Existing Annotations Review

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

Core Functions

Acts as a ubiquitin-binding selective autophagy cargo receptor that bridges K48/K63-polyubiquitinated cargo (recognized by its UBA domain) to lipidated ATG8/LC3 family proteins (bound by its LIR regions) on the phagophore, delivering ubiquitinated substrates for macroautophagic degradation; functions in parallel with and as a heterooligomer of SQSTM1/p62.

Molecular Function:

ubiquitin binding

Directly Involved In:

macroautophagy

Cellular Locations:

cytosol phagophore assembly site

Supporting Evidence:

PMID:19250911
NBR1 and p62 act as receptors for selective autophagosomal degradation of
PMID:19427866
the nbr1 UBA domain binds to lysine-48 and -63 linked polyubiquitin-B chains

Functions as an autophagy cargo adaptor that simultaneously engages cargo and the phagophore/ATG8 machinery, promoting the formation and clearance of ubiquitinated protein aggregates (aggrephagy); this aggregation-promoting activity is inhibited by GSK3-mediated phosphorylation at Thr-586.

Molecular Function:

autophagy cargo adaptor activity

Directly Involved In:

aggrephagy

Cellular Locations:

autophagosome

Supporting Evidence:

PMID:24879152
NBR1 phosphorylation by GSK3 at Thr586 prevents the aggregation of ubiquitinated proteins
PMID:34471133
roles of p62, NBR1 and TAX1BP1 in ubiquitin condensate formation and autophagy initiation

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 antiviral-restricting pathway is hijacked by influenza A virus PB1.

Molecular Function:

autophagy cargo adaptor activity

Directly Involved In:

negative regulation of type I interferon production

Cellular Locations:

cytosol

Supporting Evidence:

PMID:35914352
NBR1 mediates autophagic degradation of IRF3 to negatively regulate type I

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000052

Gene Ontology annotation based on curation of immunofluorescence data

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:19250911

A role for NBR1 in autophagosomal degradation of ubiquitinated substrates.

NBR1 is a ubiquitin-binding selective autophagy receptor that interacts with SQSTM1 and ATG8-family proteins and mediates autophagosomal degradation of ubiquitinated substrates.

PMID:19427866

Interactions with LC3 and polyubiquitin chains link nbr1 to autophagic protein turnover.

The NBR1 UBA domain binds K48- and K63-linked polyubiquitin; NBR1 binds LC3-A; ubiquitin binding (not PB1/p62 interaction) is required to target NBR1 to LC3/polyubiquitin bodies.

PMID:19822672

Spred2 interaction with the late endosomal protein NBR1 down-regulates fibroblast growth factor receptor signaling.

NBR1 is a late endosomal protein that binds the EVH1 domain of Spred2; Spred2-mediated attenuation of FGF signaling depends on NBR1 and redirects activated receptors to lysosomal degradation.

PMID:19946888

Defining the membrane proteome of NK cells.

PMID:20010802

Nix is a selective autophagy receptor for mitochondrial clearance.

PMID:20368287

Interactome mapping of the phosphatidylinositol 3-kinase-mammalian target of rapamycin pathway identifies deformed epidermal autoregulatory factor-1 as a new glycogen synthase kinase-3 interactor.

PMID:20417604

The selective macroautophagic degradation of aggregated proteins requires the PI3P-binding protein Alfy.

Alfy/WDFY3 scaffolds selective macroautophagy of aggregated proteins by bridging p62(SQSTM1)/NBR1-positive aggregates to the autophagic machinery.

PMID:20562859

Network organization of the human autophagy system.

PMID:20808283

NBR1 is a new PB1 signalling adapter in Th2 differentiation and allergic airway inflammation in vivo.

T-cell-specific NBR1-deficient mice show impaired Th2 differentiation and reduced allergic airway inflammation; NBR1 acts as a PB1-domain signaling adapter.

PMID:21296869

Broad activation of the ubiquitin-proteasome system by Parkin is critical for mitophagy.

