BIG2

Summary

Gene Symbol: BIG2
Description: ADP ribosylation factor guanine nucleotide exchange factor 2
Alias: BIG2, PVNH2, dJ1164I10.1, brefeldin A-inhibited guanine nucleotide-exchange protein 2, ADP-ribosylation factor guanine nucleotide-exchange factor 2 (brefeldin A-inhibited), brefeldin A-inhibited GEP 2
Species: human
Products:     BIG2

Top Publications

  1. Islam A, Shen X, Hiroi T, Moss J, Vaughan M, Levine S. The brefeldin A-inhibited guanine nucleotide-exchange protein, BIG2, regulates the constitutive release of TNFR1 exosome-like vesicles. J Biol Chem. 2007;282:9591-9 pubmed
    ..We investigated whether the brefeldin A (BFA)-inhibited guanine nucleotide-exchange proteins, BIG1 and/or BIG2, are required for TNFR1 release from human umbilical vein endothelial cells...
  2. Lovrecic L, Slavkov I, Dzeroski S, Peterlin B. ADP-ribosylation factor guanine nucleotide-exchange factor 2 (ARFGEF2): a new potential biomarker in Huntington's disease. J Int Med Res. 2010;38:1653-62 pubmed
    ..Little is known about the latter, but the former warrants further analysis as it is known to be associated with intracellular vesicular trafficking, disturbances of which characterize Huntington's disease. ..
  3. Lowery J, Szul T, Seetharaman J, Jian X, Su M, Forouhar F, et al. Novel C-terminal motif within Sec7 domain of guanine nucleotide exchange factors regulates ADP-ribosylation factor (ARF) binding and activation. J Biol Chem. 2011;286:36898-906 pubmed publisher
    ..We determined the crystal structure of human BIG2 Sec7d...
  4. Kuroda F, Moss J, Vaughan M. Regulation of brefeldin A-inhibited guanine nucleotide-exchange protein 1 (BIG1) and BIG2 activity via PKA and protein phosphatase 1gamma. Proc Natl Acad Sci U S A. 2007;104:3201-6 pubmed
    Brefeldin A-inhibited guanine nucleotide-exchange proteins (GEPs) BIG1 and BIG2 activate ADP-ribosylation factor (ARF) GTPases, which are required for vesicular trafficking...
  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
    b>BIG2 is a guanine nucleotide exchange factor (GEF) for the ADP-ribosylation factor (ARF) family of small GTPases, which regulate membrane association of COPI and adaptor protein (AP)-1 coat protein complexes...
  6. Li H, Adamik R, Pacheco Rodriguez G, Moss J, Vaughan M. Protein kinase A-anchoring (AKAP) domains in brefeldin A-inhibited guanine nucleotide-exchange protein 2 (BIG2). Proc Natl Acad Sci U S A. 2003;100:1627-32 pubmed
    ..proteins (GEPs) that activate ADP-ribosylation factor (ARF) GTPases, brefeldin A-inhibited GEP2, BIG2, contains an approximately 200-aa Sec7 domain that is responsible for this catalytic activity and its inhibition by ..
  7. Shin H, Morinaga N, Noda M, Nakayama K. BIG2, a guanine nucleotide exchange factor for ADP-ribosylation factors: its localization to recycling endosomes and implication in the endosome integrity. Mol Biol Cell. 2004;15:5283-94 pubmed
    ..b>BIG2 is one of brefeldin A-inhibited guanine nucleotide exchange factors for the ARF GTPases and is associated mainly ..
  8. Sheen V, Ganesh V, Topcu M, Sebire G, Bodell A, Hill R, et al. Mutations in ARFGEF2 implicate vesicle trafficking in neural progenitor proliferation and migration in the human cerebral cortex. Nat Genet. 2004;36:69-76 pubmed
    ..ARFGEF2 encodes the large (>200 kDa) brefeldin A (BFA)-inhibited GEF2 protein (BIG2), which is required for vesicle and membrane trafficking from the trans-Golgi network (TGN)...
