Protein-coding gene in the species Homo sapiens
MAPK7 |
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Available structures |
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PDB | Ortholog search: PDBe RCSB |
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List of PDB id codes |
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2Q8Y, 4B99, 4IC7, 4IC8, 4ZSJ, 4ZSL, 5BYZ, 5BYY, 4ZSG |
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Identifiers |
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Aliases | MAPK7, BMK1, ERK4, ERK5, PRKM7, mitogen-activated protein kinase 7 |
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External IDs | OMIM: 602521; MGI: 1346347; HomoloGene: 2060; GeneCards: MAPK7; OMA:MAPK7 - orthologs |
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Gene location (Human) |
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![Chromosome 17 (human)](//upload.wikimedia.org/wikipedia/commons/thumb/0/00/Ideogram_human_chromosome_17.svg/300px-Ideogram_human_chromosome_17.svg.png) | Chr. | Chromosome 17 (human)[1] |
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| Band | 17p11.2 | Start | 19,377,721 bp[1] |
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End | 19,383,544 bp[1] |
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Gene location (Mouse) |
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![Chromosome 11 (mouse)](//upload.wikimedia.org/wikipedia/commons/thumb/a/a5/Ideogram_house_mouse_chromosome_11.svg/260px-Ideogram_house_mouse_chromosome_11.svg.png) | Chr. | Chromosome 11 (mouse)[2] |
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| Band | 11|11 B2 | Start | 61,488,812 bp[2] |
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End | 61,494,406 bp[2] |
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RNA expression pattern |
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Bgee | Human | Mouse (ortholog) |
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Top expressed in | - ganglionic eminence
- stromal cell of endometrium
- popliteal artery
- tibial arteries
- sural nerve
- ventricular zone
- ectocervix
- granulocyte
- right ovary
- skin of leg
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| Top expressed in | - granulocyte
- tail of embryo
- genital tubercle
- ventricular zone
- neural tube
- epiblast
- ganglionic eminence
- yolk sac
- internal carotid artery
- external carotid artery
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| More reference expression data |
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BioGPS | ![](//upload.wikimedia.org/wikipedia/commons/thumb/a/af/PBB_GE_MAPK7_207292_s_at_fs.png/250px-PBB_GE_MAPK7_207292_s_at_fs.png)
![](//upload.wikimedia.org/wikipedia/commons/thumb/3/32/PBB_GE_MAPK7_35617_at_fs.png/250px-PBB_GE_MAPK7_35617_at_fs.png) | More reference expression data |
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Gene ontology |
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Molecular function | - transferase activity
- nucleotide binding
- protein kinase activity
- mitogen-activated protein kinase binding
- kinase activity
- protein binding
- ATP binding
- protein serine/threonine kinase activity
- MAP kinase activity
| Cellular component | - cytoplasm
- cytosol
- PML body
- nucleoplasm
- nucleus
| Biological process | - cellular response to transforming growth factor beta stimulus
- negative regulation of endothelial cell apoptotic process
- cell differentiation
- phosphorylation
- negative regulation of ERK5 cascade
- cellular response to laminar fluid shear stress
- positive regulation of transcription from RNA polymerase II promoter in response to stress
- cellular response to growth factor stimulus
- negative regulation of apoptotic process
- regulation of angiogenesis
- negative regulation of response to cytokine stimulus
- protein phosphorylation
- negative regulation of MAP kinase activity
- peptidyl-serine phosphorylation
- cell cycle
- negative regulation of cyclic-nucleotide phosphodiesterase activity
- negative regulation of heterotypic cell-cell adhesion
- negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
- negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
- negative regulation of inflammatory response
- cAMP-mediated signaling
- signal transduction
- positive regulation of transcription by RNA polymerase II
- cellular response to hydrogen peroxide
- MAPK cascade
- axon guidance
- negative regulation of calcineurin-NFAT signaling cascade
- regulation of gene expression
- intracellular signal transduction
- cellular response to organic substance
| Sources:Amigo / QuickGO |
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Orthologs |
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Species | Human | Mouse |
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Entrez | | |
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Ensembl | | |
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UniProt | | |
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RefSeq (mRNA) | |
