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Information on EC 2.7.11.24 - mitogen-activated protein kinase

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EC Tree
IUBMB Comments
Phosphorylation of specific tyrosine and threonine residues in the activation loop of this enzyme by EC 2.7.12.2, mitogen-activated protein kinase kinase (MAPKK) is necessary for enzyme activation. Once activated, the enzyme phosphorylates target substrates on serine or threonine residues followed by a proline . A distinguishing feature of all MAPKs is the conserved sequence Thr-Xaa-Tyr (TXY). Mitogen-activated protein kinase (MAPK) signal transduction pathways are among the most widespread mechanisms of cellular regulation. Mammalian MAPK pathways can be recruited by a wide variety of stimuli including hormones (e.g. insulin and growth hormone), mitogens (e.g. epidermal growth factor and platelet-derived growth factor), vasoactive peptides (e.g. angiotensin-II and endothelin), inflammatory cytokines of the tumour necrosis factor (TNF) family and environmental stresses such as osmotic shock, ionizing radiation and ischaemic injury.
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UNIPROT: P28482
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Word Map
The enzyme appears in viruses and cellular organisms
Reaction Schemes
+
a [protein]-(L-serine/L-threonine)
=
+
a [protein]-(L-serine/L-threonine) phosphate
Synonyms
mapk, p38, erk1/2, p38 mapk, mitogen-activated protein kinase, map kinase, extracellular signal-regulated kinase, p38 mitogen-activated protein kinase, p38mapk, p38 map kinase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
extracellular regulated kinase
-
extracellular signal-regulated kinase
-
extracellular signal-regulated kinase 2
-
mitogen-activated protein kinase 1
-
cp38a
-
-
-
-
cp38b
-
-
-
-
CSAID binding protein
-
-
-
-
CSBP
-
-
-
-
Cytokine suppressive anti-inflammatory drug binding protein
-
-
-
-
ERK5
-
-
-
-
MAP kinase MXI2
-
-
-
-
MAP kinase p38 beta
-
-
-
-
MAP kinase p38 delta
-
-
-
-
MAP kinase p38 gamma
-
-
-
-
MAP kinase p38a
-
-
-
-
MAP kinase p38alpha
-
-
-
-
MAP kinase p38b
-
-
-
-
MAPK
-
-
-
-
mitogen-activated protein kinase
-
-
-
-
Mitogen-activated protein kinase p38 beta
-
-
-
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Mitogen-activated protein kinase p38 delta
-
-
-
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Mitogen-activated protein kinase p38 gamma
-
-
-
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Mitogen-activated protein kinase p38a
-
-
-
-
Mitogen-activated protein kinase p38alpha
-
-
-
-
Mitogen-activated protein kinase p38b
-
-
-
-
p38b
-
-
-
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SAPK2A
-
-
-
-
stress-activated protein kinase 2a
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:protein phosphotransferase (MAPKK-activated)
Phosphorylation of specific tyrosine and threonine residues in the activation loop of this enzyme by EC 2.7.12.2, mitogen-activated protein kinase kinase (MAPKK) is necessary for enzyme activation. Once activated, the enzyme phosphorylates target substrates on serine or threonine residues followed by a proline [6]. A distinguishing feature of all MAPKs is the conserved sequence Thr-Xaa-Tyr (TXY). Mitogen-activated protein kinase (MAPK) signal transduction pathways are among the most widespread mechanisms of cellular regulation. Mammalian MAPK pathways can be recruited by a wide variety of stimuli including hormones (e.g. insulin and growth hormone), mitogens (e.g. epidermal growth factor and platelet-derived growth factor), vasoactive peptides (e.g. angiotensin-II and endothelin), inflammatory cytokines of the tumour necrosis factor (TNF) family and environmental stresses such as osmotic shock, ionizing radiation and ischaemic injury.
