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CYTH3  -  cytohesin 3

Homo sapiens

Synonyms: ARF nucleotide-binding site opener 3, ARNO3, Cytohesin-3, GRP1, General receptor of phosphoinositides 1, ...
 
 
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Disease relevance of PSCD3

  • Body weight remained suppressed (p < 0.05) in Grps 3, 5, and 6 for 3 days and in Grps 3 and 6 (p < 0.05) for an additional 3 days; Grps 2 and 4 did not differ from Grp 1 [1].
  • The ultrastructure of a giant neuron (GRP1) identified in the right parietal ganglion of Lymnaea stagnalis was examined [2].
 

High impact information on PSCD3

  • GRP1 binds phosphatidylinositol-3,4,5-trisphosphate [PtdIns(3,4, 5)P3] through a pleckstrin homology (PH) domain and displays a region of high sequence similarity to the yeast Sec7 protein [3].
  • GRP1 and cytohesin-1 appear to connect receptor-activated PI 3-kinase signaling pathways with proteins that mediate biological responses such as cell adhesion and membrane trafficking [3].
  • We have determined the structure of the Grp1 PH domain in the unliganded form and bound to inositol 1,3,4,5-tetraphosphate [4].
  • Here, we report crystal structures for dual specificity variants of the Grp1 and ARNO PH domains in either the unliganded form or in complex with the head groups of PtdIns(4,5)P(2) and PtdIns(3,4,5)P(3) [5].
  • Structural determinants of phosphoinositide selectivity in splice variants of Grp1 family PH domains [5].
 

Biological context of PSCD3

 

Anatomical context of PSCD3

 

Associations of PSCD3 with chemical compounds

  • ADP-ribosylation factor 6 as a target of guanine nucleotide exchange factor GRP1 [11].
  • However, the GRP1 PH domain was unique among these proteins in its striking selectivity for PtdIns(3,4, 5)P(3) versus phosphatidylinositol 4,5-diphosphate (PtdIns(4,5)P(2)), for which it exhibits about 650-fold lower apparent affinity [13].
  • Distinct polyphosphoinositide binding selectivities for pleckstrin homology domains of GRP1-like proteins based on diglycine versus triglycine motifs [13].
  • Using EMSA, we have determined that addition of GRP1 diminishes the formation of TR/TR homodimers and TR/retinoid X receptor heterodimers on TREs, which could explain the effect of GRP1 on transcription [8].
  • Furthermore, GRP1 can accommodate addition of glycerol or diacetylglycerol to the 1-phosphate of Ins(1,3,4,5)P4, data that are consistent with its proposed role as a putative PtdIns(3,4,5)P3 receptor [12].
 

Other interactions of PSCD3

  • We now describe a human Sec7 domain-containing GEF referred to as ARNO3 [14].
  • Overexpression of ARNO3 in mammalian cells results in (i) fragmentation of the Golgi apparatus, (ii) redistribution of Golgi resident proteins as well as the coat component beta-COP, and (iii) inhibition of SEAP transport (secreted form of alkaline phosphatase) [14].
  • Yeast two-hybrid screening revealed that GRASP interacted strongly with the General Receptor for Phosphoinositides 1 (GRP1), a brefeldin A-insensitive guanine nucleotide exchange factor for the ADP-ribosylation factor family of proteins [15].
 

