# SEA and GATOR 10 Years Later
## 4 Structural Features of the SEA and GATOR Complexes
### Seacat/Gator2  
SEACAT and GATOR2 have components that moonlight between functionally unrelated complexes and are structurally connected with vesicle-coating scaffolds. The SEACAT/GATOR2 complex closely resembles the membrane coating assemblies, such as COPII vesicles, nuclear pore complexes and HOPS/CORVET complexes [8; 31; 32; 33]. It also shares common subunits with both COPII (Sec13/SEC13) and nuclear pore complex (Sec13/SEC13 and Seh1/SEH1L). Sea4/MIOS contains N-terminal WD40 repeats arranged into a \(\beta\)-propeller structure followed by an \(\alpha\)-solenoid stretch, which is a structure that is characteristic for proteins that form oligomeric coats (e.g., clathrin and Sec31) in vesicle-coating complexes [3; 33] (Figure 2B). Furthermore, every protein in SEACAT contains a \(\beta\)-propeller (and Sea3 probably has two \(\beta\)-propellers), a domain common in coating assemblies [34]. Lastly, there are two dimers, Seh1-Sea4 and Sec13-Sea3 [3; 13], that could be analogues to the Sec13-Sec31 dimer, which forms the structural unit of the COPII complex [35]. These dimeric interactions in the SEACAT are most probably conserved, because it was found that the Seh1 in _Drosophila_ also directly interacts with Sea4/Mio [36].  
Sea4 also contains a C-terminal RING domain, which, together with its \(\beta\) -propeller and \(\alpha\) -solenoid motifs, makes it closely resemble several protein subunits of the homotypic fusion and protein sorting (HOPS) and class C core vacuole/endosome tethering (CORVET) complexes, which have been implicated in the tethering of membranes prior to their fusion. HOPS and CORVET are associated with the vacuoles/lysosomes and endosomes, respectively, and play a role in endosomal and vacuolar assembly and trafficking, as well as in nutrient transport and autophagy [32; 37]. Sea2/WDR24 and Sea3/WDR59 also have a C-terminal RING domain. Clusters of RING domains are associated with E3 ubiquitin ligase activity, suggesting SEACAT might have such a role. In _S. cerevisiae_, the RING domains appear to be crucial for maintaining the interactions between Sea2, Sea3, Sea4 and the rest of the complex. For example, Sea4 that lacks the RING domain can only interact with Seh1, whereas Sea2 or Sea3 without the RING domain are no longer able to interact with any of the SEACAT complex components [13]. In addition, Sea3 contains an RWD domain that is enriched in \(\beta\)-sheets and common in proteins that also contain a RING motif and a \(\beta\)-propeller [38]. The RWD domain of Sea3 significantly resembles the RWD domain of the GCN2 protein, which is involved in general amino acid sensing and that of ubiquitin-conjugating E2 enzymes [39]. Given that SEACAT contains three proteins with RING domains, as well as numerous \(\beta\)-propeller domains that can mediate the recognition of phospho-substrate within E3 ligase complexes [40], it will be very interesting to investigate whether SEACAT/GATOR2 can act as a E3 ubiquitin ligase, and if this is the case, what are its possible targets.  
The presence of the same folds and fold arrangements in both the SEA complex and in coating and tethering assemblies, and the fact that they contain the same \"moonlighting\" components, are suggestive that these complexes share a common evolutionary origin (see below). The majority of intracellular membranes are likely a result of the evolutionary expansion of an ancestral membrane-curving module--termed the \"protocoatomer\" complex [31; 34]. The SEA complex is a member of the coatomer group, and its existence, thus, provides further evidence that an expansion of the protocoatomer family underpins much of the functional diversity of the endomembrane system.