Topological analysis of TMEM180, a newly identified membrane protein that is highly expressed in colorectal cancer cells

New target molecules for diagnosis of and drug development for colorectal cancer (CRC) are always in great demand. Previously, we identified a new colorectal cancer-specific protein, TMEM180, and successfully developed an anti-TMEM180 monoclonal antibody (mAb) for the diagnosis and treatment of CRC. Although TMEM180 is classified as a member of the cation symporter family and multi-pass membrane protein, little is known about its function. In this study, we examined topology of this membrane protein and analyzed its function. Using a homology model of human TMEM180, we experimentally determined that the protein has 12 transmembrane domains, and that its N-terminal and C-termini are exposed extracellularly. Moreover, we found that the putative cation-binding site of TMEM180 is conserved among orthologs, and that its position is similar to that of melibiose transporter MelB. These results suggest that TMEM180 acts as a cation symporter. Our topological analysis based on the homology model provides insight into functional and structural roles of TMEM180 that may help to elucidate the pathology of CRC. (C) 2019 The Authors. Published by Elsevier Inc.