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9.B.214 The ER to Golgi Transport Factor (ER/G-TF) Family 

Secretory proteins are transported from the endoplasmic reticulum to the Golgi apparatus via COPII- coated intermediates. Yeast Erv29p is a transmembrane protein cycling between these compartments. It is conserved across eukaryotic species, with one ortholog found in each genome studied, including the surf-4 protein in mammals (Foley et al. 2007). Yeast Erv29p acts as a receptor, loading a specific subset of soluble cargo, including glycosylated alpha factor pheromone precursor and carboxypeptidase Y, into vesicles. As the eukaryotic secretory pathway is highly conserved, mammalian surf-4 may perform a similar role in the transport of unknown substrates. Foley et al. 2007 reported the membrane topology of yeast Erv29p, which they concluded contains four transmembrane domains with both termini exposed to the cytosol although the hydropathy plot suggests 7 or 8 TMSs. Two luminal loops may contain a recognition site for hydrophobic export signals on soluble cargo.

Golgi enzymes are largely type II transmembrane proteins consisting of a short N-terminal cytosolic tail, a relatively short TMS and a lumenal 'stem/stalk' region which acts as a spacer between the catalytic domain and the lipid bilayer. The cytosolic tail, the TMS and the stem are responsible for the specific localisation of these enzymes within sub-Golgi compartments via multiple mechanisms. In addition, the catalytic domains of some Golgi enzymes are secreted as a consequence of proteolytic cleavage within their TMSs or stem regions (Welch and Munro 2019).

References associated with 9.B.214 family:

Foley, D.A., H.J. Sharpe, and S. Otte. (2007). Membrane topology of the endoplasmic reticulum to Golgi transport factor Erv29p. Mol. Membr. Biol. 24: 259-268. 17520482
Kim, J., C.M. Hong, S.M. Park, D.H. Shin, J.Y. Kim, S.M. Kwon, J.H. Kim, C.D. Kim, D.S. Lim, and D. Lee. (2018). SURF4 has oncogenic potential in NIH3T3 cells. Biochem. Biophys. Res. Commun. 502: 43-47. 29777698
Nambi, S., J.E. Long, B.B. Mishra, R. Baker, K.C. Murphy, A.J. Olive, H.P. Nguyen, S.A. Shaffer, and C.M. Sassetti. (2015). The Oxidative Stress Network of Mycobacterium tuberculosis Reveals Coordination between Radical Detoxification Systems. Cell Host Microbe 17: 829-837. 26067605
Shen, Y., H.M. Gu, S. Qin, and D.W. Zhang. (2022). Surf4, cargo trafficking, lipid metabolism, and therapeutic implications. J Mol. Cell Biol. [Epub: Ahead of Print] 36574593
Wang, X., H. Wang, B. Xu, D. Huang, C. Nie, L. Pu, G.J.M. Zajac, H. Yan, J. Zhao, F. Shi, B.T. Emmer, J. Lu, R. Wang, X. Dong, J. Dai, W. Zhou, C. Wang, G. Gao, Y. Wang, C. Willer, X. Lu, Y. Zhu, and X.W. Chen. (2020). Receptor-Mediated ER Export of Lipoproteins Controls Lipid Homeostasis in Mice and Humans. Cell Metab. [Epub: Ahead of Print] 33186557
Welch, L.G. and S. Munro. (2019). A tale of short tails, through thick and thin: investigating the sorting mechanisms of Golgi enzymes. FEBS Lett. 593: 2452-2465. 31344261
Zhang, Y., V. Srivastava, and B. Zhang. (2023). Mammalian cargo receptors for endoplasmic reticulum-to-Golgi transport: mechanisms and interactions. Biochem Soc Trans 51: 971-981. 37334845