Background: | Stress-activated serine/threonine-protein kinase involved in cytokines production, endocytosis, cell migration, chromatin remodeling 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. MAPKAPK2 and MAPKAPK3, share the same function and substrate specificity, but MAPKAPK3 kinase activity and level in protein expression are lower compared to MAPKAPK2. Phosphorylates HSP27/HSPB1, KRT18, KRT20, 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, such as 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. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. Also acts as a modulator of Polycomb-mediated repression. |
Synonyms: | MAP kinase-activated protein kinase 3; EC 2.7.11.1; MAPK-activated protein kinase 3; MAPKAP kinase 3; MAPKAPK-3 |
UniProt Protein Function: | MAPKAPK3: a member of the MAPKAPK family of protein kinases. Activated by growth inducers and stress stimulation of cells. In vitro studies demonstrated that ERK, p38 MAP kinase and Jun N-terminal kinase were all able to phosphorylate and activate this kinase, which suggested the role of this kinase as an integrative element of signaling in both mitogen and stress responses. This kinase was reported to interact with, phosphorylate and repress the activity of E47, which is a basic helix-loop-helix transcription factor known to be involved in the regulation of tissue-specific gene expression and cell differentiation. |
UniProt Protein Details: | Protein type:Protein kinase, CAMK; Protein kinase, Ser/Thr (non-receptor); Kinase, protein; EC 2.7.11.1; CAMK group; MAPKAPK family; MAPKAPK subfamily Chromosomal Location of Human Ortholog: 3p21.3 Cellular Component: cytoplasm; cytosol; nucleoplasm; nucleus Molecular Function:ATP binding; calcium-dependent protein serine/threonine kinase activity; calmodulin binding; calmodulin-dependent protein kinase activity; MAP kinase kinase activity; protein binding; protein serine/threonine kinase activity; signal transducer activity Biological Process: activation of MAPK activity; cell surface receptor linked signal transduction; innate immune response; MyD88-dependent toll-like receptor signaling pathway; MyD88-independent toll-like receptor signaling pathway; nerve growth factor receptor signaling pathway; peptidyl-serine phosphorylation; protein amino acid autophosphorylation; Ras protein signal transduction; response to cytokine stimulus; response to lipopolysaccharide; response to stress; signal transduction; 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; vascular endothelial growth factor receptor signaling pathway |
NCBI Summary: | This gene encodes a member of the Ser/Thr protein kinase family. This kinase functions as a mitogen-activated protein kinase (MAP kinase)- activated protein kinase. MAP kinases are also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This kinase was shown to be activated by growth inducers and stress stimulation of cells. In vitro studies demonstrated that ERK, p38 MAP kinase and Jun N-terminal kinase were all able to phosphorylate and activate this kinase, which suggested the role of this kinase as an integrative element of signaling in both mitogen and stress responses. This kinase was reported to interact with, phosphorylate and repress the activity of E47, which is a basic helix-loop-helix transcription factor known to be involved in the regulation of tissue-specific gene expression and cell differentiation. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Sep 2011] |
UniProt Code: | Q16644 |
NCBI GenInfo Identifier: | 74762148 |
NCBI Gene ID: | 7867 |
NCBI Accession: | Q16644.1 |
UniProt Secondary Accession: | Q16644,B5BU67, |
UniProt Related Accession: | Q16644 |
Molecular Weight: | |
NCBI Full Name: | MAP kinase-activated protein kinase 3 |
NCBI Synonym Full Names: | mitogen-activated protein kinase-activated protein kinase 3 |
NCBI Official Symbol: | MAPKAPK3 |
NCBI Official Synonym Symbols: | 3PK; MK-3; MAPKAP3; MAPKAP-K3; MAPKAPK-3 |
NCBI Protein Information: | MAP kinase-activated protein kinase 3 |
UniProt Protein Name: | MAP kinase-activated protein kinase 3 |
UniProt Synonym Protein Names: | Chromosome 3p kinase; 3pK |
Protein Family: | MAP kinase-activated protein kinase |
UniProt Gene Name: | MAPKAPK3 |
UniProt Entry Name: | MAPK3_HUMAN |