ARF6 explained

ADP-ribosylation factor 6 (ARF6) is a member of the ADP ribosylation factor family of GTP-binding proteins. ARF6 has a variety of cellular functions that are frequently involved in trafficking of biological membranes and transmembrane protein cargo. ARF6 has specifically been implicated in endocytosis of plasma membrane proteins and also, to a lesser extent, plasma membrane protein recycling.

Function

This gene encodes a member of the human ARF gene family, which is part of the Ras superfamily. The ARF genes encode small guanine nucleotide-binding proteins that stimulate the ADP-ribosyltransferase activity of cholera toxin and play a role in vesicular trafficking and as activators of phospholipase D. The product of this gene is localized to the plasma membrane, and regulates vesicular trafficking, remodelling of membrane lipids, and signaling pathways that lead to actin remodeling. A pseudogene of this gene is located on chromosome 7.^[1]

ARF6 can interact with βarrestin upon receptor activation.

Interactions

ARF6 has been shown to interact with:

• ARRB1^[2]
• ARFIP2^{[3] [4]}
• CHRM3^[5]
• EXOC5^[6]
• KIAA0090^[7]
• Rac1^[8]

Further reading

• Sabe H . Requirement for Arf6 in cell adhesion, migration, and cancer cell invasion . J. Biochem. . 134 . 4 . 485–9 . 2004 . 14607973 . 10.1093/jb/mvg181 .
• Joseph AM, Kumar M, Mitra D . Nef: "necessary and enforcing factor" in HIV infection . Curr. HIV Res. . 3 . 1 . 87–94 . 2005 . 15638726 . 10.2174/1570162052773013 .
• Tsuchiya M, Price SR, Tsai SC, Moss J, Vaughan M . Molecular identification of ADP-ribosylation factor mRNAs and their expression in mammalian cells . J. Biol. Chem. . 266 . 5 . 2772–7 . 1991 . 10.1016/S0021-9258(18)49913-9 . 1993656 . free .
• Stearns T, Willingham MC, Botstein D, Kahn RA . ADP-ribosylation factor is functionally and physically associated with the Golgi complex . Proc. Natl. Acad. Sci. U.S.A. . 87 . 3 . 1238–42 . 1990 . 2105501 . 53446 . 10.1073/pnas.87.3.1238 . 1990PNAS...87.1238S . free .
• D'Souza-Schorey C, Stahl PD . Myristoylation is required for the intracellular localization and endocytic function of ARF6 . Exp. Cell Res. . 221 . 1 . 153–9 . 1995 . 7589240 . 10.1006/excr.1995.1362 .
• D'Souza-Schorey C, Li G, Colombo MI, Stahl PD . A regulatory role for ARF6 in receptor-mediated endocytosis . Science . 267 . 5201 . 1175–8 . 1995 . 7855600 . 10.1126/science.7855600 . 1995Sci...267.1175D . 23249341 .
• Welsh CF, Moss J, Vaughan M . ADP-ribosylation factors: a family of approximately 20-kDa guanine nucleotide-binding proteins that activate cholera toxin . Mol. Cell. Biochem. . 138 . 1–2 . 157–66 . 1995 . 7898460 . 10.1007/BF00928458 . 42819002 .
• Amor JC, Harrison DH, Kahn RA, Ringe D . Structure of the human ADP-ribosylation factor 1 complexed with GDP . Nature . 372 . 6507 . 704–8 . 1995 . 7990966 . 10.1038/372704a0 . 1994Natur.372..704C . 4362056 .
• Orcl L, Palmer DJ, Amherdt M, Rothman JE . Coated vesicle assembly in the Golgi requires only coatomer and ARF proteins from the cytosol . Nature . 364 . 6439 . 732–4 . 1993 . 8355790 . 10.1038/364732a0 . 1993Natur.364..732O . 4348442 .
• Helms JB, Palmer DJ, Rothman JE . Two distinct populations of ARF bound to Golgi membranes . J. Cell Biol. . 121 . 4 . 751–60 . 1993 . 8491770 . 2119793 . 10.1083/jcb.121.4.751 .
• Cavenagh MM, Whitney JA, Carroll K, ((Zhang Cj)), Boman AL, Rosenwald AG, Mellman I, Kahn RA . Intracellular distribution of Arf proteins in mammalian cells. Arf6 is uniquely localized to the plasma membrane . J. Biol. Chem. . 271 . 36 . 21767–74 . 1996 . 8702973 . 10.1074/jbc.271.36.21767 . free .
• D'Souza-Schorey C, Boshans RL, McDonough M, Stahl PD, Van Aelst L . A role for POR1, a Rac1-interacting protein, in ARF6-mediated cytoskeletal rearrangements . EMBO J. . 16 . 17 . 5445–54 . 1997 . 9312003 . 1170175 . 10.1093/emboj/16.17.5445 .
• Frank S, Upender S, Hansen SH, Casanova JE . ARNO is a guanine nucleotide exchange factor for ADP-ribosylation factor 6 . J. Biol. Chem. . 273 . 1 . 23–7 . 1998 . 9417041 . 10.1074/jbc.273.1.23 . free .
• Yang CZ, Heimberg H, D'Souza-Schorey C, Mueckler MM, Stahl PD . Subcellular distribution and differential expression of endogenous ADP-ribosylation factor 6 in mammalian cells . J. Biol. Chem. . 273 . 7 . 4006–11 . 1998 . 9461590 . 10.1074/jbc.273.7.4006 . free .
• Mao M, Fu G, Wu JS, Zhang QH, Zhou J, Kan LX, Huang QH, He KL, Gu BW, Han ZG, Shen Y, Gu J, Yu YP, Xu SH, Wang YX, Chen SJ, Chen Z . Identification of genes expressed in human CD34(+) hematopoietic stem/progenitor cells by expressed sequence tags and efficient full-length cDNA cloning . Proc. Natl. Acad. Sci. U.S.A. . 95 . 14 . 8175–80 . 1998 . 9653160 . 20949 . 10.1073/pnas.95.14.8175 . 1998PNAS...95.8175M . free .
• Andreev J, Simon JP, Sabatini DD, Kam J, Plowman G, Randazzo PA, Schlessinger J . Identification of a new Pyk2 target protein with Arf-GAP activity . Mol. Cell. Biol. . 19 . 3 . 2338–50 . 1999 . 10022920 . 84026 . 10.1128/MCB.19.3.2338.
• Radhakrishna H, Al-Awar O, Khachikian Z, Donaldson JG . ARF6 requirement for Rac ruffling suggests a role for membrane trafficking in cortical actin rearrangements . J. Cell Sci. . 112 . 6 . 855–66 . 1999 . 10.1242/jcs.112.6.855 . 10036235 .
• Kim HS . Assignment of the human ADP-ribosylation factor 6 (ARF6) gene to chromosome 7q22.1 by radiation hybrid mapping . Cytogenet. Cell Genet. . 84 . 1–2 . 94 . 1999 . 10343114 . 10.1159/000015225 . 31452287 .
• Langille SE, Patki V, Klarlund JK, Buxton JM, Holik JJ, Chawla A, Corvera S, Czech MP . ADP-ribosylation factor 6 as a target of guanine nucleotide exchange factor GRP1 . J. Biol. Chem. . 274 . 38 . 27099–104 . 1999 . 10480924 . 10.1074/jbc.274.38.27099 . free .
• Honda A, Nogami M, Yokozeki T, Yamazaki M, Nakamura H, Watanabe H, Kawamoto K, Nakayama K, Morris AJ, Frohman MA, Kanaho Y . Phosphatidylinositol 4-phosphate 5-kinase alpha is a downstream effector of the small G protein ARF6 in membrane ruffle formation . Cell . 99 . 5 . 521–32 . 1999 . 10589680 . 10.1016/S0092-8674(00)81540-8 . free .
• Ikeda S, Ushio-Fukai M, Zuo L, Tojo T, Dikalov S, Patrushev NA, Alexander RW . Novel role of ARF6 in vascular endothelial growth factor-induced signaling and angiogenesis . Circ. Res. . 96 . 4 . 467–75 . 2005 . 15692085 . 10.1161/01.RES.0000158286.51045.16 . free .