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NM_002749 NM_139032 NM_139033 NM_139034 |
| NM_001291033 NM_001291034 NM_001291035 NM_001291036 NM_001291037
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NM_011841 NM_001361989 |
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RefSeq (protein) | |
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NP_002740 NP_620601 NP_620602 NP_620603 |
| NP_001277962 NP_001277963 NP_001277964 NP_001277965 NP_001277966
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NP_035971 NP_001348918 |
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Location (UCSC) | Chr 17: 19.38 – 19.38 Mb | Chr 11: 61.49 – 61.49 Mb |
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PubMed search | [3] | [4] |
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Wikidata |
View/Edit Human | View/Edit Mouse |
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Mitogen-activated protein kinase 7 also known as MAP kinase 7 is an enzyme that in humans is encoded by the MAPK7 gene.[5][6]
Function
MAPK7 is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is specifically activated by mitogen-activated protein kinase kinase 5 (MAP2K5/MEK5). It is involved in the downstream signaling processes of various receptor molecules including receptor tyrosine kinases, and G protein-coupled receptors. In response to extracellular signals, this kinase translocates to the cell nucleus, where it regulates gene expression by phosphorylating, and activating different transcription factors. Four alternatively spliced transcript variants of this gene encoding two distinct isoforms have been reported.[7]
MAPK7 is also critical for cardiovascular development [8] and is essential for endothelial cell function.[9][10]
Interactions
MAPK7 has been shown to interact with:
ERK5 (= MAPK7) Inhibitors
XMD8-92 was one of the first described ERK5 inhibitors and was used in several pharmacological studies as tool compound. However, XMD8-92 hits BRD4 as an off-target[17] leading to false or inconclusive results. Consequently, ERK5 inhibitors with improved selectivity (void of the BRD4 off-target effect) such as AX15836[17] and BAY-885[18] were developed and should preferably be used for future pharmacological studies. BAY-885 fulfils the quality criteria for a 'Donated Chemical Probe' as defined by the Structural Genomics Consortium.[19] In 2020, it was demonstrated that ATP-competitive inhibitors paradoxically activate ERK5 signalling.[20] A recent review discussed the modulation of ERK5 activity as a therapeutic anti-cancer strategy.[21]
ERK5 (= MAPK7) Degrader
Based on a close analog of the ERK5 inhibitor BAY-885[18] the Proteolysis Targeting Chimera[22] (PROTAC) INY-06-061[23] was developed which allows to compare the phenotypes resulting from ERK5 inhibition versus degradation.
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000166484 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000001034 – 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.
- ^ Purandare SM, Lee JD, Patel PI (March 1999). "Assignment of big MAP kinase (PRKM7) to human chromosome 17 band p11.2 with somatic cell hybrids". Cytogenetics and Cell Genetics. 83 (3–4): 258–259. doi:10.1159/000015199. PMID 10072598. S2CID 31186896.
- ^ a b 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): 12665–12669. doi:10.1074/jbc.270.21.12665. PMID 7759517.
- ^ "Entrez Gene: MAPK7 mitogen-activated protein kinase 7".
- ^ Hayashi M, Lee JD (December 2004). "Role of the BMK1/ERK5 signaling pathway: lessons from knockout mice". Journal of Molecular Medicine. 82 (12): 800–808. doi:10.1007/s00109-004-0602-8. PMID 15517128. S2CID 8499230.
- ^ Roberts OL, Holmes K, Müller J, Cross DA, Cross MJ (December 2009). "ERK5 and the regulation of endothelial cell function". Biochemical Society Transactions. 37 (Pt 6): 1254–1259. doi:10.1042/BST0371254. PMID 19909257.
- ^ Roberts OL, Holmes K, Müller J, Cross DA, Cross MJ (September 2010). "ERK5 is required for VEGF-mediated survival and tubular morphogenesis of primary human microvascular endothelial cells". Journal of Cell Science. 123 (Pt 18): 3189–3200. doi:10.1242/jcs.072801. PMID 20736307.
- ^ English JM, Pearson G, Hockenberry T, Shivakumar L, White MA, Cobb MH (October 1999). "Contribution of the ERK5/MEK5 pathway to Ras/Raf signaling and growth control". The Journal of Biological Chemistry. 274 (44): 31588–31592. doi:10.1074/jbc.274.44.31588. PMID 10531364.
- ^ Cameron SJ, Malik S, Akaike M, Lerner-Marmarosh N, Yan C, Lee JD, et al. (May 2003). "Regulation of epidermal growth factor-induced connexin 43 gap junction communication by big mitogen-activated protein kinase1/ERK5 but not ERK1/2 kinase activation". The Journal of Biological Chemistry. 278 (20): 18682–18688. doi:10.1074/jbc.M213283200. PMID 12637502.
- ^ a b Yang CC, Ornatsky OI, McDermott JC, Cruz TF, Prody CA (October 1998). "Interaction of myocyte enhancer factor 2 (MEF2) with a mitogen-activated protein kinase, ERK5/BMK1". Nucleic Acids Research. 26 (20): 4771–4777. doi:10.1093/nar/26.20.4771. PMC 147902. PMID 9753748.
