C6ORF108 Human
Description
Overview of C6ORF108 Human
C6ORF108, also known as RCL (c-Myc-responsive protein), is a human gene encoding a novel enzyme with deoxynucleoside 5'-monophosphate N-glycosidase activity. This enzyme catalyzes the cleavage of the N-glycosidic bond in deoxynucleoside 5'-monophosphates (dNMPs), producing deoxyribose 5'-phosphate and free nucleobases . Key identifiers include:
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UniProt ID: O43598 (human)
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Entrez Gene ID: 10591
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Gene Aliases: DNPH1, RCL, dJ330M21.3
The protein is stimulated by c-Myc, a transcription factor linked to cell proliferation, differentiation, and apoptosis. While its exact biological role remains under investigation, studies in rats suggest involvement in cellular proliferation and c-Myc-mediated tumorigenesis .
Functional Role and Biochemical Activity
RCL defines a new enzymatic pathway in nucleotide catabolism, with dGMP (deoxyguanosine monophosphate) as the preferred substrate . Its activity yields:
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Deoxyribose 5'-phosphate (feeds into glycolysis or salvage pathways)
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Purine/pyrimidine bases (recycled in nucleotide synthesis or angiogenesis)
Enzymatic Specificity
| Substrate | Activity (Relative to dGMP) | Notes |
|---|---|---|
| dGMP | 100% | Optimal substrate |
| dAMP | Moderate | Purine bases preferred |
| dTMP | Low | Pyrimidine bases tolerated |
This activity distinguishes RCL from N-deoxyribosyltransferases, which transfer deoxyribosyl groups rather than hydrolyzing them .
Active Site Probing
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Mutagenesis: Ser-17 → Glu mutation prevents substrate binding by disrupting hydrogen bonding .
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Substrate Analogues: Phosphomimetic compounds (e.g., replacing 5'-phosphate with sulfate) block activity, confirming phosphate group importance .
Therapeutic Potential
RCL products (e.g., deoxyribose 5'-phosphate) are linked to:
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Purine salvage pathways (critical for cancer cell proliferation)
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Angiogenesis (via nucleobase-dependent signaling)
Recombinant Production and Applications
RCL is commonly produced in E. coli or HEK-293 cells, with >95% purity achieved via chromatography .
Pathological Links
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Tumorigenesis: c-Myc overexpression upregulates RCL, promoting cell proliferation and angiogenesis .
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Therapeutic Targeting: Inhibitors of RCL could disrupt nucleotide salvage and metabolic pathways in cancer .
Future Directions
Research priorities include:
Product Specs
GGDRLIHEQD LEWLQQADVV VAEVTQPSLG VGYELGRAVA FNKRILCLFR PQSGRVLSAM IRGAADGSRF QVWDYEEGEV EALLDRYFEA
DPPGQVAASP DPTT.
Q&A
C6orf108 (Chromosome 6 Open Reading Frame 108) is a gene with emerging significance in both oncology and neurodegenerative research. Below are structured FAQs addressing key academic research considerations, supported by experimental evidence from peer-reviewed studies and patent disclosures.
What is the functional role of C6orf108 in cellular processes?
C6orf108 is implicated in cellular proliferation and c-Myc-mediated transformation, with rat studies suggesting its involvement in oncogenic pathways . Experimental approaches to study its function include:
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siRNA knockdown: Designed sequences (e.g., siRNA2 targeting SH3PXD2B) with 30-40% sequence variability
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Expression analysis: qPCR and Western blot to measure transcript/protein levels in cancer models
| Key Functional Insights | Experimental Evidence |
|---|---|
| Proliferation regulation | siRNA-mediated knockdown reduces cancer cell growth |
| c-Myc interaction | Co-expression studies in rat models |
How is C6orf108 expression regulated in human tissues?
Epigenetic modifiers, particularly CpG-SNPs, influence C6orf108 expression. The rs9357140 SNP alters DNA methylation and correlates with:
What experimental models are optimal for studying C6orf108 in cancer biology?
Methodological recommendations:
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In vitro: Use siRNA libraries (e.g., SEQ ID #11-12 ) with 10-40% sequence variability to account for transcript diversity.
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In vivo: Xenograft models with CRISPR-Cas9 C6orf108 knockouts to assess tumorigenicity .
| Model | Advantage | Limitation |
|---|---|---|
| siRNA knockdown | High specificity for isoform targeting | Off-target effects at >40% sequence divergence |
| Transgenic mice | Recapitulates c-Myc interactions | Time-intensive validation |
How to resolve conflicting data on C6orf108’s role in neurodegeneration vs. cancer?
Contradiction analysis framework:
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Context-dependent expression: Compare RNA-seq datasets from cancer (TCGA) vs. neurodegenerative (GTEx) cohorts .
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Pathway enrichment: Use STRING-DB to identify tissue-specific protein interactors (e.g., HLA-DRB1 in brain vs. SH3PXD2B in cancer) .
What controls are critical for C6orf108 loss-of-function studies?
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Off-target controls: Include scramble siRNA + rescue plasmid (e.g., pCMV-C6orf108)
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Phenotypic validation: Combine IncuCyte proliferation assays with RNA-FISH for transcript localization
Table 1: C6orf108-Associated Pathways
| Pathway | Cancer Role | Neurodegenerative Role | Key Interactors |
|---|---|---|---|
| c-Myc signaling | Pro-tumorigenic | Not reported | SH3PXD2B, TRPC6 |
| HLA-DRB1 | Limited evidence | Microglial activation | LOC101929163 |
Table 2: siRNA Design Parameters for C6orf108 Studies
Product Science Overview
C6ORF108 encodes a protein that is involved in several biochemical functions. The gene produces two alternative transcripts encoding different proteins. The recombinant form of this protein is typically produced in Escherichia coli (E. coli) and is often tagged with a His-tag for purification purposes . The recombinant protein consists of 194 amino acids, including a 20 amino acid His-tag at the N-terminus, and has a molecular mass of approximately 21.2 kDa .
The exact function of C6ORF108 is not fully understood. However, studies in rats suggest that it plays a role in cellular proliferation and c-Myc-mediated transformation . The protein has been shown to catalyze the cleavage of the N-glycosidic bond of deoxyribonucleoside 5’-monophosphates, yielding deoxyribose 5-phosphate and a purine or pyrimidine base . This activity suggests a role in nucleotide metabolism and DNA repair processes.
C6ORF108 is involved in several pathways and interacts with various proteins and molecules. These interactions have been detected through methods such as yeast two-hybrid, co-immunoprecipitation, and pull-down assays . Some of the proteins that interact with C6ORF108 include TERF1, FTSJ1, POT1, PILRA, and BRCA1 . These interactions indicate that C6ORF108 may have a broader role in cellular processes beyond its enzymatic activity.
Recombinant C6ORF108 is used in various research applications, including studies on gene expression regulation, protein-protein interactions, and cellular signaling pathways. The availability of recombinant C6ORF108 allows researchers to investigate its function and mechanism in a controlled environment, providing insights into its role in human health and disease .