CAS REGISTRY NUMBER
COMMENTARY hide
142243-02-5
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + focal adhesion kinase
ADP + phosphorylated focal adhesion kinase
show the reaction diagram
phosphorylation of FAK at S910, which promotes the disassembly of focal adhesion (hemidesmosome disruption) during cell migration
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(R)-N-(2-hydroxyl-1-phenylethyl)-4-[5-methyl-2-(phenylamino)-pyrimidin-4-yl]-1H-pyrrole-2-carboxamide
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(S)-4-[2-(2,3-dimethylphenylamino)-5-methylpyrimidin-4-yl]-N-[1-(3-chlorophenyl)-2-hydroxyethyl]-1H-pyrrole-2-carboxamide
-
(S)-4-[2-(2-chlorophenylamino)-5-methylpyrimidin-4-yl]-N-[1-phenyl-2-hydroxyethyl]-1H-pyrrole-2-carboxamide
-
(S)-4-[2-(2-ethylphenylamino)-5-methylpyrimidin-4-yl]-N-[1-(3-chlorophenyl)-2-hydroxyethyl]-1H-pyrrole-2-carboxamide
-
(S)-4-[2-(2-ethylphenylamino)-5-methylpyrimidin-4-yl]-N-[1-phenyl-2-hydroxyethyl]-1H-pyrrole-2-carboxamide
-
(S)-4-[2-(2-fluorophenylamino)-5-methylpyrimidin-4-yl]-N-[1-phenyl-2-hydroxyethyl]-1H-pyrrole-2-carboxamide
-
(S)-4-[2-(2-hydroxyphenylamino)-5-methylpyrimidin-4-yl]-N-[1-phenyl-2-hydroxyethyl]-1H-pyrrole-2-carboxamide
-
(S)-4-[2-(2-methylphenylamino)-5-methylpyrimidin-4-yl]-N-[1-(3-chlorophenyl)-2-hydroxyethyl]-1H-pyrrole-2-carboxamide
-
(S)-4-[2-(2-methylphenylamino)-5-methylpyrimidin-4-yl]-N-[1-phenyl-2-hydroxyethyl]-1H-pyrrole-2-carboxamide
-
(S)-4-[2-(2-trifluoromethylphenylamino)-5-methylpyrimidin-4-yl]-N-[1-phenyl-2-hydroxyethyl]-1H-pyrrole-2-carboxamide
-
(S)-4-[2-(3-fluoro-2-methylphenylamino)-5-methylpyrimidin-4-yl]-N-[1-(3-chlorophenyl)-2-hydroxyethyl]-1H-pyrrole-2-carboxamide
-
(S)-4-[2-(4-chloro-2-fluorophenylamino)-5-methylpyrimidin-4-yl]-N-[1-(3-chlorophenyl)-2-hydroxyethyl]-1H-pyrrole-2-carboxamide
-
(S)-4-[2-(4-chloro-2-methylphenylamino)-5-methylpyrimidin-4-yl]-N-[1-(3-chlorophenyl)-2-hydroxyethyl]-1H-pyrrole-2-carboxamide
-
(S)-4-[2-(benzo[d]1,3-dioxolylamino)-5-methylpyrimidin-4-yl]-N-[1-(3-chlorophenyl)-2-hydroxyethyl]-1H-pyrrole-2-carboxamide
-
(S)-N-(2-hydroxyl-1-phenylethyl)-4-[5-methyl-2-(phenylamino)-pyrimidin-4-yl]-1H-pyrrole-2-carboxamide
-
(S)-N-[1-(3-chlorophenyl)-2-hydroxyethyl]-4-[-2-(2,2-difluorobenzo[d][1,3]dioxol-4-ylamino)-5-methylpyrimidin-4-yl]-1H-pyrrole-2-carboxamide
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(S)-N-[1-(3-chlorophenyl)-2-hydroxyethyl]-4-[-2-(2,3-dihydro-1H-inden-4-ylamino)-5-methylpyrimidin-4-yl]-1H-pyrrole-2-carboxamide
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(S)-N-[1-(3-chlorophenyl)-2-hydroxyethyl]-4-[-2-(2,3-dihydrobenzo[b][1,4]dioxin-5-ylamino)-5-methylpyrimidin-4-yl]-1H-pyrrole-2-carboxamide
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(S)-N-[1-(3-chlorophenyl)-2-hydroxyethyl]-4-[5-methyl-2(5,6,7,8-tetrahydronaphthalen-1-ylamino)pyrimidin-4-yl]-1H-pyrrole-2-carboxamide
