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MAPK1

From Wikipedia, the free encyclopedia
Protein-coding gene in the species Homo sapiens
MAPK1
Available structures
PDBOrtholog search:PDBeRCSB
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
AliasesMAPK1, ERK, ERK-2, ERK2, ERT1, MAPK2, P42MAPK, PRKM1, PRKM2, p38, p40, p41, p41mapk, p42-MAPK, mitogen-activated protein kinase 1, NS13
External IDsOMIM:176948;MGI:1346858;HomoloGene:37670;GeneCards:MAPK1;OMA:MAPK1 - orthologs
Gene location (Human)
Chromosome 22 (human)
Chr.Chromosome 22 (human)[1]
Chromosome 22 (human)
Genomic location for MAPK1
Genomic location for MAPK1
Band22q11.22Start21,759,657bp[1]
End21,867,680bp[1]
Gene location (Mouse)
Chromosome 16 (mouse)
Chr.Chromosome 16 (mouse)[2]
Chromosome 16 (mouse)
Genomic location for MAPK1
Genomic location for MAPK1
Band16 A3|16 10.53 cMStart16,801,246bp[2]
End16,865,317bp[2]
RNA expression pattern
Bgee
HumanMouse (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
Cellular component
Biological process
Sources:Amigo /QuickGO
Orthologs
SpeciesHumanMouse
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 MbChr 16: 16.8 – 16.87 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Mitogen-activated protein kinase 1 (MAPK 1), also known asERK2, is anenzyme that in humans is encoded by theMAPK1gene.[5]

Function

[edit]

The protein encoded by this gene is a member of theMAP kinase family. MAP kinases, also known asextracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such asproliferation,differentiation, transcription regulation and development. The activation of thiskinase requires itsphosphorylation by upstreamkinases. Upon activation, this kinase translocates to thenucleus of the stimulated cells, where itphosphorylates nuclear targets. Two alternatively spliced transcript variants encoding the same protein, but differing in theUTRs, have been reported for this gene.[6] MAPK1 contains multiple amino acid sites that are phosphorylated and ubiquitinated.[7]

Interactions

[edit]

MAPK1 has been shown tointeract with:

Clinical significance

[edit]

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

See also

[edit]

References

[edit]
  1. ^abcGRCh38: Ensembl release 89: ENSG00000100030Ensembl, May 2017
  2. ^abcGRCm38: Ensembl release 89: ENSMUSG00000063358Ensembl, 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. Retrieved2020-10-31.
  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. ^abcEblen 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. ^abSanz-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. ^abYeung 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. ^abWaskiewicz 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. ^abSmith 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. ^abRoux 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. ^abZhao 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.
  41. ^Maekawa M, Nishida E, Tanoue T (October 2002)."Identification of the Anti-proliferative protein Tob as a MAPK substrate".J. Biol. Chem.277 (40):37783–7.doi:10.1074/jbc.M204506200.PMID 12151396.
  42. ^Ma L, Chen Z, Erdjument-Bromage H, Tempst P, Pandolfi PP (April 2005)."Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis".Cell.121 (2):179–93.doi:10.1016/j.cell.2005.02.031.PMID 15851026.S2CID 18663447.
  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.
  45. ^"Expression of MAPK1 in cancer - Summary - The Human Protein Atlas".www.proteinatlas.org.

Further reading

[edit]

External links

[edit]
MAP kinase activation
Initiation
MAP kinase kinase kinase (MAP3K or MKKK)
MAP kinase kinase (MAP2K or MKK)
MAP kinase
Phosphatase
PDB gallery
  • 1erk: STRUCTURE OF SIGNAL-REGULATED KINASE
    1erk: STRUCTURE OF SIGNAL-REGULATED KINASE
  • 1gol: COORDINATES OF RAT MAP KINASE ERK2 WITH AN ARGININE MUTATION AT POSITION 52
    1gol: COORDINATES OF RAT MAP KINASE ERK2 WITH AN ARGININE MUTATION AT POSITION 52
  • 1pme: STRUCTURE OF PENTA MUTANT HUMAN ERK2 MAP KINASE COMPLEXED WITH A SPECIFIC INHIBITOR OF HUMAN P38 MAP KINASE
    1pme: STRUCTURE OF PENTA MUTANT HUMAN ERK2 MAP KINASE COMPLEXED WITH A SPECIFIC INHIBITOR OF HUMAN P38 MAP KINASE
  • 1tvo: The structure of ERK2 in complex with a small molecule inhibitor
    1tvo: The structure of ERK2 in complex with a small molecule inhibitor
  • 1wzy: Crystal structure of human ERK2 complexed with a pyrazolopyridazine derivative
    1wzy: Crystal structure of human ERK2 complexed with a pyrazolopyridazine derivative
  • 2erk: PHOSPHORYLATED MAP KINASE ERK2
    2erk: PHOSPHORYLATED MAP KINASE ERK2
  • 2fys: Crystal structure of Erk2 complex with KIM peptide derived from MKP3
    2fys: Crystal structure of Erk2 complex with KIM peptide derived from MKP3
  • 2gph: Docking motif interactions in the MAP kinase ERK2
    2gph: Docking motif interactions in the MAP kinase ERK2
  • 2ojg: Crystal structure of ERK2 in complex with N,N-dimethyl-4-(4-phenyl-1H-pyrazol-3-yl)-1H-pyrrole-2-carboxamide
    2ojg: Crystal structure of ERK2 in complex with N,N-dimethyl-4-(4-phenyl-1H-pyrazol-3-yl)-1H-pyrrole-2-carboxamide
  • 2oji: Crystal structure of ERK2 in complex with N-benzyl-4-(4-(3-chlorophenyl)-1H-pyrazol-3-yl)-1H-pyrrole-2-carboxamide
    2oji: Crystal structure of ERK2 in complex with N-benzyl-4-(4-(3-chlorophenyl)-1H-pyrazol-3-yl)-1H-pyrrole-2-carboxamide
  • 2ojj: Crystal structure of ERK2 in complex with (S)-N-(1-(3-chloro-4-fluorophenyl)-2-hydroxyethyl)-4-(4-(3-chlorophenyl)-1H-pyrazol-3-yl)-1H-pyrrole-2-carboxamide
    2ojj: Crystal structure of ERK2 in complex with (S)-N-(1-(3-chloro-4-fluorophenyl)-2-hydroxyethyl)-4-(4-(3-chlorophenyl)-1H-pyrazol-3-yl)-1H-pyrrole-2-carboxamide
  • 3erk: THE COMPLEX STRUCTURE OF THE MAP KINASE ERK2/SB220025
    3erk: THE COMPLEX STRUCTURE OF THE MAP KINASE ERK2/SB220025
  • 4erk: THE COMPLEX STRUCTURE OF THE MAP KINASE ERK2/OLOMOUCINE
    4erk: THE COMPLEX STRUCTURE OF THE MAP KINASE ERK2/OLOMOUCINE
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)
  • -
Low-density-lipoprotein receptor kinase (EC 2.7.11.29)
  • -
Receptor protein serine/threonine kinase (EC 2.7.11.30)
MAP2K
Activity
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