NBR1 (Next to BRCA1 gene 1 protein) is a multidomain ubiquitin-binding selective autophagy receptor (cargo receptor) that, together with and parallel to its partner SQSTM1/p62, bridges ubiquitinated cargo to the ATG8/LC3 family on the forming autophagosome. Its domain architecture comprises an N-terminal PB1 domain that mediates self-oligomerization and heterodimerization with SQSTM1/p62, a ZZ-type zinc finger, two ATG8/LC3-interacting (LIR) regions that bind MAP1LC3A/B/C and GABARAP/GABARAPL1/GABARAPL2, and a C-terminal ubiquitin-associated (UBA) domain that binds K48- and K63-linked polyubiquitin. By simultaneously engaging polyubiquitinated substrates through its UBA domain and lipidated ATG8 proteins through its LIR motifs, NBR1 delivers ubiquitinated proteins to autophagosomes and also nucleates ubiquitin-positive condensates, promoting the formation of protein aggregates that are then cleared by macroautophagy (aggrephagy). NBR1 is predominantly cytoplasmic/cytosolic and is found at the phagophore assembly site and within autophagosomes, is delivered to and degraded in lysosomes, and additionally localizes to peroxisomal membranes (where it acts with p62 as a receptor for ubiquitinated PEX5 during pexophagy), to late endosomes, and, in striated muscle, to the sarcomeric M line in association with titin. Beyond bulk and aggregate clearance, NBR1 mediates selective autophagic degradation of specific innate-immune signaling factors, targeting ubiquitinated IRF3 and MAVS to autophagosomes and thereby negatively regulating type I interferon production; this pathway is exploited by influenza A virus, whose PB1 protein hijacks NBR1 to degrade MAVS. NBR1 also clears the senescence-associated factor SRBD1 and acts as a PB1-domain signaling scaffold in additional contexts. Its aggregation-promoting activity is modulated by GSK3-mediated phosphorylation at Thr-586. Through orthology, NBR1 is also implicated in p38/MAPK scaffolding and in the negative regulation of osteoblast differentiation and bone mineralization.
Definition: An autophagy cargo adaptor activity in which the adaptor bridges a ubiquitinated peroxisomal protein (such as ubiquitinated PEX5) or peroxisomal membrane to a phagophore-conjugated ATG8-family protein, targeting the peroxisome for selective autophagic degradation (pexophagy).
Justification: NBR1 (with SQSTM1) acts as the receptor for ubiquitinated PEX5 / peroxisomal membrane proteins during pexophagy (Reactome R-HSA-9664873), a specific selective-autophagy role not captured by the generic GO:0160247 autophagy cargo adaptor activity.
Parent term: autophagy cargo adaptor activity
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000407 phagophore assembly site | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (PAN-GO) inference that NBR1 is active at the phagophore assembly site, where the autophagy receptor engages cargo and ATG8 during autophagosome biogenesis. Reason: Consistent with NBR1's well-established role as a selective autophagy cargo receptor that functions at the site of autophagosome formation; corroborated by ATG8/LC3 binding and in vitro autophagy-initiation data. Supporting Evidence: PMID:34471133 roles of p62, NBR1 and TAX1BP1 in ubiquitin condensate formation and autophagy initiation |
| GO:0016236 macroautophagy | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of involvement in macroautophagy, the core process in which NBR1 functions as a selective cargo receptor. Reason: Core biological process; directly supported by experimental evidence that NBR1 mediates autophagosomal degradation of ubiquitinated substrates. Supporting Evidence: PMID:19250911 NBR1 and p62 act as receptors for selective autophagosomal degradation of |
