UFD1 (Ubiquitin recognition factor in ER-associated degradation protein 1; also UFD1L, ubiquitin fusion degradation protein 1) is an essential ubiquitin-binding cofactor of the AAA+ ATPase VCP/p97. It forms the obligate UFD1-NPL4 heterodimer, the principal substrate-recruiting adaptor of p97, and with VCP constitutes the VCP-NPL4-UFD1 segregase. UFD1 binds (poly)ubiquitin and, together with NPL4, recognizes ubiquitinated substrates and presents them to p97 for ATP-driven extraction and unfolding, after which they are degraded by the proteasome. The complex is central to endoplasmic-reticulum-associated degradation (ERAD), driving retrotranslocation of misfolded proteins from the ER to the cytosol, and participates in many other p97-dependent processes including the cellular response to misfolded proteins, ribosome-associated quality control, spindle disassembly and nuclear-envelope reformation at the end of mitosis, and Golgi membrane reassembly. UFD1 also contributes to a non-canonical p97 function in innate immunity, acting (with NPLOC4/VCP) as a negative regulator of type I interferon production by binding RIG-I (RIGI) and recruiting RNF125 for its degradation, and it couples the ER stress response to cell-cycle control via interaction with USP13. The gene lies within the 3q29 / DiGeorge (22q11)-associated genomic context and is developmentally expressed. UFD1 localizes to the cytosol, ER and nucleus.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0036503 ERAD pathway | IBA GO_REF:0000033 | ACCEPT | Summary: UFD1 (with NPL4/VCP) is a core component of ERAD, driving retrotranslocation of misfolded ER proteins. Reason: Core process supported by UniProt function and experimental evidence. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt necessary for the export of misfolded proteins from the ER to the |
| GO:0031593 polyubiquitin modification-dependent protein binding | IBA GO_REF:0000033 | ACCEPT | Summary: UFD1 binds polyubiquitin chains, the core molecular function letting the UFD1-NPL4 heterodimer recognize ubiquitinated substrates for p97. Reason: Directly supported; UFD1 is a ubiquitin-recognition factor that binds ubiquitinated proteins. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt The ternary complex containing UFD1, VCP and NPLOC4 binds |
| GO:0034098 VCP-NPL4-UFD1 AAA ATPase complex | IBA GO_REF:0000033 | ACCEPT | Summary: UFD1 is a defining subunit of the VCP-NPL4-UFD1 segregase complex. Reason: Core complex membership, well documented. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt VCP-NPL4-UFD1 AAA ATPase complex |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Nuclear localization, consistent with nuclear p97 functions. Reason: Documented nuclear localization; the adaptor acts in multiple compartments, so retained as non-core. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt SUBCELLULAR LOCATION: Nucleus |
| GO:0005829 cytosol | IEA GO_REF:0000044 | ACCEPT | Summary: Cytosolic localization, the principal compartment where the p97 segregase operates. Reason: Cytosolic localization is well supported and is the major site of the adaptor function. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt Cytoplasm, cytosol |
| GO:0006511 ubiquitin-dependent protein catabolic process | IEA GO_REF:0000002 | ACCEPT | Summary: UFD1 is integral to ubiquitin-dependent proteasomal degradation as the p97 substrate-recruiting cofactor. Reason: Core biological-process role. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt ubiquitin-dependent proteolytic |
| GO:0030970 retrograde protein transport, ER to cytosol | IEA GO_REF:0000117 | ACCEPT | Summary: UFD1 (with NPL4/VCP) mediates retrotranslocation of misfolded proteins from the ER to the cytosol. Reason: Directly supported core process. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt necessary for the export of misfolded proteins from the ER to the |
| GO:0005515 protein binding | IPI PMID:18775313 UBXD7 binds multiple ubiquitin ligases and implicates p97 in... | KEEP AS NON CORE | Summary: Interaction with VCP (P55072) and NPLOC4 (Q8TAT6), the core complex partners. Bare protein binding term. Reason: Central interactions but bare protein binding is uninformative; captured by the complex annotations. Supporting Evidence: file:human/UFD1/UFD1-goa.tsv UniProtKB:P55072 |
