Ask about this productRelated genes to: RPN2 antibody
- Gene:
- RPN2 NIH gene
- Name:
- ribophorin II
- Previous symbol:
- -
- Synonyms:
- SWP1, RPNII, RIBIIR, RPN-II
- Chromosome:
- 20q11.23
- Locus Type:
- gene with protein product
- Date approved:
- 2001-06-22
- Date modifiied:
- 2016-10-05
Related products to: RPN2 antibody
Related articles to: RPN2 antibody
- The 26S proteasome is the endpoint of the ubiquitin-proteasome system, an essential pathway for maintaining cellular homeostasis through targeted degradation of misfolded, damaged, and obsolete proteins. Substrates labeled with ubiquitin are directed to the 26S proteasome by binding to one or more ubiquitin receptors. However, ubiquitin-dependent degradation occurs even when the canonical receptor sites are mutated, suggesting the presence of additional, unidentified binding sites. Here we created photo-crosslinkable probes for ubiquitin interactions by incorporating the unnatural amino acid p-benzoyl-L-phenylalanine into ubiquitin. We show that these probes can be used to measure apparent affinities for known receptors and to reveal novel ubiquitin-binding sites on the yeast 26S proteasome. Through photo-crosslinking mass-spectrometry experiments we identified a groove on the top of the proteasome, formed by Rpn2, Rpn9, Rpn10, and Rpn12, that serves as an additional ubiquitin-binding interface. Our photo-crosslinkable probes thus serve as versatile tools for the characterization of ubiquitin-protein interactions and the identification of ubiquitin-binding domains. - Source: PubMed
Publication date: 2026/04/22
MacRae Nicole SDong Ken CHarimoto HiromitsuMartin Andreas - Congenital disorders of glycosylation (CDGs) are a phenotypically diverse group of genetic conditions arising from pathogenic variants in various glycosylation pathways. The most prevalent are N-glycosylation disorders. Here, we present clinical and biochemical data on two siblings with a neurodevelopmental disorder and a pathogenic homozygous nonsense variant in ribophorin I (RPN1), an essential component of the oligosaccharyltransferase (OST) complex. Both affected individuals showed a classical type I serum transferrin profile, while lymphoblasts revealed that the variant resulted in a truncated RPN1 protein with reduced levels. The protein stability of other essential OST complex components, including STT3 OST complex catalytic subunit A (STT3A), RPN2, and dolichyl-diphosphooligosaccharide (DDOST), was also significantly reduced. Structural modeling of both OST-A and OST-B complexes shows that RPN1 truncation eliminates a C-terminal four-helix bundle, which interacts with the translating ribosome. This interaction is necessary and specific for the co-translational activity of the OST-A complex. Supporting this observation, hypoglycosylation of an OST-A-specific substrate protein was observed, while OST-B-specific substrates were unaffected. These data convey that a rare loss-of-function RPN1 variant causes an autosomal recessive CDG characterized by neurodevelopmental deficits. - Source: PubMed
Publication date: 2026/04/03
Ng Bobby GZhang WenyueNeil Jennifer EDanish MarwaMarafi DanaKamal Tarek MBastaki LailaAl Saffar MunaYang EdwardHe MiaoWalsh Christopher AMochida Ganeshwaran HFreeze Hudson H - Agriculture workers are especially at risk from insecticide (INSECT) exposure, which is associated with neurological disorders, such as Parkinson's disease (PD). The present study evaluated the mechanism of neurotoxicity induction in a commercial insect containing chlorpyrifos (50%) and cypermethrin (5%) in Caenorhabditis elegans models, as well as the neuroprotective efficacy of two custom peptides (CPs), HNP (heptadeca-neuropeptide) and TNP (trideca-neuropeptide), derived from snake venom nerve growth factor. CPs significantly mitigated INSECT-induced neurotoxicity by preventing chemosensory alterations, reducing oxidative stress (reactive oxygen species generation), restoring mitochondrial membrane potential, lowering nitrite and lipid peroxidation levels, and inhibiting acetylcholinesterase disruption in the N2 (wild-type) strain of C. elegans. CPs pretreatment significantly reduced dopaminergic neuron damage from INSECT exposure in C. elegans (BZ555 strain) and reduced accumulation of α-synuclein, a hallmark of PD, by a marked elevation in the expression of key autophagy genes (lgg-1, atg-7, lgg-2, atg-18, epg-5, vps-34) and proteasomal degradation components (rpn-2, rpt-4, ubc-12) in the transgenic (NL5901) strain of C. elegans. Quantitative reverse transcription polymerase chain reaction revealed that CPs pretreatment modulates the INSECT-induced upregulation of p38 mitogen-activated protein kinase (MAPK)/antioxidant/heat shock response/genes and delays apoptosis in C. elegans. However, TNP conferred slightly greater neuroprotective effects than HNP. Proteomic analysis demonstrated that TNP downregulated genes in the skn-1 oxidative stress pathway, thereby suppressing pro-apoptotic signalling and neuronal injury. CPs at a 10 mg/kg dose (i.v. route) did not demonstrate acute, subacute, and sub-chronic toxic effects in Swiss albino mice, and they significantly reduced (p ≤ 0.05) the levels of proinflammatory cytokines IL-1β, IL-6, and TNF-α, as compared to controls. The pharmacokinetic profiling demonstrated that TNP effectively penetrates the blood-brain barrier (8.95%) in Wistar rats, indicating its potential central nervous system bioavailability. - Source: PubMed