| GO:0043130 ubiquitin binding | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of ubiquitin binding, the core molecular function of the UBA domain that recognizes K48/K63 polyubiquitin on cargo. Reason: Core molecular function; experimentally demonstrated for the NBR1 UBA domain, redundant with the IDA annotation. Supporting Evidence: PMID:19427866 the nbr1 UBA domain binds to lysine-48 and -63 linked polyubiquitin-B chains |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic transfer of cytoplasmic localization from the UniProt subcellular location, the dominant compartment where NBR1 operates. Reason: Correct but generic; the more specific cytosol and autophagosome/phagophore localizations better capture NBR1's site of action. Supporting Evidence: file:human/NBR1/NBR1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005764 lysosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic transfer of lysosomal localization; NBR1 is delivered to lysosomes with its cargo and degraded there. Reason: Experimentally supported endpoint localization (NBR1 is degraded in lysosomes) but reflects cargo delivery rather than a distinct functional compartment. Supporting Evidence: file:human/NBR1/NBR1-uniprot.txt Is targeted to lysosomes for degradation |
| GO:0005776 autophagosome | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic assignment (multiple IEA methods) of autophagosome localization, where NBR1 is sequestered with cargo via ATG8/LC3 binding. Reason: Correct and functionally central localization; NBR1 binds lipidated ATG8 proteins and is incorporated into autophagosomes. Supporting Evidence: file:human/NBR1/NBR1-uniprot.txt Cytoplasmic vesicle, autophagosome |
| GO:0005778 peroxisomal membrane | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA machine-learning assignment of peroxisomal membrane localization, consistent with NBR1's role with p62 as a receptor for ubiquitinated peroxisomal proteins during pexophagy. Reason: Functionally grounded localization tied to the pexophagy role (a specific selective-autophagy substrate), corroborated by the Reactome pexophagy reactions; secondary to the general cytosolic receptor function. Supporting Evidence: Reactome:R-HSA-9664881 NBR1 binds ATM:Ub-p-PEX5:SQSTM1 |
| GO:0008270 zinc ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro-based electronic assignment of zinc ion binding, reflecting the ZZ-type zinc finger that coordinates two Zn2+ ions. Reason: Structurally supported (ZZ-type zinc finger with eight coordinating residues) but a structural/cofactor-binding property rather than the receptor's core cargo-bridging function. Supporting Evidence: file:human/NBR1/NBR1-uniprot.txt ZN_FING 212..264 |
| GO:0031430 M band | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic transfer of sarcomeric M-line localization (by similarity to the mouse ortholog), reflecting NBR1's titin-associated role in striated muscle. Reason: Tissue-specific (cardiac/skeletal muscle) localization in association with titin; a real but secondary, non-core compartment relative to the general autophagy-receptor function. Supporting Evidence: file:human/NBR1/NBR1-uniprot.txt Cytoplasm, myofibril, sarcomere, M line |
| GO:0005515 protein binding | IPI PMID:19250911 A role for NBR1 in autophagosomal degradation of ubiquitinat... | KEEP AS NON CORE | Summary: Interactions with SQSTM1/p62 (PB1-PB1) and ATG8-family proteins (MAP1LC3A/B/C, GABARAP, GABARAPL1/2) from the foundational autophagy-receptor study. Bare protein binding is uninformative. Reason: Records functionally central interactions (p62 and ATG8 proteins) underpinning the receptor function, but the bare protein binding term is uninformative per curation guidelines; captured better by ubiquitin binding and the cargo-receptor function. Supporting Evidence: file:human/NBR1/NBR1-uniprot.txt Interacts with SQSTM1 (PubMed:19250911) |
| GO:0005515 protein binding | IPI PMID:19427866 Interactions with LC3 and polyubiquitin chains link nbr1 to ... | KEEP AS NON CORE | Summary: Interactions with LC3-A, polyubiquitin, USP8 and p14/Robld3. Bare protein binding is uninformative. Reason: Records real interactions (LC3, USP8) but bare protein binding is uninformative; the informative content is captured by ubiquitin binding and ATG8 binding. Supporting Evidence: PMID:19427866 Nbr1 also binds to the autophagic effector protein LC3-A via a novel binding site |
| GO:0005515 protein binding | IPI PMID:20010802 Nix is a selective autophagy receptor for mitochondrial clea... | KEEP AS NON CORE | Summary: Interaction reported in the Nix/mitophagy receptor study (NBR1 in the LC3/GABARAP receptor network). Bare protein binding is uninformative. Reason: High-relevance receptor-network context but bare protein binding is uninformative. Supporting Evidence: PMID:20010802 the mitochondrial protein Nix is a selective autophagy receptor by binding to |
