PEST domains

Dysbindin family paralogs and isoforms known in humans. See textQ Section 2.2.3 for explanation of segmentation of the proteins into an amino terminal region (NTR), coiled-coil domain (CCD) divided into two helices (HI and H2), and a carboxy terminal region (CTR) consisting of the dysbindin domain (DD), PEST domain (PD), and uncharacterized areas X1-X3. Dysbindin-1 B is not found in the mouse... 

Dysbindin-IA is the full-length isoform, the mouse ortholog of which was the first dysbindin protein identified (Benson et al., 2001). This is the protein meant when dysbindin is used without qualification. Dysbindin-1A is a 351 aa protein in humans orthologs in other species are 339-362 aa in length. Such orthologs have been identified not only in humans and mice, but also in the cow, pig, rat, chicken, frog, zebrafish, and amphioxus ( Table 2.2-1). There is also some evidence for dysbindin-lA in sheep (NP 01119821) and the chimpanzee (XP 001169961) in the NCBI database. All known dysbindin-lA orthologs have one or more PEST domain at or near the end of the CTR (e.g., see Table 2.2-3). 

Clear PEST domains in dysbindin proteins3 (i.e., aa sequences with PEST scores > 5.0)... 

Dysbindin-lC is a 270 aa protein in humans and a 271 aa protein in mice ( Table 2.2-1) in both species it lacks an NTR and thus begins with the CCD ( Figures 2.2-1 and O 2.2-3). It is otherwise identical to dysbindin-1 A, but not a degradation product of that isoform since it is the product of a different mRNA. While the first promoter in DTNBP1 probably drives transcription for dysbindin-1 A, the second promoter in that gene may drive transcription for dysbindin-1C (see Figure 2.2-8b). At the end of the CTR in both these isoforms is a clear PEST domain ( Table 2.2-3). 

As illustrated in Figure 2.2-1, dysbindin-2 consists of an NTR of variable length and a relatively long CTR. The latter consists of the DD ( Table 2.2-2), X segments 1-3, and a PEST domain (O Table 2.2-3). As noted above, we discuss the various segments of dysbindin proteins later in Section 2.2.3. 

As illustrated in Figure 2.2-1, dysbindin-3 consists of an NTR and a CTR made up of the DD and X segments 1 and 2. This paralog has no clear PEST domain as discussed in Section 2.2.33.2. Dysbindin-3 differs from both dysbindin-1 and -2 in several ways identified in Section 2.2.2.2.2. 

Signal Response Ankyrin Repeat terminal PEST Domain (SRD) containing Dom n sequence... 

Detailed analysis of the sequence reveals the presence of a lipocalin motif (amino acids 108-121) (Bugos et al., 1998). This motif was also described for the violaxanthin de-epoxidase. Apart from this motif, which would imply a similar tertiary structure, there are no other common sequences between the two proteins. It is realistic to consider that the de-epoxidase and the epoxidase enzymes might have the same basic tertiary structure considering that they both function on the same molecule (anthera-xanthin). Sequence analysis of the pepper ZE cDNA also showed that it contained possible PEST domains, conserved regions identified in rapidly degraded proteins (Rogers et al, 1986). 

Liu Z.P., Galindo R.L., and Wasserman S.A. 1997. A role for CKll phosphorylation of the cactus PEST domain in dorsoventral patterning of the Drosophila embryo. Genes Dev. 11 3413-3422. 

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