Protein Domain : IPR021160

Type:  Family Name:  Mitogen-activated protein (MAP) kinase kinase kinase kinase
Description:  Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process. Protein kinases fall into three broad classes, characterised with respect to substrate specificity []:Serine/threonine-protein kinasesTyrosine-protein kinasesDual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins)Protein kinase function is evolutionarily conserved from Escherichia coli to human []. Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation []. Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved [], leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases [].Eukaryotic serine-threonine mitogen-activated protein (MAP) kinases are key regulators of cellular signal transduction systems and are conserved from Saccharomyces cerevisiae(Baker's yeast) to human beings. MAPK pathways are signalling cascades differentially regulated by growth factors, mitogens, hormones and stress which mediate cell growth, differentiation and survival. MAPK activity is regulated through a (usually) three-tiered cascade composed of a MAPK, a MAPK kinase (MAPKK, MEK) and a MAPK kinase kinase (MAPKK, MEKK). Substrates for the MAPKs include other kinases and transcription factors []. Mammals express at least four distinctly related groups of MAPKs, extracellularly-regulated kinases (ERKs), c-jun N-terminal kinases (JNKs), p38 proteins and ERK5. Plant MAPK pathways have attracted increasing interest, resulting in the isolation of a large number of different components of MAPK cascades. MAPKs play important roles in the signalling of most plant hormones and in developmental processes []. In the budding yeast S. cerevisiae, four separate but structurally related mitogen-activated protein kinase (MAPK)activation pathways are known, regulating mating, cell integrity and osmosity [].Enzymes in this family are characterised by two domains separated by a deep channel where potential substrates might bind. The N-terminal domain creates a binding pocket for the adenine ring of ATP, and the C-terminal domain contains the catalytic base, magnesium binding sites and phosphorylation lip []. Almost all MAPKs possess a conserved TXY motif in which both the threonine andtyrosine residues are phosphorylated during activation of the enzyme by upstream dual-specificity MAP kinase kinases (MAPKKs).This group represents a mitogen-activated protein kinase kinase kinase kinase, which may play a role in the response to environmental stress. It appears to act upstream of the JUN N-terminal pathway []. Short Name:  MAPKKKK

0 Child Features

5 Contains

DB identifier Type Name
IPR000719 Domain Protein kinase domain
IPR011009 Domain Protein kinase-like domain
IPR002290 Domain Serine/threonine/dual specificity protein kinase, catalytic domain
IPR001180 Domain Citron homology (CNH) domain
IPR017441 Binding_site Protein kinase, ATP binding site

1 Cross References

Identifier
PIRSF038172

0 Found In

2 GO Annotations

GO Term Gene Name
GO:0004672 IPR021160
GO:0005524 IPR021160

2 Ontology Annotations

GO Term Gene Name
GO:0004672 IPR021160
GO:0005524 IPR021160

0 Parent Features

0 Proteins

10 Publications

First Author Title Year Journal Volume Pages PubMed ID
            3291115
            12368087
            12471243
            15078142
            15320712
            11242034
            11057833
            8607979
            8910361
            9275185