MAPK1

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, NS13
External IDs	OMIM: 176948; MGI: 1346858; HomoloGene: 37670; GeneCards: MAPK1; OMA:MAPK1 - orthologs
Gene location (Human) Chr. Chromosome 22 (human) [1] Band 22q11.22 Start 21,759,657 bp [1] End 21,867,680 bp [1]
Gene location (Mouse) Chr. Chromosome 16 (mouse) [2] Band 16 A3|16 10.53 cM Start 16,801,246 bp [2] End 16,865,317 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in middle temporal gyrus postcentral gyrus Brodmann area 23 entorhinal cortex superior frontal gyrus external globus pallidus pons visceral pleura skin of thigh skin of hip Top expressed in dentate gyrus of hippocampal formation granule cell olfactory tubercle superior frontal gyrus primary visual cortex entorhinal cortex perirhinal cortex hippocampus proper CA3 field amygdala anterior amygdaloid area More reference expression data BioGPS 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 protein binding protein kinase binding DNA binding nucleotide binding RNA polymerase II CTD heptapeptide repeat 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 nucleus extracellular exosome perikaryon late endosome Golgi apparatus spindle axon early endosome mitotic spindle pseudopodium extracellular region nucleoplasm azurophil granule lumen ficolin-1-rich granule lumen plasma membrane postsynaptic density membrane protein-containing 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 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 viral process response to toxic substance regulation of stress-activated MAPK cascade chemical synaptic transmission growth hormone receptor signaling pathway via JAK-STAT cytosine metabolic process phosphorylation outer ear morphogenesis response to estrogen chemotaxis response to lipopolysaccharide thyroid gland development response to epidermal growth factor positive regulation of telomerase activity sensory perception of pain peptidyl-threonine phosphorylation trachea formation lipopolysaccharide-mediated signaling pathway mammary gland epithelial cell proliferation 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 population 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 potentiation regulation of ossification regulation of phosphatidylinositol 3-kinase signaling neutrophil degranulation regulation of gene expression cellular response to organic substance human ageing 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 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 NM_028991 RefSeq (protein) NP_002736 NP_620407 NP_001033752 NP_036079 NP_001344044 Location (UCSC) Chr 22: 21.76 – 21.87 Mb Chr 16: 16.8 – 16.87 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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

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]

Interactions

MAPK1 has been shown to interact with:

• ADAM17, ^[8]
• CIITA, ^[9]
• DUSP1, ^{[10] [11]}
• DUSP3, ^[12]
• ELK1, ^{[13] [14]}
• FHL2, ^[15]
• HDAC4, ^[16]
• MAP2K1, ^{[17] [18] [19] [20] [21] [22]}
• MAP3K1 ^[23]
• MAPK14, ^{[17] [24]}
• MKNK1, ^[25]
• MKNK2, ^{[25] [26]}
• Myc, ^{[27] [28] [29]}
• NEK2, ^[30]
• PEA15, ^[31]
• PTPN7, ^{[32] [33]}
• Phosphatidylethanolamine binding protein 1, ^[19]
• RPS6KA1, ^{[13] [34] [35]}
• RPS6KA2, ^{[35] [36]}
• RPS6KA3, ^{[34] [36]}
• SORBS3, ^[37]
• STAT5A, ^{[38] [39]}
• TNIP1, ^[40]
• TOB1, ^[41]
• TSC2, ^[42]
• UBR5, ^[13] and
• VAV1. ^{[43] [44]}

Clinical significance

Mutations in MAPK1 are implicated in many types of cancer. ^[45]

