Rab geranylgeranyl transferase

Disorder characterized by atrophy ofthe choroid (the thin membrane covering most of the posterior of the eye between the retina and sclera) and degeneration of the retinal pigment epithelium resulting in night blindness. The disease is caused by mutations in Rab escort protein Repl (component A of Rab geranylgeranyl transferase). 

Seabra, M.C., Goldstein, J.L., Sndhof, T.C., et al. (1992). Rab geranylgeranyl transferase A multisubunit enzyme that prenylates GTP-binding proteins terminating in Cys-X-Cys or Cys-Cys. J Biol Chem 267 14497-14503. 

Coxon, F.P., Helfrich, M.H., Larijani, B., et al. (2001). Identification of a novel phospho-nocarboxylate inhibitor of Rab geranylgeranyl transferase that specifically prevents Rab prenylation in osteoclasts and macrophages. J Biol Chem 276 48213 8222. 

Coxon, F.P., Ebetino, F.H., Mules, E.H., et al. (2005). Phosphonocarboxylate inhibitors of Rab geranylgeranyl transferase disrupt the prenylation and membrane localization of Rab proteins in osteoclasts in vitro and in vivo. Bone 37 349-358. 

Baron, R.A., Tavare, R., Figueiredo, A.C., et al. (2009). Phosphonocarboxylates inhibit the second geranylgeranyl addition by Rab geranylgeranyl transferase. J Biol Chem 284 6861-6868. 

Seabra, M. C., Brown, M. S Goldstein, J. L. (1993). Retinal degeneration in choroideremia deficiency of rab geranylgeranyl transferase. Science 259,377-381. 

Prenylated small GTPases represent major hubs in most membrane-connected signaling networks. Rab prenylation is mediated by Rab geranylgeranyl transferase (RabGGTase), which works together with an adaptor protein, Rab escort protein (REP). Rab cycling between membranes and the cytosol is made possible by interaction with the GDP dissociation inhibitor (GDI). Both GDI and REP function as molecular chaperones, which can solubilize the prenylated Rab proteins in the cytosol. 

Geranylgeranylation Geranylgeranyl Transferase I (GGTase I) Side chain of Cys No Intracellular plasma membrane, Golgi, endosome, lyso-some, vesicle, other endomembranes Rho, Rab, Ras... 

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