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Chemical Compound Review

SureCN122460     2-aminopurin-6-one

Synonyms: AC1L9YSZ, AKOS006371525
 
 
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Disease relevance of guanine

 

Psychiatry related information on guanine

  • Our findings implicate gain-of-function mutations in a RAS guanine nucleotide exchange factor in disease for the first time and define a new mechanism by which upregulation of the RAS pathway can profoundly change human development [5].
  • BACKGROUND: This study examines recent suggestions from a number of investigators that signal-transducing guanine nucleotide-binding (G) proteins may be involved in the pathophysiology of bipolar affective disorder and may represent molecular targets for lithium's mood-stabilizing actions [6].
  • We found a novel point mutation, substitution of cytosine for guanine, at nucleotide 2119 (amyloid precursor protein 770 messenger RNA transcript) in a patient with late-onset Alzheimer's disease [7].
  • In six patients with pseudohypoparathyroidism (PHP) who were deficient in guanine nucleotide-binding stimulatory protein (Ns) activity, the response to endogenous arginine vasopressin (AVP) was tested during water deprivation [8].
  • As disturbances in guanine nucleotide binding (G) protein-coupled phosphoinositide second messenger systems have been implicated in bipolar disorder, we examined whether the abundance of G alpha q/11 and phospholipase C (PLC)-beta 1 two key transducing proteins in this signaling pathway, are altered in this disorder [9].
 

High impact information on guanine

  • These binding sites are insensitive to the effects of guanine nucleotides and appear to be rapidly internalized [10].
  • The affinity of the oligopeptide chemoattractant receptor on polymorphonuclear leukocytes and macrophages is heterogeneous and dynamically regulated by guanine nucleotides and prior agonist exposure [10].
  • The GoLoco motif is a 19-amino-acid sequence with guanine nucleotide dissociation inhibitor activity against G-alpha subunits of the adenylyl-cyclase-inhibitory subclass [11].
  • Members of the Rho family of small Ras-like GTPases--including RhoA, -B, and -C, Rac1 and -2, and Cdc42--exhibit guanine nucleotide-binding activity and function as molecular switches, cycling between an inactive GDP-bound state and an active GTP-bound state [12].
  • Here, we report that Rabex-5, a guanine nucleotide exchange factor for Rab5, binds to Ub through two independent UBDs [13].
 

Chemical compound and disease context of guanine

 

Biological context of guanine

 

Anatomical context of guanine

  • Antisera against murine Son of sevenless (Sos) recognize a protein of M(r) 155,000 in rat-1 fibroblasts with specific guanine nucleotide exchange activity toward p21c-Ha-ras [23].
  • In a genetic screen for regulators of muscle development in Drosophila, we discovered a gene encoding a guanine nucleotide exchange factor, called loner, which is required for myoblast fusion [24].
  • EphA receptors regulate growth cone dynamics through the novel guanine nucleotide exchange factor ephexin [25].
  • The predicted sequence of the protein (alsin) may indicate a mechanism for motor-neuron degeneration, as it may include several cell-signaling motifs with known functions, including three associated with guanine-nucleotide exchange factors for GTPases (GEFs) [2].
  • Here, we show that the C. elegans Rho/Rac-family guanine nucleotide exchange factor, VAV-1, which is homologous to the mammalian Vav proto-oncogene, has a crucial role in all three behaviors. vav-1 mutants die as larvae because VAV-1 function is required in the pharynx for synchronous contraction of the musculature [26].
 

Associations of guanine with other chemical compounds

  • Here we report a rare cytosine to guanine mutation in the XIST minimal promoter that underlies both epigenetic and functional differences between the two X chromosomes in nine females from two unrelated families [27].
  • Direct genomic DNA sequencing and restriction fragment length polymorphism analysis demonstrated that all three affected individuals had the guanine to thymine 4993 transversion [28].
  • Transport is inhibited by the guanine nucleotide analog GTP gamma S. sec23 mutant cells have a temperature-sensitive defect in endoplasmic reticulum-to-Golgi transport in vivo [29].
  • Cardiac m2 muscarinic acetylcholine receptors reduce heart rate by coupling to heterotrimeric (alpha beta gamma) guanine nucleotide-binding (G) proteins that activate IKACh, an inward rectifier K+ channel (IRK) [30].
  • To test whether the point mutation found in the Greek non-deletion HPFH (guanine to adenine at nucleotide position -117) is the cause of the raised gamma-globin levels in the adult stage and is not just a linked polymorphism, we engineered this mutation into a gamma-globin gene [31].
 

