9.B.135 The Membrane Trafficking Yip (Yip) Family
The YIP1 family of proteins are small membrane proteins with 5 putative TMSs with roles in membrane trafficking from the ER to the golgi. In yeast they participate in vesicle biogenesis and mediate the association of Rab proteins with membranes. Yeast YIP1 is an essential gene and can be fully complemented by a human counterpart, suggesting that the essential function of Yip1p is evolutionarily conserved (Chen and Collins, 2005). Prokaryotic homologues are found in family 9.B.29 and possibly family 3.A.1.122.
Human YIPF3 and YIPF4 are localized to the cis-Golgi. YIPF3 is synthesized in the ER as a N-glycosylated form (40 kDa), is then O-glycosylated in the Golgi and finally is cleaved at its C-terminal luminal domain. YIPF3 and YIPF4 form a complex in the Golgi apparatus. The knockdown of YIPF3 or YIPF4 in HeLa cells induced fragmentation of the Golgi apparatus (Tanimoto et al., 2011). Mutation of Yip1 domain family, member 6 (Yipf6), induces spontaneous intestinal inflammation in mice (Brandl et al., 2012).
S. cerevisiae contains four YIPFs: Yip1p, Yif1p, Yip4p, and Yip5p. Yip1p and Yif1p bind to each other and play a role in budding of transport vesicles and/or fusion of vesicles to target membranes. Human cells have nine family members that have overlapping functions. These YIPF proteins are divided into two sub-families: YIPFα/Yip1p and YIPFβ/Yif1p. A YIPFα molecule forms a complex with a specific partner YIPFβ molecule. A basic tetrameric complex is formed from two molecules of each partner YIPF protein, and this tetramer forms a higher order oligomer (Shaik et al. 2019). Three distinct YIPF protein complexes are formed from pairs of YIPFα and YIPFβ proteins. These are differently localized in either the early, middle, or late compartments of the Golgi apparatus and are recycled between adjacent compartments. Because a YIPF protein is predicted to have five TMSs, a YIPF tetramer complex is predicted to have 20 TMSs. This high number of TMSs suggests that YIPF complexes function as channels, transporters, or transmembrane receptors (Shaik et al. 2019).