8.A.230.  The TMEM72 (TMEM72) Family 

Transmembrane protein 72 (TMEM72) is involved in normal kidney development and tumorigenesis in renal cell carcinoma, but its biochemical function is not known.   TMEM72 family members have (usually) four N-terminal TMSs and a long C-terminal hydrophilic tail. TMEM72 is localized to the plasma membrane but not the outer mitochondrial membrane. The TMSs are needed for proper protein folding or assembly, but the C-terminal region of TMEM72 is necessary for protein transport (Ding et al. 2023). In fact, the proximal C-terminal region is responsible for anterograde protein transport.  KRKKRKAAPEVLA, which corresponds to amino acid positions 132-144 in the human TMEM72, participates in efficient cellular transport. The motifs 132KRKKRK137 and 139APEVLA144 are associated with COPII and are considered to cooperate with membrane trafficking. Because efficient membrane trafficking is crucial for cells to maintain normal function, these data may contribute to elucidating the pathogenesis of membrane trafficking-associated diseases.  Bladder cancer (and probably other cancer) immunophenotypes revealed down-regulation of TMEM72 (Wrzesiński et al. 2015).