CDC-48.1 is the C. elegans ortholog of mammalian p97/VCP, a highly conserved AAA+ ATPase that functions as a molecular chaperone. It forms homohexameric or heterohexameric rings (with CDC-48.2) and uses ATP hydrolysis to generate mechanical force for unfolding substrate proteins, disassembling protein complexes, and disaggregating protein aggregates. CDC-48.1 is essential for ER-associated degradation (ERAD), working with UFD-1/NPL-4 adaptors to extract misfolded proteins from the ER for proteasomal degradation. It also functions in DNA replication by promoting degradation of CDT-1 and disassembly of replication complexes, cell cycle progression, chromatin-associated protein degradation, mitotic spindle disassembly, and spermatogenesis regulation. CDC-48.1 works with various UBX domain-containing cofactors (UBXN-1 through UBXN-6) that determine substrate specificity.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: CDC-48.1 localizes to the nucleus where it functions in DNA replication, chromatin-associated degradation, and cell cycle regulation (PMID:22735043, PMID:26842564). Reason: Nuclear localization is well-supported by phylogenetic inference from orthologs and directly confirmed by experimental evidence in C. elegans showing CDC-48 associates with chromatin and functions in nuclear processes. Supporting Evidence: PMID:22735043 CDC-48/p97 is a AAA (ATPases associated with diverse cellular activities) chaperone involved in protein conformational changes such as the disassembly of protein complexes PMID:26842564 cellular fractionation of C. elegans embryonic lysates confirmed high abundance of UBXN-3, CDC-48 and CDT-1 in purified nuclei file:worm/cdc-48/cdc-48-deep-research-falcon.md model: Edison Scientific Literature |
| GO:0016887 ATP hydrolysis activity | IBA GO_REF:0000033 | ACCEPT | Summary: ATP hydrolysis activity is the core enzymatic function of CDC-48.1. The protein contains two AAA ATPase domains (D1 and D2) that hydrolyze ATP with positive cooperativity (PMID:21454554, PMID:18782221). Reason: This is a core molecular function of CDC-48.1, confirmed by multiple direct biochemical assays showing ATPase activity with defined kinetic parameters. Supporting Evidence: PMID:21454554 The ATPase activity of the N-terminal AAA domain was very low at physiological temperature, whereas the C-terminal AAA domain showed high ATPase activity in a coordinated fashion with positive cooperativity PMID:18782221 CDC-48.1 and CDC-48.2 suppress the aggregation of a huntingtin (Htt) exon1 fragment containing an expanded polyQ repeat in vitro |
| GO:0051228 mitotic spindle disassembly | IBA GO_REF:0000033 | ACCEPT | Summary: CDC-48.1 is involved in mitotic spindle disassembly through its role in chromatin decondensation and nuclear envelope re-assembly at the end of mitosis. Reason: Phylogenetically conserved function supported by IBA from yeast Cdc48 and consistent with C. elegans functional data showing CDC-48 is required for post-mitotic chromatin decondensation. Supporting Evidence: PMID:18728180 Our analysis of the CDC-48(UFD-1/NPL-4) complex identified a general role in S phase progression of mitotic cells essential for embryonic cell division and germline development of adult worms |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: CDC-48.1 localizes to the cytosol where it functions in ERAD and proteasomal degradation pathways (PMID:16647269, PMID:20977550). Reason: Cytosolic localization is phylogenetically conserved and confirmed by experimental studies in C. elegans showing CDC-48 functions in cytoplasmic protein degradation pathways. Supporting Evidence: PMID:20977550 UBXN-1, UBXN-2 and UBXN-3 colocalized with CDC-48 in spermatocytes but not mature sperm |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: CDC-48.1 is a key component of the ubiquitin-proteasome system, binding polyubiquitinated substrates and facilitating their delivery