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Gene Review

ARFGEF1  -  ADP-ribosylation factor guanine nucleotide...

Homo sapiens

Synonyms: ADP-ribosylation factor guanine nucleotide-exchange factor 1, ARFGEP1, BIG1, Brefeldin A-inhibited GEP 1, Brefeldin A-inhibited guanine nucleotide-exchange protein 1, ...
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Disease relevance of ARFGEF1

  • In tinnitus patients, the magnetic wave M200 (corresponding to the electric wave P200, or P2) is delayed and only poorly developed or even completely missing, while the amplitude of the magnetic wave M100 (corresponding to the electric wave N100, or N1) is significantly augmented [1].

Psychiatry related information on ARFGEF1

  • P200 was lower to positive, neutral and negative slides in the PTSD group compared to both other groups [2].
  • OBJECTIVE: To study activity of auditory cortex reflected by the N100 and P200 components of the auditory evoked potentials during memorization and scanning of short-term memory stores [3].
  • Data indicated that adult dyslexic readers had significantly slower reaction times and longer P300 latencies than control readers in most of the experimental tasks and delayed P200 latencies for the lexical decision task [4].
  • Although the changes in P300 and N200 induced by sleep deprivation are due to sleepiness, which may slow cognitive processing and decrease the efficiency of mental processing, the increase in P200 may be related with increased anxiety, negative mood, and fatigue [5].

High impact information on ARFGEF1

  • The 50% reduced efficiency in VSVG vesicle release from the TGN in vitro after depletion of p200/myosin II could be reestablished to control levels by the addition of purified nonmuscle myosin II [6].
  • These results indicate a previously unrecognized role for BIG1 in the glycosylation of beta1 by Golgi enzymes, which is critical for its function in developmental and other vital cell processes [7].
  • By electron microscopy, Golgi membranes in BIG1-depleted cells were less sharply defined than those in mock or BIG2 siRNA-treated cells, with more vesicle-like structures at the transface [7].
  • Interaction of BIG2, a brefeldin A-inhibited guanine nucleotide-exchange protein, with exocyst protein Exo70 [8].
  • Also of note, ARF was never detected among proteins precipitated from purified nuclei by anti-BIG1 antibodies, although microscopically the two proteins do appear sometimes to be colocalized in the nucleus [9].

Biological context of ARFGEF1

  • One is a approximately 209-kDa protein 99.5% identical in deduced amino acid sequence (1, 849 residues) to a BFA-inhibited ARF GEP (p200) from bovine brain [10].
  • BFA treatment of transiently or stably transfected cells resulted in the redistribution of Golgi markers and in loss of cell viability, thereby indicating that overproduction of p200 may not be sufficient to overcome the toxic effect [11].
  • Changes in N100, P200 and P300 brain event-related potentials (ERP) elicited by auditory stimulation and electroencephalographic beta-activity were used to assess effects on neurological activity [12].
  • We recently cloned a novel SRF cofactor, termed zipzap/p200, which is a zinc finger protein yet to be characterized [13].
  • We determined that zipzap/p200 is a 200-kDa protein with two classic C2H2 zinc fingers at the carboxyl terminus where the nucleotide sequence was highly conserved among human, mouse, and rat [13].

Anatomical context of ARFGEF1

  • BIG2 is one of brefeldin A-inhibited guanine nucleotide exchange factors for the ARF GTPases and is associated mainly with the trans-Golgi network [14].
  • 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 [15].
  • The components peaking at approximately 100 ms (N100) and 200 ms (P200) that reflect activity of primary auditory cortex were identified and peak amplitudes and latencies were measured [3].
  • These findings suggest that a P200 abnormality represents the frontal lobe dysfunction, and a P300 abnormality represents the left temporal lobe dysfunction in schizophrenia [16].
  • Using a standard CNV paradigm, 21 EEG electrodes and topographic mapping analysis, the post-warning (S1) auditory N100a b c, P200, P300 (binaural clicks) and CNV activity were recorded in three additional patients after extensive dorsolateral and/or medial prefrontal cortex ablations, verified through CT/MRI examinations [17].

