RPN-10 is the 26S proteasome non-ATPase regulatory subunit 4, a core ubiquitin receptor component of the 19S regulatory particle. The protein contains a von Willebrand factor type A (vWFA) domain and two ubiquitin-interacting motifs (UIMs) that mediate recognition and binding of polyubiquitinated substrates for proteasomal degradation. RPN-10 delivers ubiquitin-conjugated proteins to the 26S proteasome for destruction and is essential for normal ubiquitin-proteasome system (UPS) function. In C. elegans, RPN-10 has specialized roles in sex determination through regulation of TRA-2 protein turnover, and loss of rpn-10 causes feminization by eliminating hermaphrodite spermatogenesis. The protein also influences autophagy-lysosome pathway activity and proteostasis responses to stress.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation based on phylogenetic inference from orthologs including human PSMD4 (P55036), Drosophila, and other species. Nuclear localization is well-established for this proteasome subunit family. Supported by direct experimental evidence in C. elegans (PMID:26828939). Reason: Phylogenetic inference is consistent with experimental data. PMID:26828939 directly demonstrated nuclear localization of RPN-10 in C. elegans using fluorescence microscopy. The IBA annotation is therefore well-supported by both phylogenetic conservation and species-specific experimental validation. Supporting Evidence: PMID:26828939 RPN-10 is expressed broadly and localizes to the cytoplasm and nucleus file:worm/rpn-10/rpn-10-deep-research-falcon.md model: Edison Scientific Literature |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation derived from phylogenetic analysis across multiple species including Drosophila, yeast, and Arabidopsis orthologs. RPN-10/PSMD4 is a well-characterized ubiquitin receptor of the proteasome essential for substrate recognition and degradation. Reason: This is the core function of RPN-10 as a proteasomal ubiquitin receptor. The protein delivers polyubiquitinated substrates to the 26S proteasome for degradation. This function is conserved across eukaryotes and is consistent with the biochemical role of the UIM domains present in RPN-10. Supporting Evidence: PMID:17050737 The ubiquitin-binding RPN-10 protein serves as a ubiquitin receptor that delivers client proteins to the 26S proteasome |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation from phylogenetic inference using human PSMD4 (P55036) as reference. Cytosolic localization is expected for proteasome subunits and supported by experimental evidence in C. elegans. Reason: Cytosolic localization is consistent with the role of RPN-10 as part of the cytosolic proteasome. PMID:26828939 demonstrated that RPN-10 localizes to the cytoplasm in C. elegans, supporting this IBA annotation. Supporting Evidence: PMID:26828939 RPN-10 is expressed broadly and localizes to the cytoplasm and nucleus |
| GO:0008540 proteasome regulatory particle, base subcomplex | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation placing RPN-10 in the base subcomplex of the 19S regulatory particle. Based on phylogenetic inference from yeast, Arabidopsis, and other eukaryotic orthologs. Reason: RPN-10/S5a/PSMD4 is a well-characterized component of the 19S regulatory particle base subcomplex across eukaryotes. The protein directly associates with the 20S proteasome core via the vWFA domain while its UIM domains extend to capture ubiquitinated substrates. Supporting Evidence: PMID:17050737 The ubiquitin-binding RPN-10 protein serves as a ubiquitin receptor that delivers client proteins to the 26S proteasome |
| GO:0031593 polyubiquitin modification-dependent protein binding | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation for the molecular function of binding polyubiquitinated substrates. This is mediated by the two UIM (ubiquitin-interacting motif) domains present in RPN-10 at positions 216-235 and 273-292. Reason: This is the core molecular function of RPN-10 as a proteasomal ubiquitin receptor. The protein contains two well-characterized UIM domains that specifically recognize and bind polyubiquitin chains on substrate proteins destined for proteasomal degradation. InterPro confirms presence of UIM domain (IPR003903). This binding activity is essential for the substrate delivery function. Supporting Evidence: PMID:17050737 The ubiquitin-binding RPN-10 protein serves as a ubiquitin receptor that delivers client proteins to the 26S proteasome |
| GO:0000502 proteasome complex | IEA GO_REF:0000043 | ACCEPT | Summary: IEA annotation based on UniProtKB keyword mapping (KW-0647 Proteasome). This is a more general term than the specific base subcomplex annotation. Reason: This is a valid broader annotation. While GO:0008540 (proteasome regulatory particle, base subcomplex) is more specific and preferred, the general proteasome complex annotation is not incorrect. RPN-10 is indeed part of the 26S proteasome complex. Both annotations can coexist as the specific term is a child of the general term. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: IEA annotation based on UniProtKB subcellular location vocabulary mapping. Redundant with IBA and IDA annotations for the same term. Reason: Although redundant with higher-quality evidence (IBA and IDA), the IEA annotation is consistent with experimental findings. Nuclear localization is confirmed by PMID:26828939 which directly observed RPN-10 in both cytoplasm and nucleus. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: IEA annotation based on UniProtKB subcellular location vocabulary mapping. Redundant with IDA annotation for the same location. Reason: Although redundant with higher-quality IDA evidence, this IEA annotation is consistent with experimental observations from PMID:26828939 demonstrating cytoplasmic localization. |