| GO:0005515 protein binding | IPI PMID:20368287 Interactome mapping of the phosphatidylinositol 3-kinase-mam... | KEEP AS NON CORE | Summary: Interaction from a PI3K-mTOR pathway interactome map. Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative. Supporting Evidence: PMID:20368287 Interactome mapping of the phosphatidylinositol 3-kinase |
| GO:0005515 protein binding | IPI PMID:20417604 The selective macroautophagic degradation of aggregated prot... | KEEP AS NON CORE | Summary: Interaction in the Alfy/WDFY3 aggrephagy scaffold study (NBR1/p62-positive aggregate clearance). Bare protein binding is uninformative. Reason: Relevant aggrephagy context (Alfy bridges p62/NBR1 aggregates to the autophagy machinery) but bare protein binding is uninformative. Supporting Evidence: PMID:20417604 Alfy is recruited to intracellular inclusions and scaffolds a complex between |
| GO:0005515 protein binding | IPI PMID:20562859 Network organization of the human autophagy system. | KEEP AS NON CORE | Summary: Interaction from a network analysis of the human autophagy system. Bare protein binding is uninformative. Reason: Autophagy-network interactome; bare protein binding is uninformative. Supporting Evidence: PMID:20562859 Network organization of the human autophagy system |
| GO:0005515 protein binding | IPI PMID:20808283 NBR1 is a new PB1 signalling adapter in Th2 differentiation ... | KEEP AS NON CORE | Summary: Interaction(s) from the Th2/PB1 signalling adapter study. Bare protein binding is uninformative. Reason: Relevant to NBR1's PB1-domain signaling-adapter role in Th2 differentiation but bare protein binding is uninformative. Supporting Evidence: PMID:20808283 NBR1 is a new PB1 signalling adapter in Th2 differentiation |
| GO:0005515 protein binding | IPI PMID:24879152 Phosphorylation of NBR1 by GSK3 modulates protein aggregatio... | KEEP AS NON CORE | Summary: Interaction with GSK3 (which phosphorylates NBR1 at Thr-586 to modulate aggregation). Bare protein binding is uninformative. Reason: Records a functionally relevant GSK3 interaction but bare protein binding is uninformative. Supporting Evidence: PMID:24879152 NBR1 phosphorylation by GSK3 at Thr586 prevents the aggregation of ubiquitinated proteins |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: High-throughput proteome-scale (HuRI) interactome interaction. Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative. Supporting Evidence: PMID:25416956 A proteome-scale map of the human interactome network |
| GO:0005515 protein binding | IPI PMID:29568061 An AP-MS- and BioID-compatible MAC-tag enables comprehensive... | KEEP AS NON CORE | Summary: Interaction/localization from a MAC-tag (AP-MS/BioID) study. Bare protein binding is uninformative. Reason: High-throughput proximity/interaction mapping; bare protein binding is uninformative. Supporting Evidence: PMID:29568061 MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations |
| GO:0005515 protein binding | IPI PMID:30824926 Isoform-specific GSK3A activity is negatively correlated wit... | KEEP AS NON CORE | Summary: GSK3A-related interaction from a sperm-motility study. Bare protein binding is uninformative. Reason: Records a GSK3A interaction context but bare protein binding is uninformative. Supporting Evidence: PMID:30824926 Isoform-specific GSK3A activity is negatively correlated with human sperm |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: High-throughput cell-specific (BioPlex) interactome interaction. Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative. Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome |
| GO:0005515 protein binding | IPI PMID:34524948 Global Proximity Interactome of the Human Macroautophagy Pat... | KEEP AS NON CORE | Summary: Proximity-interactome interaction from a global map of the human macroautophagy pathway. Bare protein binding is uninformative. Reason: High-relevance macroautophagy proximity interactome but bare protein binding is uninformative. Supporting Evidence: PMID:34524948 Global Proximity Interactome of the Human Macroautophagy Pathway |
