Figure 1.

Human proteome contains multiple VAP proteins and FFAT motifs. (a) Schematic representation of VAP proteins forming MCS. ER-localized VAPA interacts with FFAT motif of Golgi-bound OSBP to create MCS between two organelles. (b) Human genome encodes five MSP-domain-containing VAP proteins that localize in the ER. The lengths of the linker regions between transmembrane helices and MSP domains are different in VAP proteins. Note that only VAPA and VAPB contain predicted coiled coil regions. (c) VAP proteins form two separate protein complexes in the ER as VAPA-VAPB-MOSPD2 and MOSPD1-MOSPD3 complexes. (d) The canonical FFAT motif contains the E-F-F-D-A-X-E consensus sequence preceded by acidic residues. Shortlist of proteins with reported FFAT and FFAT-related motifs. The panel on the right depicts the FFAT, phospho-FFAT (p-FFAT) and FFNT scores of each sequence. The score values represent the divergence of the sequences from the defined canonical motifs, e.g. OSBP, contains the canonical FFAT, has the score of 0. The motif the sequence is reported to belong is shown by a red asterisk. Note that RMDN3 and IncV contain tandem FFAT/FFAT-related motifs. The position 4 of the motif requires phosphorylation in phospho-FFAT (shown with a dagger^†). The phenylalanine at the position 9 is accommodated in the secondary hydrophobic pocket of MOSPD2-MSP (shown with a double dagger^‡). (e) Two examples, VPS13C and AKAP11, of proteins predicted to contain all three FFAT-related motifs.