<p>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 [<cite idref="PUB00005115"/>]:</p><p> <ul> <li>Serine/threonine-protein kinases</li><li>Tyrosine-protein kinases</li><li>Dual specific protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins)</li> </ul> </p><p>Protein kinase function has been evolutionarily conserved from <taxon tax_id="562">Escherichia coli</taxon> to human [<cite idref="PUB00020114"/>]. Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation [<cite idref="PUB00015362"/>]. 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 [<cite idref="PUB00034898"/>], leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases [<cite idref="PUB00034899"/>].</p><p>Haem-based sensor proteins are important regulators of the adaptive response to changing levels of oxygen, carbon monoxide and nitric oxide in a wide variety of organisms. These proteins act as haem sensors by coupling a regulatory haem-binding domain to a second motif that acts as a transmitter for the haem-based signal. These transmitter motifs are commonly found in signal transduction molecules and include protein kinases, cyclic phosphodiesterases, chemotaxis receptors, and basic helix-loop-helix and helix-turn-helix transcription factors. In contrast, the regulatory domains found in these sensors contain novel motifs for haem-binding. These include the haem-binding Per-Arnt-Sim (PAS) domain, the Globin-Coupled Sensor (GCS), the cAMP-like-receptor domain, and the Haem-NO-Binding (HNOB) domain [<cite idref="PUB00035227"/>].</p> <p>Proteins in this entry contain one or more haem regulatory motifs and phosphorylate the alpha subunit of EIF-2 in response to various stress conditions to shut down translation initiation.</p> Haem-Regulated Eukaryotic Initiation Factor EIF-2-Alpha Kinase