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Names & Taxonomy

Uniprot ID:: P49137
Entry Name:: MAPK2_HUMAN
Status:: reviewed
Protein Names:: MAP kinase-activated protein kinase 2 (MAPK-activated protein kinase 2) (MAPKAP kinase 2) (MAPKAP-K2) (MAPKAPK-2) (MK-2) (MK2) (EC 2.7.11.1)
Gene Names:: MAPKAPK2
Gene Names Primary:: MAPKAPK2
Organism:: Homo sapiens (Human)

Structure

Length:: 400
Sequence:: MLSNSQGQSPPVPFPAPAPPPQPPTPALPHPPAQPPPPPPQQFPQFHVKSGLQIKKNAIIDDYKVTSQVLGLGINGKVLQIFNKRTQEKFALKMLQDCPKARREVELHWRASQCPHIVRIVDVYENLYAGRKCLLIVMECLDGGELFSRIQDRGDQAFTEREASEIMKSIGEAIQYLHSINIAHRDVKPENLLYTSKRPNAILKLTDFGFAKETTSHNSLTTPCYTPYYVAPEVLGPEKYDKSCDMWSLGVIMYILLCGYPPFYSNHGLAISPGMKTRIRMGQYEFPNPEWSEVSEEVKMLIRNLLKTEPTQRMTITEFMNHPWIMQSTKVPQTPLHTSRVLKEDKERWEDVKEEMTSALATMRVDYEQIKIKKIEDASNPLLLKRRKKARALEAAALAH
Proteomes:: UP000005640

Subcellular location

Subcellular Location:: Cytoplasm

Function

Function:: Stress-activated serine/threonine-protein kinase involved in cytokines production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. Phosphorylates ALOX5, CDC25B, CDC25C, ELAVL1, HNRNPA0, HSF1, HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to dissociate HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impair their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins ELAVL1, HNRNPA0, PABPC1 and TTP/ZFP36, leading to regulate the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity leading to inhibition of dependent degradation of ARE-containing transcript. Also involved in late G2/M checkpoint following DNA damage through a process of post-transcriptional mRNA stabilization: following DNA damage, relocalizes from nucleus to cytoplasm and phosphorylates HNRNPA0 and PARN, leading to stabilize GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3.
Catalytic Activity:: ATP + a protein = ADP + a phosphoprotein.
Enzyme Regulation:: ENZYME REGULATION: Activated following phosphorylation by p38-alpha/MAPK14 following various stresses. Inhibited following sumoylation. Specifically inhibited by pyrrolopyridine inhibitors.
Active Site:: ACT_SITE 186 186 Proton acceptor.
Gene Ontology Go:: centrosome
cytoplasm
cytosol
extracellular exosome
nucleoplasm
nucleus
ATP binding
calcium-dependent protein serine/threonine kinase activity
calmodulin binding
calmodulin-dependent protein kinase activity
protein kinase activity
protein serine/threonine kinase activity
signal transducer activity
3'-UTR-mediated mRNA stabilization
activation of MAPK activity
arachidonic acid metabolic process
cellular response to DNA damage stimulus
cellular response to heat
cellular response to vascular endothelial growth factor stimulus
G2 DNA damage checkpoint
gene expression
inflammatory response
innate immune response
inner ear development
leukotriene metabolic process
macropinocytosis
MAPK cascade
MyD88-dependent toll-like receptor signaling pathway
MyD88-independent toll-like receptor signaling pathway
neurotrophin TRK receptor signaling pathway
p38MAPK cascade
peptidyl-serine phosphorylation
positive regulation of tumor necrosis factor biosynthetic process
protein autophosphorylation
protein phosphorylation
Ras protein signal transduction
regulation of cellular response to heat
regulation of interleukin-6 production
regulation of mRNA stability
regulation of tumor necrosis factor production
response to cytokine
response to lipopolysaccharide
response to stress
small molecule metabolic process
stress-activated MAPK cascade
toll-like receptor 10 signaling pathway
toll-like receptor 2 signaling pathway
toll-like receptor 3 signaling pathway
toll-like receptor 4 signaling pathway
toll-like receptor 5 signaling pathway
toll-like receptor 9 signaling pathway
toll-like receptor signaling pathway
toll-like receptor TLR1:TLR2 signaling pathway
toll-like receptor TLR6:TLR2 signaling pathway
TRIF-dependent toll-like receptor signaling pathway
vascular endothelial growth factor receptor signaling pathway
Gene Ontology Biological Process:: 3'-UTR-mediated mRNA stabilization
activation of MAPK activity
arachidonic acid metabolic process
cellular response to DNA damage stimulus
cellular response to heat
cellular response to vascular endothelial growth factor stimulus
G2 DNA damage checkpoint
gene expression
inflammatory response
innate immune response
inner ear development
leukotriene metabolic process
macropinocytosis
MAPK cascade
MyD88-dependent toll-like receptor signaling pathway
MyD88-independent toll-like receptor signaling pathway
neurotrophin TRK receptor signaling pathway
p38MAPK cascade
peptidyl-serine phosphorylation
positive regulation of tumor necrosis factor biosynthetic process
protein autophosphorylation
protein phosphorylation
Ras protein signal transduction
regulation of cellular response to heat
regulation of interleukin-6 production
regulation of mRNA stability
regulation of tumor necrosis factor production
response to cytokine
response to lipopolysaccharide
response to stress
small molecule metabolic process
stress-activated MAPK cascade
toll-like receptor 10 signaling pathway
toll-like receptor 2 signaling pathway
toll-like receptor 3 signaling pathway
toll-like receptor 4 signaling pathway
toll-like receptor 5 signaling pathway
toll-like receptor 9 signaling pathway
toll-like receptor signaling pathway
toll-like receptor TLR1:TLR2 signaling pathway
toll-like receptor TLR6:TLR2 signaling pathway
TRIF-dependent toll-like receptor signaling pathway
vascular endothelial growth factor receptor signaling pathway
Gene Ontology Molecular Function:: ATP binding
calcium-dependent protein serine/threonine kinase activity
calmodulin binding
calmodulin-dependent protein kinase activity
protein kinase activity
protein serine/threonine kinase activity
signal transducer activity
Gene Ontology Cellular Component:: centrosome
cytoplasm
cytosol
extracellular exosome
nucleoplasm
nucleus
Keywords:: 3D-structure
ATP-binding
Alternative splicing
Complete proteome
Cytoplasm
DNA damage
Isopeptide bond
Kinase
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
Serine/threonine-protein kinase
Transferase
Ubl conjugation
Interacts With:: Q00613; P04792; Q16539; Q9QWH1

Names & Taxonomy

Structure

Subcellular location

Function

Publication