adp ribosylation factor 1


Summary: ADP-RIBOSYLATION FACTOR 1 is involved in regulating intracellular transport by modulating the interaction of coat proteins with organelle membranes in the early secretory pathway. It is a component of COAT PROTEIN COMPLEX I. This enzyme was formerly listed as EC

Top Publications

  1. Seidel R, Amor J, Kahn R, Prestegard J. Conformational changes in human Arf1 on nucleotide exchange and deletion of membrane-binding elements. J Biol Chem. 2004;279:48307-18 pubmed
    ..Results from NMR experiments presented here on Arf1.GDP and Delta17Arf1.GDP in solution reveal substantial structural differences that can only be associated with N-terminal truncation. ..
  2. Lay D, L Grosshans B, Heid H, Gorgas K, Just W. Binding and functions of ADP-ribosylation factor on mammalian and yeast peroxisomes. J Biol Chem. 2005;280:34489-99 pubmed
    ..ScARF1 regulated this process in a positive manner, and ScARF3 regulated it in a negative manner. ..
  3. Robert C, Cherfils J, Mouawad L, Perahia D. Integrating three views of Arf1 activation dynamics. J Mol Biol. 2004;337:969-83 pubmed
    ..Large-scale collective movements in the Arf1-Sec7d complex appear to participate in the insertion of the Sec7d Glu finger into the GDP binding site to promote actual nucleotide release. ..
  4. Mossessova E, Corpina R, Goldberg J. Crystal structure of ARF1*Sec7 complexed with Brefeldin A and its implications for the guanine nucleotide exchange mechanism. Mol Cell. 2003;12:1403-11 pubmed
    ..Thus, the Sec7 domain may act as a dual catalyst, facilitating both nucleotide release and conformational switching on ARF proteins. ..
  5. Shinotsuka C, Yoshida Y, Kawamoto K, Takatsu H, Nakayama K. Overexpression of an ADP-ribosylation factor-guanine nucleotide exchange factor, BIG2, uncouples brefeldin A-induced adaptor protein-1 coat dissociation and membrane tubulation. J Biol Chem. 2002;277:9468-73 pubmed
    ..These observations indicate that BFA-induced AP-1 dissociation from TGN membranes and tubulation of TGN membranes are not coupled events and suggest that a BFA target other than ARF-GEFs exists in the cell. ..
  6. Spang A. ARF1 regulatory factors and COPI vesicle formation. Curr Opin Cell Biol. 2002;14:423-7 pubmed
  7. Rein U, Andag U, Duden R, Schmitt H, Spang A. ARF-GAP-mediated interaction between the ER-Golgi v-SNAREs and the COPI coat. J Cell Biol. 2002;157:395-404 pubmed
    ..The mechanisms by which v-SNAREs interact with COPI and COPII coat proteins seem to be different and may play a key role in determining specificity in vesicle budding...
  8. Donaldson J. Arfs, phosphoinositides and membrane traffic. Biochem Soc Trans. 2005;33:1276-8 pubmed
    ..Arf1 can also stimulate the activity of phosphatidylinositol kinases and recruit coat proteins and actin cytoskeletal elements to the Golgi complex. ..
  9. Jackson C, Casanova J. Turning on ARF: the Sec7 family of guanine-nucleotide-exchange factors. Trends Cell Biol. 2000;10:60-7 pubmed
    ..A separate subclass of Sec7-domain proteins is involved in signal transduction and possess a domain that mediates membrane binding in response to extracellular signals. ..

More Information


  1. Lee F, Stevens L, Hall L, Murtagh J, Kao Y, Moss J, et al. Characterization of class II and class III ADP-ribosylation factor genes and proteins in Drosophila melanogaster. J Biol Chem. 1994;269:21555-60 pubmed
    ..These observations are consistent with the conclusion that the three classes of ARFs are present in non-mammalian as well as mammalian species. ..