| GO:0005515 protein binding | IPI PMID:20414249 Imbalances in p97 co-factor interactions in human proteinopa... | KEEP AS NON CORE | Summary: Interaction with VCP and NPLOC4 captured as bare protein binding. Reason: Central interactions but bare protein binding is uninformative. Supporting Evidence: file:human/UFD1/UFD1-goa.tsv UniProtKB:P55072 |
| GO:0005515 protein binding | IPI PMID:21645854 Hierarchical binding of cofactors to the AAA ATPase p97. | KEEP AS NON CORE | Summary: Interaction with NPLOC4 (Q8TAT6) captured as bare protein binding. Reason: Central interaction but bare protein binding is uninformative. Supporting Evidence: file:human/UFD1/UFD1-goa.tsv UniProtKB:Q8TAT6 |
| GO:0005515 protein binding | IPI PMID:25959826 Quantitative interaction proteomics of neurodegenerative dis... | KEEP AS NON CORE | Summary: Interaction with huntingtin (HTT, P42858). Bare protein binding term. Reason: A documented interaction but bare protein binding is uninformative and not part of the core function. Supporting Evidence: file:human/UFD1/UFD1-goa.tsv UniProtKB:P42858 |
| GO:0005515 protein binding | IPI PMID:26712280 Characterization of an Additional Binding Surface on the p97... | KEEP AS NON CORE | Summary: Interaction with VCP (P55072). Bare protein binding term. Reason: Central interaction but bare protein binding is uninformative. Supporting Evidence: file:human/UFD1/UFD1-goa.tsv UniProtKB:P55072 |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI interactome interaction with NPLOC4 (Q8TAT6). Bare protein binding. Reason: High-throughput interaction; bare protein binding is uninformative. Supporting Evidence: file:human/UFD1/UFD1-goa.tsv UniProtKB:Q8TAT6 |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: Neurodegeneration interactome interaction with HTT (P42858). Bare protein binding. Reason: High-throughput interaction; bare protein binding is uninformative. Supporting Evidence: file:human/UFD1/UFD1-goa.tsv UniProtKB:P42858 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: BioPlex interactome interactions (VCP, NPLOC4). Bare protein binding. Reason: High-throughput interactions; bare protein binding is uninformative. Supporting Evidence: file:human/UFD1/UFD1-goa.tsv UniProtKB:P55072 |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | KEEP AS NON CORE | Summary: Interactome interaction with VCP (P55072). Bare protein binding. Reason: High-throughput interaction; bare protein binding is uninformative. Supporting Evidence: file:human/UFD1/UFD1-goa.tsv UniProtKB:P55072 |
| GO:0005515 protein binding | IPI PMID:37776851 Analysis of proteome-wide degradation dynamics in ALS SOD1 i... | KEEP AS NON CORE | Summary: Interactome interaction with VCP (P55072). Bare protein binding. Reason: High-throughput interaction; bare protein binding is uninformative. Supporting Evidence: file:human/UFD1/UFD1-goa.tsv UniProtKB:P55072 |
| GO:0005737 cytoplasm | IEA GO_REF:0000107 | ACCEPT | Summary: Cytoplasmic localization, consistent with the cytosolic site of segregase action. Reason: Cytoplasmic/cytosolic localization is well supported. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt Cytoplasm, cytosol |
| GO:0034098 VCP-NPL4-UFD1 AAA ATPase complex | IEA GO_REF:0000120 | ACCEPT | Summary: UFD1 is part of the VCP-NPL4-UFD1 complex. Reason: Core complex membership. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt VCP-NPL4-UFD1 AAA ATPase complex |
| GO:0036435 K48-linked polyubiquitin modification-dependent protein binding | IEA GO_REF:0000107 | ACCEPT | Summary: UFD1 (in UFD1-NPL4) recognizes K48-linked polyubiquitin, the canonical degradation signal presented to p97. Reason: Consistent with the well-established K48-linked polyubiquitin recognition by the UFD1-NPL4 cofactor. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt The ternary complex containing UFD1, VCP and NPLOC4 binds |