  9. Yamaji R, Adamik R, Takeda K, Togawa A, Pacheco Rodriguez G, Ferrans V, et al. Identification and localization of two brefeldin A-inhibited guanine nucleotide-exchange proteins for ADP-ribosylation factors in a macromolecular complex. Proc Natl Acad Sci U S A. 2000;97:2567-72 pubmed
    ..A (BFA)-inhibited guanine nucleotide-exchange proteins for ADP-ribosylation factors, 200-kDa BIG1 and 190-kDa BIG2, were copurified from bovine brain cytosol associated with >670-kDa macromolecular complexes...

More Information

Publications50

  1. Boal F, Stephens D. Specific functions of BIG1 and BIG2 in endomembrane organization. PLoS ONE. 2010;5:e9898 pubmed publisher
    ..Among the human BFA-sensitive large Arf-GEFs, the function of the two closely related BIG1 and BIG2 is still not clear, and recent studies have raised the question of functional redundancy between the two proteins...
  2. Li C, Kuo J, Waterman C, Kiyama R, Moss J, Vaughan M. Effects of brefeldin A-inhibited guanine nucleotide-exchange (BIG) 1 and KANK1 proteins on cell polarity and directed migration during wound healing. Proc Natl Acad Sci U S A. 2011;108:19228-33 pubmed publisher
  3. Togawa A, Morinaga N, Ogasawara M, Moss J, Vaughan M. Purification and cloning of a brefeldin A-inhibited guanine nucleotide-exchange protein for ADP-ribosylation factors. J Biol Chem. 1999;274:12308-15 pubmed
    ..p200, be named BIG1 for (brefeldin A-inhibited GEP1) and the second, which encodes a approximately 202-kDa protein, BIG2. A protein containing sequences found in BIG2 had been purified earlier from bovine brain...
  4. Charych E, Yu W, Miralles C, Serwanski D, Li X, Rubio M, et al. The brefeldin A-inhibited GDP/GTP exchange factor 2, a protein involved in vesicular trafficking, interacts with the beta subunits of the GABA receptors. J Neurochem. 2004;90:173-89 pubmed
    We have found that the brefeldin A-inhibited GDP/GTP exchange factor 2 (BIG2) interacts with the beta subunits of the gamma-aminobutyric acid type-A receptor (GABA(A)R)...
  5. Lu J, Tiao G, Folkerth R, Hecht J, Walsh C, Sheen V. Overlapping expression of ARFGEF2 and Filamin A in the neuroependymal lining of the lateral ventricles: insights into the cause of periventricular heterotopia. J Comp Neurol. 2006;494:476-84 pubmed
    ..ARFGEF2 encodes for the protein brefeldin-inhibited guanine exchange factor 2 (BIG2)...
  6. Shen X, Xu K, Fan Q, Pacheco Rodriguez G, Moss J, Vaughan M. Association of brefeldin A-inhibited guanine nucleotide-exchange protein 2 (BIG2) with recycling endosomes during transferrin uptake. Proc Natl Acad Sci U S A. 2006;103:2635-40 pubmed
    ..Brefeldin A-inhibited guanine nucleotide-exchange protein (BIG)1 and BIG2 activate ARFs by accelerating replacement of bound GDP with GTP...
  7. Ishizaki R, Shin H, Mitsuhashi H, Nakayama K. Redundant roles of BIG2 and BIG1, guanine-nucleotide exchange factors for ADP-ribosylation factors in membrane traffic between the trans-Golgi network and endosomes. Mol Biol Cell. 2008;19:2650-60 pubmed publisher
    b>BIG2 and BIG1 are closely related guanine-nucleotide exchange factors (GEFs) for ADP-ribosylation factors (ARFs) and are involved in the regulation of membrane traffic through activating ARFs and recruiting coat protein complexes, such as ..