  2. Spang A, Matsuoka K, Hamamoto S, Schekman R, Orci L. Coatomer, Arf1p, and nucleotide are required to bud coat protein complex I-coated vesicles from large synthetic liposomes. Proc Natl Acad Sci U S A. 1998;95:11199-204 pubmed
    ..We conclude that Arf1p-GTP and coatomer comprise the minimum apparatus necessary to create a COPI-coated vesicle...
  3. Reinhard C, Schweikert M, Wieland F, Nickel W. Functional reconstitution of COPI coat assembly and disassembly using chemically defined components. Proc Natl Acad Sci U S A. 2003;100:8253-7 pubmed
    ..Bourgoin, S., Randazzo, P. A., et al. (2002) J. Cell Biol. 159, 69-78]. Thus, a complete round of COPI coat assembly and disassembly has been reconstituted with purified components defining the core machinery of COPI vesicle biogenesis...
  4. McCartney A, Greenwood J, Fabian M, White K, Mullen R. Localization of the tomato bushy stunt virus replication protein p33 reveals a peroxisome-to-endoplasmic reticulum sorting pathway. Plant Cell. 2005;17:3513-31 pubmed publisher
    ..These results provide insight into virus-induced intracellular rearrangements and reveal a peroxisome-to-pER sorting pathway, raising new mechanistic questions regarding the biogenesis of peroxisomes in plants...
  5. Chen C, Graham T. An arf1Delta synthetic lethal screen identifies a new clathrin heavy chain conditional allele that perturbs vacuolar protein transport in Saccharomyces cerevisiae. Genetics. 1998;150:577-89 pubmed
  6. Kawasaki M, Nakayama K, Wakatsuki S. Membrane recruitment of effector proteins by Arf and Rab GTPases. Curr Opin Struct Biol. 2005;15:681-9 pubmed
  7. Gommel D, Memon A, Heiss A, Lottspeich F, Pfannstiel J, Lechner J, et al. Recruitment to Golgi membranes of ADP-ribosylation factor 1 is mediated by the cytoplasmic domain of p23. EMBO J. 2001;20:6751-60 pubmed
    Binding to Golgi membranes of ADP ribosylation factor 1 (ARF1) is the first event in the initiation of COPI coat assembly. Based on binding studies, a proteinaceous receptor has been proposed to be critical for this process...
  8. Morinaga N, Moss J, Vaughan M. Cloning and expression of a cDNA encoding a bovine brain brefeldin A-sensitive guanine nucleotide-exchange protein for ADP-ribosylation factor. Proc Natl Acad Sci U S A. 1997;94:12926-31 pubmed
  9. Ménétrey J, Perderiset M, Cicolari J, Dubois T, Elkhatib N, El Khadali F, et al. Structural basis for ARF1-mediated recruitment of ARHGAP21 to Golgi membranes. EMBO J. 2007;26:1953-62 pubmed
    ..Our data demonstrate that two well-known small GTPase-binding motifs, the PH domain and the alpha helical motif, can combine to create a novel mode of binding to Arfs. ..
  10. Jones D, Morris J, Morgan C, Kondo H, Irvine R, Cockcroft S. Type I phosphatidylinositol 4-phosphate 5-kinase directly interacts with ADP-ribosylation factor 1 and is responsible for phosphatidylinositol 4,5-bisphosphate synthesis in the golgi compartment. J Biol Chem. 2000;275:13962-6 pubmed
    ..ARF1 increased Type I PIP 5-kinase activity in a guanine nucleotide-dependent manner, identifying this enzyme as a direct effector for ARF1. ..
  11. Presley J, Ward T, Pfeifer A, Siggia E, Phair R, Lippincott Schwartz J. Dissection of COPI and Arf1 dynamics in vivo and role in Golgi membrane transport. Nature. 2002;417:187-93 pubmed
    ..This role for Arf1/coatomer might provide a model for investigating the behaviour of other coat protein systems within cells. ..