| GO:0036501 UFD1-NPL4 complex | IEA GO_REF:0000120 | ACCEPT | Summary: UFD1 forms an obligate heterodimer with NPLOC4 (the UFD1-NPL4 complex). Reason: Core complex membership. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt Heterodimer with NPLOC4 |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | IEA GO_REF:0000041 | ACCEPT | Summary: UFD1-mediated substrate extraction feeds proteasomal degradation. Reason: Core process; the segregase delivers extracted substrates to the proteasome. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt where they are degraded by the proteasome |
| GO:0006511 ubiquitin-dependent protein catabolic process | NAS PMID:28819009 The AAA+ ATPase p97, a cellular multitool. | ACCEPT | Summary: p97 review describing UFD1-NPL4 in ubiquitin-dependent degradation. Reason: Consistent with the core degradative role. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt where they are degraded by the proteasome |
| GO:0006511 ubiquitin-dependent protein catabolic process | NAS PMID:33712450 The p97-UBXN1 complex regulates aggresome formation. | ACCEPT | Summary: p97-UBXN1 aggresome study placing UFD1 in ubiquitin-dependent degradation. Reason: Consistent with the core degradative role of the p97 machinery. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt where they are degraded by the proteasome |
| GO:0034098 VCP-NPL4-UFD1 AAA ATPase complex | IPI PMID:18775313 UBXD7 binds multiple ubiquitin ligases and implicates p97 in... | ACCEPT | Summary: Experimental (IPI) demonstration of UFD1 within the VCP-NPL4-UFD1 complex. Reason: Core complex membership supported by direct interaction evidence. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt VCP-NPL4-UFD1 AAA ATPase complex |
| GO:0034098 VCP-NPL4-UFD1 AAA ATPase complex | IPI PMID:20414249 Imbalances in p97 co-factor interactions in human proteinopa... | ACCEPT | Summary: Experimental (IPI) demonstration of UFD1 within the VCP-NPL4-UFD1 complex. Reason: Core complex membership supported by direct interaction evidence. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt VCP-NPL4-UFD1 AAA ATPase complex |
| GO:0034098 VCP-NPL4-UFD1 AAA ATPase complex | NAS PMID:28819009 The AAA+ ATPase p97, a cellular multitool. | ACCEPT | Summary: p97 review describing the VCP-NPL4-UFD1 complex. Reason: Core complex membership. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt VCP-NPL4-UFD1 AAA ATPase complex |
| GO:0034098 VCP-NPL4-UFD1 AAA ATPase complex | IPI PMID:39329031 Study of Clinical Characteristics of Intellectual Disability... | ACCEPT | Summary: ComplexPortal-curated complex membership. The cited PMID:39329031 (an intellectual-disability clinical study from Morocco) does not concern the p97 complex and appears to be a mis-citation, though the complex membership is well established. Reason: UFD1 is unambiguously part of the VCP-NPL4-UFD1 complex; the complex assertion is accepted while the attached reference is a wrong-identifier citation (flagged in reference_review). Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt VCP-NPL4-UFD1 AAA ATPase complex |
| GO:0036503 ERAD pathway | NAS PMID:28819009 The AAA+ ATPase p97, a cellular multitool. | ACCEPT | Summary: p97 review describing UFD1-NPL4's role in ERAD. Reason: Core process. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt necessary for the export of misfolded proteins from the ER to the |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | NAS PMID:39329031 Study of Clinical Characteristics of Intellectual Disability... | ACCEPT | Summary: ComplexPortal-curated process annotation; the attached PMID:39329031 is a mis-citation, but the proteasomal degradation role is correct. Reason: UFD1 participates in proteasome-mediated degradation as a p97 cofactor; assertion accepted, reference flagged as wrong identifier. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt where they are degraded by the proteasome |
| GO:1904949 ATPase complex | NAS PMID:28819009 The AAA+ ATPase p97, a cellular multitool. | KEEP AS NON CORE | Summary: UFD1 is part of an AAA+ ATPase (p97) complex. Reason: Generic parent of the specific VCP-NPL4-UFD1 complex annotation. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt VCP-NPL4-UFD1 AAA ATPase complex |
