Gene Symbol: ARFGAP1
Description: ADP ribosylation factor GTPase activating protein 1
Alias: ARF1GAP, HRIHFB2281, ADP-ribosylation factor GTPase-activating protein 1, ARF1-directed GTPase-activating protein
Species: human
Products:     ARFGAP1

Top Publications

  1. Zhang C, Yu Y, Zhang S, Liu M, Xing G, Wei H, et al. Characterization, chromosomal assignment, and tissue expression of a novel human gene belonging to the ARF GAP family. Genomics. 2000;63:400-8 pubmed
    We have identified and characterized a novel human ADP-ribosylation factor GTPase-activating protein (ARFGAP1) gene that is related to other members of the ARF GAP family...
  2. Bai M, Gad H, Turacchio G, Cocucci E, Yang J, Li J, et al. ARFGAP1 promotes AP-2-dependent endocytosis. Nat Cell Biol. 2011;13:559-67 pubmed publisher
    ..The GTPase-activating protein (GAP) for ADP-ribosylation factor 1 (ARF1), ARFGAP1, is a known component of the COPI complex...
  3. Saitoh A, Shin H, Yamada A, Waguri S, Nakayama K. Three homologous ArfGAPs participate in coat protein I-mediated transport. J Biol Chem. 2009;284:13948-57 pubmed publisher
    b>ArfGAP1 is a prototype of GTPase-activating proteins for ADP-ribosylation factors (ARFs) and has been proposed to be involved in retrograde transport from the Golgi apparatus to the endoplasmic reticulum (ER) by regulating the uncoating ..
  4. Beck R, Adolf F, Weimer C, Bruegger B, Wieland F. ArfGAP1 activity and COPI vesicle biogenesis. Traffic. 2009;10:307-15 pubmed publisher
    ..Various and opposing reports exist on a role of ArfGAP1 in COPI vesicle biogenesis...
  5. 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. ..
  6. Parnis A, Rawet M, Regev L, Barkan B, Rotman M, Gaitner M, et al. Golgi localization determinants in ArfGAP1 and in new tissue-specific ArfGAP1 isoforms. J Biol Chem. 2006;281:3785-92 pubmed
    The Arf1-directed GTPase-activating protein ArfGAP1 is a Golgi-localized protein that controls the dynamics of the COPI coat of carriers that mediate transport in the endoplasmic reticulum-Golgi shuttle...
  7. Lippincott Schwartz J, Liu W. Insights into COPI coat assembly and function in living cells. Trends Cell Biol. 2006;16:e1-4 pubmed
    ..Here, we present images and movies characterizing the dynamics of protein components of the COPI coat in living cells. We discuss the self-assembly of these coat components into a molecular machine for sorting and trafficking membranes. ..
  8. Xiong Y, Yuan C, Chen R, Dawson T, Dawson V. ArfGAP1 is a GTPase activating protein for LRRK2: reciprocal regulation of ArfGAP1 by LRRK2. J Neurosci. 2012;32:3877-86 pubmed publisher
    ..Here, we identify ArfGAP1 as the first GAP for LRRK2...
  9. Yang J, Lee S, Gao M, Bourgoin S, Randazzo P, Premont R, et al. ARFGAP1 promotes the formation of COPI vesicles, suggesting function as a component of the coat. J Cell Biol. 2002;159:69-78 pubmed
    ..the formation of COPI vesicles by incubating Golgi membrane with purified soluble components, and find that ARFGAP1 in the presence of GTP promotes vesicle formation and cargo sorting...

More Information


  1. Cukierman E, Huber I, Rotman M, Cassel D. The ARF1 GTPase-activating protein: zinc finger motif and Golgi complex localization. Science. 1995;270:1999-2002 pubmed
    ..Thus, the GAP is likely to be recruited to the Golgi by an ARF1-dependent mechanism. ..
  2. 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. ..
  3. Huber I, Rotman M, Pick E, Makler V, Rothem L, Cukierman E, et al. Expression, purification, and properties of ADP-ribosylation factor (ARF) GTPase activating protein-1. Methods Enzymol. 2001;329:307-16 pubmed
  4. Stafa K, Trancikova A, Webber P, Glauser L, West A, Moore D. GTPase activity and neuronal toxicity of Parkinson's disease-associated LRRK2 is regulated by ArfGAP1. PLoS Genet. 2012;8:e1002526 pubmed publisher
    ..we identify a novel functional interaction between LRRK2 and ADP-ribosylation factor GTPase-activating protein 1 (ArfGAP1)...