Parkin-mediated mitochondrial ubiquitination drives mitophagy; NBR1 colocalizes with mitochondria in this context.

PMID:24692539

Solution structure of the ubiquitin-associated (UBA) domain of human autophagy receptor NBR1 and its interaction with ubiquitin and polyubiquitin.

NMR structure of the NBR1 UBA domain bound to ubiquitin/polyubiquitin; F929A abolishes ubiquitin binding.

PMID:25416956

A proteome-scale map of the human interactome network.

PMID:29568061

An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations.

PMID:30824926

Isoform-specific GSK3A activity is negatively correlated with human sperm motility.

PMID:33226137

Receptor-mediated clustering of FIP200 bypasses the role of LC3 lipidation in autophagy.

NBR1 flux is a selective-autophagy readout; TAX1BP1/TBK1 enforce cargo specificity by clustering FIP200 around NBR1 cargo; NBR1 interacts with TAX1BP1.

PMID:33577621

The PB1 protein of influenza A virus inhibits the innate immune response by targeting MAVS for NBR1-mediated selective autophagic degradation.

NBR1 recognizes ubiquitinated MAVS and delivers it to autophagosomes for degradation; influenza A virus PB1 hijacks NBR1; NBR1 deficiency impairs MAVS degradation.

PMID:33961781

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.

PMID:34471133

Reconstitution defines the roles of p62, NBR1 and TAX1BP1 in ubiquitin condensate formation and autophagy initiation.

In vitro reconstitution shows NBR1 (with p62 and TAX1BP1) drives condensation of ubiquitinated proteins and autophagy initiation.

PMID:34524948

Global Proximity Interactome of the Human Macroautophagy Pathway.

PMID:24879152

Phosphorylation of NBR1 by GSK3 modulates protein aggregation.

NBR1 binds ubiquitin and MAP1LC3 to ensure ubiquitinated protein degradation; GSK3 phosphorylation at Thr-586 prevents aggregation of ubiquitinated proteins; reduced NBR1 phosphorylation correlates with aggregation in inclusion body myositis.

PMID:35914352

NBR1 mediates autophagic degradation of IRF3 to negatively regulate type I interferon production.

NBR1 binds IRF3 and targets it for autophagic-lysosomal degradation, negatively regulating type I IFN production; NBR1 is induced upon viral infection.

PMID:38169523

Selective Autophagy Receptor NBR1 Retards Nucleus Pulposus Cell Senescence by Directing the Clearance of SRBD1.

NBR1 interacts with SRBD1 and clears it via the autophagic-lysosomal pathway, retarding nucleus pulposus cell senescence.

Reactome:R-HSA-9664867

NBR1 binds MAP1LC3B

Reactome:R-HSA-9664880

MAP1LC3B binds ATM dimer:Ub-p-PEX5:SQSTM1:NBR1

Reactome:R-HSA-9664881

NBR1 binds ATM:Ub-p-PEX5:SQSTM1

Suggested Experiments

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.

Deep Research

Falcon

(NBR1-deep-research-falcon.md)

Research Report: Human NBR1 (UniProt Q14596) — Functional Annotation and Current Understanding Falcon Edison Scientific Literature 24 citations 2 artifacts 2026-06-14T16:11:08.685984

Edison artifact artifact-00 (text/markdown)

## Context ID: pqac-00000025 The requested information on NBR1's domain architecture and its role as a selective autophagy receptor is presented in the followin (image/png)

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Research Report: Human NBR1 (UniProt Q14596) — Functional Annotation and Current Understanding

1) Target verification (gene/protein identity)

The target protein is human NBR1 (Neighbor of BRCA1 gene 1; UniProt Q14596), an evolutionarily conserved selective autophagy receptor (“sequestosome-1–like receptor”, SLR) with a characteristic multi-domain architecture (PB1, ZZ, FW, LIR(s), UBA) and additional membrane-association features (amphipathic helix) described in authoritative reviews focused on NBR1. (rasmussen2022nbr1thearchetypal pages 1-2, rasmussen2022nbr1thearchetypal pages 4-6)