  8. Ishizaki R, Shin H, Iguchi Ariga S, Ariga H, Nakayama K. AMY-1 (associate of Myc-1) localization to the trans-Golgi network through interacting with BIG2, a guanine-nucleotide exchange factor for ADP-ribosylation factors. Genes Cells. 2006;11:949-59 pubmed
    ..Interestingly, we have found that AMY-1 interacts with BIG2 and BIG1, both of which are high molecular weight guanine-nucleotide exchange factors for ADP-ribosylation factors (..
  9. Shinotsuka C, Waguri S, Wakasugi M, Uchiyama Y, Nakayama K. Dominant-negative mutant of BIG2, an ARF-guanine nucleotide exchange factor, specifically affects membrane trafficking from the trans-Golgi network through inhibiting membrane association of AP-1 and GGA coat proteins. Biochem Biophys Res Commun. 2002;294:254-60 pubmed
    b>BIG2 is one of the guanine nucleotide exchange factors (GEFs) for the ADP-ribosylation factor (ARF) family of small GTPases, which regulate membrane association of COPI and AP-1 coat protein complexes and GGA proteins...
  10. Manolea F, Claude A, Chun J, Rosas J, Melancon P. Distinct functions for Arf guanine nucleotide exchange factors at the Golgi complex: GBF1 and BIGs are required for assembly and maintenance of the Golgi stack and trans-Golgi network, respectively. Mol Biol Cell. 2008;19:523-35 pubmed
    ..In contrast, knockdown of BIG1 and BIG2 caused loss of clathrin adaptor proteins and redistribution of several TGN markers, but had no impact on COPI and ..
  11. Bardón Cancho E, Muñoz Jiménez L, Vázquez López M, Ruíz Martín Y, García Morín M, Barredo Valderrama E. Periventricular nodular heterotopia and dystonia due to an ARFGEF2 mutation. Pediatr Neurol. 2014;51:461-4 pubmed publisher
    ..388C>T in exon 4. The presence of dyskinetic movements in individuals with acquired microcephaly could be a manifestation of periventricular nodular heterotopia due to ARFGEF2 mutation. ..
  12. Skorobogata O, Escobar Restrepo J, Rocheleau C. An AGEF-1/Arf GTPase/AP-1 ensemble antagonizes LET-23 EGFR basolateral localization and signaling during C. elegans vulva induction. PLoS Genet. 2014;10:e1004728 pubmed publisher
    ..AGEF-1 is homologous to the mammalian BIG1 and BIG2 Arf GTPase guanine nucleotide exchange factors (GEFs), which regulate secretory traffic between the Trans-Golgi ..
  13. Conti V, Carabalona A, Pallesi Pocachard E, Parrini E, Leventer R, Buhler E, et al. Periventricular heterotopia in 6q terminal deletion syndrome: role of the C6orf70 gene. Brain. 2013;136:3378-94 pubmed publisher
    ..2 Mb region. Our data suggest that, of the genes within this minimal critical region, C6orf70 plays a major role in the control of neuronal migration and its haploinsufficiency or mutation causes periventricular nodular heterotopia. ..
  14. Yilmaz S, Gokben S, Serdaroglu G, Eraslan C, Mancini G, Tekin H, et al. The expanding phenotypic spectrum of ARFGEF2 gene mutation: Cardiomyopathy and movement disorder. Brain Dev. 2016;38:124-7 pubmed publisher
    ..In case of ARFGEF2 gene mutation, screening for cardiomyopathy may be indicated. ..
  15. Tonelli M, Espinoza S, Gainetdinov R, Cichero E. Novel biguanide-based derivatives scouted as TAAR1 agonists: Synthesis, biological evaluation, ADME prediction and molecular docking studies. Eur J Med Chem. 2017;127:781-792 pubmed publisher
    ..Phenyl (BIG2, BIG4, BIG8 and BIG22) or benzyl (BIG10-BIG16) biguanides were found to be selective murine and human TAAR1 ..