| GO:1904949 ATPase complex | NAS PMID:33712450 The p97-UBXN1 complex regulates aggresome formation. | KEEP AS NON CORE | Summary: UFD1 is part of an AAA+ ATPase (p97) complex. Reason: Generic parent of the specific complex annotation. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt VCP-NPL4-UFD1 AAA ATPase complex |
| GO:1904949 ATPase complex | NAS PMID:39329031 Study of Clinical Characteristics of Intellectual Disability... | KEEP AS NON CORE | Summary: UFD1 is part of an AAA+ ATPase complex; the attached PMID:39329031 is a mis-citation. Reason: Generic parent of the specific complex annotation; reference flagged as wrong identifier. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt VCP-NPL4-UFD1 AAA ATPase complex |
| GO:0005634 nucleus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity-inferred nuclear localization. Reason: Consistent with documented nuclear localization; non-core. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt SUBCELLULAR LOCATION: Nucleus |
| GO:0072344 rescue of stalled cytosolic ribosome | NAS PMID:35452614 Ribosome-associated quality-control mechanisms from bacteria... | KEEP AS NON CORE | Summary: UFD1/p97 participates in ribosome-associated quality control, extracting ubiquitinated nascent chains/factors from stalled ribosomes. Reason: A genuine p97-dependent RQC role per the cited review, but one of many p97 processes; non-core relative to the ubiquitin-binding adaptor function. Supporting Evidence: PMID:35452614 Ribosome-associated quality-control mechanisms from bacteria to humans |
| GO:1990112 RQC complex | NAS PMID:35452614 Ribosome-associated quality-control mechanisms from bacteria... | KEEP AS NON CORE | Summary: Annotation placing UFD1 in the ribosome-associated quality-control (RQC) complex. Reason: p97-UFD1-NPL4 functions with RQC but is a recruited cofactor module rather than a constitutive core RQC subunit; non-core. Supporting Evidence: PMID:35452614 Ribosome-associated quality-control mechanisms from bacteria to humans |
| GO:1990116 ribosome-associated ubiquitin-dependent protein catabolic process | NAS PMID:35452614 Ribosome-associated quality-control mechanisms from bacteria... | KEEP AS NON CORE | Summary: UFD1/p97 extracts ubiquitinated nascent chains for degradation in RQC. Reason: A genuine p97-dependent RQC process; non-core relative to the general adaptor function. Supporting Evidence: PMID:35452614 Ribosome-associated quality-control mechanisms from bacteria to humans |
| GO:0036503 ERAD pathway | IMP PMID:24089527 Caveolin-1 interacts with Derlin-1 and promotes ubiquitinati... | ACCEPT | Summary: UFD1 functions in ERAD, demonstrated in a p97-dependent degradation context (caveolin-1/Derlin-1/COX-2). Reason: Experimentally supported (IMP) core process. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt necessary for the export of misfolded proteins from the ER to the |
| GO:0071218 cellular response to misfolded protein | IMP PMID:24089527 Caveolin-1 interacts with Derlin-1 and promotes ubiquitinati... | ACCEPT | Summary: UFD1 participates in the cellular response to misfolded proteins as part of the p97 degradation machinery. Reason: Experimentally supported; consistent with UFD1's role in clearing misfolded proteins. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt necessary for the export of misfolded proteins from the ER to the |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9755507 | ACCEPT | Summary: Reactome cytosolic localization. Reason: Cytosol is a principal site of segregase function. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt Cytoplasm, cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9758088 | ACCEPT | Summary: Reactome cytosolic localization. Reason: Cytosol is a principal site of segregase function. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt Cytoplasm, cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9758090 | ACCEPT | Summary: Reactome cytosolic localization. Reason: Cytosol is a principal site of segregase function. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt Cytoplasm, cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9948427 | ACCEPT | Summary: Reactome cytosolic localization. Reason: Cytosol is a principal site of segregase function. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt Cytoplasm, cytosol |