  12. Pasqualato S, Menetrey J, Franco M, Cherfils J. The structural GDP/GTP cycle of human Arf6. EMBO Rep. 2001;2:234-8 pubmed
    ..The structure also allows further insight into the lack of spontaneous GTPase activity of Arf proteins. ..
  13. Chardin P, Paris S, Antonny B, Robineau S, Beraud Dufour S, Jackson C, et al. A human exchange factor for ARF contains Sec7- and pleckstrin-homology domains. Nature. 1996;384:481-4 pubmed
    ..We propose that other proteins with a Sec7 domain regulate different members of the ARF family. ..
  14. Beck R, Sun Z, Adolf F, Rutz C, Bassler J, Wild K, et al. Membrane curvature induced by Arf1-GTP is essential for vesicle formation. Proc Natl Acad Sci U S A. 2008;105:11731-6 pubmed publisher
    ..Strikingly, this mutant was not able to deform membranes, suggesting that GTP-induced dimerization of Arf1 is a critical step inducing membrane curvature during the formation of coated vesicles. ..
  15. Furman C, Short S, Subramanian R, Zetter B, Roberts T. DEF-1/ASAP1 is a GTPase-activating protein (GAP) for ARF1 that enhances cell motility through a GAP-dependent mechanism. J Biol Chem. 2002;277:7962-9 pubmed
    ..In contrast, the inhibition of cell spreading by DEF-1 was not dependent on GAP activity, indicating that spreading and motility are altered by DEF-1 through different pathways. ..
  16. Goldberg J. Structural and functional analysis of the ARF1-ARFGAP complex reveals a role for coatomer in GTP hydrolysis. Cell. 1999;96:893-902 pubmed
    ..Thus, a tripartite complex controls the GTP hydrolysis reaction triggering disassembly of COPI vesicle coats. ..
  17. Bui Q, Golinelli Cohen M, Jackson C. Large Arf1 guanine nucleotide exchange factors: evolution, domain structure, and roles in membrane trafficking and human disease. Mol Genet Genomics. 2009;282:329-50 pubmed publisher
  18. Kahn R, Clark J, Rulka C, Stearns T, Zhang C, Randazzo P, et al. Mutational analysis of Saccharomyces cerevisiae ARF1. J Biol Chem. 1995;270:143-50 pubmed
    ..Two high-copy suppressors of this conditional phenotype were cloned and sequenced. One of these suppressors, SFS4, was found to be identical to PBS2/HOG4, recently shown to encode a microtubule-associated protein kinase kinase in yeast. ..
  19. Lee S, Yang J, Hong W, Premont R, Hsu V. ARFGAP1 plays a central role in coupling COPI cargo sorting with vesicle formation. J Cell Biol. 2005;168:281-90 pubmed
    ..key components of coat protein I (COPI) transport participate in cargo sorting, we find that, instead of ADP ribosylation factor 1 (ARF1), its GTPase-activating protein (GAP) plays a direct role in promoting the binding of cargo ..
  20. Faure J, Stalder R, Borel C, Sobo K, Piguet V, Demaurex N, et al. ARF1 regulates Nef-induced CD4 degradation. Curr Biol. 2004;14:1056-64 pubmed
    ..Finally, a dominant-negative ARF1 mutant blocks the migration of the Nef-CD4 complex to lysosomes. Our results support a model in which ARF1 is the immediate downstream partner of Nef for CD4 lysosomal targeting. ..
  21. Boulay P, Cotton M, Melancon P, Claing A. ADP-ribosylation factor 1 controls the activation of the phosphatidylinositol 3-kinase pathway to regulate epidermal growth factor-dependent growth and migration of breast cancer cells. J Biol Chem. 2008;283:36425-34 pubmed publisher
    ..These results uncover a novel molecular mechanism by which ARF1 regulates breast cancer cell growth and invasion during cancer progression. ..