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(S)-N-[1-(3-chlorophenyl)-2-hydroxyethyl]-4-[5-methyl-2-(phenylamino)pyrimidin-4-yl]-1H-pyrrole-2-carboxamide
-
(S)-N-[1-(3-fluorophenyl)-2-hydroxyethyl]-4-[5-methyl-2-(phenylamino)pyrimidin-4-yl]-1H-pyrrole-2-carboxamide
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(S)-N-[1-(3-methylphenyl)-2-hydroxyethyl]-4-[5-methyl-2-(phenylamino)pyrimidin-4-yl]-1H-pyrrole-2-carboxamide
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N-[(1S)-1-(3-chloro-4-fluorophenyl)-2-hydroxyethyl]-4-[4-(3-chlorophenyl)-1H-pyrazol-3-yl]-1H-pyrrole-3-carboxamide
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PD98059
an ERK inhibitor
U0126
inhibitor of Erk2
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
mycosporine-glycine
mycosporine-like amino acids shinorine, mycosporine-glycine, and porphyra are purified from Chlamydomonas hedlyei and Porphyra yezoensis activate kinase ERK and JNK, especially JNK
porphyra
mycosporine-like amino acids shinorine, mycosporine-glycine, and porphyra are purified from Chlamydomonas hedlyei and Porphyra yezoensis activate kinase ERK and JNK, especially JNK
shinorine
mycosporine-like amino acids shinorine, mycosporine-glycine, and porphyra are purified from Chlamydomonas hedlyei and Porphyra yezoensis activate kinase ERK and JNK, especially JNK
additional information
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00067
(R)-N-(2-hydroxyl-1-phenylethyl)-4-[5-methyl-2-(phenylamino)-pyrimidin-4-yl]-1H-pyrrole-2-carboxamide
-
0.000002 - 0.000003
(S)-4-[2-(2,3-dimethylphenylamino)-5-methylpyrimidin-4-yl]-N-[1-(3-chlorophenyl)-2-hydroxyethyl]-1H-pyrrole-2-carboxamide
0.000002
(S)-4-[2-(2-chloro-4-fluorophenylamino)-5-methylpyrimidin-4-yl]- N-[1-(3-chlorophenyl)-2-hydroxyethyl]-1H-pyrrole-2-carboxamide
Ki below 0.000002 mM, potent, selective, and orally bioavailable inhibitor of ERK
0.000002
(S)-4-[2-(2-chlorophenylamino)-5-methylpyrimidin-4-yl]-N-[1-phenyl-2-hydroxyethyl]-1H-pyrrole-2-carboxamide
Ki below 0.000002 mM
0.000002
(S)-4-[2-(2-ethylphenylamino)-5-methylpyrimidin-4-yl]-N-[1-(3-chlorophenyl)-2-hydroxyethyl]-1H-pyrrole-2-carboxamide
Ki below 0.000002 mM
0.000003
(S)-4-[2-(2-ethylphenylamino)-5-methylpyrimidin-4-yl]-N-[1-phenyl-2-hydroxyethyl]-1H-pyrrole-2-carboxamide
-
0.000002
(S)-4-[2-(2-fluorophenylamino)-5-methylpyrimidin-4-yl]-N-[1-phenyl-2-hydroxyethyl]-1H-pyrrole-2-carboxamide
Ki below 0.000002 mM
0.000004
(S)-4-[2-(2-hydroxyphenylamino)-5-methylpyrimidin-4-yl]-N-[1-phenyl-2-hydroxyethyl]-1H-pyrrole-2-carboxamide
-
0.000002
(S)-4-[2-(2-methylphenylamino)-5-methylpyrimidin-4-yl]-N-[1-(3-chlorophenyl)-2-hydroxyethyl]-1H-pyrrole-2-carboxamide
Ki below 0.000002 mM
0.000002
(S)-4-[2-(2-methylphenylamino)-5-methylpyrimidin-4-yl]-N-[1-phenyl-2-hydroxyethyl]-1H-pyrrole-2-carboxamide
