Domains paralogy

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... 

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. 

Further discussion of the dysbindin family is limited to dysbindin-1 since little is known about other family members apart from the fact that dysbindin-2B is a casein kinase 1 binding partner and a stem cell factor apoptosis response protein. In contrast, much has been learned about dysbindin-1 since its discovery was reported by Benson et al. (2001). It is the only member of the dysbindin family known to exist in invertebrates, specifically the fruit fly, and may thus date back 600 million years. Unlike all other dysbindin paralogs, it contains a coiled coil domain (CCD) allowing extensive interactions with other proteins. A leucine zipper motif in the CCD changed in the course of evolution in a manner permitting more durable interactions with binding partners. 

Proteins with sequence homology to aaRSs perform diverse cellular functions (5) (Fig. 4b). Some of these proteins resulted from aaRS gene duplications and are called paralogs. Other paralogs are composed of just one domain of an aaRS that has multiple domains. 

Several aaRSs possess amino acid editing domains, which hydrolytically clear mistakes in cis (3) (Table 1). Interestingly however, some archaeal and bacterial synthetases rely on paralogs of editing domains that hydrolyze mischarged products in tram (10, 11). These products include the YbaK and ProX (or PrdX), which edit Ala-tRNA , and AlaX that hydrolyzes mischarged Ser-tRNA and Gly-tRNA . 

Several aaRS-like proteins are involved in metabobc pathways (1). For example, E. coli asparagine synthase, an aspartyl-tRNA synthetase (AspRS)-like enzyme, catalyzes the synthesis of asparagine from aspartate and ATP. A paralog of LysRS-II, called PoxA/GenX, is important for pyruvate oxidase activity in E. coli and Salmonella typhimurium and for virulence in S. typhimurium. The E. coli biotin synthetase/repressor protein (BirA), which has a domain that resembles structurally the seryl-tRNA synthetase (SerRS) catalytic domain, activates biotin to modify posttranslationaUy various metabolic proteins involved in carboxylation and decarboxylation. BirA can also bind DNA and regulate its own transcription using biotin as a corepressor. A histidyl-tRNA synthetase (HisRS)-hke protein from Lactococcus lactis, HisZ is involved in the allosteric activation of the phosphoribosyl-transferase reaction. 

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