to the proteasome for degradation (PMID:16647269, PMID:21673654). Reason: This is a core function of p97/VCP family proteins. CDC-48.1 extracts ubiquitinated substrates from complexes and membranes for proteasomal degradation, a function conserved from yeast to humans. Supporting Evidence: PMID:16647269 the AAA ATPase p97/VCP/CDC48 is required in this pathway for protein dislocation across the ER membrane and subsequent ubiquitin dependent degradation by the 26S proteasome in the cytosol PMID:21673654 EGF signalling alters protein homoeostasis in adults by increasing UPS activity and polyubiquitination, while decreasing protein aggregation |
| GO:0031593 polyubiquitin modification-dependent protein binding | IBA GO_REF:0000033 | ACCEPT | Summary: CDC-48.1 binds Lys-48-linked polyubiquitin chains on substrate proteins, enabling their extraction and delivery to the proteasome (PMID:16647269). Reason: This is the substrate recognition mechanism for CDC-48/p97 proteins. Binding to polyubiquitinated substrates is mediated through adaptor proteins and is essential for ERAD and other degradation pathways. Supporting Evidence: PMID:16647269 the AAA ATPase p97/VCP/CDC48 is required in this pathway for protein dislocation across the ER membrane and subsequent ubiquitin dependent degradation by the 26S proteasome |
| GO:0030970 retrograde protein transport, ER to cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: CDC-48.1 is required for retro-translocation of misfolded proteins from the ER lumen to the cytosol for ERAD (PMID:16647269). Reason: This is a core function of CDC-48/p97 in ERAD. The protein provides the ATP-dependent force needed to extract substrates through the ER membrane retrotranslocon. Supporting Evidence: PMID:16647269 these data suggest an evolutionarily conserved retro-translocation machinery at the endoplasmic reticulum |
| GO:0034098 VCP-NPL4-UFD1 AAA ATPase complex | IBA GO_REF:0000033 | ACCEPT | Summary: CDC-48.1 forms a complex with UFD-1 and NPL-4 adaptors, the C. elegans equivalent of the mammalian VCP-NPL4-UFD1 complex (PMID:16647269, PMID:20977550). Reason: The CDC-48/UFD-1/NPL-4 complex is phylogenetically conserved and has been directly demonstrated in C. elegans through co-immunoprecipitation. Supporting Evidence: PMID:16647269 both p97 homologs interact with UFD-1/NPL-4 in a similar CDC-48(UFD-1/NPL-4) complex PMID:26842564 UBXN-3 and NPL-4 have been shown to simultaneously bind to single CDC-48 hexamers in vivo |
| GO:0097352 autophagosome maturation | IBA GO_REF:0000033 | ACCEPT | Summary: CDC-48.1 is involved in autophagosome maturation, a phylogenetically conserved function of p97/VCP proteins. Reason: p97/VCP is known to function in autophagy in mammals and other organisms. The IBA annotation reflects this conserved function. |
| GO:0000166 nucleotide binding | IEA GO_REF:0000043 | ACCEPT | Summary: CDC-48.1 contains two AAA ATPase domains that bind ATP. This general term is captured by the more specific ATP binding annotation. Reason: Nucleotide binding is an accurate but general descriptor. CDC-48.1 binds ATP through its two AAA domains. While redundant with more specific terms, this IEA annotation is not incorrect. |
| GO:0005524 ATP binding | IEA GO_REF:0000120 | ACCEPT | Summary: CDC-48.1 binds ATP through its two AAA ATPase domains (D1 and D2). ATP binding to D1 induces conformational changes that regulate D2 ATPase activity (PMID:21454554, PMID:24055316). Reason: ATP binding is essential for CDC-48.1 function and is inferred correctly from InterPro domain annotations (AAA ATPase domains). Supporting Evidence: PMID:21454554 p97 is composed of two conserved AAA (ATPases associated with diverse cellular activities) domains, which form a tandem hexameric ring |
