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. Author manuscript; available in PMC: 2015 Jan 15.
Published in final edited form as: Annu Rev Virol. 2014 Nov 1;1:261–283. doi: 10.1146/annurev-virology-031413-085537

Figure 3.

Figure 3

Three models of IFITM protein transmembrane topology. (a) The predicted type III transmembrane topology with endoplasmic reticulum–luminal N and C termini. In support of this model, several flow cytometry studies have localized IFITM1 or IFITM3 N termini to the cellular exterior (7, 45, 58, 61). (b) An intramembrane topology was proposed based on the findings of posttranslational modifications. Ubiquitylation and phosphorylation of NTD amino acids support cytosolic localization of the N terminus (49, 59). Palmitoylation of a C-terminal cysteine in the short TM2/IM2 region of mouse Ifitm1 is consistent with a cytosolic orientation of the C terminus (60). (c) More recent work has shown that murine Ifitm3 can adopt at least two different topologies. The predominant topology, however, has an intracellular N terminus and extracellular C terminus (61). Abbreviations: CIL, conserved intracellular loop; CTD, C-terminal domain; IMD, intramembrane domain (previously denoted as IM1 or TM1); NTD, N-terminal domain; TMD, transmembrane domain (previously denoted as IM2 or TM2).