MAPK1

Mitogen-activated protein kinase 1, also known as MAPK1, p42MAPK, and ERK2, is an enzyme that in humans is encoded by the MAPK1 gene.[5]

MAPK1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1PME, 1TVO, 1WZY, 2OJG, 2OJI, 2OJJ, 2Y9Q, 3D42, 3D44, 3I5Z, 3I60, 3SA0, 3TEI, 3W55, 4FMQ, 4FUX, 4FUY, 4FV0, 4FV1, 4FV2, 4FV3, 4FV4, 4FV5, 4FV6, 4FV7, 4FV8, 4FV9, 4G6N, 4G6O, 4H3P, 4H3Q, 4IZ5, 4IZ7, 4IZA, 4N0S, 4NIF, 4O6E, 4QTA, 4QTE, 4ZZM, 4ZZN, 4ZZO, 5BUE, 5BUI, 5BUJ, 4QP1, 4QP2, 4QP3, 4QP4, 4QP6, 4QP7, 4QP8, 4QP9, 4QPA, 4XJ0, 5BVD, 5BVE, 5BVF, 5AX3, 4ZXT, 5K4I
Identifiers
Aliases	MAPK1, ERK, ERK-2, ERK2, ERT1, MAPK2, P42MAPK, PRKM1, PRKM2, p38, p40, p41, p41mapk, p42-MAPK, mitogen-activated protein kinase 1
External IDs	OMIM: 176948 MGI: 1346858 HomoloGene: 37670 GeneCards: MAPK1
Gene location (Human) Chr. Chromosome 22 (human)[1] Band 22q11.22 Start 21,754,500 bp[1] End 21,867,680 bp[1]
Gene location (Mouse) Chr. Chromosome 16 (mouse)[2] Band 16 A3|16 10.53 cM Start 16,983,382 bp[2] End 17,047,453 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • phosphatase binding • ATP binding • protein kinase activity • transcription factor binding • transferase activity • mitogen-activated protein kinase kinase kinase binding • phosphotyrosine residue binding • GO:0001948 protein binding • protein kinase binding • DNA binding • nucleotide binding • RNA polymerase II carboxy-terminal domain kinase activity • protein serine/threonine kinase activity • kinase activity • identical protein binding • MAP kinase activity • double-stranded DNA binding • MAP kinase kinase activity Cellular component • cytoplasm • cytosol • focal adhesion • microtubule organizing center • mitochondrion • caveola • dendrite cytoplasm • cytoskeleton • cell nucleus • extracellular exosome • perikaryon • late endosome • Golgi apparatus • spindle • axon • early endosome • mitotic spindle • pseudopodia • extracellular region • nucleoplasm • azurophil granule lumen • ficolin-1-rich granule lumen • cell membrane • GO:0097483, GO:0097481 postsynaptic density • membrane • macromolecular complex Biological process • caveolin-mediated endocytosis • positive regulation of telomere capping • response to exogenous dsRNA • cardiac neural crest cell development involved in heart development • positive regulation of translation • cellular response to DNA damage stimulus • platelet activation • Fc-epsilon receptor signaling pathway • protein phosphorylation • face development • cellular response to granulocyte macrophage colony-stimulating factor stimulus • regulation of sequence-specific DNA binding transcription factor activity • animal organ morphogenesis • cell cycle • ERBB signaling pathway • apoptotic process • B cell receptor signaling pathway • regulation of transcription, DNA-templated • regulation of protein stability • Fc-gamma receptor signaling pathway involved in phagocytosis • thymus development • negative regulation of cell differentiation • ERK1 and ERK2 cascade • labyrinthine layer blood vessel development • transcription, DNA-templated • positive regulation of transcription, DNA-templated • heart development • GO:0022415 viral process • response to toxic substance • regulation of stress-activated MAPK cascade • chemical synaptic transmission • JAK-STAT cascade involved in growth hormone signaling pathway • cytosine metabolic process • phosphorylation • outer ear morphogenesis • response to estrogen • chemotaxis • response to lipopolysaccharide • thyroid gland development • response to epidermal growth factor • activation of MAPK activity • positive regulation of telomerase activity • nociception • peptidyl-threonine phosphorylation • trachea formation • lipopolysaccharide-mediated signaling pathway • mammary gland epithelial cell proliferation • GO:0007243 intracellular signal transduction • lung morphogenesis • neural crest cell development • positive regulation of cell migration • regulation of early endosome to late endosome transport • response to stress • positive regulation of telomere maintenance via telomerase • MAPK cascade • axon guidance • fibroblast growth factor receptor signaling pathway • positive regulation of peptidyl-threonine phosphorylation • peptidyl-serine phosphorylation • positive regulation of cell proliferation • regulation of cellular response to heat • Bergmann glial cell differentiation • regulation of Golgi inheritance • T cell receptor signaling pathway • regulation of cytoskeleton organization • signal transduction • long-term synaptic potentiation • regulation of ossification • regulation of phosphatidylinositol 3-kinase signaling • neutrophil degranulation • regulation of gene expression • cellular response to organic substance • aging • learning or memory • positive regulation of gene expression • diadenosine tetraphosphate biosynthetic process • regulation of cellular pH • cellular response to amino acid starvation • cellular response to reactive oxygen species • response to nicotine • decidualization • stress-activated MAPK cascade • positive regulation of cardiac muscle cell proliferation • cellular response to cadmium ion • cellular response to tumor necrosis factor • cellular response to dopamine • activation of MAPKK activity • positive regulation of protein import into nucleus Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	5594	26413
Ensembl	ENSG00000100030	ENSMUSG00000063358
UniProt	P28482	P63085
RefSeq (mRNA)	NM_138957 NM_002745	NM_001038663 NM_011949 NM_001357115
RefSeq (protein)	NP_002736 NP_620407	NP_001033752 NP_036079 NP_001344044
Location (UCSC)	Chr 22: 21.75 – 21.87 Mb	Chr 16: 16.98 – 17.05 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

