Dysbindin domain

Dysbindin-2 ( Dysbindin Domain-Containing Protein 2, DBNDD2). 124... 

More members of the dysbindin protein family are known in humans than in any other species at present. In articular, there are eight human proteins with dysbindin domains listed by the National Center for Biotechnology Information (NCBI http //www.ncbi.nlm.nih.gov/) and/or by the Universal Protein Resource (UniProt http //www.pir.uniprot.org/index.shtml). They are schematically shown in Figure 2.2-1, which... 

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... 

Human Q9BQY9 1) Dysbindin domain-containing protein 2 (DBNDD2) 2) Hypothalamic protein HSMNP1 DBNDD2 (55861) [15881]... 

Human (NP 001036075) [Q9H9R9] Dysbindin domain-containing protein 1 (DBNDD1), isoform 1 DBNDD1 (79007) [28455] 16q24.3 NM 001042610 158 17.03 (None) (None)... 

Dysbindin domain (DD) locations in humans, mice, rats, and frogs9... 

Dysbindin-3 (=Dysbindin Domain-Containing Protein 1, DBNDD1)... 

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. 

Evolutionary conservation of predicted coiled-coil domains (CCDs) in dysbindin-1 orthologs of diverse vertebrate species and an invertebrate (i.e.. Drosophila melanogaster). For explanation of the graphs, see O Figure 2.2-3 legend... 

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. 

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