  16. Hong E, Kim J, Kim J, Lim D, Kim M, Kim J. BIG2-ARF1-RhoA-mDia1 Signaling Regulates Dendritic Golgi Polarization in Hippocampal Neurons. Mol Neurobiol. 2018;55:7701-7716 pubmed publisher
    ..From mouse brain lysates, we identified Brefeldin A-inhibited guanine exchange factor 2 (BIG2) as a novel Rho GTPase regulatory protein involved in dendrite growth and maintenance...
  17. Mitra S, Bastos C, Chesworth S, Frye C, Bult Ito A. Strain and sex based characterization of behavioral expressions in non-induced compulsive-like mice. Physiol Behav. 2017;168:103-111 pubmed publisher
    ..cognitive-, and depression-like behaviors among male and proestrus female replicate strains each of BIG (BIG1, BIG2) and SMALL (SML1, SML2) nest-builders, and randomly-bred Controls (C1, C2)...
  18. Corso J, Pan K, Walter R, Doebele C, Mohr S, Bohnenberger H, et al. Elucidation of tonic and activated B-cell receptor signaling in Burkitt's lymphoma provides insights into regulation of cell survival. Proc Natl Acad Sci U S A. 2016;113:5688-93 pubmed publisher
    ..Thus, this study provides a comprehensive dataset for tonic and activated BCR signaling and identifies effector proteins that may be relevant for BL cell survival and thus may help to develop new BL treatments. ..
  19. Anders N, Nielsen M, Keicher J, Stierhof Y, Furutani M, Tasaka M, et al. Membrane association of the Arabidopsis ARF exchange factor GNOM involves interaction of conserved domains. Plant Cell. 2008;20:142-51 pubmed publisher
    ..Our results suggest a general model of large ARF-GEF function in which regulated changes in protein conformation control membrane association of the exchange factor and, thus, activation of ARFs. ..
  20. Kamei Y, Takeda Y, Teramoto K, Tsutsumi O, Taketani Y, Watanabe K. Human NB-2 of the contactin subgroup molecules: chromosomal localization of the gene (CNTN5) and distinct expression pattern from other subgroup members. Genomics. 2000;69:113-9 pubmed
    ..The human NB-2 gene (CNTN5) was mapped to chromosome 11q21-q22.2 by fluorescence in situ hybridization. Our results suggest that the NB-2 gene may contribute to human neurological disorders. ..
  21. Mitra S, Bult Ito A. Attenuation of compulsive-like behavior by fluvoxamine in a non-induced mouse model of obsessive-compulsive disorder. Behav Pharmacol. 2017;: pubmed publisher
    ..to fluvoxamine, a common obsessive-compulsive disorder (OCD) drug, in two different mouse strains (BIG1 and BIG2) with a spontaneous compulsive-like phenotype...
  22. Kitakura S, Adamowski M, Matsuura Y, Santuari L, Kouno H, Arima K, et al. BEN3/BIG2 ARF GEF is Involved in Brefeldin A-Sensitive Trafficking at the trans-Golgi Network/Early Endosome in Arabidopsis thaliana. Plant Cell Physiol. 2017;58:1801-1811 pubmed publisher
    ..Here, we show that BEN3 encodes a member of BIG family ARF GEFs, BIG2. BEN3/BIG2 tagged with fluorescent proteins co-localized with markers for the TGN/early endosome (EE)...
  23. de Wit M, de Coo I, Halley D, Lequin M, Mancini G. Movement disorder and neuronal migration disorder due to ARFGEF2 mutation. Neurogenetics. 2009;10:333-6 pubmed publisher
  24. Zhang J, Neal J, Lian G, Hu J, Lu J, Sheen V. Filamin A regulates neuronal migration through brefeldin A-inhibited guanine exchange factor 2-dependent Arf1 activation. J Neurosci. 2013;33:15735-46 pubmed publisher
    ..factor guanine exchange factor 2 [ARFGEF2; encoding brefeldin-A-inhibited guanine exchange factor-2 (BIG2)] genes give rise to this disorder...