  5. Peters D, Kay L, Eswaran J, Lakey J, Soundararajan M. Human Miro Proteins Act as NTP Hydrolases through a Novel, Non-Canonical Catalytic Mechanism. Int J Mol Sci. 2018;19: pubmed publisher
    ..Together, the data presented here indicate novel catalytic functions of human Miro atypical GTPases through altered catalytic mechanisms. ..
  6. Mafakheri S, Flörke R, Kanngießer S, Hartwig S, Espelage L, de Wendt C, et al. AKT and AMP-activated protein kinase regulate TBC1D1 through phosphorylation and its interaction with the cytosolic tail of insulin-regulated aminopeptidase IRAP. J Biol Chem. 2018;293:17853-17862 pubmed publisher
    ..Moreover, our data indicate that recruitment of TBC1D1 to GLUT4-containing vesicles and not its GAP activity is regulated by insulin and contraction-mediated phosphorylation. ..
  7. Kim S, Fernandez Martinez J, Sampathkumar P, Martel A, Matsui T, Tsuruta H, et al. Integrative structure-function mapping of the nucleoporin Nup133 suggests a conserved mechanism for membrane anchoring of the nuclear pore complex. Mol Cell Proteomics. 2014;13:2911-26 pubmed publisher
    ..Finally, the model of ScNup133 allowed us to annotate a potential ArfGAP1 lipid packing sensor (ALPS) motif in Sc and VpNup133 and discuss its potential significance in the context of the ..
  8. Kossler N, Stricker S, Rödelsperger C, Robinson P, Kim J, Dietrich C, et al. Neurofibromin (Nf1) is required for skeletal muscle development. Hum Mol Genet. 2011;20:2697-709 pubmed publisher
    ..Our results demonstrate a requirement of neurofibromin for muscle formation and maintenance. This previously unrecognized function of neurofibromin may contribute to the musculoskeletal problems in NF1 patients. ..
  9. Quartino P, Fidelio G, Manneville J, Goud B, Ambroggio E. Detecting phospholipase activity with the amphipathic lipid packing sensor motif of ArfGAP1. Biochem Biophys Res Commun. 2018;505:290-294 pubmed publisher
    The amphipathic lipid packing sensor (ALPS) motif of ArfGAP1 brings this GTPase activating protein to membranes of high curvature...
  10. Kawada D, Kobayashi H, Tomita T, Nakata E, Nagano M, Siekhaus D, et al. The yeast Arf-GAP Glo3p is required for the endocytic recycling of cell surface proteins. Biochim Biophys Acta. 2015;1853:144-56 pubmed publisher
    ..These findings suggest novel roles for Arf-GAP Glo3p in endocytic recycling of cell surface proteins. ..
  11. Grigorenko B, Khrenova M, Nemukhin A. Amide-imide tautomerization in the glutamine side chain in enzymatic and photochemical reactions in proteins. Phys Chem Chem Phys. 2018;20:23827-23836 pubmed publisher
    ..We also propose to validate the glutamine-assisted mechanism of enzymatic GTP hydrolysis by using IR spectroscopy in a proper range of wavenumbers. ..
  12. Nepal B, Leveritt J, Lazaridis T. Membrane Curvature Sensing by Amphipathic Helices: Insights from Implicit Membrane Modeling. Biophys J. 2018;114:2128-2141 pubmed publisher
    ..membrane model 1 is tested on the wild-types and mutants of the antimicrobial peptide magainin, the ALPS motif of arfgap1, ?-synuclein, and an ENTH domain. In these systems, the model is in qualitative agreement with experiments...
  13. Meyer D, Crottet P, Maco B, Degtyar E, Cassel D, Spiess M. Oligomerization and dissociation of AP-1 adaptors are regulated by cargo signals and by ArfGAP1-induced GTP hydrolysis. Mol Biol Cell. 2005;16:4745-54 pubmed
    ..On GTP hydrolysis induced by the GTPase-activating protein ArfGAP1, the complexes were disassembled and AP-1 dissociated from the membrane...
