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. 2020 Oct 9;16(4):700–706. doi: 10.4103/1673-5374.295332

Figure 4.

Figure 4

Consensus sequence for CK2 mediated phosphorylation.

The AIS motif of Nav channels and the requirements for CK2-mediated phosphorylation. S represents serine residues; E refers to glutamate, and D refers to aspartate. D and E assist CK2 to find suitable serine for phosphorylation (Meggio and Pinna, 2003; Nishi et al., 2014). The positions of residues within the motif are represented by n – 1, n, n + 1, and so on. The potential targets of CK2 for phosphorylation are serine/threonine residues in a motif surrounded by any of the acidic residues, such as E and D. CK2-mediated phosphorylation of serine/threonine requires at least one acidic residue between the n – 4 to n + 7 positions (Meggio and Pinna, 2003; Nishi et al., 2014). The most favorable serine for CK2-mediated phosphorylation is when an acidic residue is present at the n + 3 position within a motif. In some instances, the phosphorylation by CK2 is enabled when an acidic residue is present at the n + 1 position and this is the second most preferred position after n + 3 (Meggio and Pinna, 2003; Nishi et al., 2014). The minimum consensus sequence for CK2 phosphorylation is S/T, X, X, D/E/pS/pT, where S/T is a serine or threonine in the nth position, followed by any type residue at the n + 1 and n + 2 positions. At the n + 3 position, D/E/pS/pT stands for aspartate (D) or glutamate (E) or phosphorylated serine/threonine (pS/ pT), respectively. Phosphorylated serine or threonine mimics the function of acidic residues and makes serine/threonine at the n position suitable for CK2 phosphorylation. The presence of basic residues (lysine, proline, and lysine) at the n + 1, n + 2, or n + 3 positions has a negative impact on CK2-mediated phosphorylation. In this figure, the presence of a negative residue (E) at n + 3 in the sequence makes S at the nth position suitable for phosphorylation by CK2 (Fache et al., 2004). S at the nth position is phosphorylated first because it is near the N-terminal when compared to the other serine residues. Similarly, other serine residues in the AIS motif can be identified as targets for CK2 by assuming them at n positions and by checking nearby for the presence of negative residues (D/E/pS/pT). AIS: Axon initial segment; CK2: casein kinase 2; Nav: voltage-gated sodium channel.