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

Cytohesin-1, a protein abundant in cells of the immune system, has been proposed to be a human homolog of the Saccharomyces cerevisiae Sec7 gene product, which is crucial in protein transport. More recently, the same protein has been reported to be a regulatory factor for the alphaLbeta2 integrin in lymphocytes. Overexpression of human or yeast ADP-ribosylation factor (ARF) genes rescues yeast with Sec7 defects, restoring secretory pathway function. ARFs, 20-kDa guanine nucleotide-binding proteins initially identified by their ability to stimulate cholera toxin ADP-ribosyltransferase activity and now recognized as critical components in intracellular vesicular transport, exist in an inactive cytosolic form with GDP bound (ARF-GDP). Interaction with a guanine nucleotide-exchange protein (GEP) accelerates exchange of GDP for GTP, producing the active ARF-GTP. Both soluble and particulate GEPs have been described. To define better the interaction between ARF and Sec7-related proteins, effects of cytohesin-1, synthesized in Escherichia coli, on ARF activity were evaluated. Cytohesin-1 enhanced binding of 35S-labeled guanosine 5'-[gamma-thio]triphosphate [35S]GTP[gammaS] or [3H]GDP to ARF purified from bovine brain (i.e., it appeared to function as an ARF-GEP). Addition of cytohesin-1 to ARF3 with [35S]GTP[gammaS] bound, accelerated [35S]GTP[gammaS] release to a similar degree in the presence of unlabeled GDP or GTP[gammaS] and to a lesser degree with GDP[betaS]; release was negligible without added nucleotide. Cytohesin-1 also increased ARF1 binding to a Golgi fraction, but its effect was not inhibited by brefeldin A (BFA), a drug that reversibly inhibits Golgi function. In this regard, it differs from a recently reported BFA-sensitive ARF-GEP that contains a Sec7 domain.
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PMID:Cytohesin-1, a cytosolic guanine nucleotide-exchange protein for ADP-ribosylation factor. 905 Aug 49

ADP-ribosylation factor domain protein 1 (ARD1) is a multifunctional protein that belongs to the family of 20-kDa ARF proteins. The ARD1 gene encodes a 64-kDa protein with a structure comprising an 18-kDa ADP-ribosylation factor (ARF) domain at the C-terminus (amino acids 403-574), and a 46-kDa N-terminal domain (amino acids 1-402) that contains, from the translation start site, a RING finger domain, two predicted B-Boxes, and a coiled-coil protein interaction motif, which places it among the TRIM (tripartite motif) or RBCC (RING, B-Box, coiled-coil) protein families. Recombinant ARD1 (amino acids 1-574) or its RING finger domain (amino acids 1-110) produced polyubiquitylated proteins when incubated in vitro with a mammalian E1, an E2 enzyme (UbcH6 or UbcH5a, -5b, or -5c), ATP, and ubiquitin. Via its C-terminal ARF domain, recombinant ARD1 binds guanine nucleotides, through which it can enhance, in a GTP-dependent manner, cholera toxin ADP-ribosyltransferase activity. Unlike ARFs, ARD1, but not its ARF domain, exhibits significant GTPase activity. Hydrolysis of GTP bound to the C-terminal ARF domain was stimulated by addition of the 46-kDa N-terminal domain (amino acids 1-402) via its GTPase activating protein (GAP) activity. The rate of GDP dissociation from the C-terminal ARF domain in ARD1, is slowed by the adjacent 15 amino acids, which act as a GDP-dissociation inhibitor (GDI) domain. Cytohesin-1, known already as a guanine nucleotide-exchange factor (GEF) ARF activator, also specifically activated recombinant human ARD1, via activation of the ARF domain. Overexpressed ARD1 fusion proteins were associated with structures resembling lysosomes and Golgi membranes, as well as the nucleus, in different types of cells, and sequences potentially responsible for the intracellular localizations were identified.
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PMID:ADP-ribosylation factor domain protein 1 (ARD1), a multifunctional protein with ubiquitin E3 ligase, GAP, and ARF domains. 1641 70