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PSMG1  -  proteasome (prosome, macropain) assembly...

Homo sapiens

Synonyms: C21-LRP, C21LRP, Chromosome 21 leucine-rich protein, DSCR2, Down syndrome critical region protein 2, ...
 
 
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Disease relevance of DSCR2

 

High impact information on DSCR2

  • These data demonstrate that altered neuronal proliferation/apoptosis and disrupted ependymal cilia are the main factors contributing to hydrocephalus in PAC1-overexpressing mice [5].
  • We have expressed 2, 4, or 6 copies of a GPCR--the human PAC1 receptor with a 130-kb transgene in the mouse nervous system in a pattern closely resembling that of the endogenous gene [5].
  • Finally, we also analyzed whether the presence of flanking viral TRS had any effect on the functional activity of the minimal concatemeric junction (pac2-pac1) [2].
  • We now show that the unique sequence element formed at the junction of HHV-6B genome concatemers (pac2-pac1) is necessary and sufficient for virally mediated cleavage of plasmid DNAs containing the HHV-6B lytic-phase origin of DNA replication (oriLyt) [2].
  • Consistent with this notion, we determined that the most BrdU positive NPCs differentiated to astrocytes through PAC1 signaling [6].
 

Biological context of DSCR2

 

Anatomical context of DSCR2

  • Our analyses suggest that, although DSCR2 is associated with the endoplasmic reticulum, it is not an integral membrane protein and it is maintained on the cytoplasmic side of the ER by indirect interaction with the ER membrane or with another protein [10].
  • It was previously suggested that DSCR2 is located in the plasma membrane as an integral membrane protein [10].
  • The expression analysis of the DSCR2 gene in different human tumour derived cell lines indicates that the gene is expressed in all proliferating cell lines tested [7].
  • The levels of the DSCR2 mRNA correlate with cellular growth of T98G and Jurkat cells in response to different treatments [7].
  • It has been well established that the PACAP/PAC1 system induces differentiation of neural progenitor cells (NPCs) through the Gs-mediated cAMP-dependent signaling pathway [6].
 

Associations of DSCR2 with chemical compounds

  • We have called to this novel gene c21-LRP (chromosome 21 leucine-rich protein) and, because of its location in the DS-2 region, it could be a candidate for some of the DS anomalies [8].
  • The activation of glycoprotein IIb-IIIa and surface expression of P-selectin were identified with antibodies (PAC-1 and anti-CD62) [11].
  • The only trend observed was lower reduction in PAC-1 binding following clopidogrel in PlA(2) carriers (P=0.065) [12].
  • AGI-1067 resulted in significant inhibition of a variety of activation-dependent platelet biomarkers in healthy volunteers, including adenosine diphosphate-induced platelet aggregation and decreased surface platelet expression of glycoprotein IIb/IIIa antigen, activity with PAC-1 antibody, and glycoprotein Ib (CD42b) [13].
 

Other interactions of DSCR2

 

Analytical, diagnostic and therapeutic context of DSCR2

  • Intrathecal administration of the PAC1 receptor antagonist, PACAP6-38 (10 nM), significantly (P < or = 0.05) reduced intermicturition, threshold and micturition pressures in chronic (3-6 weeks) spinal cord injured rats but intravesical administration (100-300 nM) was without effect [14].
  • The influence of FVIII on platelet function was investigated by flow cytometric analysis of P-selectin expression (CD62P) and PAC-1 binding before and after submaximal stimulation with TRAP-6 (5 microM final concentration), by confocal microscopy and by platelet aggregometry [15].

References

  1. Characterization of human telomeric repeat sequences from human herpesvirus 6 and relationship to replication. Gompels, U.A., Macaulay, H.A. J. Gen. Virol. (1995) [Pubmed]
  2. Functional identification and analysis of cis-acting sequences which mediate genome cleavage and packaging in human herpesvirus 6. Deng, H., Dewhurst, S. J. Virol. (1998) [Pubmed]
  3. Neuroendocrine tumors express PAC1 receptors. Lieu, S.N., Oh, D.S., Pisegna, J.R., Germano, P.M. Ann. N. Y. Acad. Sci. (2006) [Pubmed]
  4. Flow cytometric evaluation of platelet activation in chronic autoimmune thrombocytopenia. Panzer, S., Höcker, L., Vormittag, R., Rieger, M., Koren, D., Dunkler, D., Pabinger, I. Pediatric blood & cancer. (2006) [Pubmed]
  5. Expression of the human PAC1 receptor leads to dose-dependent hydrocephalus-related abnormalities in mice. Lang, B., Song, B., Davidson, W., MacKenzie, A., Smith, N., McCaig, C.D., Harmar, A.J., Shen, S. J. Clin. Invest. (2006) [Pubmed]
  6. PACAP/PAC1 autocrine system promotes proliferation and astrogenesis in neural progenitor cells. Nishimoto, M., Furuta, A., Aoki, S., Kudo, Y., Miyakawa, H., Wada, K. Glia (2007) [Pubmed]
  7. Down syndrome critical region gene 2: expression during mouse development and in human cell lines indicates a function related to cell proliferation. Vidal-Taboada, J.M., Lu, A., Pique, M., Pons, G., Gil, J., Oliva, R. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  8. Identification and characterization of a new gene from human chromosome 21 between markers D21S343 and D21S268 encoding a leucine-rich protein. Vidal-Taboada, J.M., Sanz, S., Egeo, A., Scartezzini, P., Oliva, R. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  9. PACAP and VIP promote initiation of electrophysiological activity in differentiating embryonic stem cells. Chafai, M., Louiset, E., Basille, M., Cazillis, M., Vaudry, D., Rostène, W., Gressens, P., Vaudry, H., Gonzalez, B.J. Ann. N. Y. Acad. Sci. (2006) [Pubmed]
  10. DSCR2, a Down syndrome critical region protein, is localized to the endoplasmic reticulum of mammalian cells. Possik, P.A., Sommer, C.A., Issa Hori, J., Machado-Santelli, G.M., Jamur, M.C., Henrique-Silva, F. European journal of histochemistry : EJH. (2004) [Pubmed]
  11. Greater inhibitory effects of bivalirudin compared with unfractionated heparin plus eptifibitide on thrombin-induced platelet activation. Schneider, D.J., Keating, F., Sobel, B.E. Coron. Artery Dis. (2006) [Pubmed]
  12. Genetic polymorphisms of the platelet receptors P2Y(12), P2Y(1) and GP IIIa and response to aspirin and clopidogrel. Lev, E.I., Patel, R.T., Guthikonda, S., Lopez, D., Bray, P.F., Kleiman, N.S. Thromb. Res. (2007) [Pubmed]
  13. The In Vitro Effects of a Novel Vascular Protectant, AGI-1067, on Platelet Aggregation and Major Receptor Expression in Subjects With Multiple Risk Factors for Vascular Disease. Serebruany, V., Malinin, A., Scott, R. J. Cardiovasc. Pharmacol. Ther. (2006) [Pubmed]
  14. A role for pituitary adenylate cyclase activating polypeptide (PACAP) in detrusor hyperreflexia after spinal cord injury (SCI). Zvara, P., Braas, K.M., May, V., Vizzard, M.A. Ann. N. Y. Acad. Sci. (2006) [Pubmed]
  15. Factor VIII is a positive regulator of platelet function. Obergfell, A., Sturm, A., Speer, C.P., Walter, U., Grossmann, R. Platelets (2006) [Pubmed]
 
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