- ^ Buschbeck M, Eickhoff J, Sommer MN, Ullrich A (August 2002). "Phosphotyrosine-specific phosphatase PTP-SL regulates the ERK5 signaling pathway". The Journal of Biological Chemistry. 277 (33): 29503–29509. doi:10.1074/jbc.M202149200. PMID 12042304.
- ^ Hayashi M, Tapping RI, Chao TH, Lo JF, King CC, Yang Y, Lee JD (March 2001). "BMK1 mediates growth factor-induced cell proliferation through direct cellular activation of serum and glucocorticoid-inducible kinase". The Journal of Biological Chemistry. 276 (12): 8631–8634. doi:10.1074/jbc.C000838200. PMID 11254654.
- ^ Zheng Q, Yin G, Yan C, Cavet M, Berk BC (March 2004). "14-3-3beta binds to big mitogen-activated protein kinase 1 (BMK1/ERK5) and regulates BMK1 function". The Journal of Biological Chemistry. 279 (10): 8787–8791. doi:10.1074/jbc.M310212200. PMID 14679215.
- ^ a b Lin EC, Amantea CM, Nomanbhoy TK, Weissig H, Ishiyama J, Hu Y, et al. (October 2016). "ERK5 kinase activity is dispensable for cellular immune response and proliferation". Proceedings of the National Academy of Sciences of the United States of America. 113 (42): 11865–11870. Bibcode:2016PNAS..11311865L. doi:10.1073/pnas.1609019113. PMC 5081620. PMID 27679845.
- ^ a b Nguyen D, Lemos C, Wortmann L, Eis K, Holton SJ, Boemer U, et al. (January 2019). "Discovery and Characterization of the Potent and Highly Selective (Piperidin-4-yl)pyrido[3,2- d]pyrimidine Based in Vitro Probe BAY-885 for the Kinase ERK5". Journal of Medicinal Chemistry. 62 (2): 928–940. doi:10.1021/acs.jmedchem.8b01606. PMID 30563338. S2CID 56478089.
- ^ "Donated chemical probes". SGC. 2018-06-12. Retrieved 2023-07-26.
- ^ "Small molecule ERK5 kinase inhibitors paradoxically activate ERK5 signalling: be careful what you wish for…". Biochemical Society Transactions.
- ^ Miller, Duncan C.; Harnor, Suzannah J.; Martin, Mathew P.; Noble, Richard A.; Wedge, Stephen R.; Cano, Celine (2023). "Modulation of ERK5 Activity as a Therapeutic Anti-Cancer Strategy". Journal of Medicinal Chemistry. 66 (7): 4491–4502. doi:10.1021/acs.jmedchem.3c00072. PMC 10108346. PMID 37002872.
- ^ Luh LM, Scheib U, Juenemann K, Wortmann L, Brands M, Cromm PM (September 2020). "Prey for the Proteasome: Targeted Protein Degradation-A Medicinal Chemist's Perspective". Angewandte Chemie. 59 (36): 15448–15466. doi:10.1002/anie.202004310. PMC 7496094. PMID 32428344.
- ^ You I, Donovan KA, Krupnick NM, Boghossian AS, Rees MG, Ronan MM, et al. (November 2022). "Acute pharmacological degradation of ERK5 does not inhibit cellular immune response or proliferation". Cell Chemical Biology. 29 (11): 1630–1638.e7. doi:10.1016/j.chembiol.2022.09.004. PMC 9675722. PMID 36220104.
Further reading
- Lee JD, Ulevitch RJ, Han J (August 1995). "Primary structure of BMK1: a new mammalian map kinase". Biochemical and Biophysical Research Communications. 213 (2): 715–724. doi:10.1006/bbrc.1995.2189. PMID 7646528.
- Warn-Cramer BJ, Lampe PD, Kurata WE, Kanemitsu MY, Loo LW, Eckhart W, Lau AF (February 1996). "Characterization of the mitogen-activated protein kinase phosphorylation sites on the connexin-43 gap junction protein". The Journal of Biological Chemistry. 271 (7): 3779–3786. doi:10.1074/jbc.271.7.3779. PMID 8631994.
- Kato Y, Kravchenko VV, Tapping RI, Han J, Ulevitch RJ, Lee JD (December 1997). "BMK1/ERK5 regulates serum-induced early gene expression through transcription factor MEF2C". The EMBO Journal. 16 (23): 7054–7066. doi:10.1093/emboj/16.23.7054. PMC 1170308. PMID 9384584.
- English JM, Pearson G, Baer R, Cobb MH (February 1998). "Identification of substrates and regulators of the mitogen-activated protein kinase ERK5 using chimeric protein kinases". The Journal of Biological Chemistry. 273 (7): 3854–3860. doi:10.1074/jbc.273.7.3854. PMID 9461566.