| GO:0005634 nucleus | IEA GO_REF:0000117 | ACCEPT | Summary: Nuclear localization is inferred by machine learning and confirmed experimentally (PMID:22735043, PMID:18728180). Reason: This is a duplicate of the IBA annotation but with IEA evidence. Both are correct as CDC-48.1 localizes to both cytoplasm and nucleus. Supporting Evidence: PMID:22735043 CDC-48/p97 is required for proper meiotic chromosome segregation via controlling AIR-2/Aurora B kinase localization in Caenorhabditis elegans |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: CDC-48.1 is present in the cytoplasm where it functions in ERAD and proteasomal degradation (PMID:16647269, PMID:20977550). Reason: Cytoplasmic localization is correctly inferred from UniProt subcellular location data and confirmed by experimental studies. Supporting Evidence: PMID:20977550 UBXN-1, UBXN-2 and UBXN-3 colocalized with CDC-48 in spermatocytes but not mature sperm |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000117 | ACCEPT | Summary: CDC-48.1 associates with the ER membrane during ERAD to extract misfolded proteins for degradation (PMID:16647269). Reason: ER membrane association is consistent with CDC-48.1's role in retro-translocation during ERAD. Supporting Evidence: PMID:16647269 the AAA ATPase p97/VCP/CDC48 is required in this pathway for protein dislocation across the ER membrane |
| GO:0009792 embryo development ending in birth or egg hatching | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: CDC-48.1 is essential for embryonic development in C. elegans. RNAi knockdown causes embryonic lethality, especially when combined with cdc-48.2 depletion (PMID:16647269, PMID:18728180). Reason: While CDC-48.1 is required for embryonic development, this is a pleiotropic phenotype resulting from its core functions in ERAD, DNA replication, and cell cycle control rather than a primary developmental function. Supporting Evidence: PMID:16647269 RNAi mediated depletion of the corresponding genes induces ER stress resulting in hypersensitivity to conditions which induce increased levels of unfolded proteins in the ER lumen PMID:18728180 These developmental defects result from activation of the DNA replication checkpoint caused by replication stress |
| GO:0010498 proteasomal protein catabolic process | IEA GO_REF:0000117 | ACCEPT | Summary: CDC-48.1 facilitates proteasomal degradation by extracting ubiquitinated substrates and delivering them to the proteasome. Reason: This is a core function of CDC-48.1, closely related to its role in ERAD and ubiquitin-dependent protein degradation. Supporting Evidence: PMID:16647269 subsequent ubiquitin dependent degradation by the 26S proteasome in the cytosol |
| GO:0016787 hydrolase activity | IEA GO_REF:0000120 | ACCEPT | Summary: CDC-48.1 has ATP hydrolase (ATPase) activity through its AAA domains. This general term is subsumed by the more specific ATP hydrolysis activity. Reason: Hydrolase activity is correctly inferred from domain annotations. While redundant with ATP hydrolysis activity, it is not incorrect. |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000120 | ACCEPT | Summary: ATP hydrolysis activity is inferred from AAA ATPase domain annotations and confirmed by direct enzymatic assays (PMID:21454554). Reason: Correctly inferred core function, also supported by IDA and IBA evidence. Supporting Evidence: PMID:21454554 We characterized the ATP hydrolysis mechanism of CDC-48.1, a p97 homolog of Caenorhabditis elegans |
| GO:0017111 ribonucleoside triphosphate phosphatase activity | IEA GO_REF:0000117 | MODIFY | Summary: This term is a parent of ATP hydrolysis activity. CDC-48.1 specifically hydrolyzes ATP, not other NTPs. Reason: While technically correct as a parent term of ATP hydrolysis activity, this annotation is too general. CDC-48.1 is an ATPase; there is no evidence it has significant activity on other ribonucleoside triphosphates. Proposed replacements: ATP hydrolysis activity |
