Protein: 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) (P49137)
Organism: Homo sapiens (Human)
Function: Stress-activated serine/threonine-protein kinase involved in cytokine 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, CEP131, ELAVL1, HNRNPA0, HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Phosphorylates HSF1; leading to the interaction with HSP90 proteins and inhibiting HSF1 homotrimerization, DNA-binding and transactivation activities. Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to the dissociation of HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impairment of 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 the regulation of 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 transcripts. Phosphorylates CEP131 in response to cellular stress induced by ultraviolet irradiation which promotes binding of CEP131 to 14-3-3 proteins and inhibits formation of novel centriolar satellites. 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 stabilization of GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3.
Subcellular location: Cytoplasm {ECO:0000269|PubMed:20932473}. Nucleus {ECO:0000269|PubMed:20932473}. Note=Phosphorylation and subsequent activation releases the autoinhibitory helix, resulting in the export from the nucleus into the cytoplasm.
Sequence: MLSNSQGQSPPVPFPAPAPPPQPPTPALPHPPAQPPPPPPQQFPQFHVKSGLQIKKNAIIDDYKVTSQVLGLGINGKVLQIFNKRTQEKFALKMLQDCPKARREVELHWRASQCPHIVRIVDVYENLYAGRKCLLIVMECLDGGELFSRIQDRGDQAFTEREASEIMKSIGEAIQYLHSINIAHRDVKPENLLYTSKRPNAILKLTDFGFAKETTSHNSLTTPCYTPYYVAPEVLGPEKYDKSCDMWSLGVIMYILLCGYPPFYSNHGLAISPGMKTRIRMGQYEFPNPEWSEVSEEVKMLIRNLLKTEPTQRMTITEFMNHPWIMQSTKVPQTPLHTSRVLKEDKERWEDVKEEMTSALATMRVDYEQIKIKKIEDASNPLLLKRRKKARALEAAALAH
InterPro domains: - IPR011009: Protein kinase-like domain superfamily (homologous_superfamily) [59-369]
- IPR008271: Serine/threonine-protein kinase, active site (active_site) [182-194]
- IPR017441: Protein kinase, ATP binding site (binding_site) [70-93]
- IPR000719: Protein kinase domain (domain) [64-325]
- IPR027442: MAP kinase activated protein kinase, C-terminal (homologous_superfamily) [333-400]
Interaction partners: - Mitogen-activated protein kinase 14
- Heat shock protein beta-1
- Mitogen-activated protein kinase 11
- mRNA decay activator protein ZFP36L1
- mRNA decay activator protein ZFP36
- Mitogen-activated protein kinase 13
- Mitogen-activated protein kinase 12
- MAP kinase-activated protein kinase 3
- Lymphocyte-specific protein 1
- Dual specificity mitogen-activated protein kinase kinase 6
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0016740 (transferase activity), GO:0140096 (catalytic activity, acting on a protein), GO:0005515 (protein binding), GO:0016772 (transferase activity, transferring phosphorus-containing groups), GO:0004672 (protein kinase activity), GO:0004674 (protein serine/threonine kinase activity), GO:0016301 (kinase activity), GO:0016773 (phosphotransferase activity, alcohol group as acceptor), GO:0004712 (protein serine/threonine/tyrosine kinase activity), GO:0004708 (MAP kinase kinase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0044419 (biological process involved in interspecies interaction between organisms), GO:0002376 (immune system process), GO:0023052 (signaling), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0009605 (response to external stimulus), GO:0048856 (anatomical structure development), GO:0042221 (response to chemical), GO:0048584 (positive regulation of response to stimulus), GO:0019222 (regulation of metabolic process), GO:0051240 (positive regulation of multicellular organismal process), GO:0002684 (positive regulation of immune system process), GO:0006807 (nitrogen compound metabolic process), GO:0002682 (regulation of immune system process), GO:0051239 (regulation of multicellular organismal process), GO:0071704 (organic substance metabolic process), GO:0009892 (negative regulation of metabolic process), GO:0065008 (regulation of biological quality), GO:0044237 (cellular metabolic process), GO:0009607 (response to biotic stimulus), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0009893 (positive regulation of metabolic process), GO:0051716 (cellular response to stimulus), GO:0002253 (activation of immune response), GO:0048523 (negative regulation of cellular process), GO:0051707 (response to other organism), GO:0007154 (cell communication), GO:0007165 (signal transduction), GO:0044238 (primary metabolic process), GO:0002764 (immune response-regulating signaling pathway), GO:0032103 (positive regulation of response to external stimulus), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:0043487 (regulation of RNA stability), GO:1901564 (organonitrogen compound metabolic process), GO:0043207 (response to external biotic stimulus), GO:0035556 (intracellular signal transduction), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0080134 (regulation of response to stress), GO:0019538 (protein metabolic process), GO:0048513 (animal organ development), GO:0060255 (regulation of macromolecule metabolic process), GO:0002700 (regulation of production of molecular mediator of immune response), GO:0032101 (regulation of response to external stimulus), GO:1901700 (response to oxygen-containing compound), GO:0001817 (regulation of cytokine production), GO:0031324 (negative regulation of cellular metabolic process), GO:0043170 (macromolecule metabolic process), GO:0010033 (response to organic substance), GO:0002218 (activation of innate immune response), GO:0006793 (phosphorus metabolic process), GO:0009894 (regulation of catabolic process), GO:0002831 (regulation of response to biotic stimulus), GO:0050776 (regulation of immune response), GO:0002757 (immune response-activating signaling pathway), GO:0002833 (positive regulation of response to biotic stimulus), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0002702 (positive regulation of production of molecular mediator of immune response), GO:0002697 (regulation of immune effector process), GO:0009617 (response to bacterium), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0050778 (positive regulation of immune response), GO:0031323 (regulation of cellular metabolic process), GO:0009895 (negative regulation of catabolic process), GO:0001819 (positive regulation of cytokine production), GO:0031349 (positive regulation of defense response), GO:0002699 (positive regulation of immune effector process), GO:0080090 (regulation of primary metabolic process), GO:0031347 (regulation of defense response), GO:0045089 (positive regulation of innate immune response), GO:0002720 (positive regulation of cytokine production involved in immune response), GO:0032496 (response to lipopolysaccharide), GO:0002758 (innate immune response-activating signaling pathway), GO:0045088 (regulation of innate immune response), GO:0043488 (regulation of mRNA stability), GO:0031330 (negative regulation of cellular catabolic process), GO:0000165 (MAPK cascade), GO:0002718 (regulation of cytokine production involved in immune response), GO:0002237 (response to molecule of bacterial origin), GO:0010628 (positive regulation of gene expression), GO:0006796 (phosphate-containing compound metabolic process), GO:0010468 (regulation of gene expression), GO:0031098 (stress-activated protein kinase signaling cascade), GO:0036211 (protein modification process), GO:0043412 (macromolecule modification), GO:0043489 (RNA stabilization), GO:0033993 (response to lipid), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0051252 (regulation of RNA metabolic process), GO:0031329 (regulation of cellular catabolic process), GO:0051253 (negative regulation of RNA metabolic process), GO:0045934 (negative regulation of nucleobase-containing compound metabolic process), GO:1902373 (negative regulation of mRNA catabolic process), GO:0061013 (regulation of mRNA catabolic process), GO:0051403 (stress-activated MAPK cascade), GO:0002221 (pattern recognition receptor signaling pathway), GO:1903312 (negative regulation of mRNA metabolic process), GO:0006468 (protein phosphorylation), GO:1902369 (negative regulation of RNA catabolic process), GO:0016310 (phosphorylation), GO:0048255 (mRNA stabilization), GO:1903311 (regulation of mRNA metabolic process), GO:0010608 (post-transcriptional regulation of gene expression), GO:0060907 (positive regulation of macrophage cytokine production), GO:0002224 (toll-like receptor signaling pathway), GO:0002755 (MyD88-dependent toll-like receptor signaling pathway)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005829 (cytosol), GO:0005737 (cytoplasm), GO:0031974 (membrane-enclosed lumen), GO:0005654 (nucleoplasm), GO:0043233 (organelle lumen), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0031981 (nuclear lumen), GO:0005634 (nucleus)