Ask about this productRelated genes to: SSR4 antibody
- Gene:
- SSR4 NIH gene
- Name:
- signal sequence receptor subunit 4
- Previous symbol:
- -
- Synonyms:
- TRAPD
- Chromosome:
- Xq28
- Locus Type:
- gene with protein product
- Date approved:
- 1997-11-04
- Date modifiied:
- 2016-05-05
Related products to: SSR4 antibody
Related articles to: SSR4 antibody
- Porcine reproductive and respiratory syndrome (PRRS) is a major economic burden to the global swine industry. Here, we identify the endoplasmic reticulum (ER) translocon component SSR4 as a critical host factor co-opted by PRRSV. We demonstrate that the viral non-structural protein Nsp2 physically interacts with SSR4 via its PLP2 and hypervariable domains and selectively upregulates its expression during infection by prolonging its protein half-life. Functional studies revealed that SSR4 is a proviral factor essential for efficient PRRSV replication. Mechanistically, SSR4 is required for the full activation of the PRRSV-induced ER stress response, specifically modulating the PERK-eIF2α and IRE1α-XBP1 axes of the unfolded protein response. Notably, Nsp2 itself acts as a key inducer of ER stress and mediates the upregulation of SSR4, suggesting a potential feed-forward loop that sustains a virus-favorable ER environment. This relationship is finely balanced, as pharmacological disruption of ER homeostasis using either the inducer tunicamycin (TU) or the chemical chaperone 4-phenylbutyric acid (4-PBA) potently inhibited viral replication. Importantly, TU and another inducer, dithiothreitol, exhibited potent, broad-spectrum antiviral activity against multiple PRRSV genotypes in both cell lines and primary porcine alveolar macrophages. Our study delineates a novel pathogenesis model where PRRSV Nsp2 hijacks SSR4 to engineer a proviral ER stress niche. The Nsp2-SSR4-ER stress axis represents a promising target for the development of broad-spectrum antiviral strategies against PRRS.IMPORTANCEThis study provides significant insights into porcine reproductive and respiratory syndrome virus (PRRSV) pathogenesis by identifying a novel and specific virus-host interface. We demonstrate that PRRSV, through its Nsp2 protein, hijacks a specific component of the host endoplasmic reticulum (ER) translocon SSR4 to orchestrate a tailored ER stress response conducive to viral replication. This mechanism is distinct from a general disruption of the TRAP complex, highlighting a precise viral strategy. Furthermore, the finding that pharmacological agents, which dysregulate this hijacked pathway-particularly ER stress inducers-act as potent, broad-spectrum antivirals challenges the conventional view of ER stress as a uniformly host-protective response. Our work not only uncovers a key molecular determinant of PRRSV replication but also validates the Nsp2-SSR4-ER stress axis as a promising and novel target for the development of much-needed, broad-spectrum therapeutic interventions against this economically devastating swine pathogen. - Source: PubMed
Publication date: 2026/04/23
Li YingchaoGao HongyanLiu ZhongLu ManShen YangXing YajingWang YuWu XiaotongYang PingpingYuan HongjieHou YanmengCai YumeiLi BaoquanXiao Yihong - Congenital disorders of glycosylation type Iy (SSR4-CDG, CDG1Y) is an ultra-rare X-linked disorder caused by pathogenic variants in the gene, encoding a subunit of the translocon-associated protein (TRAP) complex. While typically recognized for neurodevelopmental and facial features, its full neonatal spectrum, particularly regarding cardiac involvement, remains under-characterized. - Source: PubMed
Publication date: 2026/03/25