  25. Islam A, Jones H, Hiroi T, Lam J, Zhang J, Moss J, et al. cAMP-dependent protein kinase A (PKA) signaling induces TNFR1 exosome-like vesicle release via anchoring of PKA regulatory subunit RIIbeta to BIG2. J Biol Chem. 2008;283:25364-71 pubmed publisher
    ..We have shown that the brefeldin A-inhibited guanine nucleotide exchange protein BIG2 associates with TNFR1 and selectively modulates the release of TNFR1 exosome-like vesicles via an ARF1- and ARF3-..
  26. Ellong E, Soni K, Bui Q, Sougrat R, Golinelli Cohen M, Jackson C. Interaction between the triglyceride lipase ATGL and the Arf1 activator GBF1. PLoS ONE. 2011;6:e21889 pubmed publisher
    ..We suggest that interaction of GBF1 with ATGL may be involved in the membrane trafficking pathway mediated by GBF1, Arf1 and COPI that contributes to the localization of ATGL to lipid droplets. ..
  27. Dehring D, Adler A, Hosseini A, Hicke L. A C-terminal sequence in the guanine nucleotide exchange factor Sec7 mediates Golgi association and interaction with the Rsp5 ubiquitin ligase. J Biol Chem. 2008;283:34188-96 pubmed publisher
    ..These observations identify a new functional region within the Sec7/BIG family of Arf GEFs that is required for trans-Golgi network localization. ..
  28. Banne E, Atawneh O, Henneke M, Brockmann K, Gartner J, Elpeleg O, et al. West syndrome, microcephaly, grey matter heterotopia and hypoplasia of corpus callosum due to a novel ARFGEF2 mutation. J Med Genet. 2013;50:772-5 pubmed publisher
    ..Here, we describe a novel ARFGEF2 mutation in five related patients presenting with WS, microcephaly, periventricular heterotopia and thin corpus callosum. ..
  29. Tanyalçin I, Verhelst H, Halley D, Vanderhasselt T, Villard L, Goizet C, et al. Elaborating the phenotypic spectrum associated with mutations in ARFGEF2: case study and literature review. Eur J Paediatr Neurol. 2013;17:666-70 pubmed publisher
    The BIG2 protein, coded by ARFGEF2 indirectly assists neuronal proliferation and migration during cortical development. Mutations in ARFGEF2 have been reported as a rare cause of periventricular heterotopia...
  30. Mick E, McGough J, Deutsch C, Frazier J, Kennedy D, Goldberg R. Genome-wide association study of proneness to anger. PLoS ONE. 2014;9:e87257 pubmed publisher
    ..These results suggest that signaling pathways regulating intracellular calcium homeostasis, which are relevant to memory, learning, and neuronal survival, may in part underlie the expression of Angry Temperament. ..
  31. Le K, Li C, Ye G, Moss J, Vaughan M. Arf guanine nucleotide-exchange factors BIG1 and BIG2 regulate nonmuscle myosin IIA activity by anchoring myosin phosphatase complex. Proc Natl Acad Sci U S A. 2013;110:E3162-70 pubmed publisher
    Brefeldin A-inhibited guanine nucleotide-exchange factors BIG1 and BIG2 activate, through their Sec7 domains, ADP ribosylation factors (Arfs) by accelerating the replacement of Arf-bound GDP with GTP for initiation of vesicular transport ..
  32. Xu K, Shen X, Li H, Pacheco Rodriguez G, Moss J, Vaughan M. Interaction of BIG2, a brefeldin A-inhibited guanine nucleotide-exchange protein, with exocyst protein Exo70. Proc Natl Acad Sci U S A. 2005;102:2784-9 pubmed
    ..Mammalian brefeldin A-inhibited guanine nucleotide-exchange proteins, BIG1 and BIG2, are important activators of ADP-ribosylation factors for vesicular trafficking...
  33. Padilla P, Chang M, Pacheco Rodriguez G, Adamik R, Moss J, Vaughan M. Interaction of FK506-binding protein 13 with brefeldin A-inhibited guanine nucleotide-exchange protein 1 (BIG1): effects of FK506. Proc Natl Acad Sci U S A. 2003;100:2322-7 pubmed
    BIG1 and BIG2 are brefeldin A-inhibited guanine nucleotide-exchange proteins that activate ADP-ribosylation factors (ARFs), critical components of vesicular trafficking pathways...
