The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

CHM  -  choroideremia (Rab escort protein 1)

Homo sapiens

Synonyms: Choroideremia protein, DXS540, GGTA, HSD-32, REP-1, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of CHM


Psychiatry related information on CHM

  • Molecular analysis of four males with mental retardation and deletions of Xq21 places the putative MR region in Xq21.1 between DXS233 and CHM [6].
  • To clarify the pathophysiological differences of the cerebrovascular reserve capacity in relation to cerebral cognitive impairments between vascular dementia (VaD) and persistent vegetative state (PVS), we evaluated acetazolamide (ACZ) vasoreactivity testing by transcranial harmonic perfusion imaging (HPI) and Doppler sonography (TCD) [7].
  • HDT alters cerebral lateralization for motor control and this may be responsible for slowing in perceptual-motor performance in Space. TCD monitoring may be required for motor performance tasks in Space [8].
  • A significantly (p < 0.05) decrease in TCD measures was found in right and left MCA and BA of dementia patients with respect to controls [9].
  • High nicotine dependence combined with TCD pathological finding significantly discriminated successes and failures, suggesting that smokers with pathological TCD need specific therapeutic approach with more social support, individualized coping skills and cognitive restructuring [10].

High impact information on CHM

  • Sequence-conserved regions common to GDI and the choroideraemia gene product, which delivers Rab to catalytic subunits of Rab geranylgeranyltransferase II, are clustered on one face of the molecule [11].
  • Choroideraemia (tapetochoroidal dystrophy, TCD), a common form of X-linked blindness, is characterized by progressive dystrophy of the choroid, retinal pigment epithelium and retina [12].
  • The cDNAs encompass an open reading frame of 948 base pairs that is structurally altered in eight TCD patients with deletions, and in a female patient with a balanced translocation involving Xq21 [12].
  • Posttranslational geranylgeranylation of Rab GTPases is catalyzed by Rab geranylgeranyltransferase (RabGGTase), which consists of a catalytic alpha/beta heterodimer and an accessory Rab escort protein (REP) [13].
  • Comparing the structure of REP-1 with the closely related RabGDI, we conclude that the specificity of the REP:RabGGTase interaction is defined by differently positioned phenylalanine residues conserved in the REP and GDI subfamilies [13].

Chemical compound and disease context of CHM


Biological context of CHM

  • REP functions as a molecular chaperone that presents Rab proteins to the RabGGTase and after prenylation delivers them to their target membrane [17].
  • Finally, in an affected male who did not have a mutation in any of the CHM exons or their splice sites, the deletion of a complete exon from the CHM mRNA was observed [18].
  • Choroideremia (CHM) is a progressive chorioretinal degeneration caused by mutations in the widely expressed CHM gene on chromosome Xq21 [18].
  • These included two partial CHM gene deletions and an insertion of a full-length L1 retrotransposon into the coding region of the CHM gene, a type of mutation that has not been previously reported as a cause of CHM [18].
  • We have searched for mutations of the CHM gene in patients with choroideremia by analysis of individual CHM exons and adjacent intronic sequences PCR-amplified from genomic DNA and by reverse transcription (RT)-PCR analysis of the coding region of the CHM mRNA [18].

Anatomical context of CHM

  • These data suggest that REP-1 is per se sufficient to chaperone newly prenylated rab proteins to their target membranes [19].
  • To assess the relative accuracy of p57(KIP2) immunostaining and molecular diagnosis by nuclear DNA microsatellite polymorphisms in discriminating CHM from its mimics, we analyzed archival tissue from 33 case patients (7 with a definitive diagnosis of CHM, 16 with a possible diagnosis of HM, and 10 with normal placentas) by both methods [20].
  • The evaluation of AgNORs in cytotrophoblasts contributes to a reliable discrimination of CHM and PHM; this fairly simple and economical method could serve as an useful addition to conventional methods of diagnosis in gestational trophoblastic disease [21].
  • Based on structural information and biophysical measurements, we propose mechanistic and thermodynamic models for GDI and Rab escort protein-mediated interaction of RabGTPase with intracellular membranes [22].
  • Furthermore, levels of Xi expression varied among cell lines that expressed REP1 [23].