Zhao LingxiaZeng LingkongYi MinghuiYuan Wenhao - Chinese hamster ovary (CHO) cells are widely utilised in the biopharmaceutical industry to produce therapeutic proteins. Understanding the mechanisms of endoplasmic reticulum (ER) stress and its interplay with protein degradation pathways remains pivotal for improving production efficiency and product quality. In this study, we investigated the proteomic responses of CHO-K1 (non-producer), CHO DP-12 (IgG-producer), and NISTCHO (IgG-producer) cell lines under ER stress induced by a combination of the proteasome inhibitor MG132 and the glycosylation inhibitor tunicamycin. Viability, cell growth, and IgG titre were measured after 24 h, 48 h, and 72 h of treatment and the 48 h timepoint was used for the comparative analysis of the proteomic data across the three cell lines. Proteasome inhibition with MG132 intensified ER stress and altered ER-associated protein degradation (ERAD). Combined tunicamycin + MG132 treatment was associated with cell line-specific proteomic changes: NISTCHO upregulated ER translocation and glycoprotein quality control proteins (SSR4, SEC24C, UGGT1), CHO DP-12 activated redox/disulfide regulators (DNAJC10, CAPN1), while CHO-K1 showed broad proteome shifts, suggesting differences in baseline stress handling. These findings provide mechanistic insights into ER stress and protein quality control in CHO cells, offering a foundation for strategies to enhance cell line robustness and optimise biopharmaceutical production. - Source: PubMed
Publication date: 2026/02/10
Sideri Christiana-KondyloRyan DavidHenry MichaelEfeoglu EsenMeleady Paula - Esophageal squamous cell carcinoma (ESCC) is a highly aggressive cancer with a poor prognosis, and its molecular mechanisms remain unclear. Our previous research identified the signal sequence receptor subunit delta (SSR4) of the TRAP complex as a potential ESCC biomarker. The TRAP complex, composed of SSR1, SSR2, SSR3, and SSR4, is essential for protein translocation, folding, and quality control, crucial for cellular balance. While individual TRAP subunits have been studied, a comprehensive understanding of their roles in human diseases is lacking. - Source: PubMed
Publication date: 2026/02/06
Zhang JiaqiWan XingGong Aixia - : Congenital disorders of glycosylation (CDG) are rare inborn errors of metabolism with multisystemic manifestations. SSR4-CDG is an ultra-rare X-linked subtype caused by pathogenic variants in , a component of the translocon-associated protein (TRAP) complex essential for protein translocation and N-glycosylation. : We report a two-year-old Malaysian male presenting with global developmental delay, central hypotonia, microcephaly with complete agenesis of the corpus callosum, recurrent infections, bilateral vesicoureteral reflux, and failure to thrive. Growth parameters (weight, length, and head circumference) were persistently below the expected percentiles, indicating postnatal growth restriction. Initial metabolic and biochemical investigations for global developmental delay were unremarkable, apart from mild hyperammonemia. Transferrin isoform analysis demonstrated a type I CDG pattern, raising suspicion of a glycosylation defect. : Transferrin glycopeptide LC-MS/MS showed impaired N-glycan occupancy at both glycosylation sites (Asn432 and Asn630), with reduced fully sialylated glycoforms and increased non-glycosylated peptides. Targeted metabolomics using triple quadrupole LC-MS/MS revealed systemic abnormalities, including elevated arginine and phenylalanine, reduced glutamate, increased lysophosphatidylcholine (C24:0-LPC), and generalized depletion of free and acylcarnitines. Whole-exome sequencing identified a novel hemizygous variant (c.98del; ) on the X chromosome, predicted to produce a truncated, nonfunctional protein. : This is the first Malaysian patient with SSR4-CDG, comprehensively characterized using a multi-omics diagnostic workflow. The integration of glycoproteomics, metabolomics, and exome sequencing provided a detailed biochemical fingerprint that expands the clinical, genetic, and metabolic spectrum of SSR4-CDG and demonstrates the diagnostic and translational value of multi-omics approaches in inborn errors of metabolism. - Source: PubMed
Publication date: 2025/12/08
Abu Bakar NurulaminHamzan Nurul IzzatiMajawit Elyssa MilusAhmad Ridzuan Siti NurwaniHassan Noor HafizahHabib AnasufizaNgu Lock-Hock