Notes and References

1. Web site: Entrez Gene: ARF6 ADP-ribosylation factor 6.
2. Claing A, Chen W, Miller WE, Vitale N, Moss J, Premont RT, Lefkowitz RJ . beta-Arrestin-mediated ADP-ribosylation factor 6 activation and beta 2-adrenergic receptor endocytosis . J. Biol. Chem. . 276 . 45 . 42509–13 . November 2001 . 11533043 . 10.1074/jbc.M108399200 . free .
3. D'Souza-Schorey C, Boshans RL, McDonough M, Stahl PD, Van Aelst L . A role for POR1, a Rac1-interacting protein, in ARF6-mediated cytoskeletal rearrangements . EMBO J. . 16 . 17 . 5445–54 . September 1997 . 9312003 . 1170175 . 10.1093/emboj/16.17.5445 .
4. Shin OH, Exton JH . Differential binding of arfaptin 2/POR1 to ADP-ribosylation factors and Rac1 . Biochem. Biophys. Res. Commun. . 285 . 5 . 1267–73 . August 2001 . 11478794 . 10.1006/bbrc.2001.5330 .
5. Mitchell R, Robertson DN, Holland PJ, Collins D, Lutz EM, Johnson MS . ADP-ribosylation factor-dependent phospholipase D activation by the M3 muscarinic receptor . J. Biol. Chem. . 278 . 36 . 33818–30 . September 2003 . 12799371 . 10.1074/jbc.M305825200 . free .
6. Prigent M, Dubois T, Raposo G, Derrien V, Tenza D, Rossé C, Camonis J, Chavrier P . ARF6 controls post-endocytic recycling through its downstream exocyst complex effector . J. Cell Biol. . 163 . 5 . 1111–21 . December 2003 . 14662749 . 2173613 . 10.1083/jcb.200305029 .
7. Prieto C, De Las Rivas J . APID: Agile Protein Interaction DataAnalyzer . Nucleic Acids Res. . 34 . Web Server issue . W298–302 . July 2006 . 16845013 . 1538863 . 10.1093/nar/gkl128 . dead . https://web.archive.org/web/20100409025355/http://bioinfow.dep.usal.es/apid/html/home.htm . 2010-04-09 .
8. Peru y Colón de Portugal RL, Acevedo SF, Rodan AR, Chang LY, Eaton BA, Rothenfluh A . Adult neuronal Arf6 controls ethanol-induced behavior with Arfaptin downstream of Rac1 and RhoGAP18B . J. Neurosci. . 32 . 49 . 17706–13 . December 2012 . 23223291 . 3535434 . 10.1523/JNEUROSCI.1944-12.2012 .