9.B.9.1.1
Galectin-9 or Lgals9, but also called the Urate transporter (UAT).  Galectin 9 is reported to be the sugar-regulated urate transporter/channel UAT. It is of 354 aas with an uncertain number of TMSs. UAT is a multifunctional protein that can function as a urate channel/transporter, a regulator of thymocyte-epithelial cell interactions, a tumor antigen, an eosinophil chemotactic factor, and a mediator of apoptosis (Lipkowitz et al. 2002). The urate channel activity is regulated by sugars and adenosine (Lipkowitz et al. 2002). The presence and possible functions of at least 4 isoforms of UAT and a closely related gene hUAT2 were discussed (Lipkowitz et al. 2002). UAT is targeted to the plasma membranes of multiple epithelium-derived cell lines and, in polarized cells, is targeted to both apical and basolateral membranes. The amino and carboxy termini of UAT were both detected on the cytoplasmic side of plasma membranes, whereas cell surface biotinylation studies demonstrated that UAT is not merely a cytosolic membrane-associated protein but contains at least one extracellular domain. UAT is capable of forming both homo- and hetero-multimers (Rappoport et al. 2001). Recombinant UAT prepared from a cloned rat renal cDNA library functions as a selective voltage-sensitive urate transporter/channel when in lipid bilayers. UAT may be the mammalian electrogenic urate transporter. Two compounds, oxonate (a competitive uricase inhibitor) and pyrazinoate, that inhibit renal electrogenic urate transport also block UAT activity. Of note, oxonate selectively blocks from the cytoplasmic side of the channel while pyrazinoate only blocks from the channel's extracellular face. Like oxonate, anti-uricase (an electrogenic transport inhibitor) also selectively blocks channel activity from the cytoplasmic side. Adenosine blocks from the extracellular side exclusively while xanthine blocks from both sides. These effects are consistent with newly identified regions of homology to uricase and the adenosine A1/A3 receptor in UAT and localize these homologous regions to the cytoplasmic and extracellular faces of UAT, respectively. Additionally, computer analyses identified four putative alpha-helical transmembrane domains, two beta sheets, and blocks of homology to the E and B loops of aquaporin-1 within UAT. The experimental observations substantiate the proposal that UAT is the  renal electrogenic urate transporter with a proposed molecular structure (Leal-Pinto et al. 1999). The human urate transporter/channel, hUAT, has also been characterized (Leal-Pinto et al. 2002). Galectin-9C is 71% identical to this protein (Pang et al. 2022).