Ki below 0.000002 mM
0.000004
(S)-4-[2-(2-trifluoromethylphenylamino)-5-methylpyrimidin-4-yl]-N-[1-phenyl-2-hydroxyethyl]-1H-pyrrole-2-carboxamide
-
0.000034
(S)-4-[2-(3-fluoro-2-methylphenylamino)-5-methylpyrimidin-4-yl]-N-[1-(3-chlorophenyl)-2-hydroxyethyl]-1H-pyrrole-2-carboxamide
-
0.000005
(S)-4-[2-(4-chloro-2-fluorophenylamino)-5-methylpyrimidin-4-yl]-N-[1-(3-chlorophenyl)-2-hydroxyethyl]-1H-pyrrole-2-carboxamide
-
0.000005
(S)-4-[2-(4-chloro-2-methylphenylamino)-5-methylpyrimidin-4-yl]-N-[1-(3-chlorophenyl)-2-hydroxyethyl]-1H-pyrrole-2-carboxamide
-
0.000002
(S)-4-[2-(benzo[d]1,3-dioxolylamino)-5-methylpyrimidin-4-yl]-N-[1-(3-chlorophenyl)-2-hydroxyethyl]-1H-pyrrole-2-carboxamide
Ki below 0.000002 mM
0.000002
(S)-N-(2-hydroxyl-1-phenylethyl)-4-[5-methyl-2-(phenylamino)-pyrimidin-4-yl]-1H-pyrrole-2-carboxamide
Ki below 0.000002 mM
0.000002
(S)-N-[1-(3-chlorophenyl)-2-hydroxyethyl]-4-[-2-(2,2-difluorobenzo[d][1,3]dioxol-4-ylamino)-5-methylpyrimidin-4-yl]-1H-pyrrole-2-carboxamide
Ki below 0.000002 mM
0.000002
(S)-N-[1-(3-chlorophenyl)-2-hydroxyethyl]-4-[-2-(2,3-dihydro-1H-inden-4-ylamino)-5-methylpyrimidin-4-yl]-1H-pyrrole-2-carboxamide
Ki below 0.000002 mM
0.000015
(S)-N-[1-(3-chlorophenyl)-2-hydroxyethyl]-4-[-2-(2,3-dihydrobenzo[b][1,4]dioxin-5-ylamino)-5-methylpyrimidin-4-yl]-1H-pyrrole-2-carboxamide
-
0.000013
(S)-N-[1-(3-chlorophenyl)-2-hydroxyethyl]-4-[5-methyl-2(5,6,7,8-tetrahydronaphthalen-1-ylamino)pyrimidin-4-yl]-1H-pyrrole-2-carboxamide
-
0.000002
(S)-N-[1-(3-chlorophenyl)-2-hydroxyethyl]-4-[5-methyl-2-(phenylamino)pyrimidin-4-yl]-1H-pyrrole-2-carboxamide
Ki below 0.000002 mM
0.000002
(S)-N-[1-(3-fluorophenyl)-2-hydroxyethyl]-4-[5-methyl-2-(phenylamino)pyrimidin-4-yl]-1H-pyrrole-2-carboxamide
Ki below 0.000002 mM
0.000002
(S)-N-[1-(3-methylphenyl)-2-hydroxyethyl]-4-[5-methyl-2-(phenylamino)pyrimidin-4-yl]-1H-pyrrole-2-carboxamide
Ki below 0.000002 mM
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
from airway tissue
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
ERK inhibition using PD98059 causes reduction of wound healing by up to 15%
metabolism
mycosporine-like amino acids promote wound healing through focal adhesion kinase (FAK, EC 2.7.10.2) and mitogen-activated protein kinases (MAP kinases) signaling pathway in keratinocytes
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
MK01_HUMAN
360
0
41390
Swiss-Prot
other Location (Reliability: 3)
PDB
SCOP
CATH
UNIPROT
ORGANISM
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
characterization of cDNA
heterogeneous expression in different tissues
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
the inhibitors of Erk2 or antioxidants may be exploited for prevention of cadmium-induced neurodegenerative diseases
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Owaki, H.; Makar, R.; Boulton, T.G.; Cobb, M.H.; Geppert, T.D.