  22. Ward T, Polishchuk R, Caplan S, Hirschberg K, Lippincott Schwartz J. Maintenance of Golgi structure and function depends on the integrity of ER export. J Cell Biol. 2001;155:557-70 pubmed
    ..Instead, they suggest that the Golgi complex is a dynamic, steady-state system, whose membranes can be nucleated and are maintained by the activities of the Sar1-COPII and Arf1-coatomer systems...
  23. Ooi C, Dell Angelica E, Bonifacino J. ADP-Ribosylation factor 1 (ARF1) regulates recruitment of the AP-3 adaptor complex to membranes. J Cell Biol. 1998;142:391-402 pubmed
    ..This finding suggests that ARF1 is not a regulator of specific coat proteins, but rather is a ubiquitous molecular switch that acts as a transducer of diverse signals influencing coat assembly. ..
  24. Niu T, Pfeifer A, Lippincott Schwartz J, Jackson C. Dynamics of GBF1, a Brefeldin A-sensitive Arf1 exchange factor at the Golgi. Mol Biol Cell. 2005;16:1213-22 pubmed
    ..These results suggest that an Arf1-GBF1-BFA complex is formed and has a longer residence time on Golgi membranes than GBF1 or Arf1 alone. ..
  25. Aoe T, Cukierman E, Lee A, Cassel D, Peters P, Hsu V. The KDEL receptor, ERD2, regulates intracellular traffic by recruiting a GTPase-activating protein for ARF1. EMBO J. 1997;16:7305-16 pubmed
    ..Because ERD2 overexpression enhances the recruitment of GAP to membranes and results in a phenotype that reflects ARF1 inactivation, our findings suggest that ERD2 regulates ARF1 GAP, and thus regulates ARF1-mediated transport. ..
  26. Liu Y, Prestegard J. Measurement of one and two bond N-C couplings in large proteins by TROSY-based J-modulation experiments. J Magn Reson. 2009;200:109-18 pubmed publisher
    ..GTPgammas protein bound to small lipid bicelles, a system with an effective molecule weight of approximately 70kDa. ..
  27. Pavel J, Harter C, Wieland F. Reversible dissociation of coatomer: functional characterization of a beta/delta-coat protein subcomplex. Proc Natl Acad Sci U S A. 1998;95:2140-5 pubmed
    ..Herein we describe isolation of a subcomplex of coatomer consisting of beta- and delta-COPs that is able to bind to Golgi membranes in an ARF1- and GTP-dependent manner. ..
  28. Yahara N, Sato K, Nakano A. The Arf1p GTPase-activating protein Glo3p executes its regulatory function through a conserved repeat motif at its C-terminus. J Cell Sci. 2006;119:2604-12 pubmed
    ..We name this region the Glo3 motif and present evidence that the motif is required for the function of Glo3p in vivo. ..
  29. Antonny B, Bigay J, Casella J, Drin G, Mesmin B, Gounon P. Membrane curvature and the control of GTP hydrolysis in Arf1 during COPI vesicle formation. Biochem Soc Trans. 2005;33:619-22 pubmed
    ..As a result, the coat should be stable as long as the bud remains attached and should disassemble as soon as membrane fission occurs. ..
  30. Ambroggio E, Sorre B, Bassereau P, Goud B, Manneville J, Antonny B. ArfGAP1 generates an Arf1 gradient on continuous lipid membranes displaying flat and curved regions. EMBO J. 2010;29:292-303 pubmed publisher
  31. Macia E, Chabre M, Franco M. Specificities for the small G proteins ARF1 and ARF6 of the guanine nucleotide exchange factors ARNO and EFA6. J Biol Chem. 2001;276:24925-30 pubmed
    ..Thus selectivity for ARF1 or ARF6 must depend on subtle folding differences between the ARFs switch regions that interact with the Sec7 domains. ..
  32. Antonny B, Huber I, Paris S, Chabre M, Cassel D. Activation of ADP-ribosylation factor 1 GTPase-activating protein by phosphatidylcholine-derived diacylglycerols. J Biol Chem. 1997;272:30848-51 pubmed
    ..Thus, the phospholipase D pathway may provide a feedback mechanism that promotes GTP hydrolysis on ARF1 and the consequent uncoating of vesicles. ..