Associations of CHM with chemical compounds

  • We demonstrate here that REP-1 can also associate with RabGGTase in the absence of Rab protein and that this interaction is dramatically strengthened by the presence of phosphoisoprenoids such as GGpp [24].
  • We previously showed that two major cysteine endopeptidases, REP-1 and REP-2, were present in germinated rice ( Oryza sativa L.) seeds, and that REP-1 was the enzyme that digests seed storage proteins [25].
  • In this work, we show that RabGGTase can form a stable complex with Rab7-REP in the absence of its lipid substrate geranylgeranyl pyrophosphate [26].
  • Two major endopeptidases, REP-1 and REP-2, were present in the 40-75% saturated ammonium sulfate fraction from day-9 germinated seeds, and could be separated by hydrophobic column chromatography [27].
  • (3) Meso-erythritol dehydrogenase has been purified from the membrane fraction of G. frateurii CHM 43 [28].

Physical interactions of CHM


Other interactions of CHM

  • The REP-1 and REP-2 were purified using a combination of affinity and anion-exchange chromatography [2].
  • 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 [29].
  • Cytosolic RAB3D is associated with RAB escort protein (REP), not RAB-GDP dissociation inhibitor (GDI), in dispersed chief cells from guinea pig stomach [30].
  • We demonstrate that the complex formed from semisynthetic monoprenylated Rab7 and REP-1 represents a genuine intermediate of the Rab prenylation reaction and thus provides a unique tool for studies of the Rab prenylation mechanism [31].
  • The present study shows that REP-2 is an asparaginyl endopeptidase that acts as an activator of REP-1, and we separated it into two forms, REP-2alpha (39 kDa) and REP-2beta (40 kDa), using ion-exchange chromatography and gel filtration chromatography [25].

Analytical, diagnostic and therapeutic context of CHM

  • Finally, gel filtration analysis of cytosolic fractions from 293 cells that were coexpressing T7 epitope-tagged REP with various Myc-Rab1B constructs revealed that mutations in the alpha2 helix of Rab1B prevented the association of nascent (i.e., nonprenylated) Rab1B with REP [32].
  • METHODS: The eyes were processed for histopathologic examination, including immunocytochemistry with an antibody against the CHM gene product, REP-1, and retinal cell-specific markers [33].
  • The discrimination index for the PCR-based DNA fingerprinting techniques was 0.75 for enterobacterial repetitive intergenic consensus 1, 0.71 for M13, 0.77 for REP-1, 0.77 for REP-2, and 0.87 for multiplex PCR [34].
  • PURPOSE: To test the reliability of a corneal radius correcting factor (R factor) in calculating intraocular lens (IOL) power in eyes that developed cataract after refractive surgery and compare it with the clinical history (CHM) and double-K (DKM) methods [35].
  • METHODS: Nineteen eyes from the literature that underwent cataract extraction and IOL implantation after refractive surgery were used to compare actual postoperative and expected refractive errors utilizing the R factor, CHM, and DKM [35].


