (Pt 9): 1773–84. doi:10.1242/jcs.01040. PMID 15075238.

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000137764 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000058444 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid7759517-5] Zhou G, Bao ZQ, Dixon JE (May 1995). "Components of a new human protein kinase signal transduction pathway". The Journal of Biological Chemistry. 270 (21): 12665–9. doi:10.1074/jbc.270.21.12665. PMID 7759517.

[entrez-6] "Entrez Gene: MAP2K5 mitogen-activated protein kinase kinase 5".

[pmid11073940-7] Sun W, Kesavan K, Schaefer BC, Garrington TP, Ware M, Johnson NL, Gelfand EW, Johnson GL (Feb 2001). "MEKK2 associates with the adapter protein Lad/RIBP and regulates the MEK5-BMK1/ERK5 pathway". The Journal of Biological Chemistry. 276 (7): 5093–100. doi:10.1074/jbc.M003719200. PMID 11073940.

[pmid11158308-8] Diaz-Meco MT, Moscat J (Feb 2001). "MEK5, a new target of the atypical protein kinase C isoforms in mitogenic signaling". Molecular and Cellular Biology. 21 (4): 1218–27. doi:10.1128/MCB.21.4.1218-1227.2001. PMC 99575. PMID 11158308.

[pmid14743216-9] Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G (Feb 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nature Cell Biology. 6 (2): 97–105. doi:10.1038/ncb1086. PMID 14743216.

Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)