Names & Taxonomy

Uniprot ID:
Q16644
Entry Name:
MAPK3_HUMAN
Status:
reviewed
Protein Names:
MAP kinase-activated protein kinase 3 (MAPK-activated protein kinase 3) (MAPKAP kinase 3) (MAPKAP-K3) (MAPKAPK-3) (MK-3) (EC 2.7.11.1) (Chromosome 3p kinase) (3pK)
Gene Names:
MAPKAPK3
Gene Names Primary:
MAPKAPK3
Organism:
Homo sapiens (Human)

Structure

Length:
382
Sequence:
MDGETAEEQGGPVPPPVAPGGPGLGGAPGGRREPKKYAVTDDYQLSKQVLGLGVNGKVLECFHRRTGQKCALKLLYDSPKARQEVDHHWQASGGPHIVCILDVYENMHHGKRCLLIIMECMEGGELFSRIQERGDQAFTEREAAEIMRDIGTAIQFLHSHNIAHRDVKPENLLYTSKEKDAVLKLTDFGFAKETTQNALQTPCYTPYYVAPEVLGPEKYDKSCDMWSLGVIMYILLCGFPPFYSNTGQAISPGMKRRIRLGQYGFPNPEWSEVSEDAKQLIRLLLKTDPTERLTITQFMNHPWINQSMVVPQTPLHTARVLQEDKDHWDEVKEEMTSALATMRVDYDQVKIKDLKTSNNRLLNKRRKKQAGSSSASQGCNNQ
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Nucleus

Function

Function:
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.
Catalytic Activity:
ATP + a protein = ADP + a phosphoprotein.
Enzyme Regulation:
ENZYME REGULATION: Activated following phosphorylation by p38-alpha/MAPK14 following various stresses. Inhibited by ligand 5B (2'--5',6'-dihydrospiro- 4'(1'h)-one) and ligand P4O (2--1,5,6,7-tetrahydro- 4h-pyrrolopyridin-4-one), 2 ATP-competitive inhibitors.
Active Site:
ACT_SITE 166 166 Proton acceptor.
Gene Ontology Go:
cytoplasm
cytosol
nucleoplasm
nucleus
ATP binding
calcium-dependent protein serine/threonine kinase activity
calmodulin binding
calmodulin-dependent protein kinase activity
MAP kinase kinase activity
protein serine/threonine kinase activity
signal transducer activity
activation of MAPK activity
cell surface receptor signaling pathway
innate immune response
macropinocytosis
MyD88-dependent toll-like receptor signaling pathway
MyD88-independent toll-like receptor signaling pathway
neurotrophin TRK receptor signaling pathway
peptidyl-serine phosphorylation
protein autophosphorylation
Ras protein signal transduction
response to cytokine
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
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:
activation of MAPK activity
cell surface receptor signaling pathway
innate immune response
macropinocytosis
MyD88-dependent toll-like receptor signaling pathway
MyD88-independent toll-like receptor signaling pathway
neurotrophin TRK receptor signaling pathway
peptidyl-serine phosphorylation
protein autophosphorylation
Ras protein signal transduction
response to cytokine
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
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
MAP kinase kinase activity
protein serine/threonine kinase activity
signal transducer activity
Gene Ontology Cellular Component:
cytoplasm
cytosol
nucleoplasm
nucleus
Keywords:
3D-structure
ATP-binding
Acetylation
Complete proteome
Cytoplasm
Kinase
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
Serine/threonine-protein kinase
Transferase
Interacts With:
P27958; P04792; Q16539

Publication

PubMed ID:
8626550 8622688 19054851 15489334 8774846 10383393 10781029 15302577 15563468 18021073 19413330 20599781 18508601 21269460 22814378 19937655 21565500 17344846