| GO:0005634 nucleus | IDA PMID:26828939 Graded Proteasome Dysfunction in Caenorhabditis elegans Acti... | ACCEPT | Summary: Direct experimental evidence for nuclear localization of RPN-10 in C. elegans. Keith et al. (2016) used fluorescence microscopy to demonstrate that RPN-10 is expressed broadly and localizes to both cytoplasm and nucleus. Reason: Strong experimental evidence from direct observation. The study used RPN-10 reporter constructs to visualize subcellular localization in vivo, demonstrating presence in the nucleus. This is consistent with known proteasome localization in eukaryotes. Supporting Evidence: PMID:26828939 RPN-10 is expressed broadly and localizes to the cytoplasm and nucleus |
| GO:0005737 cytoplasm | IDA PMID:26828939 Graded Proteasome Dysfunction in Caenorhabditis elegans Acti... | ACCEPT | Summary: Direct experimental evidence for cytoplasmic localization of RPN-10 in C. elegans from fluorescence microscopy studies. Reason: Strong experimental evidence from direct visualization. Cytoplasmic localization is expected for proteasome subunits and was directly observed in the Keith et al. study using RPN-10 reporter constructs. Supporting Evidence: PMID:26828939 RPN-10 is expressed broadly and localizes to the cytoplasm and nucleus |
| GO:0006511 ubiquitin-dependent protein catabolic process | IMP PMID:17050737 Proteasomal ubiquitin receptor RPN-10 controls sex determina... | ACCEPT | Summary: IMP annotation based on mutant phenotype analysis. Shimada et al. (2006) demonstrated that rpn-10 knockdown affects proteasomal substrate degradation, and TRA-2 proteins accumulate in rpn-10-defective worms. Reason: The IMP evidence is well-supported. Loss of rpn-10 function results in accumulation of proteasomal substrates such as TRA-2, demonstrating the essential role of RPN-10 in ubiquitin-dependent protein catabolism. Supporting Evidence: PMID:17050737 TRA-2 proteins accumulated in rpn-10-defective worms |
| GO:0006511 ubiquitin-dependent protein catabolic process | IGI PMID:17050737 Proteasomal ubiquitin receptor RPN-10 controls sex determina... | ACCEPT | Summary: IGI annotation based on genetic interaction with ufd-2. The annotation references WB:WBGene00006734, which is the ufd-2 ubiquitin-fusion degradation protein. Reason: The genetic interaction between rpn-10 and ufd-2 supports the role of RPN-10 in ubiquitin-dependent protein catabolism. Co-knockdown of rpn-10 and ufd-2 demonstrated functional interaction in the ubiquitin-proteasome pathway. UFD-2 is an E4 ubiquitin ligase that works in the ubiquitin-fusion degradation pathway. Supporting Evidence: PMID:17050737 co-knockdown of rpn-10 and functionally related ubiquitin ligase ufd-2 overcomes the germline-musculinizing effect of fem-3(gf) |
| GO:0007283 spermatogenesis | IMP PMID:17050737 Proteasomal ubiquitin receptor RPN-10 controls sex determina... | KEEP AS NON CORE | Summary: IMP annotation based on mutant phenotype. rpn-10 mutants show feminization of hermaphrodites due to elimination of spermatogenesis. The annotation references WB:WBVar00250344, an rpn-10 allele. Reason: While valid experimental evidence supports this annotation, spermatogenesis is not the core function of RPN-10. Rather, the spermatogenesis defect is a consequence of RPN-10's role in degrading TRA-2, a key sex determination protein. The primary function of RPN-10 is as a ubiquitin receptor for proteasomal degradation. The spermatogenesis phenotype reflects a specific biological outcome of general UPS dysfunction affecting sex determination pathways. Supporting Evidence: PMID:17050737 We report herein that knockdown of the rpn-10 gene, but not any other proteasome subunit genes, sexually transforms hermaphrodites to females by eliminating hermaphrodite spermatogenesis in Caenorhabditis elegans |
| GO:0007283 spermatogenesis | IGI PMID:17050737 Proteasomal ubiquitin receptor RPN-10 controls sex determina... | KEEP AS NON CORE | Summary: IGI annotation based on genetic interaction with ufd-2 (WB:WBGene00006734) in the context of spermatogenesis regulation. Reason: The genetic interaction with ufd-2 in the sex determination pathway supports a role in spermatogenesis through regulation of TRA-2 degradation. However, this is a downstream phenotypic consequence of the core proteasomal function rather than a direct molecular role in spermatogenesis itself. The protein does not have a specialized spermatogenesis function - rather the UPS-dependent degradation of TRA-2 happens to be essential for proper sex determination. Supporting Evidence: PMID:17050737 TRA-2 proteins accumulated in rpn-10-defective worms. Our results show that the RPN-10-mediated ubiquitin pathway is indispensable for control of the TRA-2-mediated sex-determining pathway |
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Download this section (compressed HTML)Q: Does RPN-10 show substrate specificity or preference for particular types of polyubiquitin chains (K48 vs K63)?
Q: Is the role in paternal mitochondria elimination a direct function or downstream consequence of general UPS activity?
Experiment: Ubiquitin chain linkage specificity assays to determine if C. elegans RPN-10 UIMs have preference for K48 vs K63 polyubiquitin. Would enable more specific MF annotation.
Experiment: Tissue-specific RPN-10 rescue experiments to determine which tissues require RPN-10 for spermatogenesis phenotype. Could clarify whether spermatogenesis role is direct or indirect.
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