Letunic et al. (2017) Nucleic Acids Res doi: 10.1093/nar/gkx922
Letunic et al. (2020) Nucleic Acids Res doi: 10.1093/nar/gkaa937

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ARF ARF-like small GTPases; ARF, ADP-ribosylation factor

SMART accession number:	SM00177
Description:	Ras homologues involved in vesicular transport. Activator of phospholipase D isoforms. Unlike Ras proteins they lack cysteine residues at their C-termini and therefore are unlikely to be prenylated. ARFs are N-terminally myristoylated. Contains ATP/GTP-binding motif (P-loop).
Family alignment:	View or CHROMA formatHMM/Web logoCLUSTALW formatMSF formatFASTA formatPIR format

There are 12028 ARF domains in 11995 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Taxonomic distribution of proteins containing ARF domain.

  This tree includes only several representative species. The complete taxonomic breakdown of all proteins with ARF domain is also avaliable.

  Click on the protein counts, or double click on taxonomic names to display all proteins containing ARF domain in the selected taxonomic class.

• Cellular role (predicted cellular role)

• Binding / catalysis: GTP hydrolysis

• Literature (relevant references for this domain)

• Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

  • Luo JQ et al.
  • Functional association between Arf and RalA in active phospholipase D complex.
  • Proc Natl Acad Sci U S A. 1998; 95: 3632-7
  • Display abstract

  • Activation of phospholipase D1 (PLD1) by Arf has been implicated in vesicle transport and membrane trafficking. PLD1 has also been shown to be associated with the small GTPase RalA, which functions downstream from Ras in a Ras-RalA GTPase cascade that facilitates intracellular signal transduction. Although PLD1 associates directly with RalA, RalA has no effect upon the activity of PLD1. However, PLD1 precipitated from cell lysates with immobilized glutathione S-transferase-RalA fusion protein is active. This suggests the presence of an additional activating factor in the active RalA-PLD1 complexes. Because Arf stimulates PLD1, we looked for the presence of Arf in the active RalA-PLD1 complexes isolated from v-Src- and v-Ras-transformed cell lysates. Low levels of Arf protein were detected in RalA-PLD1 complexes; however, if guanosine 5'-[gamma-thio]triphosphate was added to activate Arf and stimulate translocation to the membrane, high levels of Arf were precipitated by RalA from cell lysates. Interestingly, deletion of 11 amino-terminal amino acids unique to Ral GTPases, which abolished the ability of RalA to precipitate PLD activity, prevented the association between RalA and Arf. Brefeldin A, which inhibits Arf GDP-GTP exchange, inhibited PLD activity in v-Src- and v-Ras-transformed cells but not in the nontransformed cells, suggesting that the association of Arf with RalA is required for the increased PLD activity induced by v-Src and v-Ras. These data implicate Arf in the transduction of intracellular signals activated by v-Src and mediated by the Ras-RalA GTPase cascade. Because both Arf and PLD1 stimulate vesicle formation in the Golgi, these data raise the possibility that vesicle formation and trafficking may play a role in the transduction of intracellular signals.

  • Exton JH
  • New developments in phospholipase D.
  • J Biol Chem. 1997; 272: 15579-82

  • Boman AL, Kahn RA
  • Arf proteins: the membrane traffic police?
  • Trends Biochem Sci. 1995; 20: 147-50
  • Display abstract

  • Cofactor for cholera toxin; activator of phospholipase D; regulator of coat-protein assembly; inhibitor of membrane traffic; ability to cause expansion of the endoplasmic reticulum and vesiculation of the Golgi; sensitivity to membrane phospholipids--each of these activities has been attributed to Arf proteins. Can a single molecular mechanism link them all?

  • Greasley SE et al.
  • The structure of rat ADP-ribosylation factor-1 (ARF-1) complexed to GDP determined from two different crystal forms.
  • Nat Struct Biol. 1995; 2: 797-806
  • Display abstract

  • The ARFs are a family of 21,000 M(r) proteins with biological roles in constitutive secretion and activation of phospholipase D. The structure of ARF-1 complexed to GDP determined from two crystal forms reveals a topology that is similar to that of the protein p21 ras with two differences: an additional amino-terminal helix and an extra beta-strand. The Mg2+ ion in ARF-1 displays a five-coordination sphere; this feature is not seen in p21 ras, due to a shift in the relative position of the DXXG motif between the two proteins. The occurrence of a dimer in one crystal form suggests that ARF-1 may dimerize during its biological function. The dimer interface involves a region of the ARF-1 molecule that is analogous to the effector domain in p21 ras and may mediate interactions with its effectors.