  33. Zhang C, Cavenagh M, Kahn R. A family of Arf effectors defined as suppressors of the loss of Arf function in the yeast Saccharomyces cerevisiae. J Biol Chem. 1998;273:19792-6 pubmed
  34. Puertollano R, Randazzo P, Presley J, Hartnell L, Bonifacino J. The GGAs promote ARF-dependent recruitment of clathrin to the TGN. Cell. 2001;105:93-102 pubmed
    ..These observations suggest that the GGAs could function to link clathrin to membrane-bound ARF.GTP. ..
  35. Behnia R, Panic B, Whyte J, Munro S. Targeting of the Arf-like GTPase Arl3p to the Golgi requires N-terminal acetylation and the membrane protein Sys1p. Nat Cell Biol. 2004;6:405-13 pubmed
    ..This suggests that the targeting of ARFRP1/Arl3p to the Golgi is mediated by a direct interaction between its acetylated N terminus and Sys1p/hSys1. ..
  36. Liu Y, Prestegard J. Direct measurement of dipole-dipole/CSA cross-correlated relaxation by a constant-time experiment. J Magn Reson. 2008;193:23-31 pubmed publisher
    ..The performances of the two methods are also quantitatively evaluated by simulation. The analysis shows that the shared constant-time CCR (SCT-CCR) method significantly improves sensitivity. ..
  37. Price H, Stark M, Smith D. Trypanosoma brucei ARF1 plays a central role in endocytosis and golgi-lysosome trafficking. Mol Biol Cell. 2007;18:864-73 pubmed
    ..We conclude that the essential Golgi-localizing T. brucei ARF1 has a primary role in the maintenance of both post-Golgi transport and endocytosis and that it is significantly divergent from other characterized ARFs. ..
  38. O Luanaigh N, Pardo R, Fensome A, Allen Baume V, Jones D, Holt M, et al. Continual production of phosphatidic acid by phospholipase D is essential for antigen-stimulated membrane ruffling in cultured mast cells. Mol Biol Cell. 2002;13:3730-46 pubmed
    ..We conclude that both activation of ARF6 by antigen and a continual PLD2 activity are essential for local phosphatidylinositol(4,5)bisphosphate generation that regulates dynamic actin cytoskeletal rearrangements. ..
  39. Honda A, Al Awar O, Hay J, Donaldson J. Targeting of Arf-1 to the early Golgi by membrin, an ER-Golgi SNARE. J Cell Biol. 2005;168:1039-51 pubmed
    ..These studies suggest that membrin recruits Arf-1 to the early Golgi and reveal distinct kinetic cycles for Arf-1 at early and late Golgi determined by different sets of Arf regulators and effectors. ..
  40. Kanoh H, Williger B, Exton J. Arfaptin 1, a putative cytosolic target protein of ADP-ribosylation factor, is recruited to Golgi membranes. J Biol Chem. 1997;272:5421-9 pubmed
    ..These results suggest that arfaptins 1 and 2 may be direct target proteins of class 1 ARFs. Arfaptin 1 may be involved in Golgi function along with ARF1. ..
  41. Chantalat S, Courbeyrette R, Senic Matuglia F, Jackson C, Goud B, Peyroche A. A novel Golgi membrane protein is a partner of the ARF exchange factors Gea1p and Gea2p. Mol Biol Cell. 2003;14:2357-71 pubmed
    ..Hence, we propose that Gmh1p acts as a positive Golgi-membrane partner for Gea function. These results are of general interest given the evolutionary conservation of both ARF-GEFs and the Gmh proteins. ..
  42. Stearns T, Willingham M, Botstein D, Kahn R. ADP-ribosylation factor is functionally and physically associated with the Golgi complex. Proc Natl Acad Sci U S A. 1990;87:1238-42 pubmed
    ..Together, these results indicate that ARF functions in intracellular protein transport to or within the Golgi apparatus, a role not predicted by the previous in vitro biochemical studies. ..
