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2.A.92 The Choline Transporter-like (CTL) Family

The CTL family (solute carrier family 44; XYPPX repeat family) includes several characterized choline transporters including CTL-1 and CTL-2. Many sequence divergent family members including several paralogues in a single organism. Some of them include a hydrophobic C-terminal Duf580 domains (residues 260-625 in CTL-1). These proteins may have 9-13 TMSs. A hydrophilic domain between putative TMSs 1 and 2 is present in CTL-1 and CTL-2. The human CTL-1 is called the CDW92 antigen.  This protein, also called SLC44A1, is present in both the plasma and mitochondrial membranes where it is able to transport choline at high affinity and in a Na+-independent manner.The properties and involvement in human diseases has been reviewed (Traiffort et al. 2013). One member of the family, TC# 2.A.92.1.7; SLC44A4, is a highly glycolsylated thiamine pyrophosphate uptake porter (Nabokina et al. 2016). Members of this family have been proposed to have the SLC44 fold (Ferrada and Superti-Furga 2022).

The topologies of skeletal muscle-specific choline transporter-like protein 1 (mCTL1) has been identified, and mCTL1 mRNA and protein expression have been characterized (Yuan et al., 2004). mCTL1 is a 653-amino-accid protein with 8-11 putative transmembrane domains, three N-glycosylations sites and seven protein kinase C phosphorylation sites. The mCTL1 gene is localized to chromosome 4B2, at 182 kb in length, and encoded by 17 exons. Although the mCTL1 mRNA was expressed in several mouse tissues such as muscle, brain, heart and testis, the protein analyses of multiple tissues and membrane vesicles revealed that mCTL1 is exclusively expressed in skeletal muscle. Expression of His-tagged mCTL1 in Cos-7 cells produced an increase in saturable choline uptake that was sensitive to a Na+-ion gradient, ethanolamine and the Ca2+-channel blocker verapamil. Members of this family are difficult to predict topologically and they show weak sequence similarity with proteins of different topologies including subunits of NADH dehydrogenase. Repeat units of various lengths can be found in some of these homologues.

References associated with 2.A.92 family:

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Nabokina, S.M., V.S. Subramanian, and H.M. Said. (2016). The human colonic thiamine pyrophosphate transporter (hTPPT) is a glycoprotein and N-linked glycosylation is important for its function. Biochim. Biophys. Acta. 1858: 866-871. 26828122
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Traiffort, E., S. O'Regan, and M. Ruat. (2013). The choline transporter-like family SLC44: properties and roles in human diseases. Mol Aspects Med 34: 646-654. 23506897
Yuan Z., L. Wagner, A. Poloumienko, M. Bakovic. (2004). Identification and expression of a mouse muscle-specific CTL1 gene. Gene. 341:305-312. 15474312
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Zirka, G., P. Robert, J. Tilburg, V. Tishkova, C.X. Maracle, P. Legendre, B.J.M. van Vlijmen, M.C. Alessi, P.J. Lenting, P.E. Morange, and G.M. Thomas. (2021). Impaired adhesion of neutrophils expressing Slc44a2/HNA-3b to VWF protects against NETosis under venous shear rates. Blood 137: 2256-2266. 33556175