Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.30 (PARP)
 13,611 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ADP-ribosylation factors (ARFs) are approximately 20-kDa guanine nucleotide-binding proteins that stimulate the ADP-ribosyltransferase activity of cholera toxin in vitro. ARFs are highly conserved, ubiquitously expressed in eukaryotic cells and appear to be involved in vesicular protein transport. The two yeast ARFs are > 60% identical to mammalian ARFs and are essential for cell viability (Stearns, T., Kahn, R. A., Botstein, D., and Hoyt, M. A. (1990) Mol. Cell. Biol. 10, 6690-6699). Although the two yeast ARF proteins are 96% identical in amino acid sequence, the yeast ARF1 gene is constitutively expressed, whereas the ARF2 gene is repressed by glucose. Human ARF5 and ARF6 and a Giardia ARF differ substantially in size and amino acid identity from other mammalian and eukaryotic ARFs but will, as befits their designation, activate cholera toxin. Expression of human ARF5, ARF6, or Giardia ARF cDNA rescued the lethal yeast ARF double mutant (arf1, arf2). Strains rescued by human ARF5, ARF6, or Giardia ARF grew much more slowly than wild-type yeast or strains rescued with yeast ARF1. We infer from the impaired growth of these rescued strains that the homologous ARFs may have specific targeting information that does not interact effectively or efficiently with the yeast protein membrane trafficking system.
 ...
PMID:Human and Giardia ADP-ribosylation factors (ARFs) complement ARF function in Saccharomyces cerevisiae. 144 92

Two major forms of phospholipase D (PLD) activity, solubilized from rat brain membranes with Triton X-100, were separated by HPLC on a heparin-5PW column with buffer containing octyl glucoside. One form was completely dependent on sodium oleate for activity. The other, which was dramatically activated by the addition of ADP-ribosylation factor (ARF) 1 and guanine 5' [gamma-thio]triphosphate, required the presence of phosphatidylinositol 4,5-bisphosphate in the phosphatidylcholine substrate for demonstration of activity, as described by others. Oleate-dependent activity was unaffected by guanine 5' [gamma-thio]triphosphate, or phosphatidylinositol 4,5-bisphosphate. Both sodium oleate-and ARF-dependent activities catalyzed transphosphatidylation, thus identifying them as PLDs. ARF-dependent PLD was activated by recombinant ARF5 (class II) and ARF6 (class III), as well as ARF1 (class I). Myristoylated recombinant ARFs were more effective than their nonmyristoylated counterparts. ARFs were originally identified as activators of cholera toxin ADP-ribosyltransferase activity. The effects of recombinant ARF proteins from the three classes on cholera toxin activity (assayed under conditions identical to those used to assay PLD activity) did not, however, correlate with those on PLD, consistent with the notion that different aspects of ARF structure are involved in the two functions.
 ...
PMID:Activation of rat brain phospholipase D by ADP-ribosylation factors 1,5, and 6: separation of ADP-ribosylation factor-dependent and oleate-dependent enzymes. 797 29

ADP-ribosylation factors (ARFs) are ubiquitous approximately 20-kDa guanine nucleotide-binding proteins that enhance the ADP-ribosyltransferase activity of cholera toxin and are involved in intracellular vesicular transport. Based on size, phylogenetic analysis, amino acid identity, and gene structure, mammalian ARFs fall into three classes (class I, ARF1, -2, and -3; class II, ARF4 and -5; class III, ARF6). A class I ARF had been identified in Drosophila melanogaster. To search for ARFs of other classes in Drosophila, polymerase chain reaction-based techniques were used, resulting in cloning of Drosophila ARF (dARF) II and dARF III with deduced amino acid sequences similar to those of class II and class III mammalian ARFs, respectively. The three Drosophila ARF genes map to different chromosomes and the coding regions have different splicing sites. dARF II mRNA, like ARF I mRNA, is fairly uniformly distributed throughout adult flies, whereas dARF III mRNA is significantly more abundant in heads than in legs or bodies. Recombinant dARF II and dARF III have biochemical and immunological properties similar to those of human ARF5 (hARF5) and hARF6, respectively. These observations are consistent with the conclusion that the three classes of ARFs are present in non-mammalian as well as mammalian species.
 ...
PMID:Characterization of class II and class III ADP-ribosylation factor genes and proteins in Drosophila melanogaster. 806 93

ADP-ribosylation factors (ARFs), a family of approximately 20-kDa guanine nucleotide-binding proteins that activate cholera toxin ADP-ribosyltransferase in vitro, have been implicated in intracellular protein trafficking and are thought to cycle between cytosolic and membrane compartments. Although isolated predominantly as soluble proteins, ARFs associate with membranes and phospholipids in a GTP-dependent manner. In contrast to other small GTP-binding proteins, ARFs are NH2 terminally myristoylated. Using a bacterial expression system, recombinant myristoylated and non-myristoylated human ARF5 were produced to investigate the role of myristoylation in its association with Golgi. The recombinant ARFs (myristoylated and non-myristoylated) exhibited similar biochemical activity as measured by GTP binding and in vitro activation of cholera toxin. Myristoylated ARF5, however, demonstrated a temperature- and GTP-dependent association with Golgi membranes, whereas non-myristoylated ARF did not bind to Golgi under any of the experimental conditions. These data indicate that myristoylation is necessary, although not sufficient, for membrane attachment, but is not necessary for activation of cholera toxin.
 ...
PMID:Effect of myristoylation on GTP-dependent binding of ADP-ribosylation factor to Golgi. 846 39