  • Kahn RA, Kern FG, Clark J, Gelmann EP, Rulka C
  • Human ADP-ribosylation factors. A functionally conserved family of GTP-binding proteins.
  • J Biol Chem. 1991; 266: 2606-14
  • Display abstract

  • A new member, hARF4, of the ADP-ribosylation factor (ARF) family, a subset of the superfamily of regulatory GTP-binding proteins, has been cloned from a cDNA expression library. Two other human ARF cDNA sequences, designated human ARF1 and ARF3, have been reported previously and are 96% identical in amino acid sequence. A human ARF1 cDNA, significantly longer than previously described clones, was obtained, by cross-species hybridization using a bovine ARF1 cDNA probe. Bovine ARF1p and human ARF1p are 100% identical while each is only 80% identical to hARF4p. Thus, hARF4p is the most divergent of the mammalian ARF proteins identified. Northern blot analysis revealed the expression of at least three different ARF messages in human placenta and adrenal carcinoma cells. Both hARF1 and hARF4 encode GTP-binding proteins with predicted molecular masses of 20,000-21,000 Da. Biochemical analysis of the purified recombinant proteins revealed a high degree of conservation of nucleotide binding properties and in vitro ARF activities. ARF is an essential gene in the yeast, Saccharomyces cerevisiae, and is encoded by two genes. Expression of either hARF1p or hARF4p in yeast was found to rescue the lethal double mutant, arf1-arf2-, thus demonstrating the functional conservation of ARF functions between yeast and man. The combination of in vivo and in vitro assays for ARF function provides a specific and unambiguous means of determining bona fide ARF proteins from divergent species from among the rapidly increasing number of structurally related, small molecular weight GTP-binding proteins.

• Structure (3D structures containing this domain)