2) Key concepts and definitions (current understanding)

2.1 Selective autophagy and selective autophagy receptors (SARs)

Autophagy sequesters intracellular material in double-membrane autophagosomes that fuse with endolysosomal compartments to form degradative autolysosomes. Selective autophagy differs from bulk autophagy by targeting defined cargo classes (e.g., aggrephagy, xenophagy, pexophagy) and typically involves cargo tagging, frequently ubiquitination, and cargo receptors that bridge cargo to autophagosome membranes. (vargas2023themechanismsand pages 1-6)

In a broad, authoritative synthesis of mammalian selective autophagy, selective cargo specificity is attributed to receptors including p62/SQSTM1, NBR1, OPTN, and NDP52, which possess both LC3-interacting region (LIR) motifs and ubiquitin-binding domains enabling them to bind cargo and recruit autophagic membranes. (vargas2023themechanismsand pages 1-6)

2.2 NBR1 as an archetypal selective autophagy receptor

A dedicated review describes NBR1 as an “archetypal” selective autophagy receptor with deep evolutionary roots and conserved modular architecture. Mechanistically, NBR1’s defining role is as a multivalent adaptor that:
- recognizes ubiquitinated cargo (via UBA),
- binds ATG8-family proteins (LC3/GABARAP) on phagophores/autophagosomes (via LIRs), and
- assembles higher-order receptor/cargo structures through additional interaction modules (PB1/CC/FW) that facilitate receptor cooperation and autophagy initiation. (rasmussen2022nbr1thearchetypal pages 1-2, rasmussen2022nbr1thearchetypal pages 4-6)

3) Molecular architecture, mechanisms, and pathways

3.1 Domain architecture and core molecular interactions

Human NBR1 contains:
- PB1 domain: mediates strong PB1–PB1 electrostatic interaction with p62; metazoan NBR1 PB1 is described as monomeric (loss of the basic binding surface) but remains recruited to p62 assemblies and can act as a chain terminator of p62 polymers, modulating p62 filament length and body formation. (rasmussen2022nbr1thearchetypal pages 6-8)
- ZZ domain (zinc-finger) and coiled-coil (CC) regions contributing to interaction capacity and assembly. (rasmussen2022nbr1thearchetypal pages 4-6, cerdatroncoso2021protumoralfunctionsof pages 7-8)
- FW (four-tryptophan) domain(s): implicated in cargo/adaptor recognition; in human NBR1, FW-domain binding partners include TAX1BP1 and MAP1B, and FW-mediated recruitment of TAX1BP1 to p62 assemblies is proposed as a coupling point to autophagy machinery. (rasmussen2022nbr1thearchetypal pages 2-4, rasmussen2022nbr1thearchetypal pages 6-8)
- Two LIR motifs (LIR1/LIR2): tether NBR1 to LC3/ATG8 proteins; LIR1 is described as dominant in cells. (rasmussen2022nbr1thearchetypal pages 1-2)
- C-terminal UBA domain: binds mono- and poly-ubiquitin, enabling NBR1 recognition of ubiquitinated cargos and (in the p62-body context) enhancing cargo clustering by bringing a high-affinity ubiquitin-binding module into p62 filaments. (rasmussen2022nbr1thearchetypal pages 6-8, cerdatroncoso2021protumoralfunctionsof pages 7-8)
- Amphipathic helix (AH) near UBA: contributes to membrane association; coincident AH+UBA binding targets NBR1 to ubiquitinated peroxisomes during pexophagy. (rasmussen2022nbr1thearchetypal pages 10-11)

The NBR1 domain schematic and associated partners are visually summarized in a JCB review figure (domain map and interaction partners). (rasmussen2022nbr1thearchetypal media 2c6d1299)

3.2 NBR1 within p62 bodies and autophagy initiation

Mechanistic synthesis indicates NBR1 is frequently recruited to p62/ubiquitin-positive bodies, where it can modulate p62 polymer properties and enhance cargo clustering. In this model, NBR1 also recruits TAX1BP1 (via FW) and links to initiation machinery (including FIP200/ULK-related components) to promote efficient selective-autophagy flux. (rasmussen2022nbr1thearchetypal pages 6-8)

