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Gene Review

VRG4  -  Vrg4p

Saccharomyces cerevisiae S288c

Synonyms: GDP-mannose transporter 1, GMT 1, GOG5, LDB3, Low dye-binding protein 3, ...
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High impact information on VRG4

  • Loss of VRG4 function leads to lethality, but several viable vrg4 mutants were isolated whose GDP-mannose transport activity was reduced but not obliterated [1].
  • The transport of GDP-mannose from its site of synthesis in the cytosol into the lumen of the Golgi is mediated by the VRG4 gene product, a nucleotide sugar transporter that is a member of a large family of related membrane proteins [1].
  • The null phenotype of these mutant vrg4 alleles can be complemented by their overexpression [1].
  • Vesicles prepared from vrg4 mutant strains were reduced in luminal GDP-mannose transport activity, but this effect could be suppressed by increasing the concentration of GDP-mannose in vitro [1].
  • Vrg4 proteins with alterations in this region were reduced in binding to guanosine 5'-[gamma-(32)P]triphosphate gamma-azidoanilide, a photoaffinity substrate analogue whose binding to Vrg4-HAp was specifically inhibited by GDP-mannose [1].

Biological context of VRG4


Anatomical context of VRG4

  • Taken together, these results suggest that the VRG4 gene plays an important role in regulating Golgi functions and in maintaining the normal organization of intracellular membranes [3].
  • The Vrg4 protein localizes to the Golgi complex in a pattern that suggests a wide distribution throughout the Golgi [2].
  • Mutant Vrg4 proteins lacking the predicted C-terminal membrane-spanning domain fail to assemble into oligomers (Abe, M., Hashimoto, H., and Yoda, K. (1999) FEBS Lett. 458, 309-312) and are unstable, while proteins lacking the N-terminal cytosolic tail are stable and multimerize efficiently, but are mislocalized to the endoplasmic reticulum (ER) [5].
  • At the nonpermissive temperature, most GMT was found in the endoplasmic reticulum of sec23ts cells, which have defective COPII, and in the vacuole of sec21ts cells, which have defective COPI [6].
  • CgVRG4 fully complements the glycosylation defect and other cell wall associated vrg4 mutant phenotypes [7].

Associations of VRG4 with chemical compounds

  • The VRG4 gene is required for GDP-mannose transport into the lumen of the Golgi in the yeast, Saccharomyces cerevisiae [2].
  • The vrg4 mutation causes a general impairment in mannosylation, affecting N-linked and O-linked glycoprotein modifications as well as the mannosylation of sphingolipids [2].
  • As the sole provider of lumenal mannose, the Vrg4 protein functions as a key regulator of glycosylation in the yeast Golgi [5].
  • Our results indicate that GMT escapes from delivery to the vacuole by recycling to the endoplasmic reticulum and retrieval requires the lysine-rich C-terminal tail that can bind to the COPI coat [6].
  • In contrast, sequence similarities to the yeast UDP-N-acetylglucosamine transporter (UDP-GlcNAc-Tr) and the GDP-mannose transporter (GDP-Man-Tr) of Leishmania donovani are restricted to a region encoding the two most C-terminally located transmembrane helices [8].

Physical interactions of VRG4

  • The C-terminal hydrophilic peptide of GMT that is exposed to the cytosol binds to Ret2p, a subunit of the COPI coat [6].

Other interactions of VRG4

  • Mutant peptide derivatives that have lost a cluster of lysine in the vicinity of the transmembrane domain had reduced binding activity to Ret2p and the GMT with this sequence was delivered to the vacuole [6].
  • Using radiation inactivation and target analysis, we have now determined the functional molecular mass of the GDPase within the Golgi membrane and whether or not the enzyme has functional associations with other Golgi membrane proteins, including mannosyltransferases and the GDP-mannose transporter [9].

Analytical, diagnostic and therapeutic context of VRG4


  1. Identification of a conserved motif in the yeast golgi GDP-mannose transporter required for binding to nucleotide sugar. Gao, X.D., Nishikawa, A., Dean, N. J. Biol. Chem. (2001) [Pubmed]
  2. The VRG4 gene is required for GDP-mannose transport into the lumen of the Golgi in the yeast, Saccharomyces cerevisiae. Dean, N., Zhang, Y.B., Poster, J.B. J. Biol. Chem. (1997) [Pubmed]
  3. The yeast VRG4 gene is required for normal Golgi functions and defines a new family of related genes. Poster, J.B., Dean, N. J. Biol. Chem. (1996) [Pubmed]
  4. Sodium orthovanadate-resistant mutants of Saccharomyces cerevisiae show defects in Golgi-mediated protein glycosylation, sporulation and detergent resistance. Kanik-Ennulat, C., Montalvo, E., Neff, N. Genetics (1995) [Pubmed]
  5. Distinct protein domains of the yeast Golgi GDP-mannose transporter mediate oligomer assembly and export from the endoplasmic reticulum. Gao, X.D., Dean, N. J. Biol. Chem. (2000) [Pubmed]
  6. Localization of GDP-mannose transporter in the Golgi requires retrieval to the endoplasmic reticulum depending on its cytoplasmic tail and coatomer. Abe, M., Noda, Y., Adachi, H., Yoda, K. J. Cell. Sci. (2004) [Pubmed]
  7. Identification of a Candida glabrata homologue of the S. cerevisiae VRG4 gene, encoding the Golgi GDP-mannose transporter. Nishikawa, A., Mendez, B., Jigami, Y., Dean, N. Yeast (2002) [Pubmed]
  8. Molecular cloning of the hamster CMP-sialic acid transporter. Eckhardt, M., Gerardy-Schahn, R. Eur. J. Biochem. (1997) [Pubmed]
  9. Regulation of yeast Golgi glycosylation. Guanosine diphosphatase functions as a homodimer in the membrane. Berninsone, P., Lin, Z.Y., Kempner, E., Hirschberg, C.B. J. Biol. Chem. (1995) [Pubmed]
  10. Progression of the stacked Golgi compartments in the yeast Saccharomyces cerevisiae by overproduction of GDP-mannose transporter. Hashimoto, H., Abe, M., Hirata, A., Noda, Y., Adachi, H., Yoda, K. Yeast (2002) [Pubmed]
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