C11ORF31 (Chromosome 11 Open Reading Frame 31), also known as SELENOH, SELH, or selenoprotein H, is a nuclear-encoded selenoprotein critical for redox regulation and cellular protection. It contains a selenocysteine (Sec) residue at its active site, encoded by the UGA codon, which requires a SECIS element in the 3' untranslated region (UTR) for proper translation . This gene belongs to the SelWTH family and is implicated in mitochondrial biogenesis, genome maintenance, and resistance to oxidative stress .
Attribute | Details |
---|---|
Synonyms | SELENOH, SELH, C17ORF10, Selenoprotein H |
Gene ID | NCBI Gene ID: 280636 |
Chromosome | Chromosome 11 |
3' UTR Feature | SECIS element for Sec incorporation |
Protein Length | 145 amino acids (recombinant form includes 23 His-tag) |
Molecular Weight | 15.8 kDa (recombinant form) |
Tissue Expression:
C11ORF31 is expressed in diverse tissues, including the brain, liver, and testes, with notable activity in neuronal cells and mitochondria-rich tissues . Expression profiles from BioGPS and HPA highlight its presence in human and mouse cell lines, suggesting conserved functional roles across species .
C11ORF31 is a nucleolar protein with oxidoreductase activity. Its selenocysteine residue enables redox-sensitive functions, including:
Redox Regulation: Neutralizes reactive oxygen species (ROS) to protect against oxidative damage .
Mitochondrial Biogenesis: Promotes mitochondrial function and energy metabolism .
Genome Maintenance: Inhibits DNA damage-induced senescence and apoptosis .
Recombinant C11ORF31 is produced in E. coli as a non-glycosylated polypeptide fused to a His-tag for purification .
C11ORF31 upregulates genes involved in glutathione synthesis and phase II detoxification, acting as a redox-sensing DNA-binding protein . Its expression is influenced by transcription factors such as NRF2, which respond to oxidative stress .
A population-based study of 2,309 colorectal cancer cases revealed interactions between C11ORF31 and lifestyle factors:
Aspirin/NSAID Use: Genetic variants in selenoprotein genes (TXNRD1, TXNRD2, C11ORF31) modified colon/rectal cancer risk in combination with anti-inflammatory drugs .
Estrogen Status: Polymorphisms in C11ORF31 and related genes (SelW1, SelS) interacted with estrogen levels to alter cancer risk .
While specific SNPs in C11ORF31 were not detailed, the gene was part of a broader analysis linking selenoprotein pathways to carcinogenesis and survival outcomes .
Cancer Therapy: Targeting C11ORF31’s redox-regulatory functions may enhance therapeutic responses to chemotherapies .
Aging and Senescence: Inhibiting cellular senescence via C11ORF31 could delay age-related diseases .
Antioxidant Strategies: Supplementation with selenium (a cofactor for selenoproteins) may mitigate oxidative damage in C11ORF31-related pathways .
C11ORF31 is a gene that encodes a selenoprotein which contains a selenocysteine (Sec) residue at its active site. This gene is also known by several synonyms including SELENOH, SELH, and C17ORF10, with the protein product being identified as SELH_HUMAN in protein databases . The gene has NCBI Gene ID 280636 and is part of the selenoprotein family, which are proteins containing the rare amino acid selenocysteine.
Aspect | Information |
---|---|
Full Name | Chromosome 11 open reading frame 31 |
Synonyms | C11orf31, C17ORF10, SELENOH, SELH |
Protein Identifier | SELH_HUMAN |
NCBI Gene ID | 280636 |
Family | Selenoprotein |
C11ORF31 contains a selenocysteine residue at its active site, which is encoded by the UGA codon (typically a stop codon). The proper translation of UGA as selenocysteine rather than termination is facilitated by a special stem-loop structure in the 3' UTR called the SECIS (selenocysteine insertion sequence) element . While the exact function of C11ORF31 is not fully characterized, as a selenoprotein, it likely contributes to cellular redox regulation and antioxidant defense mechanisms, which are common functions of selenoproteins.
The gene has 3,223 functional associations with biological entities spanning 8 categories extracted from 57 datasets, indicating its involvement in multiple biological processes and potential interactions with various molecular components .