A further development (reported as 2024 work in a 2024-05 preprint posting) argues that the NBR1 LIR region is a protein-interaction hub in which ATG8-family proteins, FIP200, and TAX1BP1 bind overlapping but distinct determinants within a short linear motif, and that phosphorylation can differentially tune binding (enhancing FIP200/ATG8 binding but not TAX1BP1 binding in the peptide-array framework). (north2025thelc3interactingregion pages 1-4)

3.3 Subcellular localization (where NBR1 acts)

Evidence from reviews and primary studies supports a predominantly cytoplasmic role for NBR1 as a receptor that localizes to:
- p62 bodies / ubiquitin-positive aggregates (cytosolic condensates),
- autophagosomal membranes via LC3/ATG8 binding,
- peroxisomes during selective removal (pexophagy) through combined AH+UBA targeting to ubiquitinated peroxisomes. (rasmussen2022nbr1thearchetypal pages 6-8, rasmussen2022nbr1thearchetypal pages 10-11)

In human nucleus pulposus cells, immunofluorescence evidence indicates NBR1 is predominantly cytoplasmic and its interaction with the cargo protein SRBD1 occurs primarily in the cytoplasm. (song2024selectiveautophagyreceptor pages 8-10)

4) Recent developments (prioritizing 2023–2024)

4.1 2024: NBR1 in intervertebral disc degeneration via selective clearance of SRBD1 (human cells; disease mechanism)

A 2024 study in International Journal of Biological Sciences investigated NBR1 in intervertebral disc degeneration (IDD) and nucleus pulposus cell (NPC) senescence, reporting:
- Proteomics after NBR1 knockdown identified 1,082 differentially expressed proteins (819 upregulated, 263 downregulated), indicating broad proteostasis remodeling when NBR1-mediated selective degradation is reduced. (song2024selectiveautophagyreceptor pages 8-10)
- Integration of IP–MS and proteomics identified SRBD1 as a candidate direct NBR1-associated substrate; SRBD1 was reported as ~50.6-fold upregulated after NBR1 knockdown at the protein level while SRBD1 mRNA did not change, consistent with NBR1 regulating SRBD1 protein stability. (song2024selectiveautophagyreceptor pages 8-10)
- Pharmacologic interrogation supported lysosomal/autophagic routing: Baf-A1 (lysosomal inhibition) significantly mitigated SRBD1 degradation, while MG132 (proteasome inhibitor) had minimal influence, supporting an autophagic-lysosomal degradation route for SRBD1. (song2024selectiveautophagyreceptor pages 8-10)
- Mechanistic downstream pathways were linked to SRBD1 accumulation: NBR1 knockdown → SRBD1 accumulation → senescence signaling via AKT1/p53 and RB/p16 pathways and pro-SASP signaling via NF-κB. (song2024selectiveautophagyreceptor pages 1-2)
- Ubiquitin-recognition was functionally required: overexpression of wild-type NBR1 (but not NBR1-ΔUBA) accelerated SRBD1 degradation, supporting a model where NBR1 uses its ubiquitin-binding capacity to drive selective cargo clearance. (song2024selectiveautophagyreceptor pages 8-10)
- Human tissue-level association: NBR1 was described as reduced in IDD, including a statistically significant reduction in NBR1-positive cells in normal (n=11) vs degenerated (n=34) human samples (P<0.01, Mann–Whitney U test). (song2024selectiveautophagyreceptor pages 5-8)

These results extend NBR1 functional annotation beyond canonical “aggregate receptor” roles to a specific, disease-relevant selective cargo–substrate relationship (NBR1→SRBD1) with defined signaling consequences. (song2024selectiveautophagyreceptor pages 1-2, song2024selectiveautophagyreceptor pages 8-10)

4.2 2024: NBR1 turnover during HSV-1 infection (xenophagy-linked antiviral defense)

