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ARF family

T H E J O U R N A L O F C E L L B I O L O G Y

JCB: COMMENT

? The Rockefeller University Press $8.00

The Journal of Cell Biology, Vol. 172, No. 5, February 27, 2006 645–650http://www.wendangku.net/doc/535d820f844769eae009ed97.html/cgi/doi/10.1083/jcb.200512057

JCB 645

Arf family history: Arfs, Arls, SARs, and other members

Arfs. Arf was fi rst discovered, purifi ed, and functionally de-

fi ned as the protein cofactor required for cholera toxin–catalyzed ADP ribosylation of the stimulatory regulatory subunit (Gs) of adenylyl cyclase (Enomoto and Gill, 1980; Kahn and Gilman, 1984) and, shortly thereafter, was shown to be a GTP-binding protein (K ahn and Gilman, 1986). Use of the acronym Arf is currently preferred to ADP ribosylation factor, as only Arf1–6 shares the cofactor activity for cholera toxin and because ADP ribosylation does not appear to be involved in any aspect of the normal cellular actions of any member of the family. The use of all capital letters (e.g., ARF1) refers specifi cally to the human gene or protein, whereas when only the fi rst letter is capitalized (e.g., Arf1), it may refer to the protein from more than one spe-cies, an activity, or a group of proteins. Since their discovery,

they have been found to be ubiquitous regulators of membrane traffi c and phospholipid metabolism in eukaryotic cells (for re-views and discussion of Arf actions see Nie et al., 2003; Burd et al., 2004; Kahn, 2004). Arfs are soluble proteins that translocate onto membranes in concert with their activation, or GTP bind-ing. The biological actions of Arfs are thought to occur on mem-branes and to result from their specifi c interactions with a large number of effectors that include coat complexes (COPI, AP-1, and AP-3), adaptor proteins (GGA1-3 and MINT1-3/X11α-γ/APBA1-3), lipid-modifying enzymes (PLD1, phosphatidylino-sitol (4,5)-kinase, and phosphatidylinositol (4)-kinase), and oth-ers. Arf proteins are activated by guanosine diphosphate (GDP) to GTP exchange, which is stimulated by the Sec7 domain of Arf guanine nucleotide exchange factors, and their activity is termi-nated upon the hydrolysis of GTP, which is stimulated by inter-action with an Arf GTPase-activating protein.

Cloning and sequencing of the fi rst Arf family member (Sewell and K ahn, 1988) led directly to the realization that Arfs are closely related to both the Ras and heterotrimeric G protein α subunit families of GTPases, and all are thought to have arisen from a common ancestor. The very high degree of conservation of Arf sequences in eukaryotes (74% between human and yeast) was also noted early on and has allowed the ready identifi cation of orthologues in every examined eukary-ote, including Giardia lamblia , which lack Ras and G protein α subunits (Murtagh et al., 1992).

Cloning by low stringency hybridization and chance led to the identifi cation of additional members of the Arf family in a wide array of eukaryotic species. The number of mammalian Arfs grew to six by 1992 (Tsuchiya et al., 1991) and were named in their order of discovery (Price et al., 1988; Bobak et al., 1989; Kahn et al., 1991; Lee et al., 1992). The fi rst confusion in the nomenclature was that the current human ARF4 was originally published with the name ARF2 (Kahn, et al., 1991). In fact, hu-mans appear to have lost the ARF2 orthologue, which is present in other mammals (including rats, mice, and cows). The combi-nation of protein sequence comparisons and intron/exon bound-aries of Arf genes led to further classifi cation of the six mammalian Arfs into classes: class I (ARF1–3 are >96% iden-tical), class II (ARF4 and ARF5 are 90% identical to each other

N omenclature for the human Arf family

of GTP-binding proteins: ARF , ARL, and SAR proteins

Richard A. Kahn,1 Jacqueline Cher? ls,2 Marek Elias,3 Ruth C. Lovering,4 Sean Munro,5 and Annette Schurmann 6

1Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322

2

Laboratoire d’Enzymologie et Biochimie Structurales, Centre National de la Recherche Scienti? que, 91198 Gif-sur-Yvette, France 3

Department of Plant Physiology, Faculty of Science, Charles University, 128 44 Prague 2, Czech Republic 4

Human Genome Organisation Gene Nomenclature Committee, Galton Laboratory, Department of Biology, University College London, London NW1 2HE, United Kingdom 5

Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 2QH, United Kingdom 6

Department of Pharmacology, German Institute of Human Nutrition Potsdam-Rehbrücke, D-14558 Nuthetal, Germany

The Ras supe rfamily is comprise d of at le ast four large familie s of re gulatory guanosine triphosphate –binding proteins, including the Arfs. The Arf family includes three different groups of proteins: the Arfs, Arf-like (Arls), and SARs. Several Arf family members have been very highly conse rve d throughout e ukaryotic e volution and have orthologues in evolutionally diverse species. The different means by which Arf family members have been identi? ed have re sulte d in an inconsiste nt and confusing array of name s. This confusion is furthe r compounde d by diffe r-e nce s in nome nclature be twe e n diffe re nt spe cie s. We propose a more consiste nt nome nclature for the human mem

b ers of the Arf family that may also serve as a guide for nomenclature in other species.

Correspondence to Richard A. Kahn: rkahn@http://www.wendangku.net/doc/535d820f844769eae009ed97.html

Abbreviations used in this paper: GDP , guanosine diphosphate; TRIM, tripartite motif.

The online version of this article contains supplemental material.

on August 12, 2011

http://www.wendangku.net/doc/535d820f844769eae009ed97.html Downloaded from Published February 27, 2006

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Supplemental Material can be found at:

ARF family

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