Mitogen-activated protein (MAP) kinase, ERK3/4 (IPR008350)
Short name: MAPK_ERK3/4
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 [PMID: 3291115]:
- Serine/threonine-protein kinases
- Tyrosine-protein kinases
- Dual 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 [PMID: 12471243]. Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation [PMID: 12368087]. 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 [PMID: 15078142], leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases [PMID: 15320712].
MAP (Mitogen Activated Protein) kinases participate in kinase cascades, whereby at least 3 protein kinases act in series, culminating in activation of MAP kinase [PMID: 10487205]. MAP kinases are activated by dual phosphorylation on both tyrosine and threonine residues of a conserved TXY motif.
ERKs (Extracellularly Regulated Kinases) belong to the family of MAP kinases. ERK 3 (also known as MAPK6) and ERK 4 (also known as MAPK4), however, have no more similarity to ERK 1 and 2 than do the other major classes of MAP kinase, JNK and p38. ERK3 is constitutively located in the nucleus, despite the lack of a traditional nuclear localisation signal [PMID: 10657254]. It is unique among MAP kinases in containing in its activation loop only a single phosphorylation site (serine 189) - other MAP kinases have the sequence TXY in this loop, but ERK3 contains SEG, with glycine in place of tyrosine.
ERK3 has no homologues in nematode or yeast genomes, indicating that it may have arisen from a relatively late gene duplication. Its structure, based on similarity to ERK2, contains segregated alpha and beta regions.
- PR01771 (ERK3ERK4MAPK)