The incorporation of selenocysteine in C11ORF31 occurs through a specialized translation mechanism where the UGA codon, normally a stop signal, is recoded to specify selenocysteine insertion. This recoding requires:
The presence of the SECIS element in the 3' UTR
Specific translational machinery including selenocysteine-specific tRNA (tRNA^[Ser]Sec)
SECIS-binding protein 2 (SBP2)
Selenocysteine-specific elongation factor (eEFSec)
These components work together to ensure the UGA codon is interpreted as a signal for selenocysteine incorporation rather than translation termination . This mechanism is crucial for experimental designs involving recombinant expression of functional C11ORF31 protein.
Based on data from the Allen Brain Atlas, C11ORF31 shows expression in both adult and developing human brain tissues . The expression patterns vary across different brain regions, providing insights into potential neurological functions of this selenoprotein.
Data Source | Expression Pattern |
---|---|
Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles | Variable expression across brain regions |
Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray | Temporal expression patterns during brain development |
Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq | Spatial expression patterns during brain development |
For researchers studying C11ORF31's potential role in neurodevelopment or neurological disorders, these expression datasets provide valuable baseline information for hypothesis generation and experimental design.
To investigate C11ORF31's biological associations, researchers can employ multiple approaches:
Co-expression network analysis: Identify genes with correlated expression patterns across tissues or conditions
Protein-protein interaction studies: Use techniques like co-immunoprecipitation or proximity labeling
Functional enrichment analysis: Examine biological pathways enriched among associated genes
RNA-binding studies: Investigate potential RNA targets if C11ORF31 functions in post-transcriptional regulation
The gene has been noted to have numerous functional associations across molecular profiles, functional terms, chemicals, diseases, and other biological entities , suggesting diverse roles that warrant further investigation.
Researchers can effectively measure C11ORF31 expression using several complementary techniques:
Quantitative RT-PCR (qRT-PCR): Design specific primers targeting C11ORF31 mRNA. Normalization to appropriate housekeeping genes like RPLPO is essential for accurate quantification .
RNA-Seq: For transcriptome-wide analysis, RNA-Seq provides comprehensive expression data. Processing with methods like GCRMA (Robust Multi-array Analysis that accounts for GC content) can normalize and summarize probe-level intensity measurements .
Western blotting: Protein-level quantification using validated antibodies against C11ORF31/SELENOH.
Method | Application | Considerations |
---|---|---|
qRT-PCR | Targeted expression analysis | Requires careful primer design and normalization to reference genes like RPLPO |
RNA-Seq | Transcriptome-wide analysis | Data processing with GCRMA; filtering out low-expression transcripts (<10 absolute expression values) |
Western blotting | Protein-level quantification | Requires validated antibodies; challenging due to potential low expression levels |
Recent proteomics studies have identified C11ORF31 in mRNA-bound proteome analyses, suggesting potential RNA-binding activities . To investigate these properties, researchers can employ:
RNA immunoprecipitation (RIP): Pull down C11ORF31-associated RNAs for identification
Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation (PAR-CLIP): A method mentioned in the proteomics study that successfully validated RNA-binding proteins
RNA electrophoretic mobility shift assays (EMSA): Confirm direct binding to specific RNA targets
Structural studies: Identify potential RNA-binding domains within the protein
For reliable results, controls for specificity and validation across multiple methodologies are essential, as demonstrated in the mRNA-bound proteome studies that identified other novel RNA-binding proteins .
As a selenoprotein, C11ORF31 expression and function are likely influenced by selenium bioavailability. To study this relationship, researchers can:
Culture cells in media with defined selenium concentrations
Use selenium-deficient experimental models supplemented with various selenium levels
Analyze hierarchical regulation among different selenoproteins under limited selenium conditions
Investigate the efficiency of selenocysteine incorporation using reporter constructs
The insertion of selenocysteine via the SECIS element is selenium-dependent, making C11ORF31 expression potentially sensitive to selenium status . This relationship may have implications for understanding C11ORF31's role in conditions associated with selenium deficiency or supplementation.
Computational prediction of C11ORF31 interaction networks can employ:
Sequence-based prediction: Using conserved motifs to predict protein-protein or protein-RNA interactions
Structural modeling: Predicting interaction interfaces based on 3D structure
Co-expression analysis: Identifying genes with correlated expression patterns across tissues/conditions
Text mining: Extracting relationships from scientific literature
Network analysis: Integrating multiple data types to build comprehensive interaction networks
These approaches can generate testable hypotheses about C11ORF31's functional interactions, guiding experimental validation efforts.