| GO:0000407 phagophore assembly site | IEA GO_REF:0000107 | ACCEPT | Summary: Electronic transfer (Ensembl Compara) of phagophore assembly site localization, where NBR1 functions during autophagosome formation. Reason: Correct and functionally central localization; redundant with the IBA phagophore assembly site annotation. Supporting Evidence: PMID:34471133 roles of p62, NBR1 and TAX1BP1 in ubiquitin condensate formation and autophagy initiation |
| GO:0005758 mitochondrial intermembrane space | IEA GO_REF:0000107 | REMOVE | Summary: Electronic transfer (Ensembl Compara) of mitochondrial intermembrane space localization. There is no experimental support for NBR1 in the mitochondrial intermembrane space; NBR1 is a cytosolic receptor that only colocalizes with mitochondria during Parkin-dependent mitophagy. Reason: Over-propagated electronic annotation with no biological support. NBR1 acts on the cytosolic face of organelles as an autophagy receptor; an intermembrane-space localization is implausible and contradicted by its known cytosolic topology and lack of a mitochondrial import signal. Supporting Evidence: file:human/NBR1/NBR1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005770 late endosome | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic transfer (Ensembl Compara) of late endosome localization, consistent with NBR1's reported late-endosomal role in Spred2-dependent FGFR down-regulation and IL-12 trafficking. Reason: Functionally grounded secondary localization (FGFR/receptor trafficking) supported by experimental work; not the core autophagy-receptor compartment. Supporting Evidence: PMID:19822672 a novel late endosomal protein that directly binds to the EVH1 domain of Spred2 |
| GO:0030500 regulation of bone mineralization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic transfer (Ensembl Compara) of a regulation-of-bone-mineralization role, derived from mouse Nbr1 osteoblast/bone studies. Reason: Real but pleiotropic, tissue-specific role inferred from the mouse ortholog (no direct human experimental evidence); secondary to the core autophagy-receptor function. Supporting Evidence: file:human/NBR1/NBR1-uniprot.txt GO:0030500; P:regulation of bone mineralization; ISS:BHF-UCL |
| GO:0032872 regulation of stress-activated MAPK cascade | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic transfer (Ensembl Compara) of a stress-activated (p38) MAPK regulation role, reflecting NBR1's reported function as a PB1-domain MAPK scaffold. Reason: Plausible PB1-domain scaffolding role inferred from orthologs; secondary/pleiotropic relative to the core autophagy function. Supporting Evidence: file:human/NBR1/NBR1-uniprot.txt GO:0032872; P:regulation of stress-activated MAPK cascade; ISS:BHF-UCL |
| GO:0045668 negative regulation of osteoblast differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic transfer (Ensembl Compara) of a negative-regulation-of-osteoblast-differentiation role, derived from mouse Nbr1 studies. Reason: Real but pleiotropic role inferred from the mouse ortholog; secondary to the core autophagy-receptor function. Supporting Evidence: file:human/NBR1/NBR1-uniprot.txt GO:0045668; P:negative regulation of osteoblast differentiation; ISS:BHF-UCL |
| GO:0051019 mitogen-activated protein kinase binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic transfer (Ensembl Compara) of MAPK binding, consistent with NBR1's reported p38/MAPK scaffolding activity. Reason: Plausible scaffolding interaction inferred from orthologs; secondary to the core ubiquitin/ATG8 binding functions. Supporting Evidence: file:human/NBR1/NBR1-uniprot.txt GO:0051019; F:mitogen-activated protein kinase binding; ISS:BHF-UCL |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Immunofluorescence-curated (HPA) cytosolic localization, the core compartment in which NBR1 operates as a receptor. Reason: Correct core localization directly supported by imaging data. Supporting Evidence: file:human/NBR1/NBR1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005737 cytoplasm | EXP PMID:19427866 Interactions with LC3 and polyubiquitin chains link nbr1 to ... | KEEP AS NON CORE | Summary: Experimental cytoplasmic localization from the LC3/polyubiquitin study. Reason: Correct but generic; the specific cytosol/autophagosome localizations better capture the site of action. Supporting Evidence: PMID:19427866 Ubiquitin-binding, but not PB1-mediated p62/SQSTM1 interaction, is required to target nbr1 to LC3 |
