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Gene Review

EXOSC3  -  exosome component 3

Homo sapiens

Synonyms: CGI-102, Exosome complex component RRP40, Exosome component 3, PCH1B, RRP40, ...
 
 
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Disease relevance of EXOSC3

 

High impact information on EXOSC3

  • The crystal structure at 2.5 A resolution of a recombinant human ICE-tetrapeptide chloromethylketone complex reveals that the holoenzyme is a homodimer of catalytic domains, each of which contains a p20 and a p10 subunit [6].
  • p10/NTF2 is a nuclear transport carrier that mediates the uptake of cytoplasmic RanGDP into the nucleus [7].
  • This finding demonstrated directly that the p10 gene promoter required other viral gene products for its activity in insect cells [1].
  • Since Drosophila DNA or S. frugiperda DNA contained no 5-methylcytosine or extremely small amounts of it, we were interested in determining the effect of site-specific methylations on the p10 gene insect virus promoter [1].
  • The p10 gene promoter was inactive in human HeLa cells and in uninfected Spodoptera frugiperda insect cells [1].
 

Chemical compound and disease context of EXOSC3

 

Biological context of EXOSC3

  • Upon transfection of the pAcp10-CAT construct, which contained 402 bp of the p10 gene of AcNPV DNA in the HindIII site of pSVO-CAT, CAT activity was determined [1].
  • In addition, coexpression of the p20 and p10 but not the p20 and ICE epsilon in Sf9 cells results in apoptosis [10].
  • These viruses encode the smallest known membrane fusion proteins (p10) [11].
  • In addition to the previously described p10 and final sigmaC gene products, the S1 genome segment encodes from the central ORF a 17-kDa basic protein (p17) of no known function [12].
  • It also confirmed earlier positions for the env and pol genes and placed unclassified protein p10 near a translational initiation site [13].
 

Anatomical context of EXOSC3

  • Binding studies indicated that these two nuclear transport carriers of different classes, p10 and Kap-beta1, compete for identical and/or overlapping binding sites at the nuclear pore complex (NPC) and that D23A p10 has an increased affinity relative to wt p10 and Kap-beta1 for these shared binding sites [7].
  • The suggested generators are as follows: n9, p9 and p10-peripheral nerve; n11, p11-dorsal column; n13a-segmental dorsal horn; p13a-spinocerebellar tract; n13b and p13b-cuneate nucleus and caudal part of the medial lemniscus; n14, p14 and p15-rostral part of the medial lemniscus; p18-thalamocortical radiation; p20-primary somatosensory cortex [14].
  • Once phosphorylated, p10 associates with microtubules in the infected cells and may thereby play a role in process formation [15].
  • These results suggest that the rudimentary p10 fusion protein has evolved a mechanism of inducing membrane merger that is highly dependent on the specific interaction of several different motifs with donor membranes [16].
  • Mutations in any of these three motifs did not influence events upstream of syncytium formation, such as p10 membrane association, protein topology, or surface expression, suggesting that these motifs are more intimately associated with the membrane fusion reaction [16].
 

Associations of EXOSC3 with chemical compounds

  • Chemical modifications of the p10 cysteine residues did not alter the affinity for poly(epsilon A) [17].
  • We now show that the p10 dicysteine motif is palmitoylated and that loss of palmitoylation correlates with a loss of fusion activity [16].
  • Budding was restored when any one of the residues was changed back to lysine or when lysines were inserted in novel positions, either within this region of MA or within the downstream p10 sequence [18].
  • Mutational and functional analyses also revealed that a triglycine motif within the transmembrane domain and the membrane-proximal basic region were essential for p10-mediated membrane fusion [16].
  • Upon cross-linking with methyl 4-mercaptobutyrimidate hydrochloride a small amount of what seems to be a heterodimer made up of the N-terminal gag protein p10 and the hydrophobic membrane glycoprotein gp36 can be observed [19].
 

Other interactions of EXOSC3

  • Here we report the cloning of full-length cDNAs, which encode putative human homologues of the Rrp40p, Rrp41p, and Rrp46p components of the exosome [20].
  • We conclude that hRrp40p, hRrp41p, and hRrp46p represent novel components of the human exosome complex [20].
 

Analytical, diagnostic and therapeutic context of EXOSC3

  • SDS-PAGE of isolated complexes showed near complete loss of the p10 subunit from initiator caspases 1 and 8 but not from the executioner caspase-6 [21].
  • Size exclusion chromatography indicated a size of approximately 60 kDa for complexes with caspases 1 and 8, consistent with a crmA.p20 species, suggesting that the p20-p10 interface and possibly the p10-p10 interface had been disrupted [21].
  • Five gag-gene-encoded structural proteins, designated p12, pp18, pp20, p30, and p10 were purified from replication-competent avian reticuloendotheliosis-associated virus (REV-A) by high-performance liquid chromatography complemented with chloroform-methanol extraction and sodium dodecyl sulfate-polyacrylamide gel electrophoresis [22].
  • Nevertheless, evidence for the association of p10 and microtubules was obtained by fluorescence microscopy and immunoelectron microscopy [23].
  • Based on amino acid composition and NH2- and COOH-terminal sequence analysis p12, pp18, p30, and p10 are distinct from one another, whereas pp20 is likely identical to pp18 in primary structure [22].

