InterPro domain: IPR001738

Rab proteins constitute a family of small GTPases that serve a regulatory role in vesicular membrane traffic [ 1 , 2 ]; C-terminal geranylgeranylation is crucial for their membrane association and function. This post-translational modification is catalysed by Rab geranylgeranyl transferase (Rab-GGTase), a multi-subunit enzyme that contains a catalytic heterodimer and an accessory component, termed Rab escort protein (REP)-1 [ 3 , 3 ]. REP-1 presents newly-synthesised Rab proteins to the catalytic component, and forms a stable complex with the prenylated proteins following the transfer reaction.

cDNA cloning of component A of rat Rab geranylgeranyl transferase (REP) confirms its resemblance to Rab3A guanine nucleotide dissociation inhibitor (GDI) and its identity with the human choroideremia gene product [ 3 ]. A genetic defect in REP underlies human choroideremia. Choroideraemia (or tapetochoroidal dystrophy) is a common form of X-linked blindness characterised by progressive dystrophy of the choroid, retinal pigment epithelium and retina [ 3 , 4 , 5 ].

1. Rab escort protein-1 is a multifunctional protein that accompanies newly prenylated rab proteins to their target membranes. EMBO J. 13, 5262-73
2. cDNA cloning of component A of Rab geranylgeranyl transferase and demonstration of its role as a Rab escort protein. Cell 73, 1091-9
3. Cloning of a gene that is rearranged in patients with choroideraemia. Nature 347, 674-7
4. Cloning and characterization of the human choroideremia gene. Hum. Mol. Genet. 3, 1041-6
5. Isolation of a candidate gene for choroideremia. Proc. Natl. Acad. Sci. U.S.A. 89, 2135-9