| GO:0006511 ubiquitin-dependent protein catabolic process | IMP PMID:26471729 A non-canonical role of the p97 complex in RIG-I antiviral s... | ACCEPT | Summary: UFD1 (with NPLOC4/VCP) promotes ubiquitin-dependent degradation of RIG-I. Reason: Directly supported by IMP; the p97-UFD1-NPL4 complex drives ubiquitin-dependent RIG-I degradation. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt recruits RNF125 to promote ubiquitination and degradation of |
| GO:0032480 negative regulation of type I interferon production | IMP PMID:26471729 A non-canonical role of the p97 complex in RIG-I antiviral s... | KEEP AS NON CORE | Summary: Through RIG-I degradation, UFD1/p97 negatively regulates type I interferon production. Reason: A genuine, experimentally supported signaling role, but specialized relative to the core p97 cofactor function. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt Acts as a negative regulator of type I interferon production |
| GO:0034098 VCP-NPL4-UFD1 AAA ATPase complex | IDA PMID:26471729 A non-canonical role of the p97 complex in RIG-I antiviral s... | ACCEPT | Summary: Direct demonstration of UFD1 within the VCP-NPL4-UFD1 complex. Reason: Core complex membership supported by direct evidence. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt VCP-NPL4-UFD1 AAA ATPase complex |
| GO:0039536 negative regulation of RIG-I signaling pathway | IMP PMID:26471729 A non-canonical role of the p97 complex in RIG-I antiviral s... | KEEP AS NON CORE | Summary: UFD1/p97 negatively regulates RIG-I signaling by promoting RIG-I degradation. Reason: A genuine specialized signaling role; non-core relative to the general p97 cofactor function. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt Acts as a negative regulator of type I interferon |
| GO:0036501 UFD1-NPL4 complex | IPI PMID:11574150 Cloning and characterization of the gene encoding human NPL4... | ACCEPT | Summary: Original study demonstrating UFD1 interacts with NPL4 (the UFD1-NPL4 heterodimer). Reason: Core complex membership supported by direct interaction evidence. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt Heterodimer with NPLOC4 |
| GO:0005515 protein binding | IPI PMID:11574150 Cloning and characterization of the gene encoding human NPL4... | KEEP AS NON CORE | Summary: Interaction with NPLOC4 (Q8TAT6). Bare protein binding term. Reason: The NPLOC4 interaction is central but bare protein binding is uninformative; captured by the UFD1-NPL4 complex annotation. Supporting Evidence: file:human/UFD1/UFD1-goa.tsv UniProtKB:Q8TAT6 |
| GO:0030970 retrograde protein transport, ER to cytosol | IMP PMID:25660456 Identification of ERAD components essential for dislocation ... | ACCEPT | Summary: UFD1 is required for dislocation of an ERAD substrate (null Hong Kong alpha-1-antitrypsin) from the ER to the cytosol. Reason: Directly supported by IMP in an ERAD dislocation assay; a core process. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt necessary for the export of misfolded proteins from the ER to the |
| GO:0034098 VCP-NPL4-UFD1 AAA ATPase complex | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence-similarity-inferred complex membership. Reason: Core complex membership corroborated by direct evidence. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt VCP-NPL4-UFD1 AAA ATPase complex |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5654985 | KEEP AS NON CORE | Summary: Reactome nucleoplasmic localization. Reason: Consistent with nuclear p97 functions; non-core. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt GO:0005654; C:nucleoplasm |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5654989 | KEEP AS NON CORE | Summary: Reactome nucleoplasmic localization. Reason: Consistent with nuclear p97 functions; non-core. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt GO:0005654; C:nucleoplasm |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6781922 | KEEP AS NON CORE | Summary: Reactome nucleoplasmic localization. Reason: Consistent with nuclear p97 functions; non-core. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt GO:0005654; C:nucleoplasm |