Associations of ARFGEF1 with chemical compounds


Other interactions of ARFGEF1

  • Here we show that the putative TGN coat protein p200 (Narula, N., I. McMorrow, G. Plopper, J. Doherty, K.S. Matlin, B. Burke, and J.L. Stow. 1992. J. Cell Biol. 114: 1113-1124) is myosin II [6].
  • In the ERP-OR sub-average, the patient group also had smaller N 100, N 200 and P 300 amplitudes, but larger P 200 amplitude (compared with normal controls) [21].
  • The polyacrylamide-based resins Biogel P-4 and P-200 did not adsorb ferredoxin at high ionic strength [22].

Analytical, diagnostic and therapeutic context of ARFGEF1

  • By immunofluorescence microscopy, BIG1 siRNA-treated cells showed less spreading and concentration of beta1 at the cell surface [7].
  • Neurophysiological phenotyping was performed with four factorized EEG/ERP parameters: EEG activation, anterior and posterior EEG synchronization, and event-related activity (N100/ P200-complex) [23].
  • The native molecular mass of AJL determined by gel filtration on a Biogel P-200 column was 52 kDa and its carbohydrate content was estimated to be 3.40% [24].
  • The P200 and N200 latencies recorded from Fz were significantly longer than in their control group (P = 0.0448 and P = 0.0107) while the prolongation in the P300 latencies was not found to be statistically significant (P = 0.0733) [25].
  • 5. Precipitating self-aggregates of concanavalin A appeared to be promoted by chondroitin sulfate at pH 7.3, but no significant precipitation occurred between the reactants at this pH even at very high concentrations, nor did soluble complexes form as determined by affinity chromatography on Sephadex G-200 or fractionation on Bio-Gel P-200 [26].