  43. Audhya A, Foti M, Emr S. Distinct roles for the yeast phosphatidylinositol 4-kinases, Stt4p and Pik1p, in secretion, cell growth, and organelle membrane dynamics. Mol Biol Cell. 2000;11:2673-89 pubmed
  44. Cohen L, Honda A, Varnai P, Brown F, Balla T, Donaldson J. Active Arf6 recruits ARNO/cytohesin GEFs to the PM by binding their PH domains. Mol Biol Cell. 2007;18:2244-53 pubmed
    ..This interaction was direct and required both inositol phospholipids and GTP. We propose a model of sequential Arf activation at the PM whereby Arf6-GTP recruits ARNO family GEFs for further activation of other Arf isoforms. ..
  45. Takeuchi M, Ueda T, Yahara N, Nakano A. Arf1 GTPase plays roles in the protein traffic between the endoplasmic reticulum and the Golgi apparatus in tobacco and Arabidopsis cultured cells. Plant J. 2002;31:499-515 pubmed
    ..These results indicate that AtArf1 play roles in the vesicular transport between the ER and the Golgi and in the maintenance of the normal Golgi organization in plant cells. ..
  46. Fischer K, Helms J, Zhao L, Wieland F. Site-specific photocrosslinking to probe interactions of Arf1 with proteins involved in budding of COPI vesicles. Methods. 2000;20:455-64 pubmed
  47. Cockcroft S, Way G, O Luanaigh N, Pardo R, Sarri E, Fensome A. Signalling role for ARF and phospholipase D in mast cell exocytosis stimulated by crosslinking of the high affinity FcepsilonR1 receptor. Mol Immunol. 2002;38:1277-82 pubmed
    ..It is suggested that ARF, by activating PLD and PIP 5-kinase activities regulate PA and PI(4,5)P(2) levels, and both are critical components of the exocytosis machinery in mast cells. ..
  48. Belov G, Fogg M, Ehrenfeld E. Poliovirus proteins induce membrane association of GTPase ADP-ribosylation factor. J Virol. 2005;79:7207-16 pubmed
    ..Taken together, the data suggest an involvement of ARF in poliovirus RNA replication. ..
  49. Levine T, Munro S. Targeting of Golgi-specific pleckstrin homology domains involves both PtdIns 4-kinase-dependent and -independent components. Curr Biol. 2002;12:695-704 pubmed
  50. Kremer W, Steiner G, Béraud Dufour S, Kalbitzer H. Conformational states of the small G protein Arf-1 in complex with the guanine nucleotide exchange factor ARNO-Sec7. J Biol Chem. 2004;279:17004-12 pubmed
    ..GTP.Mg(2+) and is able to displace the bound GTP. ..
  51. Dascher C, Balch W. Dominant inhibitory mutants of ARF1 block endoplasmic reticulum to Golgi transport and trigger disassembly of the Golgi apparatus. J Biol Chem. 1994;269:1437-48 pubmed
    ..These results are discussed in the context of the GDP and GTP-bound forms of ARF in controlling both membrane structure and vesicular traffic through the early secretory pathway. ..
  52. Huber I, Cukierman E, Rotman M, Aoe T, Hsu V, Cassel D. Requirement for both the amino-terminal catalytic domain and a noncatalytic domain for in vivo activity of ADP-ribosylation factor GTPase-activating protein. J Biol Chem. 1998;273:24786-91 pubmed
    ..Thus, a noncatalytic domain is required for GAP activity in vivo. This domain may be involved in the targeting of GAP to the Golgi membrane. ..
  53. Nie Z, Hirsch D, Randazzo P. Arf and its many interactors. Curr Opin Cell Biol. 2003;15:396-404 pubmed
    ..Recent work examining the functional relationships among the diverse Arf interactors has led to reconsideration of the prevailing paradigms for Arf action...