Extracellular signal-regulated kinases in T cells: characterization of human ERK1 and ERK2 cDNAs
Biochem. Biophys. Res. Commun.
182
1416-1422
1992
Homo sapiens (P27361), Homo sapiens (P28482), Homo sapiens
Manually annotated by BRENDA team
Gonzalez, F.A.; Raden, D.L.; Rigby, M.R.; Davis, R.J.
Heterogeneous expression of four MAP kinase isoforms in human tissues
FEBS Lett.
304
170-178
1992
Schizosaccharomyces pombe (P27638), Homo sapiens (P28482), Homo sapiens (P31152), Homo sapiens
Manually annotated by BRENDA team
Chen, L.; Liu, L.; Huang, S.
Cadmium activates the mitogen-activated protein kinase (MAPK) pathway via induction of reactive oxygen species and inhibition of protein phosphatases 2A and 5
Free Radic. Biol. Med.
45
1035-1044
2008
Homo sapiens, Homo sapiens (P27361), Homo sapiens (P28482), Rattus norvegicus, Rattus norvegicus (P21708), Rattus norvegicus (P63086)
Manually annotated by BRENDA team
Liu, W.; Liang, Q.; Balzar, S.; Wenzel, S.; Gorska, M.; Alam, R.
Cell-specific activation profile of extracellular signal-regulated kinase 1/2, Jun N-terminal kinase, and p38 mitogen-activated protein kinases in asthmatic airways
J. Allergy Clin. Immunol.
121
893-902.e2
2008
Homo sapiens (P27361), Homo sapiens (P28482), Homo sapiens
Manually annotated by BRENDA team
Aronov, A.M.; Tang, Q.; Martinez-Botella, G.; Bemis, G.W.; Cao, J.; Chen, G.; Ewing, N.P.; Ford, P.J.; Germann, U.A.; Green, J.; Hale, M.R.; Jacobs, M.; Janetka, J.W.; Maltais, F.; Markland, W.; Namchuk, M.N.; Nanthakumar, S.; Poondru, S.; Straub, J.; ter Haar, E.; Xie, X.
Structure-guided design of potent and selective pyrimidylpyrrole inhibitors of extracellular signal-regulated kinase (ERK) using conformational control
J. Med. Chem.
52
6362-6368
2009
Homo sapiens (P28482), Homo sapiens
Manually annotated by BRENDA team
Choi, Y.H.; Yang, D.J.; Kulkarni, A.; Moh, S.H.; Kim, K.W.
Mycosporine-like amino acids promote wound healing through focal adhesion kinase (FAK) and mitogen-activated protein kinases (MAP kinases) signaling pathway in keratinocytes
Mar. Drugs
13
7055-7066
2015
Homo sapiens (P27361), Homo sapiens (P28482), Homo sapiens (P45983)
Manually annotated by BRENDA team