While direct evidence specifically linking C11ORF31 to cancer is limited in the provided search results, there is an association mentioned between genetic variation in several genes including C11ORF31 and rectal cancer . To further investigate potential cancer connections, researchers can:
Analyze C11ORF31 expression across cancer types using cancer genomics databases
Perform functional studies in cancer cell lines using gene editing technologies
Investigate correlations between C11ORF31 expression/mutations and clinical outcomes
Examine the role of selenium status in cancer contexts where C11ORF31 may be implicated
The potential connection to rectal cancer suggests this might be a priority area for investigating C11ORF31's role in cancer biology .
The search results mention gene expression profiling in peripheral blood mononuclear cells in systemic Juvenile Idiopathic Arthritis (sJIA), suggesting potential involvement in inflammatory pathways . To explore this connection, researchers could:
Compare C11ORF31 expression between healthy controls and inflammatory disease samples
Analyze the effect of inflammatory cytokines on C11ORF31 expression
Investigate whether C11ORF31 modulates inflammatory signaling pathways
Examine potential interactions between C11ORF31 and known inflammatory mediators
Understanding these relationships could provide insights into C11ORF31's role in inflammatory conditions and potential therapeutic implications.
Researchers face several technical challenges when studying C11ORF31:
Challenge | Solution Approach |
---|---|
Selenoprotein expression | Use specialized expression systems with optimized SECIS elements and selenium supplementation |
Antibody specificity | Validate antibodies through multiple approaches; consider epitope tagging strategies |
Low endogenous expression | Employ sensitive detection methods; design efficient enrichment strategies |
UGA codon interpretation | Ensure experimental systems correctly interpret UGA as selenocysteine rather than termination |
Functional redundancy | Consider combinatorial approaches targeting multiple selenoproteins |
For expression studies, researchers should consider the methods described for RNA extraction and microarray hybridization to Affymetrix arrays, with appropriate normalization using methods like GCRMA . For proteomics approaches, techniques successfully used to identify RNA-binding proteins in HEK293 cells could be adapted for C11ORF31 studies .
To validate C11ORF31 function in cellular models, researchers can employ:
CRISPR-Cas9 gene editing: Generate knockout or knockin cell lines
RNA interference: Use siRNA or shRNA for transient or stable knockdown
Overexpression systems: Express wild-type or mutant versions of C11ORF31
Rescue experiments: Restore function in knockout models with wild-type or mutant constructs
Reporter assays: Monitor functional readouts related to predicted activities
When working with C11ORF31, it's important to monitor the purity and activation status of isolated cells, as demonstrated in neutrophil studies using flow cytometric analysis with surface markers like CD11b/Mac-1 and CD16 .
Several emerging technologies could significantly advance C11ORF31 research:
Single-cell transcriptomics: Reveal cell-type specific expression patterns
Spatial transcriptomics: Map expression across tissues with spatial resolution
CRISPR screens: Identify genetic interactions on a genome-wide scale
Cryo-EM structure determination: Resolve high-resolution protein structure
Proteomics approaches: Similar to those used in mRNA-bound proteome studies
These technologies could help resolve current knowledge gaps regarding C11ORF31's tissue-specific functions, interaction partners, and structural properties, providing a more comprehensive understanding of this selenoprotein.
Based on current understanding, priority research questions include:
What is the three-dimensional structure of C11ORF31 and how does the selenocysteine residue contribute to its function?
What are the direct RNA and/or protein interaction partners of C11ORF31?
How is C11ORF31 expression regulated across different tissues and developmental stages?
What are the phenotypic consequences of C11ORF31 deficiency or mutation?
How does C11ORF31 contribute to selenium's biological effects and health implications?
Addressing these questions would significantly advance understanding of C11ORF31's biological roles and potential therapeutic relevance.
The C11orf31 gene is a protein-coding gene that produces a polypeptide chain consisting of 145 amino acids . The recombinant form of this protein is typically expressed in E. coli and is purified using conventional chromatography techniques . The protein has a molecular mass of approximately 15.8 kDa .
The recombinant C11orf31 protein is expressed in E. coli and purified to a high degree of purity, often greater than 90%, as determined by SDS-PAGE . The protein is tagged with a His tag at the N-terminus to facilitate purification. The expression system and purification process ensure that the recombinant protein is suitable for various applications, including SDS-PAGE and mass spectrometry (MS) .
Recombinant C11orf31 protein is used in various research applications to study its function and role in cellular processes. It is also used to generate antibodies for research purposes. The protein’s involvement in different cellular pathways and its potential link to diseases make it a subject of interest in biomedical research.