| GO:0005737 cytoplasm | EXP PMID:35914352 NBR1 mediates autophagic degradation of IRF3 to negatively r... | KEEP AS NON CORE | Summary: Experimental cytoplasmic localization from the IRF3 autophagic-degradation study. Reason: Correct but generic; redundant with the more specific cytosol annotation. Supporting Evidence: PMID:35914352 NBR1 mediates autophagic degradation of IRF3 |
| GO:0005737 cytoplasm | EXP PMID:38169523 Selective Autophagy Receptor NBR1 Retards Nucleus Pulposus C... | KEEP AS NON CORE | Summary: Experimental cytoplasmic localization from the SRBD1-clearance study. Reason: Correct but generic; redundant with the cytosol annotation. Supporting Evidence: PMID:38169523 Selective Autophagy Receptor NBR1 |
| GO:0005764 lysosome | EXP PMID:19250911 A role for NBR1 in autophagosomal degradation of ubiquitinat... | KEEP AS NON CORE | Summary: Experimental evidence that NBR1 is targeted to lysosomes for degradation along with its cargo. Reason: Experimentally supported endpoint localization reflecting autophagic delivery and turnover rather than a distinct functional compartment. Supporting Evidence: file:human/NBR1/NBR1-uniprot.txt Is targeted to lysosomes for degradation |
| GO:0043235 signaling receptor complex | IDA PMID:19250911 A role for NBR1 in autophagosomal degradation of ubiquitinat... | UNDECIDED | Summary: Direct evidence (from the foundational study) placing NBR1 in a receptor complex (GOA renders this term as 'receptor complex'). Reason: The intended meaning is unclear. NBR1 functions as a selective-autophagy cargo receptor rather than as part of a classical signaling-receptor complex; the term may conflate 'autophagy receptor' with 'signaling receptor complex'. Deferring rather than removing an IDA annotation whose full text was read by the curator. If it refers to the cargo-receptor/ATG8 assembly, a selective-autophagy term would be more apt. Supporting Evidence: PMID:19250911 NBR1 and p62 act as receptors for selective autophagosomal degradation of |
| GO:0005778 peroxisomal membrane | TAS Reactome:R-HSA-9664867 | KEEP AS NON CORE | Summary: Reactome pexophagy curation (NBR1 binds MAP1LC3B) placing NBR1 at the peroxisomal membrane during peroxisome turnover. Reason: Functionally grounded localization tied to the pexophagy substrate context; secondary to the general cytosolic receptor function. Supporting Evidence: Reactome:R-HSA-9664867 NBR1 binds MAP1LC3B |
| GO:0005778 peroxisomal membrane | TAS Reactome:R-HSA-9664880 | KEEP AS NON CORE | Summary: Reactome pexophagy curation (MAP1LC3B binds ATM:Ub-p-PEX5:SQSTM1:NBR1). Reason: Functionally grounded pexophagy localization; secondary to the core receptor function and redundant with the other pexophagy reactions. Supporting Evidence: Reactome:R-HSA-9664880 MAP1LC3B binds ATM dimer:Ub-p-PEX5:SQSTM1:NBR1 |
| GO:0005778 peroxisomal membrane | TAS Reactome:R-HSA-9664881 | KEEP AS NON CORE | Summary: Reactome pexophagy curation (NBR1 binds ATM:Ub-p-PEX5:SQSTM1). Reason: Functionally grounded pexophagy localization; secondary to the core receptor function and redundant with the other pexophagy reactions. Supporting Evidence: Reactome:R-HSA-9664881 NBR1 binds ATM:Ub-p-PEX5:SQSTM1 |
| GO:0005739 mitochondrion | IDA PMID:21296869 Broad activation of the ubiquitin-proteasome system by Parki... | KEEP AS NON CORE | Summary: Direct evidence of NBR1 colocalization with mitochondria in the context of Parkin-mediated mitophagy. Reason: Correct colocalization (colocalizes_with qualifier) reflecting recruitment to damaged mitochondria during mitophagy; a substrate context rather than a constitutive localization. Supporting Evidence: PMID:21296869 Broad activation of the ubiquitin-proteasome system by Parkin is critical for |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | KEEP AS NON CORE | Summary: High-throughput membrane-proteome detection of NBR1 (NK-cell membrane proteome). Reason: Generic compartment from a high-throughput proteomics survey; consistent with membrane-associated autophagy/peroxisome/endosome pools but uninformative as a standalone term. Supporting Evidence: PMID:19946888 Defining the membrane proteome of NK cells |