The protein encoded by this gene is a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), 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. The activation of this kinase requires its phosphorylation by upstream kinases. Upon activation, this kinase translocates to the nucleus of the stimulated cells, where it phosphorylates nuclear targets. Two alternatively spliced transcript variants encoding the same protein, but differing in the UTRs, have been reported for this gene.[6] MAPK1 contains multiple amino acid sites that are phosphorylated and ubiquitinated.[7]

Model organisms

Mapk1 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Abnormal
Recessive lethal study	Abnormal
Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal[8]
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Abnormal[9]
Plasma immunoglobulins	Normal
Haematology	Normal
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Tail epidermis wholemount	Normal
Skin Histopathology	Normal
Brain histopathology	Normal
Salmonella infection	Normal[10]
Citrobacter infection	Normal[11]
All tests and analysis from[12][13]

Model organisms have been used in the study of MAPK1 function. A conditional knockout mouse line, called Mapk1^{tm1a(EUCOMM)Wtsi}[14][15] was generated as part of the International Knockout Mouse Consortium program—a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[16][17][18]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[12][19] Twenty seven tests were carried out on mutant mice and three significant abnormalities were observed.[12] No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice and males had decreased circulating amylase levels.[12]

Conditional deletion of Mapk1 in B cells showed a role for MAPK1 in T-cell-dependent antibody production.[20] A dominant gain-of-function mutant of Mapk1 in transgenic mice showed a role for MAPK1 in T-cell development.[21] Conditional inactivation of Mapk1 in neural progenitor cells of the developing cortex lead to a reduction of cortical thickness and reduced proliferation in neural progenitor cells.[22]

Interactions

MAPK1 has been shown to interact with:

• ADAM17,[23]
• CIITA,[24]
• DUSP1,[25][26]
• DUSP22,[27]
• DUSP3,[28]
• ELK1,[29][30]
• FHL2,[31]
• HDAC4,[32]
• MAP2K1,[33][34][35][36][37][38]
• MAP3K1[39]
• MAPK14,[33][40]
• MKNK1,[41]
• MKNK2,[41][42]
• Myc,[43][44][45]
• NEK2,[46]
• PEA15,[47]
• PTPN7,[48][49]
• Phosphatidylethanolamine binding protein 1,[35]
• RPS6KA1,[29][50][51]
• RPS6KA2,[51][52]
• RPS6KA3,[50][52]
• SORBS3,[53]
• STAT5A,[54][55]
• TNIP1,[56]
• TOB1,[57]
• TSC2,[58]
• UBR5,[29] and
• VAV1.[59][60]

Clinical significance

Mutations in MAPK1 are implicated in many types of cancer.[61]