A 2024 primary study in Cells assessed the dynamics of xenophagy-associated receptors during productive HSV-1 infection in human cells and reported:
- HSV-1 infection in H4 human neuroglioma cells reduced total ubiquitin conjugates and significantly decreased NBR1 protein levels starting from 8 hours post-infection (hpi) (densitometry normalized to β-actin; n=3 biological replicates for NBR1). (pinobelmar2024anintrinsichost pages 6-8)
- Viral load dependence: only high HSV-1 doses (approximately MOI 5–10) produced a notable reduction in receptor levels including NBR1 at 8 hpi. (pinobelmar2024anintrinsichost pages 6-8)
- In HaCaT keratinocytes, NBR1 levels significantly decreased from 4 hpi onward, and the authors highlight NBR1 and NDP52 as among the most impacted receptors. (pinobelmar2024anintrinsichost pages 8-10)
- The report also noted that NBR1 mRNA increased at late time points despite protein loss, consistent with compensatory transcriptional responses amid post-translational depletion. (pinobelmar2024anintrinsichost pages 8-10)

Functionally, this positions NBR1 within a host-defense framework where xenophagy engages receptor turnover during infection and intersects with viral strategies that modulate ubiquitin-dependent pathways. (pinobelmar2024anintrinsichost pages 1-2, pinobelmar2024anintrinsichost pages 8-10)

4.3 2023: Updated framing of receptor-based selectivity in mammalian selective autophagy

The 2023 Nature Reviews Molecular Cell Biology synthesis emphasizes that selective autophagy targets (including xenophagy and aggrephagy) rely on receptors (including NBR1) that bridge cargo to lipidated LC3 via LIR motifs and ubiquitin-binding domains, and highlights the disease relevance of selective-autophagy insufficiency for neurodegeneration and infection. (vargas2023themechanismsand pages 1-6)

5) Current applications and real-world implementations

5.1 Cancer and immune evasion (MHC-I degradation)

An NBR1-focused review summarizes evidence that in pancreatic ductal adenocarcinoma (PDAC) cells, MHC class I molecules can be degraded by NBR1-mediated selective autophagy, and that NBR1 knockdown increases total and surface MHC-I levels, linking NBR1 activity to tumor immune evasion phenotypes (antigen presentation). (rasmussen2022nbr1thearchetypal pages 11-12)

Additional cancer-related literature notes NBR1’s participation in focal adhesion turnover via selective autophagy of ubiquitylated focal adhesion components, influencing migration and metastatic phenotypes in model systems. (cerdatroncoso2021protumoralfunctionsof pages 6-7)

5.2 Degenerative disease biology (IDD) and selective-autophagy targeting

The 2024 IDD/NPC senescence study proposes a selective-autophagy-based intervention logic: rather than globally modulating autophagy, enhancing NBR1-dependent clearance of detrimental substrates (e.g., SRBD1) could be a targeted approach for degenerative disc pathology. (song2024selectiveautophagyreceptor pages 1-2)

5.3 Infection biology and host defense

The 2024 HSV-1 study provides a tractable experimental system where NBR1 and other receptors are monitored as infection progresses, offering an implementation pathway for testing antiviral xenophagy modulation (e.g., receptor turnover, ubiquitin conjugate dynamics, MOI/time dependence). (pinobelmar2024anintrinsichost pages 6-8, pinobelmar2024anintrinsichost pages 8-10)

6) Expert opinions and analysis (authoritative sources)

6.1 “Archetypal receptor” framing and cooperation with p62

Expert synthesis argues that mammalian NBR1 frequently operates in a cooperative network with p62/SQSTM1, often colocalizing with p62 and ubiquitin in pathological inclusions, and that NBR1’s recruitment to p62 bodies plus its high-affinity UBA may enhance the efficiency of ubiquitin-positive cargo clustering and selective-autophagy progression. The same synthesis cautions that because NBR1 and p62 often act together, NBR1-specific effects can be difficult to disentangle experimentally without careful genetic and biochemical designs. (rasmussen2022nbr1thearchetypal pages 11-12, rasmussen2022nbr1thearchetypal pages 6-8)