| GO:0032880 regulation of protein localization | IEA GO_REF:0000117 | ACCEPT | Summary: CDC-48.1 regulates protein localization, particularly chromatin-associated proteins like CDT-1 and AIR-2 (PMID:26842564, PMID:22735043). Reason: CDC-48.1 regulates the localization of multiple substrates through its segregase activity, extracting proteins from complexes and promoting their degradation or relocalization. Supporting Evidence: PMID:26842564 UBXN-3/FAF1 binds to the licensing factor CDT-1 and additional ubiquitylated proteins, thus promoting CDC-48/p97-dependent turnover and disassembly of DNA replication factor complexes |
| GO:0034976 response to endoplasmic reticulum stress | IEA GO_REF:0000117 | ACCEPT | Summary: CDC-48.1 is essential for the response to ER stress through its role in ERAD. Depletion causes accumulation of misfolded proteins and induction of the unfolded protein response (PMID:16647269). Reason: CDC-48.1 is a key component of the ERAD pathway that resolves ER stress by eliminating misfolded proteins. Supporting Evidence: PMID:16647269 RNAi mediated depletion of the corresponding genes induces ER stress resulting in hypersensitivity to conditions which induce increased levels of unfolded proteins in the ER lumen |
| GO:0042802 identical protein binding | IEA GO_REF:0000117 | ACCEPT | Summary: CDC-48.1 forms homohexamers through self-association (PMID:18782221, PMID:24055316). Reason: Homohexamer formation is essential for CDC-48.1 function and has been directly demonstrated biochemically. Supporting Evidence: PMID:24055316 p97 (also called VCP and CDC-48) is an AAA+ chaperone, which consists of a substrate/cofactor-binding N domain and two ATPase domains (D1 and D2), and forms a homo-hexameric ring PMID:21454554 p97 is composed of two conserved AAA (ATPases associated with diverse cellular activities) domains, which form a tandem hexameric ring |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: CDC-48.1 localizes to the perinuclear region in spermatocytes (PMID:20977550). Reason: Perinuclear localization has been directly observed by immunofluorescence. Supporting Evidence: PMID:20977550 UBXN-1, UBXN-2 and UBXN-3 colocalized with CDC-48 in spermatocytes but not mature sperm |
| GO:0098796 membrane protein complex | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: This term suggests CDC-48.1 is part of a membrane protein complex, which is not its primary form of association. Reason: While CDC-48.1 associates with the ER membrane during ERAD, it is primarily a soluble cytoplasmic/nuclear protein that transiently associates with membranes. The VCP-NPL4-UFD1 complex is the appropriate complex annotation. This annotation is misleading. |
| GO:0005515 protein binding | IPI PMID:14704431 A map of the interactome network of the metazoan C. elegans. | MARK AS OVER ANNOTATED | Summary: Protein binding detected in high-throughput Y2H interactome mapping study. Reason: "Protein binding" is too general and uninformative. CDC-48.1 has specific binding partners including UBX domain proteins, UFD-1, NPL-4, and substrates. High-throughput Y2H provides limited mechanistic insight. Supporting Evidence: PMID:14704431 more than 4000 interactions were identified from high-throughput, yeast two-hybrid (HT=Y2H) screens |
| GO:0005515 protein binding | IPI PMID:19123269 Empirically controlled mapping of the Caenorhabditis elegans... | MARK AS OVER ANNOTATED | Summary: Protein binding with CDC-48.2 (P54812) detected in Y2H interactome mapping. Reason: General protein binding is uninformative. The interaction with CDC-48.2 reflects heterohexamer formation, but this is better captured by the identical protein binding annotation. Supporting Evidence: PMID:19123269 We present an expanded Caenorhabditis elegans protein-protein interaction network, or "interactome" map derived from testing a matrix of ~ 10,000 × ~ 10,000 proteins using a highly specific high-throughput yeast two-hybrid system |
