Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi


  • Christian R. Robinson
  • Venkateswarlu KanamarlapudiEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101964


Historical Background

The ADP-ribosylation factor (Arf) family of small GTP-binding proteins regulate many cellular events by cycling between active GTP- and inactive GDP-bound forms. They depend on GTP-exchange factors (GEFs) for activation and GTPase-activating proteins (GAPs) for inactivation (Donaldson and Jackson 2011). Mammalian cells express six ARF isoforms (ARF1–ARF6), ARF1 and ARF6 are the best characterized. ARF1 regulates the membrane trafficking mainly at the Golgi, whereas ARF6 regulates endocytosis, exocytosis, and actin reorganization at the plasma membrane (Donaldson and Jackson 2011).

In the human genome, more than 30 genes are predicted to encode proteins with an ARF-GAP domain that have been classified into ten subfamilies on the basis of sequence similarities of their ARF-GAP domains (Kahn et al. 2008). The ARF GAP with dual pleckstrin homology (PH) domains (ADAP)...
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  1. Donaldson JG, Jackson CL. ARF family G proteins and their regulators: roles in membrane transport, development and disease. Nat Rev Mol Cell Biol. 2011;12:362–75.  https://doi.org/10.1038/nrm3117.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Fenner BJ, Scannell M, Prehn JH. Expanding the substantial interactome of NEMO using protein microarrays. PLoS One. 2010;5:e8799.  https://doi.org/10.1371/journal.pone.0008799.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Haase A, Nordmann C, Sedehizade F, Borrmann C, Reiser G. RanBPM, a novel interaction partner of the brain-specific protein p42IP4/centaurin alpha-1. J Neurochem. 2008;105:2237–48.PubMedCrossRefGoogle Scholar
  4. Hanck T, Stricker R, Sedehizade F, Reiser G. Identification of gene structure and subcellular localization of human centaurin alpha 2, and p42IP4, a family of two highly homologous, Ins 1,3,4,5-P4-/PtdIns 3,4,5-P3-binding, adapter proteins. J Neurochem. 2004;88:326–36.PubMedCrossRefGoogle Scholar
  5. Kahn RA, Bruford E, Inoue H, Logsdon Jr JM, Nie Z, Premont RT, et al. Consensus nomenclature for the human ArfGAP domain-containing proteins. J Cell Biol. 2008;182:1039–44.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Laukkanen MO, Cammarota F, Esposito T, Salvatore M, Castellone MD. Extracellular superoxide dismutase regulates the expression of small gtpase regulatory proteins GEFs, GAPs, and GDI. PLoS One. 2015;10:e0121441.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Pasmant E, Masliah-Planchon J, Lévy P, Laurendeau I, Ortonne N, Parfait B, et al. Identification of genes potentially involved in the increased risk of malignancy in NF1-microdeleted patients. Mol Med. 2011;17:79–87.PubMedCrossRefGoogle Scholar
  8. Shu Q, Lennemann NJ, Sarkar SN, Sadovsky Y, Coyne CB. ADAP2 is an interferon stimulated gene that restricts RNA virus entry. PLoS Pathog. 2015;11:e1005150.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Stricker R, Chow KM, Walther D, Hanck T, Hersh LB, Reiser G. Interaction of the brain-specific protein p42IP4/centaurin-alpha1 with the peptidase nardilysin is regulated by the cognate ligands of p42IP4, PtdIns(3,4,5)P3 and Ins(1,3,4,5)P4, with stereospecificity. J Neurochem. 2006;98:343–54.PubMedCrossRefGoogle Scholar
  10. Venkateswarlu K, Brandom KG, Yuh H. PI 3-kinase-dependent membrane recruitment of centaurin-alpha2 is essential for its effect on ARF6-mediated actin cytoskeleton reorganisation. J Cell Sci. 2007;120:192–801.CrossRefGoogle Scholar
  11. Venturin M, Guarnieri P, Natacci F, Stabile M, Tenconi R, Clementi M, et al. Mental retardation and cardiovascular malformations in NF1 microdeleted patients point to candidate genes in 17q11.2. J Med Genet. 2004;41:34–41.CrossRefGoogle Scholar
  12. Venturin M, Bentivegna A, Moroni R, Larizza L, Riva P. Evidence by expression analysis of candidate genes for congenital heart defects in the NF1 microdeletion interval. Ann Hum Genet. 2005;69:508–16.PubMedCrossRefGoogle Scholar
  13. Venturin M, Carra S, Gaudenzi G, Brunelli S, Gallo GR, Moncini S, et al. ADAP2 in heart development: a candidate gene for the occurrence of cardiovascular malformations in NF1 microdeletion syndrome. J Med Genet. 2014;51:436–43.PubMedCrossRefGoogle Scholar
  14. Whitley P, Gibbard AM, Koumanov F, Oldfield S, Kilgour EE, Prestwich GD, et al. Identification of centaurin-alpha2: a phosphatidylinositide-binding protein present in fat, heart and skeletal muscle. Eur J Cell Biol. 2002;81:222–30.PubMedCrossRefGoogle Scholar
  15. Zuccotti P, Cartelli D, Stroppi M, Pandini V, Venturin M, Aliverti A, et al. Centaurin-α2 interacts with β-tubulin and stabilizes microtubules. PLoS One. 2012;7:e52867.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Christian R. Robinson
    • 1
    • 2
  • Venkateswarlu Kanamarlapudi
    • 1
    Email author
  1. 1.Institute of Life Science 1, School of MedicineSwansea UniversitySwanseaUK
  2. 2.Calon Cardio-Technology Ltd, Institute of Life Science 2Medical School, Swansea UniversitySwanseaUK