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

Biochem Biophys Res Commun. 2019 Dec 10;520(3):566-572. doi: 10.1016/j.bbrc.2019.10.070. Epub 2019 Oct 12.

Abstract

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.

Keywords: Cation symporter; Colorectal cancer; Homology model; MFSD13A; TMEM180.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antibodies, Monoclonal
  • Binding Sites
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Computer Simulation
  • Conserved Sequence
  • HEK293 Cells
  • Humans
  • Membrane Proteins / chemistry*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Models, Molecular
  • Sequence Homology, Amino Acid
  • Structural Homology, Protein
  • Up-Regulation

Substances

  • Antibodies, Monoclonal
  • MFSD13A protein, human
  • Membrane Proteins