See also

• Extracellular signal-regulated kinases

References

1. GRCh38: Ensembl release 89: ENSG00000100030 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000063358 - 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.
5. Owaki H, Makar R, Boulton TG, Cobb MH, Geppert TD (February 1992). "Extracellular signal-regulated kinases in T cells: characterization of human ERK1 and ERK2 cDNAs". Biochem. Biophys. Res. Commun. 182 (3): 1416–22. doi:10.1016/0006-291X(92)91891-S. PMID 1540184.
6. "Entrez Gene: MAPK1 mitogen-activated protein kinase 1".
7. "ERK2 (human)". www.phosphosite.org. Retrieved 2020-10-31.
8. "Dysmorphology data for Mapk1". Wellcome Trust Sanger Institute.
9. "Clinical chemistry data for Mapk1". Wellcome Trust Sanger Institute.
10. "Salmonella infection data for Mapk1". Wellcome Trust Sanger Institute.
11. "Citrobacter infection data for Mapk1". Wellcome Trust Sanger Institute.
12. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
13. Mouse Resources Portal, Wellcome Trust Sanger Institute.
14. "International Knockout Mouse Consortium".
15. "Mouse Genome Informatics".
16. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
17. Dolgin E (2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
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19. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biol. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
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23. Díaz-Rodríguez E, Montero JC, Esparís-Ogando A, Yuste L, Pandiella A (June 2002). "Extracellular signal-regulated kinase phosphorylates tumor necrosis factor alpha-converting enzyme at threonine 735: a potential role in regulated shedding". Mol. Biol. Cell. 13 (6): 2031–44. doi:10.1091/mbc.01-11-0561. PMC 117622. PMID 12058067.
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25. Slack DN, Seternes OM, Gabrielsen M, Keyse SM (May 2001). "Distinct binding determinants for ERK2/p38alpha and JNK map kinases mediate catalytic activation and substrate selectivity of map kinase phosphatase-1". J. Biol. Chem. 276 (19): 16491–500. doi:10.1074/jbc.M010966200. PMID 11278799.
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28. Todd JL, Tanner KG, Denu JM (May 1999). "Extracellular regulated kinases (ERK) 1 and ERK2 are authentic substrates for the dual-specificity protein-tyrosine phosphatase VHR. A novel role in down-regulating the ERK pathway". J. Biol. Chem. 274 (19): 13271–80. doi:10.1074/jbc.274.19.13271. PMID 10224087.
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31. Purcell NH, Darwis D, Bueno OF, Müller JM, Schüle R, Molkentin JD (February 2004). "Extracellular signal-regulated kinase 2 interacts with and is negatively regulated by the LIM-only protein FHL2 in cardiomyocytes". Mol. Cell. Biol. 24 (3): 1081–95. doi:10.1128/mcb.24.3.1081-1095.2004. PMC 321437. PMID 14729955.
32. Zhou X, Richon VM, Wang AH, Yang XJ, Rifkind RA, Marks PA (December 2000). "Histone deacetylase 4 associates with extracellular signal-regulated kinases 1 and 2, and its cellular localization is regulated by oncogenic Ras". Proc. Natl. Acad. Sci. U.S.A. 97 (26): 14329–33. doi:10.1073/pnas.250494697. PMC 18918. PMID 11114188.
33. Sanz-Moreno V, Casar B, Crespo P (May 2003). "p38alpha isoform Mxi2 binds to extracellular signal-regulated kinase 1 and 2 mitogen-activated protein kinase and regulates its nuclear activity by sustaining its phosphorylation levels". Mol. Cell. Biol. 23 (9): 3079–90. doi:10.1128/mcb.23.9.3079-3090.2003. PMC 153192. PMID 12697810.
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38. Chen Z, Cobb MH (May 2001). "Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2". J. Biol. Chem. 276 (19): 16070–5. doi:10.1074/jbc.M100681200. PMID 11279118.
39. Karandikar M, Xu S, Cobb MH (December 2000). "MEKK1 binds raf-1 and the ERK2 cascade components". J. Biol. Chem. 275 (51): 40120–7. doi:10.1074/jbc.M005926200. PMID 10969079.
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Further reading

• Morishima-Kawashima M, Hasegawa M, Takio K, Suzuki M, Yoshida H, Watanabe A, Titani K, Ihara Y (1995). "Hyperphosphorylation of tau in PHF". Neurobiol. Aging. 16 (3): 365–71, discussion 371–80. doi:10.1016/0197-4580(95)00027-C. PMID 7566346.
• Jeong Y, Du R, Zhu X, et al. (2014). "Histone deacetylase isoforms regulate innate immune responses by deacetylating mitogen-activated protein kinase phosphatase-1". J Leukoc Biol. 95 (4): 651–9. doi:10.1189/jlb.1013565. PMID 24374966.
• Davis RJ (1995). "Transcriptional regulation by MAP kinases". Mol. Reprod. Dev. 42 (4): 459–67. doi:10.1002/mrd.1080420414. PMID 8607977.
• Peruzzi F, Gordon J, Darbinian N, Amini S (2002). "Tat-induced deregulation of neuronal differentiation and survival by nerve growth factor pathway". J. Neurovirol. 8 Suppl 2 (2): 91–6. doi:10.1080/13550280290167885. PMID 12491158.
• Greenway AL, Holloway G, McPhee DA, Ellis P, Cornall A, Lidman M (2003). "HIV-1 Nef control of cell signalling molecules: multiple strategies to promote virus replication". J. Biosci. 28 (3): 323–35. doi:10.1007/BF02970151. PMID 12734410.
• Meloche S, Pouysségur J (2007). "The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the G1- to S-phase transition". Oncogene. 26 (22): 3227–39. doi:10.1038/sj.onc.1210414. PMID 17496918.

External links

• MAP Kinase Resource .