References

  1. The promoter of the late p10 gene in the insect nuclear polyhedrosis virus Autographa californica: activation by viral gene products and sensitivity to DNA methylation. Knebel, D., Lübbert, H., Doerfler, W. EMBO J. (1985) [Pubmed]
  2. Small finger protein of avian and murine retroviruses has nucleic acid annealing activity and positions the replication primer tRNA onto genomic RNA. Prats, A.C., Sarih, L., Gabus, C., Litvak, S., Keith, G., Darlix, J.L. EMBO J. (1988) [Pubmed]
  3. Interleukin 1 beta (IL-1 beta) processing in murine macrophages requires a structurally conserved homologue of human IL-1 beta converting enzyme. Molineaux, S.M., Casano, F.J., Rolando, A.M., Peterson, E.P., Limjuco, G., Chin, J., Griffin, P.R., Calaycay, J.R., Ding, G.J., Yamin, T.T. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  4. Molecular characterization of the recurrent unbalanced translocation der(1;7)(q10;p10). Wang, L., Ogawa, S., Hangaishi, A., Qiao, Y., Hosoya, N., Nanya, Y., Ohyashiki, K., Mizoguchi, H., Hirai, H. Blood (2003) [Pubmed]
  5. Mechanism of inhibition of the retroviral protease by a Rous sarcoma virus peptide substrate representing the cleavage site between the gag p2 and p10 proteins. Cameron, C.E., Grinde, B., Jentoft, J., Leis, J., Weber, I.T., Copeland, T.D., Wlodawer, A. J. Biol. Chem. (1992) [Pubmed]
  6. Crystal structure of the cysteine protease interleukin-1 beta-converting enzyme: a (p20/p10)2 homodimer. Walker, N.P., Talanian, R.V., Brady, K.D., Dang, L.C., Bump, N.J., Ferenz, C.R., Franklin, S., Ghayur, T., Hackett, M.C., Hammill, L.D. Cell (1994) [Pubmed]
  7. Selective disruption of nuclear import by a functional mutant nuclear transport carrier. Lane, C.M., Cushman, I., Moore, M.S. J. Cell Biol. (2000) [Pubmed]
  8. p10, a low molecular weight single-stranded nucleic acid binding protein of murine leukemia retroviruses, shows stacking interactions of its single tryptophan residue with nucleotide bases. Casas-Finet, J.R., Jhon, N.I., Maki, A.H. Biochemistry (1988) [Pubmed]
  9. Dissimilar expression of Autographa californica multiple nucleocapsid nuclear polyhedrosis virus polyhedrin and p10 genes. Roelvink, P.W., van Meer, M.M., de Kort, C.A., Possee, R.D., Hammock, B.D., Vlak, J.M. J. Gen. Virol. (1992) [Pubmed]
  10. Cloning and expression of four novel isoforms of human interleukin-1 beta converting enzyme with different apoptotic activities. Alnemri, E.S., Fernandes-Alnemri, T., Litwack, G. J. Biol. Chem. (1995) [Pubmed]
  11. Structural and functional properties of an unusual internal fusion peptide in a nonenveloped virus membrane fusion protein. Shmulevitz, M., Epand, R.F., Epand, R.M., Duncan, R. J. Virol. (2004) [Pubmed]
  12. Sequential partially overlapping gene arrangement in the tricistronic S1 genome segments of avian reovirus and Nelson Bay reovirus: implications for translation initiation. Shmulevitz, M., Yameen, Z., Dawe, S., Shou, J., O'Hara, D., Holmes, I., Duncan, R. J. Virol. (2002) [Pubmed]
  13. Novel p19-related protein in Rous-associated virus type 61: implications for avian gag gene order. Shealy, D.J., Mosser, A.G., Rueckert, R.R. J. Virol. (1980) [Pubmed]
  14. Origin of short-latency somatosensory evoked potentials to median nerve stimulation in the cat. Comparison of the recording montages and effect of laminectomy. Kaji, R., Tanaka, R., Kawaguchi, S., McCormick, F., Kameyama, M. Brain (1986) [Pubmed]
  15. Phosphorylated baculovirus p10 is a heat-stable microtubule-associated protein associated with process formation in Sf9 cells. Cheley, S., Kosik, K.S., Paskevich, P., Bakalis, S., Bayley, H. J. Cell. Sci. (1992) [Pubmed]
  16. Palmitoylation, membrane-proximal basic residues, and transmembrane glycine residues in the reovirus p10 protein are essential for syncytium formation. Shmulevitz, M., Salsman, J., Duncan, R. J. Virol. (2003) [Pubmed]
  17. Interactions of retroviral structural proteins with single-stranded nucleic acids. Karpel, R.L., Henderson, L.E., Oroszlan, S. J. Biol. Chem. (1987) [Pubmed]
  18. Lysines close to the Rous sarcoma virus late domain critical for budding. Spidel, J.L., Craven, R.C., Wilson, C.B., Patnaik, A., Wang, H., Mansky, L.M., Wills, J.W. J. Virol. (2004) [Pubmed]
  19. Murine mammary tumor virus structural protein interactions: formation of oligomeric complexes with cleavable cross-linking agents. Racevskis, J., Sarkar, N.H. J. Virol. (1980) [Pubmed]
  20. Three novel components of the human exosome. Brouwer, R., Allmang, C., Raijmakers, R., van Aarssen, Y., Egberts, W.V., Petfalski, E., van Venrooij, W.J., Tollervey, D., Pruijn, G.J. J. Biol. Chem. (2001) [Pubmed]
  21. Cytokine response modifier a inhibition of initiator caspases results in covalent complex formation and dissociation of the caspase tetramer. Dob??, J., Swanson, R., Salvesen, G.S., Olson, S.T., Gettins, P.G. J. Biol. Chem. (2006) [Pubmed]
  22. Purification and chemical and immunological characterization of avian reticuloendotheliosis virus gag-gene-encoded structural proteins. Tsai, W.P., Copeland, T.D., Oroszlan, S. Virology (1985) [Pubmed]
  23. Autographa californica M nuclear polyhedrosis virus: microtubules and replication. Volkman, L.E., Zaal, K.J. Virology (1990) [Pubmed]
 
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