6.2 Receptor redundancy and context dependence

A 2023 study in mouse ESCs and ESC-derived neurons reported that p62 and NBR1 can be dispensable for aggrephagy in those contexts, implying redundancy across cargo receptors and/or alternative proteostasis pathways that can compensate for loss of canonical SLR functions in certain cell types. This is a key interpretive point for functional annotation: NBR1’s necessity can be cell-type and context dependent, even if its molecular capabilities as an SLR are well supported. (trapannone2023p62andnbr1 pages 7-9)

7) Statistics and data highlights (recent studies)

IDD/NPC senescence (2024, Song et al.): 1,082 differentially expressed proteins after NBR1 knockdown (819 up; 263 down) (proteomics); SRBD1 upregulated ~50.6-fold at protein level after NBR1 knockdown; reduced NBR1-positive cells in normal vs degenerated human samples (n=11 vs n=34; P<0.01). (song2024selectiveautophagyreceptor pages 8-10, song2024selectiveautophagyreceptor pages 5-8)
HSV-1 infection (2024, Pino-Belmar et al.): significant NBR1 protein reduction during infection in H4 and HaCaT cells; MOI dependence (notable reduction at MOI ~5–10); densitometric quantification normalized to β-actin with NBR1 biological replicates (n=3 in H4; NBR1 quantified also with replicate counts described in figure captions). (pinobelmar2024anintrinsichost pages 6-8, pinobelmar2024anintrinsichost pages 8-10)

8) Disease associations from a target–disease knowledgebase (Open Targets)

Open Targets lists disease associations for NBR1 (ENSG00000188554; “NBR1 autophagy cargo receptor”) including categories such as neoplasm, neurodegenerative disease, and specific cancers (e.g., gastric and ovarian cancer) with scored evidence and linked literature identifiers. These associations are useful for prioritization but should be interpreted as aggregated evidence rather than direct mechanistic proof. (OpenTargets Search: -NBR1)

9) Visual evidence (domain architecture and functional schematic)

The JCB review provides clear visuals of (i) NBR1 domain architecture and binding partners, (ii) NBR1-centered selective autophagy processes across cargo types, and (iii) NBR1’s mechanistic placement within p62 bodies and initiation machinery. (rasmussen2022nbr1thearchetypal media 2c6d1299, rasmussen2022nbr1thearchetypal media 47b06603, rasmussen2022nbr1thearchetypal media 07b5ca64)

10) Summary functional annotation (human NBR1 / UniProt Q14596)

Primary function: NBR1 is a multivalent selective autophagy cargo receptor that binds ubiquitinated cargo (UBA) and recruits autophagic membranes via ATG8/LC3 binding (LIRs), while coordinating receptor assembly and autophagy initiation through additional interaction modules (PB1/CC/FW; TAX1BP1/FIP200 connections). (rasmussen2022nbr1thearchetypal pages 1-2, rasmussen2022nbr1thearchetypal pages 6-8, north2025thelc3interactingregion pages 1-4)

Where it acts: predominantly cytoplasmic, enriched at p62/ubiquitin-positive condensates, forming autophagosomal membranes, and ubiquitinated peroxisomes during pexophagy; specific cytoplasmic cargo interactions (e.g., SRBD1) are reported in human cells. (rasmussen2022nbr1thearchetypal pages 10-11, song2024selectiveautophagyreceptor pages 8-10)

Pathways/biological processes: aggrephagy, xenophagy/antiviral defense, pexophagy, focal adhesion turnover/migration, and tumor immune evasion phenotypes (MHC-I degradation) depending on context. (rasmussen2022nbr1thearchetypal pages 10-11, rasmussen2022nbr1thearchetypal pages 11-12, cerdatroncoso2021protumoralfunctionsof pages 6-7)