ADP-ribosylation factors (ARFs) are approximately20-kDa guanine nucleotide-binding proteins that participate in vesicular transport in the Golgi and other intracellular compartments and stimulate cholera toxin ADP-ribosyltransferase activity. Both GTP binding and hydrolysis are necessary for its physiological functions, although purified mammalian ARF lacks detectable GTPase activity. An ARF GTPase-activating protein (GAP) was purified >15,000-fold from rat spleen cytosol using (NH4)2SO4 precipitation and chromatography on Ultrogel AcA 34, DEAE-Sephacel, heparin-Sepharose, hydroxylapatite, and Ultrogel AcA 44. In fractions ( approximately100-kDa proteins) from Ultrogel AcA 44, a major protein band of approximately50 kDa on SDS-polyacrylamide gel electrophoresis correlated with GAP activity, consistent with it being a homodimer, thus differing from an ARF GAP purified from rat liver (Makler, V., Cukierman, E., Rotman, M., Admon, A., and Cassel, D. (1995) J. Biol. Chem. 270, 5232-5237). Purified spleen GAP accelerated hydrolysis of GTP bound to recombinant ARF1, ARF3, ARF5, and ARF6; no effect of NH2-terminal myristoylation was observed. ARF GAP also activated GTP hydrolysis by ARL1, which is 56% identical in amino acid sequence to ARF1, but lacks ARF activity. ARD1 is a 64-kDa guanine nucleotide-binding protein that contains an 18-kDa ARF domain at its carboxyl terminus; the ARF domain lacks the amino-terminal alpha-helix found in native ARF and hence is similar to the amino-terminal truncated mutant Delta13ARF1. Both the ARF domain of ARD1 and Delta13ARF1 were poor substrates for ARF GAP. The non-ARF1 domain of ARD1 enhanced the GTPase activity of the ARF domain, but not that of the ARF proteins and Delta13ARF1, i.e. it lacks the relatively broad substrate specificity exhibited by ARF GAP.
 ...
PMID:Characterization of a GTPase-activating protein that stimulates GTP hydrolysis by both ADP-ribosylation factor (ARF) and ARF-like proteins. Comparison to the ARD1 gap domain. 879 35

Arfaptin 1, a approximately 39-kDa protein based on the deduced amino acid sequence, had been initially identified in a yeast two-hybrid screen using dominant active ARF3 (Q71L) as bait with an HL-60 cDNA library. It was suggested that arfaptin 1 may be involved in Golgi functions, since the FLAG-tagged protein was associated with Golgi membranes when expressed in COS-7 cells and could be bound to Golgi in vitro in an ADP-ribosylation factor (ARF)- and GTPgammaS-dependent, brefeldin A-inhibited fashion. Arfaptin 2, found in the same two-hybrid screen as arfaptin 1, is 60% identical in amino acid sequence and may or may not have an analogous function. We now report some effects of arfaptin 1 on ARF activation of phospholipase D and cholera toxin ADP-ribosyltransferase. Arfaptin 1 inhibited activation of both enzymes in a concentration-dependent manner and was without effect in the absence of ARF. Two ARF1 mutants that activated the toxin, one lacking 13 N-terminal amino acids and the other, in which 73 residues at the N terminus were replaced with the analogous sequence from ARL1, were not inhibited by arfaptin, consistent with the conclusion that arfaptin interaction requires the N terminus of ARF. This region has also been implicated in phospholipase D activation, but whether the two proteins interact with the same structural elements in ARF remains to be determined. Arfaptin inhibition of the action of ARF5 and ARF6 was less than that of ARF1 and ARF3; its effects were less on nonmyristoylated than myristoylated ARFs. Arfaptin effects on guanine nucleotide binding by ARFs were minimal whether or not a purified ARF guanine nucleotide-exchange protein was present. These findings indicate that arfaptin acts as an inhibitor of ARF actions in vitro, raising the possibility that it has a similar role in vivo.
 ...
PMID:Effects of arfaptin 1 on guanine nucleotide-dependent activation of phospholipase D and cholera toxin by ADP-ribosylation factor. 969 11

ADP-ribosylation factor 4 (ARF4) is a member of a family of approximately 20 kDa guanine nucleotide-binding proteins that were initially identified by their ability to stimulate the ADP-ribosyltransferase activity of cholera toxin in vitro. They have recently been shown to play a role in vesicular trafficking and as activators of phospholipase D. The organization of the human ARF4 gene was determined from a genomic clone isolated from an arrayed PAC genomic library. The gene spans approximately 12 kb and contains six exons and five introns. Translation initiates in exon 1 and terminates in exon 6. Nuclease protection experiments indicated that the major transcription initiation site is located 211 bp 5' to the start of translation. In some cell lines derived from human tissues, however, multiple initiation sites were observed. The proximal 5'-flanking region of the human ARF4 gene lacks a TATA box, is highly GC rich, and contains multiple potential Spl-binding sites. An alignment of the exons for the class I ARF genes (ARF1, ARF2, and ARF3) and class II ARF genes (ARF4 and ARF5) reveals that the members of each class share a common gene organization. The structures of the class I and II ARF genes, however, are quite distinct and support the division of the ARFs into these groups based on deduced amino acid sequence, protein size, phylogenetic analysis, and gene structure.
 ...
PMID:Cloning and characterization of the human ADP-ribosylation factor 4 gene. 1052 52