MAPK7

MAPK7
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2Q8Y, 4B99, 4IC7, 4IC8, 4ZSJ, 4ZSL, 5BYZ, 5BYY, 4ZSG
Identifiers
Aliases	MAPK7, BMK1, ERK4, ERK5, PRKM7, mitogen-activated protein kinase 7
External IDs	OMIM: 602521 MGI: 1346347 HomoloGene: 2060 GeneCards: MAPK7
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17p11.2 Start 19,377,721 bp[1] End 19,383,544 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11|11 B2 Start 61,488,812 bp[2] End 61,494,406 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ganglionic eminence stromal cell of endometrium popliteal artery sural nerve left coronary artery left uterine tube right coronary artery right lung skin of abdomen gastric mucosa Top expressed in neural tube ganglionic eminence yolk sac internal carotid artery external carotid artery spinal ganglia lens condyle cerebellar cortex lip More reference expression data BioGPS More reference expression data
Gene ontology 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
Orthologs Species Human Mouse Entrez 5598 23939 Ensembl ENSG00000166484 ENSMUSG00000001034 UniProt Q13164 Q9WVS8 RefSeq (mRNA) NM_002749 NM_139032 NM_139033 NM_139034 NM_001291033 NM_001291034 NM_001291035 NM_001291036 NM_001291037 NM_011841 NM_001361989 RefSeq (protein) NP_002740 NP_620601 NP_620602 NP_620603 NP_001277962 NP_001277963 NP_001277964 NP_001277965 NP_001277966 NP_035971 NP_001348918 Location (UCSC) Chr 17: 19.38 – 19.38 Mb Chr 11: 61.49 – 61.49 Mb PubMed search [3] [4]
Wikidata
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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

Further reading

External links

• MAP Kinase Resource Archived 2021-04-15 at the Wayback Machine.