  1. Auditory cortical basis of tinnitus. Hoke, M., Pantev, C., Lütkenhöner, B., Lehnertz, K. Acta oto-laryngologica. Supplementum. (1991) [Pubmed]
  2. Central and peripheral psychophysiological responses to trauma-related cues in subclinical posttraumatic stress disorder: a pilot study. Wessa, M., Karl, A., Flor, H. Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale. (2005) [Pubmed]
  3. The N100 auditory cortical evoked potential indexes scanning of auditory short-term memory. Conley, E.M., Michalewski, H.J., Starr, A. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology. (1999) [Pubmed]
  4. Speed of processing of the visual-orthographic and auditory-phonological systems in adult dyslexics: the contribution of "asynchrony" to word recognition deficits. Breznitz, Z., Misra, M. Brain and language. (2003) [Pubmed]
  5. Auditory event-related potentials and psychological changes during sleep deprivation. Lee, H.J., Kim, L., Kim, Y.K., Suh, K.Y., Han, J., Park, M.K., Park, K.W., Lee, D.H. Neuropsychobiology (2004) [Pubmed]
  6. Myosin II is involved in the production of constitutive transport vesicles from the TGN. Müsch, A., Cohen, D., Rodriguez-Boulan, E. J. Cell Biol. (1997) [Pubmed]
  7. BIG1, a brefeldin A-inhibited guanine nucleotide-exchange protein, is required for correct glycosylation and function of integrin beta1. Shen, X., Hong, M.S., Moss, J., Vaughan, M. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  8. Interaction of BIG2, a brefeldin A-inhibited guanine nucleotide-exchange protein, with exocyst protein Exo70. Xu, K.F., Shen, X., Li, H., Pacheco-Rodriguez, G., Moss, J., Vaughan, M. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  9. Nuclear localization and molecular partners of BIG1, a brefeldin A-inhibited guanine nucleotide-exchange protein for ADP-ribosylation factors. Padilla, P.I., Pacheco-Rodriguez, G., Moss, J., Vaughan, M. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  10. Purification and cloning of a brefeldin A-inhibited guanine nucleotide-exchange protein for ADP-ribosylation factors. Togawa, A., Morinaga, N., Ogasawara, M., Moss, J., Vaughan, M. J. Biol. Chem. (1999) [Pubmed]
  11. p200 ARF-GEP1: a Golgi-localized guanine nucleotide exchange protein whose Sec7 domain is targeted by the drug brefeldin A. Mansour, S.J., Skaug, J., Zhao, X.H., Giordano, J., Scherer, S.W., Melançon, P. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  12. Electroencephalographic effects and serum concentrations after intranasal and intravenous administration of diazepam to healthy volunteers. Lindhardt, K., Gizurarson, S., Stefánsson, S.B., Olafsson, D.R., Bechgaard, E. British journal of clinical pharmacology. (2001) [Pubmed]
  13. Zipzap/p200 is a novel zinc finger protein contributing to cardiac gene regulation. Zhang, X., Azhar, G., Zhong, Y., Wei, J.Y. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  14. BIG2, a guanine nucleotide exchange factor for ADP-ribosylation factors: its localization to recycling endosomes and implication in the endosome integrity. Shin, H.W., Morinaga, N., Noda, M., Nakayama, K. Mol. Biol. Cell (2004) [Pubmed]
  15. The Brefeldin A-inhibited Guanine Nucleotide-exchange Protein, BIG2, Regulates the Constitutive Release of TNFR1 Exosome-like Vesicles. Islam, A., Shen, X., Hiroi, T., Moss, J., Vaughan, M., Levine, S.J. J. Biol. Chem. (2007) [Pubmed]
  16. The relationship between auditory ERP and neuropsychological assessments in schizophrenia. Nagasawa, T., Kamiya, T., Kawasaki, Y., Higashima, M., Urata, K., Sakai, N., Koshino, Y. International journal of psychophysiology : official journal of the International Organization of Psychophysiology. (1999) [Pubmed]
  17. The effects on auditory neurocognitive evoked responses and contingent negative variation activity of frontal cortex lesions or ablations in man: three new case studies. Zappoli, R., Versari, A., Zappoli, F., Chiaramonti, R., Zappoli Thyrion, G.D., Grazia Arneodo, M., Zerauschek, V. International journal of psychophysiology : official journal of the International Organization of Psychophysiology. (2000) [Pubmed]
  18. The effects of ketamine vary among inbred mouse strains and mimic schizophrenia for the P80, but not P20 or N40 auditory ERP components. Connolly, P.M., Maxwell, C., Liang, Y., Kahn, J.B., Kanes, S.J., Abel, T., Gur, R.E., Turetsky, B.I., Siegel, S.J. Neurochem. Res. (2004) [Pubmed]
  19. Dishabituating effects of an ACTH 4-9 analog in a vigilance task. Born, J., Fehm-Wolfsdorf, G., Schiebe, M., Rockstroh, B., Fehm, H.L., Voigt, K.H. Pharmacol. Biochem. Behav. (1984) [Pubmed]
  20. Regulation of brefeldin A-inhibited guanine nucleotide-exchange protein 1 (BIG1) and BIG2 activity via PKA and protein phosphatase 1gamma. Kuroda, F., Moss, J., Vaughan, M. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  21. ERPs associated with and without an "orienting reflex" in patients with schizophrenia. Bahramali, H., Lim, L.C., Rennie, C., Meares, R., Gordon, E. Int. J. Neurosci. (2001) [Pubmed]
  22. Purification of multiple pea ferredoxins by chromatography at high ionic strength on unsubstituted Sepharose 4B. Ashton, A.R., Anderson, L.E. Biochim. Biophys. Acta (1981) [Pubmed]
  23. Association analysis of GABAAbeta2 and gamma2 gene polymorphisms with event-related prefrontal activity in man. Winterer, G., Smolka, M., Samochowiec, J., Mulert, C., Ziller, M., Mahlberg, R., Wuebben, Y., Gallinat, J., Rommelspacher, H., Herrman, W.M., Sander, T. Hum. Genet. (2000) [Pubmed]
  24. A tuber lectin from Arisaema jacquemontii Blume with anti-insect and anti-proliferative properties. Kaur, M., Singh, K., Rup, P.J., Kamboj, S.S., Saxena, A.K., Sharma, M., Bhagat, M., Sood, S.K., Singh, J. J. Biochem. Mol. Biol. (2006) [Pubmed]
  25. Auditory event-related potentials (P300) in partial and generalized epileptic patients. Soysal, A., Atakli, D., Atay, T., Altintas, H., Baybas, S., Arpaci, B. Seizure : the journal of the British Epilepsy Association. (1999) [Pubmed]
  26. Interactions between chondroitin sulfate and concanavalin A. Morris, J.E., Chan, S.C. Biochim. Biophys. Acta (1978) [Pubmed]
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