MAPK3

Protein-coding gene in the species Homo sapiens
MAPK3
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

2ZOQ, 4QTB

Identifiers
AliasesMAPK3, ERK-1, ERK1, ERT2, HS44KDAP, HUMKER1A, P44ERK1, P44MAPK, PRKM3, p44-ERK1, p44-MAPK, mitogen-activated protein kinase 3
External IDsOMIM: 601795 MGI: 1346859 HomoloGene: 55682 GeneCards: MAPK3
Gene location (Human)
Chromosome 16 (human)
Chr.Chromosome 16 (human)[1]
Chromosome 16 (human)
Genomic location for MAPK3
Genomic location for MAPK3
Band16p11.2Start30,114,105 bp[1]
End30,123,506 bp[1]
Gene location (Mouse)
Chromosome 7 (mouse)
Chr.Chromosome 7 (mouse)[2]
Chromosome 7 (mouse)
Genomic location for MAPK3
Genomic location for MAPK3
Band7 F3|7 69.25 cMStart126,358,773 bp[2]
End126,364,991 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • amygdala

  • cingulate gyrus

  • gastric mucosa

  • nucleus accumbens

  • rectum

  • gallbladder

  • canal of the cervix

  • prefrontal cortex

  • caudate nucleus

  • Brodmann area 9
Top expressed in
  • yolk sac

  • pyloric antrum

  • lip

  • entorhinal cortex

  • large intestine

  • colon

  • epithelium of stomach

  • duodenum

  • right lung

  • left lung
More reference expression data
BioGPS
More reference expression data
Gene ontology
Molecular function
  • phosphatase binding
  • ATP binding
  • protein kinase activity
  • MAP kinase activity
  • transferase activity
  • phosphotyrosine residue binding
  • scaffold protein binding
  • protein binding
  • nucleotide binding
  • kinase activity
  • protein serine/threonine kinase activity
  • MAP kinase kinase activity
  • identical protein binding
Cellular component
  • cytosol
  • nuclear envelope
  • focal adhesion
  • mitochondrion
  • cytoskeleton
  • nucleus
  • late endosome
  • Golgi apparatus
  • early endosome
  • pseudopodium
  • nucleoplasm
  • cytoplasm
  • plasma membrane
  • caveola
  • membrane
  • protein-containing complex
Biological process
  • caveolin-mediated endocytosis
  • positive regulation of protein phosphorylation
  • positive regulation of telomere capping
  • response to exogenous dsRNA
  • cardiac neural crest cell development involved in heart development
  • positive regulation of xenophagy
  • positive regulation of translation
  • cellular response to DNA damage stimulus
  • platelet activation
  • Fc-epsilon receptor signaling pathway
  • protein phosphorylation
  • cellular response to mechanical stimulus
  • face development
  • positive regulation of histone modification
  • regulation of DNA-binding transcription factor activity
  • DNA damage induced protein phosphorylation
  • positive regulation of ERK1 and ERK2 cascade
  • animal organ morphogenesis
  • cell cycle
  • apoptotic process
  • Fc-gamma receptor signaling pathway involved in phagocytosis
  • thymus development
  • ERK1 and ERK2 cascade
  • negative regulation of apolipoprotein binding
  • transcription, DNA-templated
  • cartilage development
  • viral process
  • response to toxic substance
  • regulation of stress-activated MAPK cascade
  • phosphorylation
  • outer ear morphogenesis
  • BMP signaling pathway
  • response to lipopolysaccharide
  • thyroid gland development
  • response to epidermal growth factor
  • positive regulation of MAP kinase activity
  • positive regulation of telomerase activity
  • peptidyl-tyrosine autophosphorylation
  • sensory perception of pain
  • positive regulation of cyclase activity
  • trachea formation
  • lipopolysaccharide-mediated signaling pathway
  • intracellular signal transduction
  • lung morphogenesis
  • neural crest cell development
  • transcription initiation from RNA polymerase I promoter
  • regulation of early endosome to late endosome transport
  • positive regulation of telomere maintenance via telomerase
  • MAPK cascade
  • positive regulation of histone acetylation
  • axon guidance
  • interleukin-1-mediated signaling pathway
  • fibroblast growth factor receptor signaling pathway
  • peptidyl-serine phosphorylation
  • regulation of cellular response to heat
  • Bergmann glial cell differentiation
  • regulation of Golgi inheritance
  • arachidonic acid metabolic process
  • regulation of cytoskeleton organization
  • positive regulation of transcription by RNA polymerase II
  • regulation of phosphatidylinositol 3-kinase signaling
  • regulation of ossification
  • positive regulation of gene expression
  • positive regulation of macrophage chemotaxis
  • cellular response to amino acid starvation
  • cellular response to reactive oxygen species
  • stress-activated MAPK cascade
  • cellular response to cadmium ion
  • cellular response to dopamine
  • positive regulation of metallopeptidase activity
  • regulation of cellular pH
  • protein-containing complex assembly
  • cellular response to tumor necrosis factor
  • regulation of gene expression
  • cellular response to organic substance
  • human ageing
  • decidualization
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

