Expansion of divergent SEA domains in cell surface proteins and nucleoporin 54

Abstract

SEA (sea urchin sperm protein, enterokinase, agrin) domains, many of which possess autoproteolysis activity, have been found in a number of cell surface and secreted proteins. Despite high sequence divergence, SEA domains were also proposed to be present in dystroglycan based on a conserved autoproteolysis motif and receptor-type protein phosphatase IA-2 based on structural similarity. The presence of a SEA domain adjacent to the transmembrane segment appears to be a recurring theme in quite a number of type I transmembrane proteins on the cell surface, such as MUC1, dystroglycan, IA-2, and Notch receptors. By comparative sequence and structural analyses, we identified dystroglycan-like proteins with SEA domains in Capsaspora owczarzaki of the Filasterea group, one of the closest single-cell relatives of metazoans. We also detected novel and divergent SEA domains in a variety of cell surface proteins such as EpCAM, a/ e-sarcoglycan, PTPRR, collectrin/Tmem27, amnionless, CD34, KIAA0319, fibrocystin-like protein, and a number of cadherins. While these proteins are mostly from metazoans or their single cell relatives such as choanoflagellates and Filasterea, fibrocystin-like proteins with SEA domains were found in several other eukaryotic lineages including green algae, Alveolata, Euglenozoa, and Haptophyta, suggesting an ancient evolutionary origin. In addition, the intracellular protein Nucleoporin 54 (Nup54) acquired a divergent SEA domain in choanoflagellates and metazoans.

Structural assembly of the megadalton-sized receptor for intestinal vitamin B12 uptake and kidney protein reabsorption

“…1 ). A SEA (for Sperm protein, Enterokinase and Agrin) domain is located in the C-terminal part of AMN directly preceding the transmembrane helix 17 . The SEA domain has a classic βαββαβ-fold 18 found in various types of proteins including initiation and elongation factors 19 .…”

A Mechanically Weak Extracellular Membrane-Adjacent Domain Induces Dimerization of Protocadherin-15

“…1 A). For PCDH15, this domain has also been labeled as extracellular linker (EL) (49), protocadherin-15 interacting-channel associated domain (PICA) (48), or sea urchin sperm protein, enterokinase, agrin (SEA) like domain (54)(55)(56). PCDH24 has a similar putative MAD, whereas FAT and CELSR cadherins all have ''unknown'' domains between their cadherin repeats and additional extracellular domains with predicted EGF, EGF-like or LamG folds (details below).…”

Enterokinase Enhances Influenza A Virus Infection by Activating Trypsinogen in Human Cell Lines

“…As its name implies, the canonical SEA domain was first detected in sea urchin sperm protein, and in EK and agrin proteins also, but its function is not well understood, except that it is known to be involved in the autoproteolysis that causes subsequent functional domains to be shed or the protein to be degraded, and it also has an effect on the carbohydrate chains nearby it (List et al, 2006 ). Recent advanced search programs have shown that many molecules contain the SEA domain, including some mucins, glycans, phosphatases, and cadherins (Pei and Grishin, 2017 ). Because the 90-bp exon of EK-X2 is inserted immediately before the autoproteolysis motif in EK, it may affect some EK functions as yet unknown or contribute a new function for the SEA domain.…”