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. 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.
9. Voong LN, Slater AR, Kratovac S, Cressman DE (April 2008). "Mitogen-activated protein kinase ERK1/2 regulates the class II transactivator". J. Biol. Chem. 283 (14): 9031–9. doi: 10.1074/jbc.M706487200 . PMC   2431044 . PMID   18245089.
10. 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.
11. Calvisi DF, Pinna F, Meloni F, Ladu S, Pellegrino R, Sini M, Daino L, Simile MM, De Miglio MR, Virdis P, Frau M, Tomasi ML, Seddaiu MA, Muroni MR, Feo F, Pascale RM (June 2008). "Dual-specificity phosphatase 1 ubiquitination in extracellular signal-regulated kinase-mediated control of growth in human hepatocellular carcinoma". Cancer Res. 68 (11): 4192–200. doi: 10.1158/0008-5472.CAN-07-6157 . PMID   18519678.
12. 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.
13. Eblen ST, Kumar NV, Shah K, Henderson MJ, Watts CK, Shokat KM, Weber MJ (April 2003). "Identification of novel ERK2 substrates through use of an engineered kinase and ATP analogs". J. Biol. Chem. 278 (17): 14926–35. doi: 10.1074/jbc.M300485200 . PMID   12594221.
14. Cano E, Hazzalin CA, Kardalinou E, Buckle RS, Mahadevan LC (November 1995). "Neither ERK nor JNK/SAPK MAP kinase subtypes are essential for histone H3/HMG-14 phosphorylation or c-fos and c-jun induction". J. Cell Sci. 108 (11): 3599–609. doi:10.1242/jcs.108.11.3599. PMID   8586671.
15. 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.
16. 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. Bibcode:2000PNAS...9714329Z. doi: 10.1073/pnas.250494697 . PMC   18918 . PMID   11114188.
17. 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.
18. Robinson FL, Whitehurst AW, Raman M, Cobb MH (April 2002). "Identification of novel point mutations in ERK2 that selectively disrupt binding to MEK1". J. Biol. Chem. 277 (17): 14844–52. doi: 10.1074/jbc.M107776200 . PMID   11823456.
19. Yeung K, Janosch P, McFerran B, Rose DW, Mischak H, Sedivy JM, Kolch W (May 2000). "Mechanism of suppression of the Raf/MEK/extracellular signal-regulated kinase pathway by the raf kinase inhibitor protein". Mol. Cell. Biol. 20 (9): 3079–85. doi:10.1128/mcb.20.9.3079-3085.2000. PMC   85596 . PMID   10757792.
20. Wunderlich W, Fialka I, Teis D, Alpi A, Pfeifer A, Parton RG, Lottspeich F, Huber LA (February 2001). "A novel 14-kilodalton protein interacts with the mitogen-activated protein kinase scaffold mp1 on a late endosomal/lysosomal compartment". J. Cell Biol. 152 (4): 765–76. doi:10.1083/jcb.152.4.765. PMC   2195784 . PMID   11266467.
21. Stippec S, Robinson FL, Cobb MH (July 2001). "Hydrophobic as well as charged residues in both MEK1 and ERK2 are important for their proper docking". J. Biol. Chem. 276 (28): 26509–15. doi: 10.1074/jbc.M102769200 . PMID   11352917.
22. 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.
23. 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.
24. Tanoue T, Maeda R, Adachi M, Nishida E (February 2001). "Identification of a docking groove on ERK and p38 MAP kinases that regulates the specificity of docking interactions". EMBO J. 20 (3): 466–79. doi:10.1093/emboj/20.3.466. PMC   133461 . PMID   11157753.
25. Waskiewicz AJ, Flynn A, Proud CG, Cooper JA (April 1997). "Mitogen-activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2". EMBO J. 16 (8): 1909–20. doi:10.1093/emboj/16.8.1909. PMC   1169794 . PMID   9155017.
26. Scheper GC, Parra JL, Wilson M, Van Kollenburg B, Vertegaal AC, Han ZG, Proud CG (August 2003). "The N and C termini of the splice variants of the human mitogen-activated protein kinase-interacting kinase Mnk2 determine activity and localization". Mol. Cell. Biol. 23 (16): 5692–705. doi:10.1128/mcb.23.16.5692-5705.2003. PMC   166352 . PMID   12897141.
27. Jin Z, Gao F, Flagg T, Deng X (September 2004). "Tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone promotes functional cooperation of Bcl2 and c-Myc through phosphorylation in regulating cell survival and proliferation". J. Biol. Chem. 279 (38): 40209–19. doi: 10.1074/jbc.M404056200 . PMID   15210690.