5595

26417

Ensembl

ENSG00000102882

ENSMUSG00000063065

UniProt

P27361

Q63844

RefSeq (mRNA)

NM_001040056
NM_001109891
NM_002746

NM_011952

RefSeq (protein)

NP_001035145
NP_001103361
NP_002737

NP_036082

Location (UCSC)Chr 16: 30.11 – 30.12 MbChr 7: 126.36 – 126.36 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Mitogen-activated protein kinase 3, also known as p44MAPK and ERK1,[5] is an enzyme that in humans is encoded by the MAPK3 gene.[6]

Function

The protein encoded by this gene is a member of the mitogen-activated protein kinase (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.[7]

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.[8]

Signaling pathways

Pharmacological inhibition of ERK1/2 restores GSK3β activity and protein synthesis levels in a model of tuberous sclerosis.[9]

Interactions

MAPK3 has been shown to interact with:

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000102882 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000063065 – 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. ^ Thomas, Gareth M.; Huganir, Richard L. (1 March 2004). "MAPK cascade signalling and synaptic plasticity". Nature Reviews Neuroscience. 5 (3): 173–183. doi:10.1038/nrn1346. ISSN 1471-003X. PMID 14976517. S2CID 205499891.
  6. ^ 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.
  7. ^ "Entrez Gene: MAPK3 mitogen-activated protein kinase 3".
  8. ^ 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.
  9. ^ Pal R, Bondar VV, Adamski CJ, Rodney GG, Sardiello M (2017). "Inhibition of ERK1/2 Restores GSK3β Activity and Protein Synthesis Levels in a Model of Tuberous Sclerosis". Sci. Rep. 7 (1): 4174. Bibcode:2017NatSR...7.4174P. doi:10.1038/s41598-017-04528-5. PMC 5482840. PMID 28646232.
  10. ^ 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.
  11. ^ 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.
  12. ^ 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.
  13. ^ 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.
  14. ^ a b 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.
  15. ^ a b 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.
  16. ^ Elion EA (September 1998). "Routing MAP kinase cascades". Science. 281 (5383): 1625–6. doi:10.1126/science.281.5383.1625. PMID 9767029. S2CID 28868990.
  17. ^ 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. PMC 5448118. PMID 10748187.
  18. ^ a b 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. doi:10.1016/S0021-9258(20)80474-8. PMID 8226933.
  19. ^ 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.
  20. ^ 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. S2CID 40413956.
  21. ^ 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.
  22. ^ 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.
  23. ^ 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.
  24. ^ 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 Activatio", Modulatory actions of neuropeptide Y on prostate cancer growth: role of MAP kinase/ERK 1/2 activation, Advances In Experimental Medicine And Biology, vol. 604, Springer, pp. 96–100, doi:10.1007/978-0-387-69116-9_7, ISBN 978-0-387-69114-5, PMID 17695723

External links

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Non-specific serine/threonine protein kinases (EC 2.7.11.1)
Pyruvate dehydrogenase kinase (EC 2.7.11.2)
Dephospho-(reductase kinase) kinase (EC 2.7.11.3)
3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring) kinase (EC 2.7.11.4)
(isocitrate dehydrogenase (NADP+)) kinase (EC 2.7.11.5)
(tyrosine 3-monooxygenase) kinase (EC 2.7.11.6)
Myosin-heavy-chain kinase (EC 2.7.11.7)
Fas-activated serine/threonine kinase (EC 2.7.11.8)
Goodpasture-antigen-binding protein kinase (EC 2.7.11.9)
  • -
IκB kinase (EC 2.7.11.10)
cAMP-dependent protein kinase (EC 2.7.11.11)
cGMP-dependent protein kinase (EC 2.7.11.12)
Protein kinase C (EC 2.7.11.13)
Rhodopsin kinase (EC 2.7.11.14)
Beta adrenergic receptor kinase (EC 2.7.11.15)
G-protein coupled receptor kinases (EC 2.7.11.16)
Ca2+/calmodulin-dependent (EC 2.7.11.17)
Myosin light-chain kinase (EC 2.7.11.18)
Phosphorylase kinase (EC 2.7.11.19)
Elongation factor 2 kinase (EC 2.7.11.20)
Polo kinase (EC 2.7.11.21)
Serine/threonine-specific protein kinases (EC 2.7.11.21-EC 2.7.11.30)
Polo kinase (EC 2.7.11.21)
Cyclin-dependent kinase (EC 2.7.11.22)
(RNA-polymerase)-subunit kinase (EC 2.7.11.23)
Mitogen-activated protein kinase (EC 2.7.11.24)
MAP3K (EC 2.7.11.25)
Tau-protein kinase (EC 2.7.11.26)
(acetyl-CoA carboxylase) kinase (EC 2.7.11.27)
  • -
Tropomyosin kinase (EC 2.7.11.28)
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Low-density-lipoprotein receptor kinase (EC 2.7.11.29)
  • -
Receptor protein serine/threonine kinase (EC 2.7.11.30)
MAP2K
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