  34. Shen X, Li C, Aponte A, Shen R, Billings E, Moss J, et al. Brefeldin A-inhibited ADP-ribosylation factor activator BIG2 regulates cell migration via integrin ?1 cycling and actin remodeling. Proc Natl Acad Sci U S A. 2012;109:14464-9 pubmed publisher
    ..Mechanisms of additional BIG2 function(s) are less clear...
  35. Pacheco Rodriguez G, Moss J, Vaughan M. BIG1 and BIG2: brefeldin A-inhibited guanine nucleotide-exchange proteins for ADP-ribosylation factors. Methods Enzymol. 2002;345:397-404 pubmed
  36. Farhat R, Ankavay M, Lebsir N, Gouttenoire J, Jackson C, Wychowski C, et al. Identification of GBF1 as a cellular factor required for hepatitis E virus RNA replication. Cell Microbiol. 2017;: pubmed publisher
    ..brefeldin A (BFA) that blocks the activity of the cellular Arf guanine nucleotide exchange factors GBF1, BIG1, and BIG2, which play a major role in reshuffling of cellular membranes...
  37. Puxeddu E, Uhart M, Li C, Ahmad F, Pacheco Rodriguez G, Manganiello V, et al. Interaction of phosphodiesterase 3A with brefeldin A-inhibited guanine nucleotide-exchange proteins BIG1 and BIG2 and effect on ARF1 activity. Proc Natl Acad Sci U S A. 2009;106:6158-63 pubmed publisher
    ..Brefeldin A-inhibited guanine nucleotide-exchange proteins (BIG)1 and BIG2 catalyze the activation of class I ARFs by accelerating replacement of bound GDP with GTP...
  38. Wang C, Saar V, Leung K, Chen L, Wong G. Human amyloid ? peptide and tau co-expression impairs behavior and causes specific gene expression changes in Caenorhabditis elegans. Neurobiol Dis. 2018;109:88-101 pubmed publisher
    ..Taken together, our C. elegans double transgenic model provides insight on the fundamental neurobiologic processes underlying human AD and recapitulates selected transcriptomic changes observed in human AD brains. ..
  39. Galindo A, Soler N, McLaughlin S, Yu M, Williams R, Munro S. Structural Insights into Arl1-Mediated Targeting of the Arf-GEF BIG1 to the trans-Golgi. Cell Rep. 2016;16:839-50 pubmed publisher
    ..by the guanine nucleotide exchange factor (GEF) GBF1 and at the trans-Golgi by the related GEF BIG1 or its paralog, BIG2. The trans-Golgi-specific targeting of BIG1 and BIG2 depends on the Arf-like GTPase Arl1...
  40. Lowery J, Szul T, Styers M, Holloway Z, Oorschot V, Klumperman J, et al. The Sec7 guanine nucleotide exchange factor GBF1 regulates membrane recruitment of BIG1 and BIG2 guanine nucleotide exchange factors to the trans-Golgi network (TGN). J Biol Chem. 2013;288:11532-45 pubmed publisher
    ..GBF1 recruits COPI to pre-Golgi and Golgi compartments, whereas BIG1 and BIG2 recruit AP1 and GGA clathrin adaptors to the trans-Golgi network (TGN) and endosomes...
  41. Li C, Le K, Kato J, Moss J, Vaughan M. Enhancement of ?-catenin activity by BIG1 plus BIG2 via Arf activation and cAMP signals. Proc Natl Acad Sci U S A. 2016;113:5946-51 pubmed publisher
    ..by antibodies against brefeldin A-inhibited guanine nucleotide-exchange factors 1 and 2 (BIG1 or BIG2) that activate ADP-ribosylation factors (Arfs) by accelerating the replacement of bound GDP with GTP...