MAPK3

Mitogen-activated protein kinase 3
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2ZOQ​, 4QTB​
Identifiers
Symbols	MAPK3 ; ERK-1; ERK1; ERT2; HS44KDAP; HUMKER1A; P44ERK1; P44MAPK; PRKM3; p44-ERK1; p44-MAPK
External IDs	OMIM: 601795 MGI: 1346859 HomoloGene: 55682 ChEMBL: 3385 GeneCards: MAPK3 Gene
EC number	2.7.11.24
Gene ontology Molecular function • phosphotyrosine binding • MAP kinase activity • protein binding • ATP binding • phosphatase binding • scaffold protein binding Cellular component • nucleus • nuclear envelope • nucleoplasm • mitochondrion • early endosome • late endosome • Golgi apparatus • cytosol • cytoskeleton • caveola • focal adhesion • microtubule cytoskeleton • pseudopodium • protein complex • extracellular exosome Biological process • MAPK cascade • activation of MAPKK activity • activation of MAPK activity • MAPK import into nucleus • positive regulation of protein phosphorylation • toll-like receptor signaling pathway • MyD88-dependent toll-like receptor signaling pathway • MyD88-independent toll-like receptor signaling pathway • transcription from RNA polymerase I promoter • transcription initiation from RNA polymerase I promoter • protein complex assembly • protein phosphorylation • apoptotic process • DNA damage induced protein phosphorylation • cell cycle • epidermal growth factor receptor signaling pathway • small GTPase mediated signal transduction • Ras protein signal transduction • axon guidance • blood coagulation • insulin receptor signaling pathway • fibroblast growth factor receptor signaling pathway • response to toxic substance • gene expression • viral process • phosphorylation • peptidyl-serine phosphorylation • cytokine-mediated signaling pathway • sensory perception of pain • arachidonic acid metabolic process • platelet activation • BMP signaling pathway • positive regulation of cyclase activity • lipopolysaccharide-mediated signaling pathway • regulation of stress-activated MAPK cascade • positive regulation of histone phosphorylation • toll-like receptor 2 signaling pathway • toll-like receptor 3 signaling pathway • toll-like receptor 4 signaling pathway • toll-like receptor 5 signaling pathway • toll-like receptor 9 signaling pathway • toll-like receptor 10 signaling pathway • cellular response to heat • positive regulation of histone acetylation • TRIF-dependent toll-like receptor signaling pathway • peptidyl-tyrosine autophosphorylation • Fc-epsilon receptor signaling pathway • Fc-gamma receptor signaling pathway involved in phagocytosis • toll-like receptor TLR1:TLR2 signaling pathway • toll-like receptor TLR6:TLR2 signaling pathway • response to exogenous dsRNA • innate immune response • positive regulation of translation • positive regulation of transcription from RNA polymerase II promoter • vascular endothelial growth factor receptor signaling pathway • neurotrophin TRK receptor signaling pathway • regulation of sequence-specific DNA binding transcription factor activity • cartilage development • stress-activated MAPK cascade • regulation of cytoskeleton organization • JAK-STAT cascade involved in growth hormone signaling pathway • lung morphogenesis • trachea formation • ERK1 and ERK2 cascade • positive regulation of ERK1 and ERK2 cascade • interleukin-1-mediated signaling pathway • response to epidermal growth factor • cellular response to mechanical stimulus • caveolin-mediated endocytosis • regulation of Golgi inheritance • regulation of cellular response to heat • regulation of early endosome to late endosome transport • negative regulation of apolipoprotein binding Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5595	26417
Ensembl	ENSG00000102882	ENSMUSG00000063065
UniProt	P27361	Q63844
RefSeq (mRNA)	NM_001040056	NM_011952
RefSeq (protein)	NP_001035145	NP_036082
Location (UCSC)	Chr 16: 30.11 – 30.12 Mb	Chr 7: 126.76 – 126.77 Mb
PubMed search

Mitogen-activated protein kinase 3 is an enzyme that in humans is encoded by the MAPK3 gene.^[1]

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 in a signaling cascade that regulates various cellular processes such as proliferation, differentiation, and cell cycle progression in response to a variety of extracellular signals. This kinase is activated by upstream kinases, resulting in its translocation to the nucleus where it phosphorylates nuclear targets. Alternatively spliced transcript variants encoding different protein isoforms have been described.^[2]

Clinical significance

It has been suggested that MAPK3, along with the gene IRAK1, is turned off by two microRNAs that were activated after the influenza A virus had been made to infect human lung cells.^[3]

Interactions

MAPK3 has been shown to interact with:

• DUSP3,^[4]
• DUSP6^[5]
• GTF2I,^[6]
• HDAC4,^[7]
• MAP2K1,^{[8][9][10][11][12]}
• MAP2K2,^[8][9][12]
• PTPN7,^[13][14][15]
• RPS6KA2,^[16][17] and
• SPIB.^[18]