| GO:0051019 mitogen-activated protein kinase binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer of MAPK binding, consistent with NBR1's reported p38/MAPK scaffolding role. Reason: Plausible scaffolding interaction inferred by similarity; secondary to the core ubiquitin/ATG8 binding functions and redundant with the IEA MAPK-binding annotation. Supporting Evidence: file:human/NBR1/NBR1-uniprot.txt GO:0051019; F:mitogen-activated protein kinase binding; ISS:BHF-UCL |
| GO:0005515 protein binding | IPI PMID:19822672 Spred2 interaction with the late endosomal protein NBR1 down... | KEEP AS NON CORE | Summary: Interaction with Spred2 in the late-endosomal FGFR down-regulation pathway. Bare protein binding is uninformative. Reason: Records a real, functionally relevant Spred2 interaction (FGFR trafficking) but bare protein binding is uninformative. Supporting Evidence: PMID:19822672 NBR1 is a highly conserved multidomain protein that interacts and colocalizes with Spred2 |
| GO:0005776 autophagosome | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence-similarity transfer of autophagosome colocalization. Reason: Correct and functionally central localization; redundant with the IEA autophagosome annotation and supported by ATG8/LC3 binding. Supporting Evidence: file:human/NBR1/NBR1-uniprot.txt Cytoplasmic vesicle, autophagosome |
| GO:0030500 regulation of bone mineralization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity (BHF-UCL) transfer of a regulation-of-bone-mineralization role from mouse Nbr1. Reason: Real but pleiotropic role inferred from the ortholog; secondary to the core autophagy function and redundant with the IEA annotation. Supporting Evidence: file:human/NBR1/NBR1-uniprot.txt GO:0030500; P:regulation of bone mineralization; ISS:BHF-UCL |
| GO:0032872 regulation of stress-activated MAPK cascade | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity (BHF-UCL) transfer of stress-activated MAPK regulation. Reason: Plausible PB1-domain scaffolding role inferred by similarity; secondary/pleiotropic and redundant with the IEA annotation. Supporting Evidence: file:human/NBR1/NBR1-uniprot.txt GO:0032872; P:regulation of stress-activated MAPK cascade; ISS:BHF-UCL |
| GO:0045668 negative regulation of osteoblast differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity (BHF-UCL) transfer of negative regulation of osteoblast differentiation from mouse Nbr1. Reason: Real but pleiotropic role inferred from the ortholog; secondary to the core function and redundant with the IEA annotation. Supporting Evidence: file:human/NBR1/NBR1-uniprot.txt GO:0045668; P:negative regulation of osteoblast differentiation; ISS:BHF-UCL |
| GO:0005770 late endosome | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer of late endosome localization, consistent with the experimentally reported FGFR-trafficking role. Reason: Functionally grounded secondary localization; redundant with the IEA late-endosome annotation. Supporting Evidence: PMID:19822672 a novel late endosomal protein that directly binds to the EVH1 domain of Spred2 |
| GO:0005829 cytosol | IDA PMID:19250911 A role for NBR1 in autophagosomal degradation of ubiquitinat... | ACCEPT | Summary: Direct cytosolic localization reported in the foundational autophagy-receptor study. Reason: Correct core localization directly demonstrated. Supporting Evidence: file:human/NBR1/NBR1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0016236 macroautophagy | IDA PMID:19250911 A role for NBR1 in autophagosomal degradation of ubiquitinat... | ACCEPT | Summary: Direct evidence that NBR1 mediates autophagosomal (macroautophagic) degradation of ubiquitinated substrates. Core biological process. Reason: Core biological process directly demonstrated; NBR1 acts as a selective autophagy cargo receptor in macroautophagy. Supporting Evidence: PMID:19250911 NBR1 and p62 act as receptors for selective autophagosomal degradation of |
