Disease relevance of CHML

• 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 [1].
• In the retina, REP-2 may be only partially effective, leading eventually to retinal degeneration and blindness [1].
• The colocalization of hCHML and Usher syndrome type II, as well as the clinical similarities between choroideremia and Usher syndrome type II, make hCHML a candidate gene for this disorder [2].
• A second set of primers directed against known repetitive sequences in Gram negative bacteria (REP1/REP2 and ERIC2) were examined to compare with RAPD as a means of fingerprinting organisms [3].

High impact information on CHML

• Using semisynthetic fluorescent Rab27A, we demonstrate that although Rab27A can be prenylated by REP-2, this reaction can be effectively inhibited by other Rab proteins, providing a possible explanation for the accumulation of unprenylated Rab27A in choroideremia [4].
• The consensus cDNA of this gene, designated human choroideremia-like (hCHML) gene, encompasses an open reading frame of 1968 base pairs [2].
• Using recombinant Rab geranylgeranyl transferase and REPs to label unprenylated cytosolic proteins, we identified one unprenylated protein in choroideremia lymphoblasts that was prenylated in vitro more efficiently by REP-1 than by REP-2 [5].
• Membrane-associated REP-2 did not colocalize with Rab3D on secretory granule membranes [6].
• Isoproterenol, an agent which induces amylase release from parotid glands, caused a shift in both REP-2 and Rab3D to less dense membrane fractions [6].

Biological context of CHML

• The gene was localized to the region of chromosome 1q43 also encompassing the kynurenine monooxygenase (KMO) and choroideremia-like Rab escort protein 2 (CHML) genes [7].
• Southern blot analysis showed that there is one gene for REP-2 in the genome, indicating that both REP-2 enzymes are generated from a single gene [8].

Associations of CHML with chemical compounds

• Colocalization of Rab3D and REP-2 on acinar cell membranes suggests that REP-2 plays a role in delivering Rab3D to parotid membranes and may regulate guanine nucleotide binding to membrane-associated Rab3D [6].
• 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 [8].
• 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 [9].

Other interactions of CHML

• The REP-1 and REP-2 were purified using a combination of affinity and anion-exchange chromatography [10].
• Identification, cDNA cloning and possible roles of seed-specific rice asparaginyl endopeptidase, REP-2 [8].

Analytical, diagnostic and therapeutic context of CHML

• However, density gradient centrifugation revealed that membrane-associated REP-2 and Rab3D colocalize on low- and high-density membrane fractions in parotid acinar cells [6].
• Northern blot analysis indicated that REP-2 mRNA was expressed in both maturing and germinating seeds [8].
• 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 [11].
• PCR using REP1/REP2 and ERIC2 primers may provide a more reliable and reproducible alternative method for fingerprinting Gram negative bacteria [3].

References