| GO:0042802 identical protein binding | IPI PMID:24055316 High-speed atomic force microscopic observation of ATP-depen... | ACCEPT | Summary: High-speed atomic force microscopy study demonstrating CDC-48.1 homohexamer formation and ATP-dependent conformational changes. Reason: This study provides direct structural evidence for CDC-48.1 self-association into hexameric rings, a core property of the protein. Supporting Evidence: PMID:24055316 we studied the conformational changes of hexameric CDC-48.1, a Caenorhabditis elegans p97 homolog, using high-speed atomic force microscopy |
| GO:0005515 protein binding | IPI PMID:25721663 Characterization of C-terminal adaptors, UFD-2 and UFD-3, of... | MODIFY | Summary: Study characterizing CDC-48 interaction with UFD-2 and UFD-3 C-terminal adaptors in regulation of polyglutamine aggregation. Reason: The study provides specific information about binding to UFD-3 adaptor. A more specific term would be informative. Proposed replacements: protein-containing complex binding Supporting Evidence: PMID:25721663 CDC-48 preferentially interacts with UFD-3 in Caenorhabditis elegans |
| GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process | IMP PMID:21673654 EGF signalling activates the ubiquitin proteasome system to ... | ACCEPT | Summary: CDC-48.1 promotes proteasomal degradation as part of the EGF signaling pathway that modulates lifespan through increased UPS activity. Reason: This captures CDC-48.1's role in facilitating proteasomal degradation, demonstrated by mutant phenotype analysis. Supporting Evidence: PMID:21673654 EGF signalling alters protein homoeostasis in adults by increasing UPS activity and polyubiquitination, while decreasing protein aggregation |
| GO:0005515 protein binding | IPI PMID:20977550 Caenorhabditis elegans UBX cofactors for CDC-48/p97 control ... | MODIFY | Summary: Study demonstrating CDC-48 interactions with multiple UBX cofactors (UBXN-1 through UBXN-6) and their role in spermatogenesis. Reason: This reflects specific binding to UBX domain adaptor proteins. More specific annotation would be preferable. Proposed replacements: protein-containing complex binding Supporting Evidence: PMID:20977550 All six UBXN proteins directly interacted with CDC-48.1 and CDC-48.2 |
| GO:0005515 protein binding | IPI PMID:23649807 The UBXN-2/p37/p47 adaptors of CDC-48/p97 regulate mitosis b... | MODIFY | Summary: Study showing UBXN-2 interaction with CDC-48 regulates Aurora A at centrosomes during mitosis. Reason: This reflects specific binding to UBXN-2 adaptor protein in the context of centrosome regulation. Proposed replacements: protein-containing complex binding Supporting Evidence: PMID:23649807 UBXN-2 and CDC-48 limit AIR-1 accumulation at centrosomes in prophase |
| GO:0034098 VCP-NPL4-UFD1 AAA ATPase complex | IDA PMID:20977550 Caenorhabditis elegans UBX cofactors for CDC-48/p97 control ... | ACCEPT | Summary: Direct evidence for CDC-48.1 forming a complex with UFD-1 and NPL-4 adaptors in C. elegans. Reason: This is well-supported by co-immunoprecipitation and functional studies showing the CDC-48/UFD-1/NPL-4 complex is essential for multiple cellular processes. Supporting Evidence: PMID:26842564 UBXN-3 and NPL-4 have been shown to simultaneously bind to single CDC-48 hexamers in vivo |
| GO:0044877 protein-containing complex binding | IDA PMID:20977550 Caenorhabditis elegans UBX cofactors for CDC-48/p97 control ... | ACCEPT | Summary: CDC-48.1 binds to protein complexes containing UBXN adaptors and substrates for extraction and processing. Reason: CDC-48.1's segregase function involves binding to and disassembling protein complexes, which is the molecular basis for this annotation. Supporting Evidence: PMID:20977550 these results suggest that UBXN-1, UBXN-2 and UBXN-3 are redundant cofactors for CDC-48/p97 and control spermatogenesis via the degradation of TRA-1A |