Gene context of guanine

  • The other locus encodes a protein that is homologous to the S. cerevisiae CDC25 protein, an activator of guanine nucleotide exchange by ras proteins [32].
  • Structural basis for guanine nucleotide exchange on Ran by the regulator of chromosome condensation (RCC1) [33].
  • We propose that CDC25 regulates adenylate cyclase by regulating the guanine nucleotide bound to RAS proteins [34].
  • In these experiments we demonstrate that purified RAS proteins, whether derived from the yeast RAS1 or RAS2 or the human H-ras genes, activate yeast adenylate cyclase in the presence of guanine nucleotides [35].
  • Although overexpressed BUD5 cannot substitute for CDC25 function, we present evidence that its gene product can bind to the guanine nucleotide binding-deficient RAS2val19ala22 gene product and thereby counteract its dominant-negative effect [36].
 

Analytical, diagnostic and therapeutic context of guanine

  • Heterotrimeric guanine-nucleotide-binding proteins (G proteins) are signal transducers that relay messages from many receptors on the cell surface to modulate various cellular processes [37].
  • Molecular cloning of cDNAs encoding a guanine-nucleotide-releasing factor for Ras p21 [38].
  • Of a series of nucleoside analogues synthesised, 9-(2-hydroxyethoxymethyl) guanine was found to have marked antiviral activity in animal models of herpes virus infections, associated with very low toxicity [39].
  • Single-molecule imaging techniques were used to reveal the binding of individual cyclic adenosine 3',5'-monophosphate molecules to heterotrimeric guanine nucleotide-binding protein coupled receptors on the surface of living Dictyostelium discoideum cells [40].
  • These latter phosphoproteins also associated with the Vav guanine nucleotide exchange factor upon TCR ligation, and were dephosphorylated by recombinant PTP1C in vitro [41].

