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:

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.

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.

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.

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]

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.

Examples:

TC#NameOrganismal TypeExample
9.B.214.1.1

Erv29 of 310 aas and 4 (determined) to 7 (predicted) TMSs (Foley et al. 2007).

Erv29 of Saccharomyces cerevisiae

 
9.B.214.1.2

Surfeit locus protein 4 of 269 aas and 8 predicted TMSs in a 4 + 4 TMS arrangement, Surf-4 or Surf4. It has amplification and increased expression in the tumor tissues of several human cancer patients. Overexpression of SURF4 leads to increased cell proliferation, migration, and maintenance of anchorage-independent growth. In addition, NIH3T3 cells overexpressing SURF4 induced tumor growth in mice (Kim et al. 2018). Surf-4, together with SAR1B (SARA2; SARB, of 198 aas and 0 TMSs; Q9Y6B6), ensures delivery of the packages to the cell membrane for secretion, and receptor-mediated ER export of lipoproteins controls lipid homeostasis in mice and humans (Wang et al. 2020).

Surf-4 of Homo sapiens

 
9.B.214.1.3

ER-derived vesicles protein ERV29 of 292 aas and 8 TMSs in a 1 + 3 + 4 TMS arrangement. This protein may be distantly related to 2.A.7.43.

ERV29 of Verticillium alfalfae

 
Examples:

TC#NameOrganismal TypeExample
9.B.214.2.1

Uncharacterized protein of the DoxX family of 139 aas and 4 TMSs.

UP of Planktothrix tepida

 
9.B.214.2.2

DoxX family protein of 137 aas and 4 TMSs.

DoxX homologue of Burkholderia ptereochthonis

 
9.B.214.2.3

DoxX/SURF4 family protein of 158 aas and 4 TMSs, YphA of unknown function.

DoxX of Rubinisphaera brasiliensis

 
9.B.214.2.4

Quinol oxidase of 145 aas and 4 TMSs. Uncharacterized membrane protein, YphA, of the DoxX/SURF4 family

YphA of Burkholderia pseudomallei

 
9.B.214.2.5

DoxX family member of 158 aas and 4 TMSs

DoxX of Candidatus Wolfebacteria bacterium

 
9.B.214.2.6

DoxX of 141 aas and 4 TMSs. The superoxide-detoxifying enzyme (SodA), DoxX, and a predicted thiol-oxidoreductase (SseA) form a membrane-associated oxidoreductase complex (MRC) that physically links radical detoxification with cytosolic thiol homeostasis. Loss of any MRC component correlated with defective recycling of mycothiol and accumulation of cellular oxidative damage (Nambi et al. 2015).

DoxX of Mycobacterium tuberculosis

 
Examples:

TC#NameOrganismal TypeExample
9.B.214.3.1

Protein of 541 aas and 6 TMSs with an N-terminal DoxX domain with 5 TMSs, and a C-terminal PHP (polymerase - histidinol-P - phosphatase) domain. 

DoxX - PHP domain protein of Lokiarchaeum sp. GC14_75

 
9.B.214.3.2

DoxX family proteinof 570 aas and 5 N-terminal TMSs within the DoxX domain.

DoxX family protein of Aequorivita soesokkakensis

 
9.B.214.3.3

DoxX domain protein of 138 aas and 4 TMSs

DoxX of Lysinibacillus sp.

 
Examples:

TC#NameOrganismal TypeExample
9.B.214.4.1

DoxX family protein of 148 aas and  4 TMSs.

DoxX of Hylemonella gracilis