REP-2, a Rab escort protein encoded by the choroideremia-like gene

Frans P M Cremers, Scott A. Armstrong, Miguel C. Seabra, Michael S. Brown, Joseph L. Goldstein

Research output: Contribution to journalArticle

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Abstract

Rab escort proteins (REPs) bind to newly synthesized Rab proteins and remain bound during and after the attachment of a geranylgeranyl (GG) group by the catalytic component of the Rab GG transferase. Transfer of the GG group is absolutely dependent on the participation of a REP. REP-1, the first characterized REP, is produced by a gene on the X chromosome that is defective in patients with choroideremia, a form of retinal degeneration. Cremers et al. (Cremers, F. P. M., Molloy, C. M., van de Pol, D. J. R., van den Hurk, J. A. J. M., Bach, I., Geurts van Kessel, A. H. M., and Ropers, H.- H. (1992) Hum. Mol. Genet. 1, 71-75) isolated a related gene designated choroideremia-like, which encodes a protein that closely resembles REP-1. In the current studies, we produced REP-1 and REP-2 by recombinant DNA methods and showed that both proteins were approximately equal in facilitating the attachment of GG groups to several Rab proteins, including Rab1A, Rab5A, and Rab6. However, REP-2 was only 25% as active as REP-1 in supporting GG attachment to Rab3A and Rab3D. The low activity toward Rab3A was increased to that of Rab1A when the COOH-terminal 12 amino acids of Rab3A were replaced with the corresponding residues of Rab1A. We suggest that REP-2 substitutes for the absent function of REP-1 in nonretinal cells of patients with choroideremia, thus preventing cellular dysfunction throughout the body. In the retina, REP-2 may be only partially effective, leading eventually to retinal degeneration and blindness.

Original languageEnglish (US)
Pages (from-to)2111-2117
Number of pages7
JournalJournal of Biological Chemistry
Volume269
Issue number3
StatePublished - Jan 21 1994

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Choroideremia
Genes
Proteins
Retinal Degeneration
rab1 GTP-Binding Proteins
Viverridae
X-Linked Genes

ASJC Scopus subject areas

  • Biochemistry

Cite this

REP-2, a Rab escort protein encoded by the choroideremia-like gene. / Cremers, Frans P M; Armstrong, Scott A.; Seabra, Miguel C.; Brown, Michael S.; Goldstein, Joseph L.

In: Journal of Biological Chemistry, Vol. 269, No. 3, 21.01.1994, p. 2111-2117.

Research output: Contribution to journalArticle

Cremers, FPM, Armstrong, SA, Seabra, MC, Brown, MS & Goldstein, JL 1994, 'REP-2, a Rab escort protein encoded by the choroideremia-like gene', Journal of Biological Chemistry, vol. 269, no. 3, pp. 2111-2117.
Cremers, Frans P M ; Armstrong, Scott A. ; Seabra, Miguel C. ; Brown, Michael S. ; Goldstein, Joseph L. / REP-2, a Rab escort protein encoded by the choroideremia-like gene. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 3. pp. 2111-2117.
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