  14. Feng M, Bao Y, Li Z, Li J, Gong M, Lam S, et al. RASAL2 activates RAC1 to promote triple-negative breast cancer progression. J Clin Invest. 2014;124:5291-304 pubmed publisher
    ..Together, these results indicate that activation of a RASAL2/ARHGAP24/RAC1 module contributes to TNBC tumorigenesis and identify a context-dependent role of RASAL2 in breast cancer. ..
  15. Shiba Y, Kametaka S, Waguri S, Presley J, Randazzo P. ArfGAP3 regulates the transport of cation-independent mannose 6-phosphate receptor in the post-Golgi compartment. Curr Biol. 2013;23:1945-51 pubmed publisher
    ..specific for ArfGAP3 and dependent on its GAP activity, because the phenotype was rescued by ArfGAP3 but not by ArfGAP1, ArfGAP2, or the GAP domain mutants of ArfGAP3. ArfGAP3 localized to the trans-Golgi network and early endosomes...
  16. Martínez Martínez N, Martínez Alonso E, Ballesta J, Martínez Menárguez J. Phospholipase D2 is involved in the formation of Golgi tubules and ArfGAP1 recruitment. PLoS ONE. 2014;9:e111685 pubmed publisher
    ..In addition, it was found that the generation of this lipid by the isoenzyme is necessary for ArfGAP1 recruitment to Golgi membranes...
  17. Braun A, Hendrick J, Eisler S, Schmid S, Hausser A, Olayioye M. The Rho-specific GAP protein DLC3 coordinates endocytic membrane trafficking. J Cell Sci. 2015;128:1386-99 pubmed publisher
    ..Taken together, these findings identify DLC3 as a novel component of the endocytic trafficking machinery, wherein it maintains organelle integrity and regulates membrane transport through the control of Rho activity. ..
  18. Liu O, Grant B. Basolateral Endocytic Recycling Requires RAB-10 and AMPH-1 Mediated Recruitment of RAB-5 GAP TBC-2 to Endosomes. PLoS Genet. 2015;11:e1005514 pubmed publisher
  19. Candiello E, Kratzke M, Wenzel D, Cassel D, Schu P. AP-1/?1A and AP-1/?1B adaptor-proteins differentially regulate neuronal early endosome maturation via the Rab5/Vps34-pathway. Sci Rep. 2016;6:29950 pubmed publisher
    ..1A binds ArfGAP1, and with higher affinity brain-specific ArfGAP1, which bind Rabex-5...
  20. Zamboni V, Armentano M, Sarò G, Ciraolo E, Ghigo A, Germena G, et al. Disruption of ArhGAP15 results in hyperactive Rac1, affects the architecture and function of hippocampal inhibitory neurons and causes cognitive deficits. Sci Rep. 2016;6:34877 pubmed publisher
    ..These findings indicate that a normal architecture and function of hippocampal inhibitory neurons is essential for higher hippocampal functions, and is exquisitely sensitive to ArhGAP15-dependent modulation of Rac1/Rac3. ..
  21. Sarowar T, Grabrucker S, Föhr K, Mangus K, Eckert M, Bockmann J, et al. Enlarged dendritic spines and pronounced neophobia in mice lacking the PSD protein RICH2. Mol Brain. 2016;9:28 pubmed publisher
  22. Bujko M, Kober P, Rusetska N, Wakuła M, Goryca K, Grecka E, et al. Aberrant DNA methylation of alternative promoter of DLC1 isoform 1 in meningiomas. J Neurooncol. 2016;130:473-484 pubmed
    ..This isoform is functional GAP protein and tumor suppressor and targeting of its expression results in the increase of DLC1 related cell processes: RHO activation and cell migration. ..
  23. Rodriguez Fernandez I, Dell Angelica E. Identification of Atg2 and ArfGAP1 as Candidate Genetic Modifiers of the Eye Pigmentation Phenotype of Adaptor Protein-3 (AP-3) Mutants in Drosophila melanogaster. PLoS ONE. 2015;10:e0143026 pubmed publisher
    ..The second critical region included the ArfGAP1 gene, which encodes a conserved GTPase-activating protein with specificity towards GTPases of the Arf family...
