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Gene Review

ARF1  -  Arf family GTPase ARF1

Saccharomyces cerevisiae S288c

Synonyms: ADP-ribosylation factor 1, D1244, YDL192W
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High impact information on ARF1

  • Budding from washed membranes can be reconstituted with purified AP3 and recombinant ARF1 [1].
  • The Sec7 domain binds to the switch regions of ARF1 and inserts residues directly into the GTPase active site [2].
  • Another set of yeast cytosolic proteins, coatomer and Arf1p (COPI), also form coated buds and vesicles from the nuclear envelope [3].
  • Arf1p, Chs5p and the ChAPs are required for export of specialized cargo from the Golgi [4].
  • In contrast, Rud3p binds to the GTPase Arf1p via this COOH-terminal "GRIP-related Arf-binding" (GRAB) domain [5].

Biological context of ARF1

  • Although the two yeast ARF proteins are 96% identical in amino acid sequence, the yeast ARF1 gene is constitutively expressed, whereas the ARF2 gene is repressed by glucose [6].
  • We previously isolated eight temperature-sensitive (ts) mutants of the yeast ARF1 gene, which showed allele-specific defects in protein transport, and classified them into three groups of intragenic complementation [7].
  • As TRS130 is an essential gene, the synthetic lethal allele (trs130-101) is a novel one that requires ARF1 for viability [8].
  • Although unable to suppress defects in several alleles of ARF1, increasing the gene dosage of YPT31/32 suppressed the cold sensitivity of gcs1(-), an Arf GTPase-activating protein (GAP) [8].
  • The interaction of the coatomer coat complex with the Golgi membrane is initiated by the active, GTP-bound state of the small GTPase ADP-ribosylation factor 1 (ARF1), whereas GTP hydrolysis triggers coatomer dissociation [9].

Anatomical context of ARF1

  • The GTPase cycle of ARF proteins that allows the uncoating and fusion of a transport vesicle with a target membrane is mediated by ARF-dependent GTPase-activating proteins (GAPs) [10].
  • Vesicle budding that results from the interaction of cytoplasmic coat proteins (coatomer and clathrin) with intracellular organelles requires a type of GTP-binding protein termed ADP-ribosylation factor (ARF) [10].
  • The ADP ribosylation factor-nucleotide exchange factors Gea1p and Gea2p have overlapping, but not redundant functions in retrograde transport from the Golgi to the endoplasmic reticulum [11].
  • While Golgi membranes stimulated the exchange of GTPgammaS for GDP on all of the ARFs tested, mammalian ARF1 was the best substrate, with an apparent Km of 5 microM [12].
  • Although both ARF1 and ARF6 were found on peroxisomes, coatomer recruitment only depended on ARF1-GTP [13].

Associations of ARF1 with chemical compounds

  • Disruption of ARF1 causes slow growth, cold sensitivity, and sensitivity to normally sublethal concentrations of fluoride ion in the medium [14].
  • The activation of the small ras-like GTPase Arf1p requires the action of guanine nucleotide exchange factors [11].
  • Agents that inhibit the Golgi membrane guanine nucleotide exchange factor (the fungal metabolite brefeldin A and trypsin treatment) selectively inhibited the guanine nucleotide exchange on mammalian ARF1 [12].
  • Incorporation of exogenous tritiated myristate into Arf1p and bacterial phospholipid biosynthetic pathways was analyzed [15].
  • An auxin response transcription factor, ARF1, bound with specificity to the DR5 AuxRE in vitro and interacted with Aux/IAA proteins in a yeast two-hybrid system [16].

Physical interactions of ARF1

  • We have previously implicated Drs2p in protein transport steps in the late secretory pathway requiring ADP-ribosylation factor (ARF) and clathrin [17].
  • Comparison with Gea2 in complex with nucleotide-free Arf1 Delta 17 [Goldberg, J. (1998) Cell 95, 237-248] reveals that Arf induces closure of the two subdomains that form the sides of its active site [18].

Regulatory relationships of ARF1

  • COPI in these mutants is released from Golgi membranes by brefeldin A, a drug that binds directly to Gea2p and blocks Arf1 activation [19].
  • In vitro, the GTPase activity of yeast ARF proteins can be stimulated by Gcs1p [20].
  • The Arf1p GTPase-activating protein Glo3p executes its regulatory function through a conserved repeat motif at its C-terminus [7].