  1. Structure of the Rab7:REP-1 complex: insights into the mechanism of Rab prenylation and choroideremia disease. Rak, A., Pylypenko, O., Niculae, A., Pyatkov, K., Goody, R.S., Alexandrov, K. Cell (2004) [Pubmed]
  2. Expression of mammalian Rab Escort protein-1 and -2 in yeast Saccharomyces cerevisiae. Sidorovitch, V., Niculae, A., Kan, N., Ceacareanu, A.C., Alexandrov, K. Protein Expr. Purif. (2002) [Pubmed]
  3. Deficient geranylgeranylation of Ram/Rab27 in choroideremia. Seabra, M.C., Ho, Y.K., Anant, J.S. J. Biol. Chem. (1995) [Pubmed]
  4. Crystallization and preliminary X-ray diffraction analysis of the Rab escort protein-1 in complex with Rab geranylgeranyltransferase. Rak, A., Reents, R., Pylypenko, O., Niculae, A., Sidorovitch, V., Thomä, N.H., Waldmann, H., Schlichting, I., Goody, R.S., Alexandrov, K. J. Struct. Biol. (2001) [Pubmed]
  5. Pitfalls in the use of random amplified polymorphic DNA (RAPD) for fingerprinting of gram negative organisms. Gao, Z., Jackson, K.M., Leslie, D.E. Pathology. (1996) [Pubmed]
  6. Molecular analysis of four males with mental retardation and deletions of Xq21 places the putative MR region in Xq21.1 between DXS233 and CHM. May, M., Colleaux, L., Murgia, A., Aylsworth, A., Nussbaum, R., Fontes, M., Schwartz, C. Hum. Mol. Genet. (1995) [Pubmed]
  7. Acetazolamide vasoreactivity in vascular dementia and persistent vegetative state evaluated by transcranial harmonic perfusion imaging and Doppler sonography. Shiogai, T., Uebo, C., Makino, M., Mizuno, T., Nakajima, K., Furuhata, H. Ann. N. Y. Acad. Sci. (2002) [Pubmed]
  8. Cerebral lateralization for motor tasks in simulated microgravity a Transcranial Doppler technique for astronauts. Njemanze, P.C. Journal of gravitational physiology : a journal of the International Society for Gravitational Physiology. (2002) [Pubmed]
  9. Transcranial Doppler ultrasonography in senile dementia: neuropsychological correlations. Caamaño, J., Gómez, M.J., Cacabelos, R. Methods and findings in experimental and clinical pharmacology. (1993) [Pubmed]
  10. Transcranial Doppler in smoking relapse prevention strategy. Blazić-Cop, N., Serić, V., Basić, V., Thaller, N., Demarin, V. Collegium antropologicum. (2001) [Pubmed]
  11. Structure and mutational analysis of Rab GDP-dissociation inhibitor. Schalk, I., Zeng, K., Wu, S.K., Stura, E.A., Matteson, J., Huang, M., Tandon, A., Wilson, I.A., Balch, W.E. Nature (1996) [Pubmed]
  12. Cloning of a gene that is rearranged in patients with choroideraemia. Cremers, F.P., van de Pol, D.J., van Kerkhoff, L.P., Wieringa, B., Ropers, H.H. Nature (1990) [Pubmed]
  13. Structure of Rab escort protein-1 in complex with Rab geranylgeranyltransferase. Pylypenko, O., Rak, A., Reents, R., Niculae, A., Sidorovitch, V., Cioaca, M.D., Bessolitsyna, E., Thomä, N.H., Waldmann, H., Schlichting, I., Goody, R.S., Alexandrov, K. Mol. Cell (2003) [Pubmed]
  14. L-erythrulose production by oxidative fermentation is catalyzed by PQQ-containing membrane-bound dehydrogenase. Moonmangmee, D., Adachi, O., Shinagawa, E., Toyama, H., Theeragool, G., Lotong, N., Matsushita, K. Biosci. Biotechnol. Biochem. (2002) [Pubmed]
  15. The impact of partial T cell depletion on overall transplant-related toxicity, graft function and survival after HLA-identical allogeneic bone marrow transplantation in standard risk adult patients with leukemia. Schots, R., Van Riet, I., Ben Othman, T., Trullemans, F., De Waele, M., Van Camp, B. Bone Marrow Transplant. (2001) [Pubmed]
  16. Transcranial Doppler ultrasonography. Newell, D.W. Neurosurg. Clin. N. Am. (1994) [Pubmed]
  17. Crystallization and preliminary X-ray diffraction analysis of monoprenylated Rab7 GTPase in complex with Rab escort protein 1. Rak, A., Pylypenko, O., Niculae, A., Goody, R.S., Alexandrov, K. J. Struct. Biol. (2003) [Pubmed]
  18. Novel types of mutation in the choroideremia ( CHM) gene: a full-length L1 insertion and an intronic mutation activating a cryptic exon. van den Hurk, J.A., van de Pol, D.J., Wissinger, B., van Driel, M.A., Hoefsloot, L.H., de Wijs, I.J., van den Born, L.I., Heckenlively, J.R., Brunner, H.G., Zrenner, E., Ropers, H.H., Cremers, F.P. Hum. Genet. (2003) [Pubmed]