  24. Li H, Xiang Y, Fan L, Zhang X, Li J, Yu C, et al. Myocardin inhibited the gap protein connexin 43 via promoted miR-206 to regulate vascular smooth muscle cell phenotypic switch. Gene. 2017;616:22-30 pubmed publisher
    ..Thus myocardin affected the gap junction by inhibited Cx43 and myocardin-miR-206-Cx43 formed a loop to regulate VSMC phenotypic switch. ..
  25. Suckling R, Poon P, Travis S, Majoul I, Hughson F, Evans P, et al. Structural basis for the binding of tryptophan-based motifs by δ-COP. Proc Natl Acad Sci U S A. 2015;112:14242-7 pubmed publisher
    ..the mode of binding and show that mammalian δ-COP binds related tryptophan-based motifs such as that from ArfGAP1 in a similar manner...
  26. Dümmer M, Michalski C, Essen L, Rath M, Galland P, Forreiter C. EHB1 and AGD12, two calcium-dependent proteins affect gravitropism antagonistically in Arabidopsis thaliana. J Plant Physiol. 2016;206:114-124 pubmed publisher
    ..Physiological analyses provided evidence that gravitropic signaling might operate via an antagonistic interaction of ARF-GAP (AGD12) and EHB1 in their Ca2+-activated states. ..
  27. Singh M, Gao H, Sun W, Song Z, Schmalzigaug R, Premont R, et al. Structure-activity relationship studies of QS11, a small molecule Wnt synergistic agonist. Bioorg Med Chem Lett. 2015;25:4838-4842 pubmed publisher
    ..The previous report of QS11, a small molecule Wnt synergist that binds to ARF GTPase-activating protein 1 (ARFGAP1), suggests a role for ARFGAP1 in the Wnt/β-catenin pathway...
  28. Fukada F, Kubo Y. Colletotrichum orbiculare Regulates Cell Cycle G1/S Progression via a Two-Component GAP and a GTPase to Establish Plant Infection. Plant Cell. 2015;27:2530-44 pubmed publisher
    ..Thus, during appressorium development, C. orbiculare Bub2/Bfa1 regulates G1/S progression via Co Tem1, and this regulation is essential to establish plant infection. ..
  29. Li H, Yang X, Yang G, Hong Z, Zhou L, Yin P, et al. Hepatitis C virus NS5A hijacks ARFGAP1 to maintain a phosphatidylinositol 4-phosphate-enriched microenvironment. J Virol. 2014;88:5956-66 pubmed publisher
    ..Whether the PI4P phosphatase Sac1 is altered by HCV remains unclear. Here, we identified ARFGAP1 to be a novel host factor for HCV replication...
  30. Yu S, Roth M. Casein kinase I regulates membrane binding by ARF GAP1. Mol Biol Cell. 2002;13:2559-70 pubmed
    ..Thus, a CKI isoform is required for protein traffic through the early secretory pathway and can modulate the amount of ARF GAP1 that can bind to membranes. ..
  31. Luo R, Jacques K, Ahvazi B, Stauffer S, Premont R, Randazzo P. Mutational analysis of the Arf1*GTP/Arf GAP interface reveals an Arf1 mutant that selectively affects the Arf GAP ASAP1. Curr Biol. 2005;15:2164-9 pubmed
    ..To test this hypothesis, we have used mutagenesis to examine the interaction of three Arf GAPs (ASAP1, AGAP1, and ArfGAP1) with switch 1, switch 2, and alpha helix3 of Arf1...
  32. Weimer C, Beck R, Eckert P, Reckmann I, Moelleken J, Brugger B, et al. Differential roles of ArfGAP1, ArfGAP2, and ArfGAP3 in COPI trafficking. J Cell Biol. 2008;183:725-35 pubmed publisher
    ..b>ArfGAP1 binds to membranes depending on their curvature...
  33. Song O, Queval C, Iantomasi R, Delorme V, Marion S, Veyron Churlet R, et al. ArfGAP1 restricts Mycobacterium tuberculosis entry by controlling the actin cytoskeleton. EMBO Rep. 2018;19:29-42 pubmed publisher
    ..We show that this pathway is controlled by Arf GTPase-activating protein 1 (ArfGAP1), as its silencing has an impact on actin cytoskeleton reorganization leading to uncontrolled uptake and ..