Other interactions of ARF1

  • Saccharomyces cerevisiae Gcs1 is an ADP-ribosylation factor GTPase-activating protein [10].
  • SEC21 encodes the gamma-subunit of coatomer, a heptameric protein complex that together with Arf1p forms the COPI coat [11].
  • This genetic interaction between arf1 and chc1 provides in vivo evidence for a role for ARF in clathrin coat assembly [21].
  • A genetic screen for synthetic lethal interactions with arf1(-) identified a recessive mutation in TRS130, one of 10 components in the trafficking protein particle (TRAPP) complex (Sacher et al., 2000) [8].
  • The ts growth arrest produced by nmt1 alleles correlates with a reduction in myristoyl-Arf1p to </=50% of total cellular Arf1p [22].

Analytical, diagnostic and therapeutic context of ARF1

  • To identify factors that functionally interact with ARF, we have performed a genetic screen in Saccharomyces cerevisiae for mutations that exhibit synthetic lethality with an arf1Delta allele and defined seven genes by complementation tests (SWA1-7 for synthetically lethal with arf1Delta) [21].
  • Antibodies raised against the C-terminal eight residues of Saccharomyces cerevisiae Arf1p were used to probe Western blots of total cellular proteins prepared from these isogenic Candida strains [23].
  • In the present study we have shown that ARF proteins belonging to the three classes, ARF1, ARF5 and ARF6, can interact with all GGA proteins in a yeast two-hybrid assay, in vitro and in vivo [24].
  • To identify new interactors of Arf1p, we performed an affinity chromatography with GTP- or GDP-bound Arf1p proteins [25].
  • By random mutagenesis of the whole open reading frame of ARF1 by error-prone PCR, we isolated eight mutants and examined their phenotypes. arf1 ts mutants showed a variety of transport defects and morphological alterations in an allele-specific manner [26].