| GO:0045977 positive regulation of mitotic cell cycle, embryonic | IGI PMID:26842564 Chromatin-associated degradation is defined by UBXN-3/FAF1 t... | ACCEPT | Summary: CDC-48.1 promotes embryonic cell cycle progression through its role in DNA replication and degradation of replication factors. Reason: The study demonstrates that CDC-48/UBXN-3 function is required for proper S phase progression and cell cycle timing. Supporting Evidence: PMID:26842564 progression of the DNA replication fork is coordinated by UBXN-3/FAF1. UBXN-3/FAF1 binds to the licensing factor CDT-1 and additional ubiquitylated proteins, thus promoting CDC-48/p97-dependent turnover and disassembly of DNA replication factor complexes |
| GO:1905634 regulation of protein localization to chromatin | IGI PMID:26842564 Chromatin-associated degradation is defined by UBXN-3/FAF1 t... | ACCEPT | Summary: CDC-48.1 regulates the chromatin association of DNA replication factors including CDT-1 and CDC-45/GINS complex components. Reason: The study directly demonstrates CDC-48 regulates chromatin association of multiple replication factors. Supporting Evidence: PMID:26842564 inactivation of UBXN-3/FAF1 stabilizes CDT-1 and CDC-45/GINS on chromatin, causing severe defects in replication fork dynamics |
| GO:0005634 nucleus | IDA PMID:22735043 CDC-48/p97 is required for proper meiotic chromosome segrega... | ACCEPT | Summary: Direct observation of CDC-48 localization in the nucleus during meiosis and mitosis in C. elegans. Reason: Nuclear localization directly demonstrated by fluorescence microscopy. Supporting Evidence: PMID:22735043 CDC-48/p97 is required for proper meiotic chromosome segregation via controlling AIR-2/Aurora B kinase localization |
| GO:0005654 nucleoplasm | IDA PMID:22735043 CDC-48/p97 is required for proper meiotic chromosome segrega... | ACCEPT | Summary: CDC-48 localizes to the nucleoplasm where it regulates meiotic chromosome segregation. Reason: Nucleoplasmic localization is consistent with CDC-48's role in regulating chromatin-associated proteins during cell division. Supporting Evidence: PMID:22735043 CDC-48s control the restricted localization of AIR-2 to the cohesion sites of homologous chromatids in meiosis I |
| GO:0005737 cytoplasm | IDA PMID:22735043 CDC-48/p97 is required for proper meiotic chromosome segrega... | ACCEPT | Summary: CDC-48 is present in the cytoplasm as shown by immunofluorescence studies. Reason: Cytoplasmic localization directly observed. Supporting Evidence: PMID:22735043 CDC-48/p97 is a AAA (ATPases associated with diverse cellular activities) chaperone involved in protein conformational changes such as the disassembly of protein complexes |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:20977550 Caenorhabditis elegans UBX cofactors for CDC-48/p97 control ... | ACCEPT | Summary: CDC-48 localizes to the perinuclear region in spermatocytes. Reason: Perinuclear localization directly demonstrated by immunofluorescence. Supporting Evidence: PMID:20977550 UBXN-1, UBXN-2 and UBXN-3 colocalized with CDC-48 in spermatocytes but not mature sperm |
| GO:0016887 ATP hydrolysis activity | IDA PMID:18854144 An Afg2/Spaf-related Cdc48-like AAA ATPase regulates the sta... | ACCEPT | Summary: This reference studies CDC-48.3, a distinct Afg2/Spaf subfamily member, not CDC-48.1. However, ATP hydrolysis activity for CDC-48.1 is well-established by other references (PMID:21454554, PMID:18782221). Reason: Although PMID:18854144 specifically studies CDC-48.3 (not CDC-48.1), the annotation of ATP hydrolysis activity is correct for CDC-48.1 based on other direct enzymatic assays (see PMID:21454554). Supporting Evidence: PMID:18854144 This screen uncovered a member of the Afg2/Spaf subfamily of Cdc48-like AAA ATPases as an essential inhibitor of AIR-2 stability and activity |