• 3D Structures of ARF domains in PDB

  PDB code	Main view	Title
  1e0s		small G protein Arf6-GDP
  1fzq		CRYSTAL STRUCTURE OF MURINE ARL3-GDP
  1hur		HUMAN ADP-RIBOSYLATION FACTOR 1 COMPLEXED WITH GDP, FULL LENGTH NON-MYRISTOYLATED
  1j2j		Crystal structure of GGA1 GAT N-terminal region in complex with ARF1 GTP form
  1ksg		Complex of Arl2 and PDE delta, Crystal Form 1
  1ksh		Complex of Arl2 and PDE delta, Crystal Form 2 (native)
  1ksj		Complex of Arl2 and PDE delta, Crystal Form 2 (SeMet)
  1moz		ADP-ribosylation factor-like 1 (ARL1) from Saccharomyces cerevisiae
  1mr3		Saccharomyces cerevisiae ADP-ribosylation Factor 2 (ScArf2) complexed with GDP-3'P at 1.6A resolution
  1o3y		Crystal structure of mouse ARF1 (delta17-Q71L), GTP form
  1r4a		Crystal Structure of GTP-bound ADP-ribosylation Factor Like Protein 1 (Arl1) and GRIP Domain of Golgin245 COMPLEX
  1r8q		FULL-LENGTH ARF1-GDP-MG IN COMPLEX WITH BREFELDIN A AND A SEC7 DOMAIN
  1r8s		ARF1[DELTA1-17]-GDP IN COMPLEX WITH A SEC7 DOMAIN CARRYING THE MUTATION OF THE CATALYTIC GLUTAMATE TO LYSINE
  1re0		Structure of ARF1-GDP bound to Sec7 domain complexed with Brefeldin A
  1rrf		NON-MYRISTOYLATED RAT ADP-RIBOSYLATION FACTOR-1 COMPLEXED WITH GDP, MONOMERIC CRYSTAL FORM
  1rrg		NON-MYRISTOYLATED RAT ADP-RIBOSYLATION FACTOR-1 COMPLEXED WITH GDP, DIMERIC CRYSTAL FORM
  1s9d		ARF1[DELTA 1-17]-GDP-MG IN COMPLEX WITH BREFELDIN A AND A SEC7 DOMAIN
  1u81		Delta-17 Human ADP Ribosylation Factor 1 Complexed with GDP
  1upt		Structure of a complex of the golgin-245 GRIP domain with Arl1
  1yzg		Structure of Human ADP-ribosylation factor-like 8
  1z6x		Structure Of Human ADP-Ribosylation Factor 4
  1z6y		Structure Of Human ADP-Ribosylation Factor-Like 5
  1zj6		Crystal structure of human ARL5
  2a5d		Structural basis for the activation of cholera toxin by human ARF6-GTP
  2a5f		Cholera toxin A1 subunit bound to its substrate, NAD+, and its human protein activator, ARF6
  2a5g		Cholera toxin A1 subunit bound to ARF6(Q67L)
  2b6h		Structure of human ADP-ribosylation factor 5
  2h16		Structure of human ADP-ribosylation factor-like 5 (ARL5)
  2h17		Structure of human ADP-ribosylation factor-like 5 (ARL5) (CASP Target)
  2h57		Crystal structure of human ADP-ribosylation factor-like 6
  2j59		Crystal structure of the ARF1:ARHGAP10-ArfBD complex
  2j5x		STRUCTURE OF THE SMALL G PROTEIN ARF6 IN COMPLEX WITH GTPGAMMAS
  2k5u		Solution structure of myirstoylated yeast ARF1 protein, GDP-bound
  2ksq		The myristoylated yeast ARF1 in a GTP and bicelle bound conformation
  2w83		Crystal structure of the ARF6 GTPase in complex with a specific effector, JIP4
  2x77		Crystal Structure of Leishmania major ADP ribosylation factor-like 1.
  3aq4		Molecular insights into plant cell proliferation disturbance by Agrobacterium protein 6b
  3bh6		Crystal structure of the RP2-Arl3 complex bound to GppNHp
  3bh7		Crystal structure of the RP2-Arl3 complex bound to GDP-AlF4
  3doe		Complex of ARL2 and BART, Crystal Form 1
  3dof		Complex of ARL2 and BART, Crystal Form 2
  3lrp		Crystal Structure of Plasmodium falciparum ADP-Ribosylation Factor 1
  3lvq		The crystal structure of ASAP3 in complex with Arf6 in transition state
  3lvr		The crystal structure of ASAP3 in complex with Arf6 in transition state soaked with Calcium
  3n5c		Crystal Structure of Arf6DELTA13 complexed with GDP
  3o47		Crystal structure of ARFGAP1-ARF1 fusion protein
  3pcr		Structure of EspG-Arf6 complex
  3tjz		Crystal Structure of Arf1 Bound to the gamma/zeta-COP Core Complex
  3vhx		The crystal structure of Arf6-MKLP1 (Mitotic kinesin-like protein 1) complex
  4bas		Structure of the Arl6 BBS3 Small GTPase from Trypanosoma brucei with bound nucleotide analogue GppNp
  4c0a		Arf1(Delta1-17)in complex with BRAG2 Sec7-PH domain
  4dcn		Crystal Structure Analysis of the Arfaptin2 BAR domain in Complex with ARL1
  4fme		EspG-Rab1-Arf6 complex
  4goj		The Crystal Structure of full length Arl3GppNHp in complex with UNC119a
  4gok		The Crystal structure of Arl2GppNHp in complex with UNC119a
  4hmy		Structural basis for recruitment and activation of the AP-1 clathrin adaptor complex by Arf1
  4kax		Crystal structure of the Grp1 PH domain in complex with Arf6-GTP
  4q66		4Q66
  4v0k		4V0K
  4v0l		4V0L
  4v0m		4V0M
  4v0n		4V0N
  4v0o		4V0O
  4y0v		4Y0V
  4ylg		4YLG
  4zi2		4ZI2
  4zi3		4ZI3
  5a1u		5A1U
  5a1v		5A1V
  5a1w		5A1W
  5a1x		5A1X
  5a1y		5A1Y
  5de3		5DE3
  5di3		5DI3
  5ee5		5EE5
  5j5c		5J5C

• Links (links to other resources describing this domain)

• PFAM	arf

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