  1. A function for the AP3 coat complex in synaptic vesicle formation from endosomes. Faúndez, V., Horng, J.T., Kelly, R.B. Cell (1998) [Pubmed]
  2. Structural basis for activation of ARF GTPase: mechanisms of guanine nucleotide exchange and GTP-myristoyl switching. Goldberg, J. Cell (1998) [Pubmed]
  3. COPI- and COPII-coated vesicles bud directly from the endoplasmic reticulum in yeast. Bednarek, S.Y., Ravazzola, M., Hosobuchi, M., Amherdt, M., Perrelet, A., Schekman, R., Orci, L. Cell (1995) [Pubmed]
  4. Arf1p, Chs5p and the ChAPs are required for export of specialized cargo from the Golgi. Trautwein, M., Schindler, C., Gauss, R., Dengjel, J., Hartmann, E., Spang, A. EMBO J. (2006) [Pubmed]
  5. The GTPase Arf1p and the ER to Golgi cargo receptor Erv14p cooperate to recruit the golgin Rud3p to the cis-Golgi. Gillingham, A.K., Tong, A.H., Boone, C., Munro, S. J. Cell Biol. (2004) [Pubmed]
  6. Human and Giardia ADP-ribosylation factors (ARFs) complement ARF function in Saccharomyces cerevisiae. Lee, F.J., Moss, J., Vaughan, M. J. Biol. Chem. (1992) [Pubmed]
  7. The Arf1p GTPase-activating protein Glo3p executes its regulatory function through a conserved repeat motif at its C-terminus. Yahara, N., Sato, K., Nakano, A. J. Cell. Sci. (2006) [Pubmed]
  8. Genetic interactions link ARF1, YPT31/32 and TRS130. Zhang, C.J., Bowzard, J.B., Greene, M., Anido, A., Stearns, K., Kahn, R.A. Yeast (2002) [Pubmed]
  9. Regulation of GTP hydrolysis on ADP-ribosylation factor-1 at the Golgi membrane. Szafer, E., Rotman, M., Cassel, D. J. Biol. Chem. (2001) [Pubmed]
  10. Saccharomyces cerevisiae Gcs1 is an ADP-ribosylation factor GTPase-activating protein. Poon, P.P., Wang, X., Rotman, M., Huber, I., Cukierman, E., Cassel, D., Singer, R.A., Johnston, G.C. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  11. The ADP ribosylation factor-nucleotide exchange factors Gea1p and Gea2p have overlapping, but not redundant functions in retrograde transport from the Golgi to the endoplasmic reticulum. Spang, A., Herrmann, J.M., Hamamoto, S., Schekman, R. Mol. Biol. Cell (2001) [Pubmed]
  12. Comparative activity of ADP-ribosylation factor family members in the early steps of coated vesicle formation on rat liver Golgi membranes. Liang, J.O., Kornfeld, S. J. Biol. Chem. (1997) [Pubmed]
  13. Binding and functions of ADP-ribosylation factor on mammalian and yeast peroxisomes. Lay, D., L Grosshans, B., Heid, H., Gorgas, K., Just, W.W. J. Biol. Chem. (2005) [Pubmed]
  14. ADP ribosylation factor is an essential protein in Saccharomyces cerevisiae and is encoded by two genes. Stearns, T., Kahn, R.A., Botstein, D., Hoyt, M.A. Mol. Cell. Biol. (1990) [Pubmed]
  15. Use of Escherichia coli strains containing fad mutations plus a triple plasmid expression system to study the import of myristate, its activation by Saccharomyces cerevisiae acyl-CoA synthetase, and its utilization by S. cerevisiae myristoyl-CoA:protein N-myristoyltransferase. Knoll, L.J., Gordon, J.I. J. Biol. Chem. (1993) [Pubmed]
  16. Aux/IAA proteins repress expression of reporter genes containing natural and highly active synthetic auxin response elements. Ulmasov, T., Murfett, J., Hagen, G., Guilfoyle, T.J. Plant Cell (1997) [Pubmed]
  17. Requirement for neo1p in retrograde transport from the Golgi complex to the endoplasmic reticulum. Hua, Z., Graham, T.R. Mol. Biol. Cell (2003) [Pubmed]
  18. Mechanism of domain closure of Sec7 domains and role in BFA sensitivity. Renault, L., Christova, P., Guibert, B., Pasqualato, S., Cherfils, J. Biochemistry (2002) [Pubmed]
  19. Mutations in a highly conserved region of the Arf1p activator GEA2 block anterograde Golgi transport but not COPI recruitment to membranes. Park, S.K., Hartnell, L.M., Jackson, C.L. Mol. Biol. Cell (2005) [Pubmed]
  20. The yeast ADP-ribosylation factor GAP, Gcs1p, is involved in maintenance of mitochondrial morphology. Huang, C.F., Chen, C.C., Tung, L., Buu, L.M., Lee, F.J. J. Cell. Sci. (2002) [Pubmed]
  21. An arf1Delta synthetic lethal screen identifies a new clathrin heavy chain conditional allele that perturbs vacuolar protein transport in Saccharomyces cerevisiae. Chen, C.Y., Graham, T.R. Genetics (1998) [Pubmed]
  22. Biochemical studies of Saccharomyces cerevisiae myristoyl-coenzyme A:protein N-myristoyltransferase mutants. Zhang, L., Jackson-Machelski, E., Gordon, J.I. J. Biol. Chem. (1996) [Pubmed]
  23. N-myristoylation of Arf proteins in Candida albicans: an in vivo assay for evaluating antifungal inhibitors of myristoyl-CoA: protein N-myristoyltransferase. Lodge, J.K., Jackson-Machelski, E., Devadas, B., Zupec, M.E., Getman, D.P., Kishore, N., Freeman, S.K., McWherter, C.A., Sikorski, J.A., Gordon, J.I. Microbiology (Reading, Engl.) (1997) [Pubmed]
  24. GGA proteins associate with Golgi membranes through interaction between their GGAH domains and ADP-ribosylation factors. Takatsu, H., Yoshino, K., Toda, K., Nakayama, K. Biochem. J. (2002) [Pubmed]
  25. Arf1p provides an unexpected link between COPI vesicles and mRNA in Saccharomyces cerevisiae. Trautwein, M., Dengjel, J., Schirle, M., Spang, A. Mol. Biol. Cell (2004) [Pubmed]
  26. Multiple roles of Arf1 GTPase in the yeast exocytic and endocytic pathways. Yahara, N., Ueda, T., Sato, K., Nakano, A. Mol. Biol. Cell (2001) [Pubmed]
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