- Grunwald ME, Yu WP, Yu HH, Yau KW (April 1998). "Identification of a domain on the beta-subunit of the rod cGMP-gated cation channel that mediates inhibition by calcium-calmodulin". The Journal of Biological Chemistry. 273 (15): 9148–9157. doi:10.1074/jbc.273.15.9148. PMID 9535905.
- Warn-Cramer BJ, Cottrell GT, Burt JM, Lau AF (April 1998). "Regulation of connexin-43 gap junctional intercellular communication by mitogen-activated protein kinase". The Journal of Biological Chemistry. 273 (15): 9188–9196. doi:10.1074/jbc.273.15.9188. PMID 9535909.
- Yang CC, Ornatsky OI, McDermott JC, Cruz TF, Prody CA (October 1998). "Interaction of myocyte enhancer factor 2 (MEF2) with a mitogen-activated protein kinase, ERK5/BMK1". Nucleic Acids Research. 26 (20): 4771–4777. doi:10.1093/nar/26.20.4771. PMC 147902. PMID 9753748.
- Kato Y, Tapping RI, Huang S, Watson MH, Ulevitch RJ, Lee JD (October 1998). "Bmk1/Erk5 is required for cell proliferation induced by epidermal growth factor". Nature. 395 (6703): 713–716. Bibcode:1998Natur.395..713K. doi:10.1038/27234. PMID 9790194. S2CID 204997780.
- Zhao M, New L, Kravchenko VV, Kato Y, Gram H, di Padova F, et al. (January 1999). "Regulation of the MEF2 family of transcription factors by p38". Molecular and Cellular Biology. 19 (1): 21–30. doi:10.1128/mcb.19.1.21. PMC 83862. PMID 9858528.
- Kamakura S, Moriguchi T, Nishida E (September 1999). "Activation of the protein kinase ERK5/BMK1 by receptor tyrosine kinases. Identification and characterization of a signaling pathway to the nucleus". The Journal of Biological Chemistry. 274 (37): 26563–26571. doi:10.1074/jbc.274.37.26563. PMID 10473620.
- English JM, Pearson G, Hockenberry T, Shivakumar L, White MA, Cobb MH (October 1999). "Contribution of the ERK5/MEK5 pathway to Ras/Raf signaling and growth control". The Journal of Biological Chemistry. 274 (44): 31588–31592. doi:10.1074/jbc.274.44.31588. PMID 10531364.
- Fukuhara S, Marinissen MJ, Chiariello M, Gutkind JS (July 2000). "Signaling from G protein-coupled receptors to ERK5/Big MAPK 1 involves Galpha q and Galpha 12/13 families of heterotrimeric G proteins. Evidence for the existence of a novel Ras AND Rho-independent pathway". The Journal of Biological Chemistry. 275 (28): 21730–21736. doi:10.1074/jbc.M002410200. PMID 10781600.
- Kato Y, Zhao M, Morikawa A, Sugiyama T, Chakravortty D, Koide N, et al. (June 2000). "Big mitogen-activated kinase regulates multiple members of the MEF2 protein family". The Journal of Biological Chemistry. 275 (24): 18534–18540. doi:10.1074/jbc.M001573200. PMID 10849446.
- Yan C, Luo H, Lee JD, Abe J, Berk BC (April 2001). "Molecular cloning of mouse ERK5/BMK1 splice variants and characterization of ERK5 functional domains". The Journal of Biological Chemistry. 276 (14): 10870–10878. doi:10.1074/jbc.M009286200. PMID 11139578.
- Hayashi M, Tapping RI, Chao TH, Lo JF, King CC, Yang Y, Lee JD (March 2001). "BMK1 mediates growth factor-induced cell proliferation through direct cellular activation of serum and glucocorticoid-inducible kinase". The Journal of Biological Chemistry. 276 (12): 8631–8634. doi:10.1074/jbc.C000838200. PMID 11254654.
- Dong F, Gutkind JS, Larner AC (April 2001). "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". The Journal of Biological Chemistry. 276 (14): 10811–10816. doi:10.1074/jbc.M008748200. PMID 11278431.
- Esparís-Ogando A, Díaz-Rodríguez E, Montero JC, Yuste L, Crespo P, Pandiella A (January 2002). "Erk5 participates in neuregulin signal transduction and is constitutively active in breast cancer cells overexpressing ErbB2". Molecular and Cellular Biology. 22 (1): 270–285. doi:10.1128/MCB.22.1.270-285.2002. PMC 134212. PMID 11739740.
External links
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Classification | |
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Kinetics | |
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