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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: P53778
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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
cp38a
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cp38b
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CSAID binding protein
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CSBP
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Cytokine suppressive anti-inflammatory drug binding protein
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ERK5
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MAP kinase MXI2
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MAP kinase p38 beta
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MAP kinase p38 delta
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MAP kinase p38 gamma
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MAP kinase p38a
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MAP kinase p38alpha
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MAP kinase p38b
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MAPK
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mitogen-activated protein kinase
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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
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Mitogen-activated protein kinase p38alpha
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Mitogen-activated protein kinase p38b
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p38b
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SAPK2A
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stress-activated protein kinase 2a
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
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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 + a protein
ADP + a phosphoprotein
show the reaction diagram
ATP + c-Jun
ADP + phosphorylated c-Jun
show the reaction diagram
ATP + Lin-1
ADP + phosphorylated Lin-1
show the reaction diagram
additional information
?
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interaction motifs of substrates are crucial for MAPK activity, motif Leu-Xaa-Leu preceded by 3-5 basic residues is abundant, docking mechanism in MAPK signalling, the recognition modules can function synergistically or competitively, MAPK determinants recognizing docking motifs, overview
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?
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
ATP + a protein
ADP + a phosphoprotein
show the reaction diagram
MAPK activate mitogen-activated proteins in several signal transduction pathways, overview
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-
?
ATP + c-Jun
ADP + phosphorylated c-Jun
show the reaction diagram
substrate of JNK
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?
ATP + Lin-1
ADP + phosphorylated Lin-1
show the reaction diagram
substrate of ERK2, negative regulation of Lin-1
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?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
additional information
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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Uniprot
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
the p38gamma C-terminus is an efficient inducer of cell death after its intracellular delivery. Binding of the C-terminal sequence of p38gamma to PTPN4 abolishes the catalytic autoinhibition of PTPN4 and thus activates the phosphatase, which can efficiently dephosphorylate the activation loop of p38gamma. The p38gamma-PTPN4 interaction promotes cellular signaling, preventing cell death induction
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
MK12_HUMAN
367
0
41940
Swiss-Prot
other Location (Reliability: 5)
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
p38gamma is phosphorylated and activated by MAPK kinase MKK6
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystal structure of p38alpha, show docking grooves for binding of substrate D-domains, i.e. of MEF2A, and of activating kinases, e.g. of MKK3b, Ile116 and Gln120 play important roles
isolated PDZ domain of protein tyrosine phosphatase non-receptor type bound to the p38gamma C-terminus, i.e. Cyto8-RETEV and p38gamma-KETPL peptides, mixing of the protein ligand solution from 5 mg/ml PTPN4-PDZ domain and the appropriate peptide at a ratio of 1:2 and 1:4 for PTPN4-PDZCyto8-RETEV and PTPN4-PDZp38gamma-KETPL, respectively, in 50 mM Tris-HCl, pH 7.5, 150 mM NaCl, 0.5 mM TCEP, sitting drop vapor diffusion method, mixing of 400 nl protein-ligand solution with 200 nl of precipitant solution containing 23% PEG 8000, 100 mM MES, pH 6.0, 200 mM calcium acetate, 0.143 mM ammonium sulfate or 1.2 M sodium dihydrogen phosphate, 0.8 M dipotassium hydrogen phosphate, 0.1 M CAPS, pH 10.5, 0.2 M lithium sulfate, 0.67 M non-detergent sulfobetaine (NDSB) 201, 18°C, X-ray diffraction structure determination and analysis at 2.09-2.35 A resolution, modeling
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Biondi, R.M.; Nebreda, A.R.
Signalling specificity of Ser/Thr protein kinases through docking-site-mediated interactions
Biochem. J.
372
1-13
2003
Homo sapiens (P53778)
Manually annotated by BRENDA team
Maisonneuve, P.; Caillet-Saguy, C.; Vaney, M.; Bibi-Zainab, E.; Sawyer, K.; Raynal, B.; Haouz, A.; Delepierre, M.; Lafon, M.; Cordier, F.; Wolff, N.
Molecular basis of the interaction of the human protein tyrosine phosphatase non-receptor type 4 (PTPN4) with the mitogen-activated protein kinase p38gamma
J. Biol. Chem.
291
16699-16708
2016
Homo sapiens (P53778), Homo sapiens
Manually annotated by BRENDA team