| GO:0005634 nucleus | HDA PMID:21630459 Proteomic characterization of the human sperm nucleus. | KEEP AS NON CORE | Summary: High-throughput direct-assay nuclear localization. Reason: Consistent with documented nuclear localization; non-core. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt SUBCELLULAR LOCATION: Nucleus |
| GO:0005515 protein binding | IPI PMID:17681147 Ufd1 is a cofactor of gp78 and plays a key role in cholester... | KEEP AS NON CORE | Summary: Interaction with USP13 (Q9UKV5), which couples the ER stress response to cell-cycle control. Bare protein binding term. Reason: A documented, functionally relevant interaction (USP13), but bare protein binding is uninformative. Supporting Evidence: file:human/UFD1/UFD1-goa.tsv UniProtKB:Q9UKV5 |
| GO:0001501 skeletal system development | TAS PMID:10024240 A molecular pathway revealing a genetic basis for human card... | KEEP AS NON CORE | Summary: Legacy annotation linking UFD1L to skeletal/developmental phenotypes in the DiGeorge/22q11 deletion context. Reason: UFD1L lies in the 22q11/DiGeorge-associated region and is developmentally expressed; a developmental-phenotype association exists but is far removed from the gene's direct molecular function. Retained as non-core (developmental/disease context). Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt developmentally expressed |
| GO:0004843 cysteine-type deubiquitinase activity | TAS PMID:9063746 UFD1L, a developmentally expressed ubiquitination gene, is d... | REMOVE | Summary: Legacy (2003 PINC, TAS) annotation asserting UFD1 has cysteine-type deubiquitinase activity. UFD1 is a ubiquitin-recognition adaptor with no catalytic protease domain and is not a deubiquitinase; this is a mis-annotation likely conflating the broader ubiquitin-fusion-degradation pathway with a catalytic DUB activity. Reason: UFD1 is a non-catalytic ubiquitin-binding cofactor of p97 (UFD1 family; no peptidase domain). No experimental evidence supports intrinsic deubiquitinase activity; the original UFD1L paper (PMID:9063746) characterizes a developmentally expressed ubiquitination-pathway gene, not a DUB. This molecular-function annotation is incorrect. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt Ubiquitin recognition factor in ER-associated degradation protein 1 |
| GO:0006511 ubiquitin-dependent protein catabolic process | TAS PMID:9063746 UFD1L, a developmentally expressed ubiquitination gene, is d... | ACCEPT | Summary: UFD1L participates in ubiquitin-dependent protein degradation, the pathway for which it was named (ubiquitin fusion degradation). Reason: Correct core process; UFD1 is an essential component of the ubiquitin-dependent proteolytic pathway. Supporting Evidence: file:human/UFD1/UFD1-uniprot.txt ubiquitin-dependent proteolytic |
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Download this section (compressed HTML)Q: How do UFD1 and NPL4 cooperate to unfold the initiating ubiquitin and engage the p97 pore, and what is the division of labor between the two subunits in substrate selection?
Q: Does the USP13 interaction reflect a regulated deubiquitination step that edits UFD1-bound substrates, coupling ER stress to cell-cycle control?
Q: What is the basis of the historical cysteine-type deubiquitinase annotation, and should related UFD1 orthologs carrying it be corrected?
Experiment: Reconstituted ERAD/retrotranslocation assays with UFD1 ubiquitin-binding mutants to dissect its contribution (vs NPL4) to substrate engagement and extraction.
Experiment: Quantitative interaction proteomics across stress conditions to map UFD1-specific cofactor and substrate partners distinct from NPL4.
Experiment: Biochemical assay testing purified UFD1 for any intrinsic isopeptidase activity to formally confirm the absence of deubiquitinase function.
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