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8.A.9 The rBAT Transport Accessory Protein (rBAT) Family

The rBAT (related to b0,+ amino acid transport) proteins have been sequenced from a variety of animals and when expressed in frog oocytes, they cause induction of cationic and neutral amino acid uptake. The ancillary proteins of the SLC3 family of amino acid transporters are esstenial for amino acid transport via the heteromeric SLC7 carriers (Palacín and Kanai 2004). The activities enhanced depend on the cell type. The rBAT and homologous 4F2hc proteins, which like rBAT proteins, stimulate amino acid transport, have 520-690 amino acids and are glycoproteins with a putative hydrophobic TMS and possibly as many as three additional amphipathic TMSs. These proteins are homologous to maltases, α-glucosidases and trehalose 6-P hydrolases. They are probably auxiliary proteins that are required for insertion of or stimulation of the activities of various porters, including some of those of the APC family (TC# 2.A.3). Some of these homologues have been shown to associate with various amino acid porters to form heterodimeric or heterotetrameric protein complexes. Computational analyses have identifies druggable mutations in human rBAT that mediate Cystinuria (Pandey et al. 2020).

The 4F2hc protein is called the cell surface antigen heavy chain, lymphocyte activation antigen and CD98. It activates the cystine/glutamate antiporter (2.A.3.8.5) and other amino acid transporters (Sato et al., 2005). CD98 in intestinal epithelia is an oligomeric and multifunctional protein (Yan et al., 2008). For 4F2hc, functional interaction with LAT1 is mediated by the N-terminal part, comprising the cytoplasmic tail, transmembrane segment and neck, in the absence of the extracellular domain. However, functional association with LAT1 is also supported by the extracellular part of 4F2hc comprising the neck and glycosidase-like domains linked to the complementary part of rBAT (Franca et al. 2005).  The ectodomains of rBAT and 4F2hc are fake or non-functional α-glucosidases (Fort et al. 2021).

rBAT dictates oligomerization of heteromeric amino acid transporters. For example, system b0,+ is a heterotetramer (b0,+AT-rBAT)2 as is system xC- (xCT-rBAT)2 although xCT-4F2hc does not effectively oligomerize (Fernandez et al., 2006). Nevertheless, a single heterodimer is the functional unit in all cases. The cytoplasmic tail and transmembrane domain of rBAT together play a dominant role in selective functional interaction with b(0,+)AT, whereas the extracellular domain of rBAT appears to facilitate specifically L-cystine uptake (Franca et al. 2005).

References associated with 8.A.9 family:

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