About Casein Kinase 1 / CK1:
The Casein Kinase 1 are protein kinases that are serine/threonine-selective enzymes. They are regulators of signal transduction pathways in most eukaryotic cell types. They are also involved in various other factors when they’re CK1 isoforms, including DNA repair and transcription, circadian rhythms, and Wnt signaling, among others.
CK1 kinases are found in various eukaryotic organisms, including humans. Several different family members (sometimes thought of as isoforms that are encoded by distinct genes) are possessed by mammals -- these are alpha, beta 1, gamma 1, gamma 2, gamma 3, delta, and epsilon. These isoforms have a range from 22 to 55 kDa, and have been found in membranes, nucleus, and cytoplasm of eukaryotes. In their kinase domains, the family members have the highest homology. They are different from other protein kinases because there is a sequence of S-I-N rather A-P-E in the kinase domain VIII.
There is a similar substrate specificity in vitro between family members. The substrate aspect is believed to be regulated in vivo via subcellular localisation and docking sites. An example of a consensus phosphorylation site is S/Tp-X-X-S/T; in this instance, S/Tp is a phospho-serine or phospho-threonine. X is an amino acid. The underlined residues refer to the target site. In this case, the CKI consensus site needs to be primed by another kinase. CK1 will also phosphorylate another, related unprimed site. Optimally, this would contain a cluster of acidic amino acids N-terminal, to the target S/T, including some acidic residue at n - 3 and a hydrophobic c-terminal to the target S/T. If there’s only an isolated acidic residue in the n- 3 position, then it will not be efficient for CK1 phosphorylation. In other important targets, such as NF-AT and beta-catenin, there is no requirement for CK1 n - 3 priming. Rather, it phosphorylates the first serine in the S-L-S sequence. This is followed by a cluster of acidic resides.
In terms of the role of CK1, activity relating to casein kinase was found to be present in nearly all cell types. They are also generally associated with multiple enzymes.
It has been observed that DBT physically interacts with PER in vitro and in vivo. This creates a stable PER complex throughout the circadian cycle. If the PER has been phosphorylated by DBT, it will be recognised by the Slimb protein -- this is a component of the Skp1/Cullin/F-Box protein, which is the process of the degraded proteins through proteasome.
CK1 can play a role in human diseases. The inhibition of CK1 might help with aberrant circadian rhythm. Mutation of CK1 could result in Familial Advanced Sleep Phase Syndrome. There is also some evidence to suggest that CK1 may play a role in what time of the day a person is at their best; whether they’re a morning or an evening person, essentially. This is connected to the length of the CK1 phosphorylation site.