| GO:0016887 ATP hydrolysis activity | IDA PMID:18782221 p97 Homologs from Caenorhabditis elegans, CDC-48.1 and CDC-4... | ACCEPT | Summary: Biochemical characterization of CDC-48.1 ATPase activity in the context of polyQ aggregate suppression. Reason: Direct enzymatic assay demonstrating ATPase activity. Supporting Evidence: PMID:18782221 CDC-48.1 and CDC-48.2 suppress the aggregation of a huntingtin (Htt) exon1 fragment containing an expanded polyQ repeat in vitro |
| GO:0016887 ATP hydrolysis activity | IDA PMID:21454554 Positive cooperativity of the p97 AAA ATPase is critical for... | ACCEPT | Summary: Detailed biochemical characterization of CDC-48.1 ATPase mechanism showing positive cooperativity between the two AAA domains. Reason: Comprehensive enzymatic analysis with kinetic parameters and mutagenesis defining the catalytic mechanism. Supporting Evidence: PMID:21454554 The ATPase activity of the N-terminal AAA domain was very low at physiological temperature, whereas the C-terminal AAA domain showed high ATPase activity in a coordinated fashion with positive cooperativity |
| GO:0005634 nucleus | IDA PMID:18728180 Cell cycle progression requires the CDC-48UFD-1/NPL-4 comple... | ACCEPT | Summary: Nuclear localization of CDC-48 demonstrated in the context of DNA replication and cell cycle studies. Reason: Nuclear localization directly observed, consistent with CDC-48's role in DNA replication control. Supporting Evidence: PMID:18728180 Our analysis of the CDC-48(UFD-1/NPL-4) complex identified a general role in S phase progression of mitotic cells essential for embryonic cell division and germline development of adult worms |
| GO:0009792 embryo development ending in birth or egg hatching | IGI PMID:16647269 A conserved role of Caenorhabditis elegans CDC-48 in ER-asso... | KEEP AS NON CORE | Summary: CDC-48.1 is required for embryonic development, with combined cdc-48.1/cdc-48.2 depletion causing embryonic lethality. Reason: Embryonic lethality is a pleiotropic phenotype reflecting CDC-48's essential roles in ERAD, cell cycle, and proteostasis rather than a specific developmental function. Supporting Evidence: PMID:16647269 RNAi mediated depletion of the corresponding genes induces ER stress resulting in hypersensitivity to conditions which induce increased levels of unfolded proteins in the ER lumen |
| GO:0034098 VCP-NPL4-UFD1 AAA ATPase complex | IPI PMID:16647269 A conserved role of Caenorhabditis elegans CDC-48 in ER-asso... | ACCEPT | Summary: Physical interaction between CDC-48 and UFD-1 demonstrated, establishing the C. elegans CDC-48/UFD-1/NPL-4 complex. Reason: Direct physical interaction evidence for complex formation. Supporting Evidence: PMID:16647269 both p97 homologs interact with UFD-1/NPL-4 in a similar CDC-48(UFD-1/NPL-4) complex |
| GO:0036503 ERAD pathway | IGI PMID:16647269 A conserved role of Caenorhabditis elegans CDC-48 in ER-asso... | ACCEPT | Summary: CDC-48.1 is a core component of the ERAD pathway in C. elegans, required for degradation of misfolded ER proteins. Reason: ERAD is a primary, well-established function of CDC-48/p97 proteins across eukaryotes. Direct genetic evidence supports this in C. elegans. Supporting Evidence: PMID:16647269 these data suggest an evolutionarily conserved retro-translocation machinery at the endoplasmic reticulum |
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Download this section (compressed HTML)Q: What is the specific mechanism by which CDC-48.1 extracts AIR-2 from chromatin during meiosis?
Q: How do different UBX domain adaptors determine CDC-48.1 substrate specificity?
Q: What is the relationship between CDC-48.1 and CDC-48.2 in terms of functional redundancy and hetero-oligomer formation?
Experiment: Determine crystal structure of CDC-48.1 with different UBX adaptors to understand substrate selection
Experiment: Identify the complete set of CDC-48.1 substrates using proximity labeling approaches
Experiment: Test whether CDC-48.1 chaperone activity (ATP-independent) contributes to polyQ suppression in vivo
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