  19. Rab escort protein-1 is a multifunctional protein that accompanies newly prenylated rab proteins to their target membranes. Alexandrov, K., Horiuchi, H., Steele-Mortimer, O., Seabra, M.C., Zerial, M. EMBO J. (1994) [Pubmed]
  20. Multiplex short tandem repeat DNA analysis confirms the accuracy of p57(KIP2) immunostaining in the diagnosis of complete hydatidiform mole. Popiolek, D.A., Yee, H., Mittal, K., Chiriboga, L., Prinz, M.K., Caragine, T.A., Budimlija, Z.M. Hum. Pathol. (2006) [Pubmed]
  21. Villous cytotrophoblast proliferating potential in complete and partial hydatidiform mole: diagnostic value of silver-stained nucleolar organizer region (AgNOR)-associated proteins. Neudeck, H., Unger, M., Hufnagl, P., Eiben, B., Peters, K., Kalla, J., Graf, R., Vogel, M. General & diagnostic pathology. (1997) [Pubmed]
  22. Structure of doubly prenylated Ypt1:GDI complex and the mechanism of GDI-mediated Rab recycling. Pylypenko, O., Rak, A., Durek, T., Kushnir, S., Dursina, B.E., Thomae, N.H., Constantinescu, A.T., Brunsveld, L., Watzke, A., Waldmann, H., Goody, R.S., Alexandrov, K. EMBO J. (2006) [Pubmed]
  23. Heterogeneous gene expression from the inactive X chromosome: an X-linked gene that escapes X inactivation in some human cell lines but is inactivated in others. Carrel, L., Willard, H.F. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  24. Phosphoisoprenoids modulate association of Rab geranylgeranyltransferase with REP-1. Thomä, N.H., Iakovenko, A., Goody, R.S., Alexandrov, K. J. Biol. Chem. (2001) [Pubmed]
  25. Identification, cDNA cloning and possible roles of seed-specific rice asparaginyl endopeptidase, REP-2. Kato, H., Sutoh, K., Minamikawa, T. Planta (2003) [Pubmed]
  26. Characterization of the ternary complex between Rab7, REP-1 and Rab geranylgeranyl transferase. Alexandrov, K., Simon, I., Yurchenko, V., Iakovenko, A., Rostkova, E., Scheidig, A.J., Goody, R.S. Eur. J. Biochem. (1999) [Pubmed]
  27. Identification and characterization of a rice cysteine endopeptidase that digests glutelin. Kato, H., Minamikawa, T. Eur. J. Biochem. (1996) [Pubmed]
  28. New quinoproteins in oxidative fermentation. Adachi, O., Moonmangmee, D., Shinagawa, E., Toyama, H., Yamada, M., Matsushita, K. Biochim. Biophys. Acta (2003) [Pubmed]
  29. REP-2, a Rab escort protein encoded by the choroideremia-like gene. Cremers, F.P., Armstrong, S.A., Seabra, M.C., Brown, M.S., Goldstein, J.L. J. Biol. Chem. (1994) [Pubmed]
  30. Cytosolic RAB3D is associated with RAB escort protein (REP), not RAB-GDP dissociation inhibitor (GDI), in dispersed chief cells from guinea pig stomach. Raffaniello, R.D., Raufman, J.P. J. Cell. Biochem. (1999) [Pubmed]
  31. Synthesis of fluorescently labeled mono- and diprenylated Rab7 GTPase. Durek, T., Alexandrov, K., Goody, R.S., Hildebrand, A., Heinemann, I., Waldmann, H. J. Am. Chem. Soc. (2004) [Pubmed]
  32. The putative "switch 2" domain of the Ras-related GTPase, Rab1B, plays an essential role in the interaction with Rab escort protein. Overmeyer, J.H., Wilson, A.L., Erdman, R.A., Maltese, W.A. Mol. Biol. Cell (1998) [Pubmed]
  33. Evaluation of retinal photoreceptors and pigment epithelium in a female carrier of choroideremia. Syed, N., Smith, J.E., John, S.K., Seabra, M.C., Aguirre, G.D., Milam, A.H. Ophthalmology (2001) [Pubmed]
  34. Use of different PCR-based DNA fingerprinting techniques and pulsed-field gel electrophoresis to investigate the epidemiology of Acinetobacter calcoaceticus-Acinetobacter baumannii complex. Liu, P.Y., Wu, W.L. Diagn. Microbiol. Infect. Dis. (1997) [Pubmed]
  35. Reliability of a new correcting factor in calculating intraocular lens power after refractive corneal surgery. Rosa, N., Capasso, L., Lanza, M., Iaccarino, G., Romano, A. Journal of cataract and refractive surgery. (2005) [Pubmed]
WikiGenes - Universities