References

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  12. Regulation of the cytoskeleton and cell adhesion by the Rho family GTPases in mammalian cells. Kaibuchi, K., Kuroda, S., Amano, M. Annu. Rev. Biochem. (1999) [Pubmed]
  13. Crystal structure of the ubiquitin binding domains of rabex-5 reveals two modes of interaction with ubiquitin. Penengo, L., Mapelli, M., Murachelli, A.G., Confalonieri, S., Magri, L., Musacchio, A., Di Fiore, P.P., Polo, S., Schneider, T.R. Cell (2006) [Pubmed]
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  16. Signaling by human herpesvirus 8 kaposin A through direct membrane recruitment of cytohesin-1. Kliche, S., Nagel, W., Kremmer, E., Atzler, C., Ege, A., Knorr, T., Koszinowski, U., Kolanus, W., Haas, J. Mol. Cell (2001) [Pubmed]
  17. Deficient guanine nucleotide regulatory unit activity in cultured fibroblast membranes from patients with pseudohypoparathyroidism type I. a cause of impaired synthesis of 3',5'-cyclic AMP by intact and broken cells. Levine, M.A., Eil, C., Downs, R.W., Spiegel, A.M. J. Clin. Invest. (1983) [Pubmed]
  18. 2'-deoxyguanosine toxicity for B and mature T lymphoid cell lines is mediated by guanine ribonucleotide accumulation. Sidi, Y., Mitchell, B.S. J. Clin. Invest. (1984) [Pubmed]
  19. The discs-large tumor suppressor gene of Drosophila encodes a guanylate kinase homolog localized at septate junctions. Woods, D.F., Bryant, P.J. Cell (1991) [Pubmed]
  20. Human genome organization: Alu, lines, and the molecular structure of metaphase chromosome bands. Korenberg, J.R., Rykowski, M.C. Cell (1988) [Pubmed]
  21. The signal recognition particle receptor mediates the GTP-dependent displacement of SRP from the signal sequence of the nascent polypeptide. Connolly, T., Gilmore, R. Cell (1989) [Pubmed]
  22. Disruption of dog-1 in Caenorhabditis elegans triggers deletions upstream of guanine-rich DNA. Cheung, I., Schertzer, M., Rose, A., Lansdorp, P.M. Nat. Genet. (2002) [Pubmed]
  23. Epidermal growth factor regulates p21ras through the formation of a complex of receptor, Grb2 adapter protein, and Sos nucleotide exchange factor. Buday, L., Downward, J. Cell (1993) [Pubmed]
  24. Control of myoblast fusion by a guanine nucleotide exchange factor, loner, and its effector ARF6. Chen, E.H., Pryce, B.A., Tzeng, J.A., Gonzalez, G.A., Olson, E.N. Cell (2003) [Pubmed]
  25. EphA receptors regulate growth cone dynamics through the novel guanine nucleotide exchange factor ephexin. Shamah, S.M., Lin, M.Z., Goldberg, J.L., Estrach, S., Sahin, M., Hu, L., Bazalakova, M., Neve, R.L., Corfas, G., Debant, A., Greenberg, M.E. Cell (2001) [Pubmed]
  26. The Rho/Rac-family guanine nucleotide exchange factor VAV-1 regulates rhythmic behaviors in C. elegans. Norman, K.R., Fazzio, R.T., Mellem, J.E., Espelt, M.V., Strange, K., Beckerle, M.C., Maricq, A.V. Cell (2005) [Pubmed]
  27. A promoter mutation in the XIST gene in two unrelated families with skewed X-chromosome inactivation. Plenge, R.M., Hendrich, B.D., Schwartz, C., Arena, J.F., Naumova, A., Sapienza, C., Winter, R.M., Willard, H.F. Nat. Genet. (1997) [Pubmed]
  28. Hereditary renal amyloidosis associated with a mutant fibrinogen alpha-chain. Benson, M.D., Liepnieks, J., Uemichi, T., Wheeler, G., Correa, R. Nat. Genet. (1993) [Pubmed]
  29. Reconstitution of SEC gene product-dependent intercompartmental protein transport. Baker, D., Hicke, L., Rexach, M., Schleyer, M., Schekman, R. Cell (1988) [Pubmed]
  30. Identification of domains conferring G protein regulation on inward rectifier potassium channels. Kunkel, M.T., Peralta, E.G. Cell (1995) [Pubmed]
  31. A single point mutation is the cause of the Greek form of hereditary persistence of fetal haemoglobin. Berry, M., Grosveld, F., Dillon, N. Nature (1992) [Pubmed]
  32. Ras1 and a putative guanine nucleotide exchange factor perform crucial steps in signaling by the sevenless protein tyrosine kinase. Simon, M.A., Bowtell, D.D., Dodson, G.S., Laverty, T.R., Rubin, G.M. Cell (1991) [Pubmed]
  33. Structural basis for guanine nucleotide exchange on Ran by the regulator of chromosome condensation (RCC1). Renault, L., Kuhlmann, J., Henkel, A., Wittinghofer, A. Cell (2001) [Pubmed]
  34. The S. cerevisiae CDC25 gene product regulates the RAS/adenylate cyclase pathway. Broek, D., Toda, T., Michaeli, T., Levin, L., Birchmeier, C., Zoller, M., Powers, S., Wigler, M. Cell (1987) [Pubmed]
  35. Differential activation of yeast adenylate cyclase by wild-type and mutant RAS proteins. Broek, D., Samiy, N., Fasano, O., Fujiyama, A., Tamanoi, F., Northup, J., Wigler, M. Cell (1985) [Pubmed]
  36. Functional cloning of BUD5, a CDC25-related gene from S. cerevisiae that can suppress a dominant-negative RAS2 mutant. Powers, S., Gonzales, E., Christensen, T., Cubert, J., Broek, D. Cell (1991) [Pubmed]
  37. The G protein G alpha12 stimulates Bruton's tyrosine kinase and a rasGAP through a conserved PH/BM domain. Jiang, Y., Ma, W., Wan, Y., Kozasa, T., Hattori, S., Huang, X.Y. Nature (1998) [Pubmed]
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  39. 9-(2-hydroxyethoxymethyl) guanine activity against viruses of the herpes group. Schaeffer, H.J., Beauchamp, L., de Miranda, P., Elion, G.B., Bauer, D.J., Collins, P. Nature (1978) [Pubmed]
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  41. Signaling capacity of the T cell antigen receptor is negatively regulated by the PTP1C tyrosine phosphatase. Pani, G., Fischer, K.D., Mlinaric-Rascan, I., Siminovitch, K.A. J. Exp. Med. (1996) [Pubmed]
 
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