References

1. García F, Zalba G, Páez G, Encío I, de Miguel C (15 May 1998). "Molecular cloning and characterization of the human p44 mitogen-activated protein kinase gene". Genomics 50 (1): 69–78. doi:10.1006/geno.1998.5315. PMID 9628824.
2. "Entrez Gene: MAPK3 mitogen-activated protein kinase 3".
3. Buggele WA, Johnson KE, Horvath CM (2012). "Influenza A virus infection of human respiratory cells induces primary microRNA expression". J. Biol. Chem. 287 (37): 31027–40. doi:10.1074/jbc.M112.387670. PMC 3438935. PMID 22822053.
4. 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.
5. Muda M, Theodosiou A, Gillieron C, Smith A, Chabert C, Camps M, Boschert U, Rodrigues N, Davies K, Ashworth A, Arkinstall S (April 1998). "The mitogen-activated protein kinase phosphatase-3 N-terminal noncatalytic region is responsible for tight substrate binding and enzymatic specificity". J. Biol. Chem. 273 (15): 9323–9. doi:10.1074/jbc.273.15.9323. PMID 9535927.
6. Kim DW, Cochran BH (February 2000). "Extracellular signal-regulated kinase binds to TFII-I and regulates its activation of the c-fos promoter". Mol. Cell. Biol. 20 (4): 1140–8. doi:10.1128/mcb.20.4.1140-1148.2000. PMC 85232. PMID 10648599.
7. 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.
8. Marti A, Luo Z, Cunningham C, Ohta Y, Hartwig J, Stossel TP, Kyriakis JM, Avruch J (January 1997). "Actin-binding protein-280 binds the stress-activated protein kinase (SAPK) activator SEK-1 and is required for tumor necrosis factor-alpha activation of SAPK in melanoma cells". J. Biol. Chem. 272 (5): 2620–8. doi:10.1074/jbc.272.5.2620. PMID 9006895.
9. Butch ER, Guan KL (February 1996). "Characterization of ERK1 activation site mutants and the effect on recognition by MEK1 and MEK2". J. Biol. Chem. 271 (8): 4230–5. doi:10.1074/jbc.271.8.4230. PMID 8626767.
10. Elion EA (September 1998). "Routing MAP kinase cascades". Science 281 (5383): 1625–6. doi:10.1126/science.281.5383.1625. PMID 9767029.
11. Yung Y, Yao Z, Hanoch T, Seger R (May 2000). "ERK1b, a 46-kDa ERK isoform that is differentially regulated by MEK". J. Biol. Chem. 275 (21): 15799–808. doi:10.1074/jbc.M910060199. PMID 10748187.
12. Zheng CF, Guan KL (November 1993). "Properties of MEKs, the kinases that phosphorylate and activate the extracellular signal-regulated kinases". J. Biol. Chem. 268 (32): 23933–9. PMID 8226933.
13. Pettiford SM, Herbst R (February 2000). "The MAP-kinase ERK2 is a specific substrate of the protein tyrosine phosphatase HePTP". Oncogene 19 (7): 858–69. doi:10.1038/sj.onc.1203408. PMID 10702794.
14. Saxena M, Williams S, Taskén K, Mustelin T (September 1999). "Crosstalk between cAMP-dependent kinase and MAP kinase through a protein tyrosine phosphatase". Nat. Cell Biol. 1 (5): 305–11. doi:10.1038/13024. PMID 10559944.
15. Saxena M, Williams S, Brockdorff J, Gilman J, Mustelin T (April 1999). "Inhibition of T cell signaling by mitogen-activated protein kinase-targeted hematopoietic tyrosine phosphatase (HePTP)". J. Biol. Chem. 274 (17): 11693–700. doi:10.1074/jbc.274.17.11693. PMID 10206983.
16. Roux PP, Richards SA, Blenis J (July 2003). "Phosphorylation of p90 ribosomal S6 kinase (RSK) regulates extracellular signal-regulated kinase docking and RSK activity". Mol. Cell. Biol. 23 (14): 4796–804. doi:10.1128/mcb.23.14.4796-4804.2003. PMC 162206. PMID 12832467.
17. Zhao Y, Bjorbaek C, Moller DE (November 1996). "Regulation and interaction of pp90(rsk) isoforms with mitogen-activated protein kinases". J. Biol. Chem. 271 (47): 29773–9. doi:10.1074/jbc.271.47.29773. PMID 8939914.
18. Mao C, Ray-Gallet D, Tavitian A, Moreau-Gachelin F (February 1996). "Differential phosphorylations of Spi-B and Spi-1 transcription factors". Oncogene 12 (4): 863–73. PMID 8632909.

Further reading

• 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.
• 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.
• Ruscica M, Dozio E, Motta M, Magni P (2007), Modulatory actions of neuropeptide Y on prostate cancer growth: role of MAP kinase/ERK 1/2 activation, Advances In Experimental Medicine And Biology 604, pp. 96–100, doi:10.1007/978-0-387-69116-9_7, ISBN 978-0-387-69114-5, PMID 17695723

External links

• MAP Kinase Resource .