| GO:0043130 ubiquitin binding | IDA PMID:19427866 Interactions with LC3 and polyubiquitin chains link nbr1 to ... | ACCEPT | Summary: Direct evidence that the NBR1 UBA domain binds K48- and K63-linked polyubiquitin chains. Core molecular function. Reason: Core molecular function; the UBA domain directly binds polyubiquitin (F929A abolishes binding), enabling recognition of ubiquitinated cargo. Supporting Evidence: PMID:19427866 the nbr1 UBA domain binds to lysine-48 and -63 linked polyubiquitin-B chains |
| GO:0160247 autophagy cargo adaptor activity | IDA PMID:34471133 Reconstitution defines the roles of p62, NBR1 and TAX1BP1 in... | NEW | Summary: Proposed (NEW) core molecular function. NBR1 acts as an autophagy cargo adaptor that bridges ubiquitinated cargo to the phagophore/ATG8 machinery; in vitro reconstitution shows it drives ubiquitin condensate formation and autophagy initiation. The current GOA captures only the component activities (ubiquitin binding, ATG8 binding) but not this integrated receptor MF. Reason: The precise molecular function of NBR1 (a selective autophagy receptor) is autophagy cargo adaptor activity; this term is supported by in vitro reconstitution and is not currently in the annotation set. Proposed replacements: autophagy cargo adaptor activity Supporting Evidence: PMID:34471133 roles of p62, NBR1 and TAX1BP1 in ubiquitin condensate formation and autophagy initiation |
| GO:0035973 aggrephagy | IMP PMID:24879152 Phosphorylation of NBR1 by GSK3 modulates protein aggregatio... | NEW | Summary: Proposed (NEW) biological process. NBR1 promotes the formation and selective autophagic degradation of ubiquitinated protein aggregates; GSK3 phosphorylation at Thr-586 inhibits this aggregation. Aggrephagy is the precise process term, more specific than the generic macroautophagy annotation. Reason: NBR1's aggregate-clearance role is specifically aggrephagy (selective degradation of protein aggregates by macroautophagy); supported by experimental aggregation/GSK3 data and not currently annotated. Proposed replacements: aggrephagy Supporting Evidence: PMID:24879152 NBR1 phosphorylation by GSK3 at Thr586 prevents the aggregation of ubiquitinated proteins |
| GO:0032480 negative regulation of type I interferon production | IMP PMID:35914352 NBR1 mediates autophagic degradation of IRF3 to negatively r... | NEW | Summary: Proposed (NEW) biological process. NBR1 targets ubiquitinated IRF3 (and MAVS) for selective autophagic degradation, thereby negatively regulating type I interferon production. This innate-immune function is well supported but not in the current annotation set. Reason: NBR1's role in IRF3/MAVS clearance specifically constitutes negative regulation of type I interferon production; supported by experimental data and not currently annotated. Proposed replacements: negative regulation of type I interferon production Supporting Evidence: PMID:35914352 NBR1 mediates autophagic degradation of IRF3 to negatively regulate type I |
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Download this section (compressed HTML)Q: To what extent are NBR1's selective-autophagy functions redundant with versus independent of SQSTM1/p62 and TAX1BP1 for specific cargo classes (aggregates, peroxisomes, IRF3/MAVS), and what determines cargo selectivity among these receptors?
Q: Are the orthology-derived roles of NBR1 in osteoblast differentiation, bone mineralization, and p38/MAPK scaffolding mechanistically separable from its ubiquitin/ATG8-dependent autophagy-receptor activity, or do they depend on the same domains?
Experiment: Domain-resolved cargo profiling using NBR1 knockout cells reconstituted with wild-type versus UBA-dead (F929A), LIR-dead (Y732A), or PB1-dead (D50R) NBR1, combined with quantitative proteomics under basal, proteotoxic, and antiviral (IRF3/MAVS-activating) conditions, to define which NBR1 domains are required for clearance of each cargo class.
Experiment: Reconstitute selective autophagy of ubiquitinated IRF3/MAVS in vitro with purified NBR1, ubiquitinated substrate, ATG8 proteins, and the FIP200/ULK machinery to determine whether NBR1 alone is sufficient for cargo condensation and autophagosome targeting or requires p62/TAX1BP1.
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