Publication date: 2026/02/26
Mahato RosyMadhubala DevBala AsisKhan Mojibur RMukherjee Ashis K - Bisphenol A (BPA), nonylphenol (NP), and octylphenol (OP) are common environmental phenolic endocrine disruptors and widely used industrial chemicals that have garnered significant attention due to their potential to disrupt endocrine functions. These compounds are known to interfere with hormonal activities, particularly those related to estrogen, and are linked to the onset and progression of breast cancer. This study aims to systematically investigate the potential relationship between BPA, NP, and OP and breast cancer risk, along with their underlying molecular mechanisms, by synthesizing data from multiple databases. We initially acquired the chemical structures and SMILES representations of BPA, NP, and OP from the PubChem database. Subsequently, we utilized multiple databases, including the Comparative Toxicogenomics Database (CTD), SEA, and Swiss Target Prediction, t0 estimate their probable biological targets. The predicted targets were standardized and consolidated to form a comprehensive target database. Breast cancer-related targets were subsequently identified from the GeneCards and DisGeNET databases, and their overlap with the targets of BPA, NP, and OP was analyzed to pinpoint potential breast cancer risk targets. To elucidate the functional pathways involved, we conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses using the DAVID database. This analysis offered insights into the molecular pathways influenced by BPA, NP, and OP in the context of breast cancer. Additionally, we utilized machine learning algorithms, specifically Least Absolute Shrinkage and Selection Operator (LASSO) regression and Support Vector Machine (SVM), to identify nuclear targets linked to BPA, NP, and OP-induced breast cancer. These nuclear targets were further validated through differential expression analysis and Receiver Operating Characteristic (ROC) curve analysis using the GEO dataset GSE42568. We also performed a Single Gene Gene Set Enrichment Analysis (GSEA) to investigate the potential regulatory mechanisms of these nuclear genes in breast cancer. The infiltration of immune cells in breast cancer tissues was analyzed using single-sample gene set enrichment analysis (ssGSEA), and the correlation between nuclear targets and immune cell infiltration was examined. Finally, molecular docking and molecular dynamics simulations were conducted to assess the binding affinity and stability of BPA, NP, and OP with their nuclear targets. In this study, we integrated network toxicology, machine learning and multi-omics validation, and identified for the first time that BPA, NP and OP may induce breast cancer through 156 common targets; among them, MAOA, MGLL, ADRA2A, RPN2, GF1R and CTSD were identified as the key causative genes, with a diagnostic efficacy of 0.80–0.94 AUC. Mechanistically, these genes are concentrated in the GPCR/MAPK/JNK, sphingolipid, and prolactin signaling pathways, which regulate the Wnt/TGF-β/chemokine network and dramatically modify the immunological infiltration of nine classes of M0-M2 macrophages and CD4⁺ T cells. Molecular docking and kinetic simulations suggested the strong affinity of BPA for MGLL, and the complex was stabilized with ≥ 3 hydrogen bonds. In conclusion, phenolic endocrine disruptors may cause breast cancer through the “multi-target-immune microenvironment-metabolic reprogramming” axis, and MAOA, MGLL, ADRA2A, and RPN2 may serve as new targets for early detection and management. - Source: PubMed
Publication date: 2026/02/11
Dou YanhongLi XiongxiongLi MengShang JinXu Ting - The stimulator of interferon genes (STING) is a central adaptor in antiviral signaling, but its role in vectors that transmit human and animal pathogens remains poorly understood. Here, we show that the tick STING homolog, tSTING, facilitates Powassan virus (POWV) infection in -- in contrast to the canonical antiviral activity of mammalian STING. Transcriptomic and functional analyses revealed that tSTING regulates N-linked glycosylation and endocytosis, pathways essential for viral entry. Silencing of , a key glycosylation enzyme, significantly reduced viral loads, establishing a mechanistic link between tSTING and glycosylation-mediated viral uptake. Moreover, parallel studies in human THP-1 cells suggest human STING (hSTING) displays an opposite phenotype, restricting POWV replication potentially through OAS1-associated antiviral mechanisms independent of glycosylation. Together, these findings reveal an evolutionary reversal of STING function between arthropods and mammals, redefining the evolutionary logic of antiviral immunity across vector-host boundaries. - Source: PubMed
Publication date: 2026/01/28
Tian Xiu-QiPaine Dakota NLópez Alejandro MarínFeng DongDu ShanshanNarasimhan SukanyaThangamani SaravananFikrig Erol