  34. Das S. Importance of an Orchestrate Participation of Each Individual Residue Present at a Catalytic Site. Mol Inform. 2017;: pubmed publisher
    ..An unorganized coupled movement leads the hydrolysis through very high energy pathways. This also reveals that the chemical transformations occurring at a catalytic site are residue specific...
  35. Chornyy S, Parnis A, Shmoish M, Cassel D. High abundance of ArfGAP1 found in the mossy fibers in hilus of the dentate gyrus region of the mouse brain. PLoS ONE. 2017;12:e0189659 pubmed publisher
    The Arf GTPase-activating protein ArfGAP1 and its brain-specific isoform ArfGAP1B play an important role in neurotransmission. Here we analyzed the distribution of ArfGAP1 in the mouse brain...
  36. Luo R, Chen P, Wagenbach M, Jian X, Jenkins L, Wordeman L, et al. Direct Functional Interaction of the Kinesin-13 Family Member Kinesin-like Protein 2A (Kif2A) and Arf GAP with GTP-binding Protein-like, Ankyrin Repeats and PH Domains1 (AGAP1). J Biol Chem. 2016;291:21350-21362 pubmed publisher
    ..of AGAP1 KD could be rescued by FLAG-AGAP1, but not by an AGAP1 mutant that did not bind Kif2A efficiently, ArfGAP1-HA or Kif2A-GFP...
  37. Natsume W, Tanabe K, Kon S, Yoshida N, Watanabe T, Torii T, et al. SMAP2, a novel ARF GTPase-activating protein, interacts with clathrin and clathrin assembly protein and functions on the AP-1-positive early endosome/trans-Golgi network. Mol Biol Cell. 2006;17:2592-603 pubmed
    ..Thus, the SMAP gene family constitutes an important ArfGAP subfamily, with each SMAP member exerting both common and distinct functions in vesicle trafficking. ..
  38. Rothman J. Mechanisms of intracellular protein transport. Nature. 1994;372:55-63 pubmed
    ..Both vesicles and their acceptor membranes carry targeting proteins which interact specifically to initiate docking. A general apparatus then assembles at the docking site and fuses the vesicle with its target...
  39. Choudhury N, Nowak J, Zuo J, Rappsilber J, Spoel S, Michlewski G. Trim25 Is an RNA-Specific Activator of Lin28a/TuT4-Mediated Uridylation. Cell Rep. 2014;9:1265-72 pubmed
    ..These findings reveal that protein-modifying enzymes, only recently shown to bind RNA, can guide the function of canonical ribonucleoprotein (RNP) complexes in cis, thereby providing an additional level of specificity. ..
  40. Majoul I, Straub M, Hell S, Duden R, Söling H. KDEL-cargo regulates interactions between proteins involved in COPI vesicle traffic: measurements in living cells using FRET. Dev Cell. 2001;1:139-53 pubmed
    ..Both p24a and p23 interact with ARF1, but only p24 interacts with ARFGAP. These findings suggest a model for how cargo-induced oligomerization of ERD2 regulates its sorting into COPI-coated buds. ..
  41. Bernards A, Settleman J. GAP control: regulating the regulators of small GTPases. Trends Cell Biol. 2004;14:377-85 pubmed
    ..So far, findings suggest that GAP activity is regulated by several mechanisms, including protein-protein interactions, phospholipid interactions, phosphorylation, subcellular translocation and proteolytic degradation. ..
  42. Luo R, Randazzo P. Kinetic analysis of Arf GAP1 indicates a regulatory role for coatomer. J Biol Chem. 2008;283:21965-77 pubmed publisher
    ..We conclude that coatomer is an allosteric regulator of Arf GAP1. The relevance of the results to the two models of Arf GAP1-mediated regulation of Arf1 is discussed. ..
  43. Gannon J, Fernandez Rodriguez J, Alamri H, Feng S, Kalantari F, Negi S, et al. ARFGAP1 is dynamically associated with lipid droplets in hepatocytes. PLoS ONE. 2014;9:e111309 pubmed publisher
    The ARF GTPase Activating Protein 1 (ARFGAP1) associates mainly with the cytosolic side of Golgi cisternal membranes where it participates in the formation of both COPI and clathrin-coated vesicles...
  44. Mossessova E, Gulbis J, Goldberg J. Structure of the guanine nucleotide exchange factor Sec7 domain of human arno and analysis of the interaction with ARF GTPase. Cell. 1998;92:415-23 pubmed