Analytical, diagnostic and therapeutic context of PSCD3

References

  1. Effects of components derived from HPLC purification of human satietin on ingestion, body weight, and taste aversion in the rat. Bellinger, L.L., Mendel, V.E. Pharmacol. Biochem. Behav. (1994) [Pubmed]
  2. Electron microscopic investigation of a giant neuron identified in the right parietal ganglion of Lymnaea stagnalis (L). Pogorelaya, N.K., Elekes, K., Kiss, I. Acta biologica Academiae Scientiarum Hungaricae. (1977) [Pubmed]
  3. Signaling by phosphoinositide-3,4,5-trisphosphate through proteins containing pleckstrin and Sec7 homology domains. Klarlund, J.K., Guilherme, A., Holik, J.J., Virbasius, J.V., Chawla, A., Czech, M.P. Science (1997) [Pubmed]
  4. Structural basis of 3-phosphoinositide recognition by pleckstrin homology domains. Lietzke, S.E., Bose, S., Cronin, T., Klarlund, J., Chawla, A., Czech, M.P., Lambright, D.G. Mol. Cell (2000) [Pubmed]
  5. Structural determinants of phosphoinositide selectivity in splice variants of Grp1 family PH domains. Cronin, T.C., DiNitto, J.P., Czech, M.P., Lambright, D.G. EMBO J. (2004) [Pubmed]
  6. Assignment of the human ARNO3 gene (PSCD3) to chromosome 7p21 by radiation hybrid mapping. Kim, H.S. Ann. Hum. Genet. (1998) [Pubmed]
  7. Insulin-dependent translocation of ARNO to the plasma membrane of adipocytes requires phosphatidylinositol 3-kinase. Venkateswarlu, K., Oatey, P.B., Tavaré, J.M., Cullen, P.J. Curr. Biol. (1998) [Pubmed]
  8. General receptor for phosphoinositides 1, a novel repressor of thyroid hormone receptor action that prevents deoxyribonucleic acid binding. Poirier, M.B., Hamann, G., Domingue, M.E., Roy, M., Bardati, T., Langlois, M.F. Mol. Endocrinol. (2005) [Pubmed]
  9. Antiserum raised against an epitope of the cholecystokinin B/gastrin receptor inhibits hepatic invasion of a human colon tumor. Watson, S.A., Clarke, P.A., Morris, T.M., Caplin, M.E. Cancer Res. (2000) [Pubmed]
  10. Molecular cloning and characterization of a novel mouse macrophage gene that encodes a nuclear protein comprising polyglutamine repeats and interspersing histidines. Cox, G.W., Taylor, L.S., Willis, J.D., Melillo, G., White, R.L., Anderson, S.K., Lin, J.J. J. Biol. Chem. (1996) [Pubmed]
  11. ADP-ribosylation factor 6 as a target of guanine nucleotide exchange factor GRP1. Langille, S.E., Patki, V., Klarlund, J.K., Buxton, J.M., Holik, J.J., Chawla, A., Corvera, S., Czech, M.P. J. Biol. Chem. (1999) [Pubmed]
  12. Nerve growth factor- and epidermal growth factor-stimulated translocation of the ADP-ribosylation factor-exchange factor GRP1 to the plasma membrane of PC12 cells requires activation of phosphatidylinositol 3-kinase and the GRP1 pleckstrin homology domain. Venkateswarlu, K., Gunn-Moore, F., Oatey, P.B., Tavaré, J.M., Cullen, P.J. Biochem. J. (1998) [Pubmed]
  13. Distinct polyphosphoinositide binding selectivities for pleckstrin homology domains of GRP1-like proteins based on diglycine versus triglycine motifs. Klarlund, J.K., Tsiaras, W., Holik, J.J., Chawla, A., Czech, M.P. J. Biol. Chem. (2000) [Pubmed]
  14. ARNO3, a Sec7-domain guanine nucleotide exchange factor for ADP ribosylation factor 1, is involved in the control of Golgi structure and function. Franco, M., Boretto, J., Robineau, S., Monier, S., Goud, B., Chardin, P., Chavrier, P. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  15. Interaction of GRASP, a protein encoded by a novel retinoic acid-induced gene, with members of the cytohesin family of guanine nucleotide exchange factors. Nevrivy, D.J., Peterson, V.J., Avram, D., Ishmael, J.E., Hansen, S.G., Dowell, P., Hruby, D.E., Dawson, M.I., Leid, M. J. Biol. Chem. (2000) [Pubmed]
  16. Localization of agonist-sensitive PtdIns(3,4,5)P3 reveals a nuclear pool that is insensitive to PTEN expression. Lindsay, Y., McCoull, D., Davidson, L., Leslie, N.R., Fairservice, A., Gray, A., Lucocq, J., Downes, C.P. J. Cell. Sci. (2006) [Pubmed]
 
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