28. Gupta S, Davis RJ (October 1994). "MAP kinase binds to the NH2-terminal activation domain of c-Myc". FEBS Lett. 353 (3): 281–5. Bibcode:1994FEBSL.353..281G. doi: 10.1016/0014-5793(94)01052-8 . PMID   7957875. S2CID   45404088.
29. Tournier C, Whitmarsh AJ, Cavanagh J, Barrett T, Davis RJ (July 1997). "Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proc. Natl. Acad. Sci. U.S.A. 94 (14): 7337–42. Bibcode:1997PNAS...94.7337T. doi: 10.1073/pnas.94.14.7337 . PMC   23822 . PMID   9207092.
30. Lou Y, Xie W, Zhang DF, Yao JH, Luo ZF, Wang YZ, Shi YY, Yao XB (August 2004). "Nek2A specifies the centrosomal localization of Erk2". Biochem. Biophys. Res. Commun. 321 (2): 495–501. doi:10.1016/j.bbrc.2004.06.171. PMID   15358203.
31. Formstecher E, Ramos JW, Fauquet M, Calderwood DA, Hsieh JC, Canton B, Nguyen XT, Barnier JV, Camonis J, Ginsberg MH, Chneiweiss H (August 2001). "PEA-15 mediates cytoplasmic sequestration of ERK MAP kinase". Dev. Cell. 1 (2): 239–50. doi: 10.1016/s1534-5807(01)00035-1 . PMID   11702783.
32. 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. S2CID   24843974.
33. 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.
34. Smith JA, Poteet-Smith CE, Malarkey K, Sturgill TW (January 1999). "Identification of an extracellular signal-regulated kinase (ERK) docking site in ribosomal S6 kinase, a sequence critical for activation by ERK in vivo". J. Biol. Chem. 274 (5): 2893–8. doi: 10.1074/jbc.274.5.2893 . PMID   9915826.
35. 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.
36. 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.
37. Mitsushima M, Suwa A, Amachi T, Ueda K, Kioka N (August 2004). "Extracellular signal-regulated kinase activated by epidermal growth factor and cell adhesion interacts with and phosphorylates vinexin". J. Biol. Chem. 279 (33): 34570–7. doi: 10.1074/jbc.M402304200 . PMID   15184391.
38. Pircher TJ, Petersen H, Gustafsson JA, Haldosén LA (April 1999). "Extracellular signal-regulated kinase (ERK) interacts with signal transducer and activator of transcription (STAT) 5a". Mol. Endocrinol. 13 (4): 555–65. doi: 10.1210/mend.13.4.0263 . PMID   10194762.
39. Dinerstein-Cali H, Ferrag F, Kayser C, Kelly PA, Postel-Vinay M (August 2000). "Growth hormone (GH) induces the formation of protein complexes involving Stat5, Erk2, Shc and serine phosphorylated proteins". Mol. Cell. Endocrinol. 166 (2): 89–99. doi:10.1016/s0303-7207(00)00277-x. PMID   10996427. S2CID   45725648.
40. Zhang S, Fukushi M, Hashimoto S, Gao C, Huang L, Fukuyo Y, Nakajima T, Amagasa T, Enomoto S, Koike K, Miura O, Yamamoto N, Tsuchida N (September 2002). "A new ERK2 binding protein, Naf1, attenuates the EGF/ERK2 nuclear signaling". Biochem. Biophys. Res. Commun. 297 (1): 17–23. doi:10.1016/s0006-291x(02)02086-7. PMID   12220502.
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43. Song JS, Gomez J, Stancato LF, Rivera J (October 1996). "Association of a p95 Vav-containing signaling complex with the FcepsilonRI gamma chain in the RBL-2H3 mast cell line. Evidence for a constitutive in vivo association of Vav with Grb2, Raf-1, and ERK2 in an active complex". J. Biol. Chem. 271 (43): 26962–70. doi: 10.1074/jbc.271.43.26962 . PMID   8900182.
44. Lee IS, Liu Y, Narazaki M, Hibi M, Kishimoto T, Taga T (January 1997). "Vav is associated with signal transducing molecules gp130, Grb2 and Erk2, and is tyrosine phosphorylated in response to interleukin-6". FEBS Lett. 401 (2–3): 133–7. Bibcode:1997FEBSL.401..133L. doi: 10.1016/s0014-5793(96)01456-1 . PMID   9013873. S2CID   32632406.
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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. S2CID   22471158.
• 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. S2CID   40126163.
• Davis RJ (1995). "Transcriptional regulation by MAP kinases". Mol. Reprod. Dev. 42 (4): 459–67. doi:10.1002/mrd.1080420414. PMID   8607977. S2CID   12842112.
• 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. S2CID   33749514.
• 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. S2CID   2245848.

External links

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