Domain/interactions quick reference

Feature (domain/motif or function)	Description/role	Key partners/cargos	Evidence/source (with publication year + journal)	URL
PB1 domain	N-terminal PB1 mediates strong PB1-PB1 interaction with p62/SQSTM1; metazoan NBR1 PB1 is monomeric but recruits NBR1 to p62 bodies and can act as a chain terminator that limits p62 filament length while promoting cargo clustering.	p62/SQSTM1; MEKK3	Rasmussen et al., 2022, Journal of Cell Biology (rasmussen2022nbr1thearchetypal pages 6-8)	https://doi.org/10.1083/jcb.202208092
ZZ zinc-finger domain	Conserved ZZ-type zinc-finger is part of canonical human NBR1 architecture shared with selective autophagy receptors; included in domain schematics for metazoan NBR1.	Protein-interaction module; specific human partners not detailed in the extracted contexts	Rasmussen et al., 2022, Journal of Cell Biology (rasmussen2022nbr1thearchetypal pages 1-2, rasmussen2022nbr1thearchetypal pages 4-6, rasmussen2022nbr1thearchetypal media 2c6d1299)	https://doi.org/10.1083/jcb.202208092
CC1 / coiled-coil regions	Coiled-coil region supports NBR1 self-interaction/oligomerization and contributes to receptor assembly during cargo capture.	NBR1 self-association; cooperative assembly with p62	Cerda-Troncoso et al., 2021, Frontiers in Oncology (cerdatroncoso2021protumoralfunctionsof pages 7-8, cerdatroncoso2021protumoralfunctionsof pages 6-7)	https://doi.org/10.3389/fonc.2020.619727
FW domain	Four-tryptophan (FW) domain is distinctive for NBR1 and participates in cargo/adaptor recognition; in human NBR1 it binds MAP1B and TAX1BP1 and helps recruit TAX1BP1 to p62 bodies.	TAX1BP1; MAP1B	Rasmussen et al., 2022, Journal of Cell Biology (rasmussen2022nbr1thearchetypal pages 2-4, rasmussen2022nbr1thearchetypal pages 6-8)	https://doi.org/10.1083/jcb.202208092
LIR motifs (LIR1/LIR2)	Human NBR1 has two LC3-interacting regions; LIR1 is the dominant functional site in cells. LIRs tether cargo-bound NBR1 to ATG8-family proteins and also connect to FIP200/TAX1BP1 through overlapping determinants in recent work.	LC3/GABARAP/ATG8 proteins; FIP200; TAX1BP1	Rasmussen et al., 2022, Journal of Cell Biology; North et al., 2025, bioRxiv (preprint reporting 2024 work) (rasmussen2022nbr1thearchetypal pages 1-2, north2025thelc3interactingregion pages 1-4)	https://doi.org/10.1083/jcb.202208092 ; https://doi.org/10.1101/2024.05.09.593318
AH + UBA region	A C-terminal amphipathic helix adjacent to the UBA helps membrane association; coincident AH-UBA binding targets NBR1 to ubiquitinated peroxisomes and contributes to membrane/peroxisome localization.	PIP-containing membranes; ubiquitinated peroxisomes	Rasmussen et al., 2022, Journal of Cell Biology (rasmussen2022nbr1thearchetypal pages 1-2, rasmussen2022nbr1thearchetypal pages 10-11)	https://doi.org/10.1083/jcb.202208092
UBA domain	C-terminal ubiquitin-associated domain binds mono- and polyubiquitin with high affinity, enabling selective recognition of ubiquitinated cargo for autophagic delivery.	Ubiquitinated protein aggregates; bacteria; peroxisomal proteins; MHC-I-associated cargo	Rasmussen et al., 2022, Journal of Cell Biology; Cerda-Troncoso et al., 2021, Frontiers in Oncology (rasmussen2022nbr1thearchetypal pages 1-2, cerdatroncoso2021protumoralfunctionsof pages 7-8, rasmussen2022nbr1thearchetypal pages 10-11)	https://doi.org/10.1083/jcb.202208092 ; https://doi.org/10.3389/fonc.2020.619727
Archetypal selective autophagy receptor	NBR1 is an evolutionarily ancient, ubiquitin-dependent selective autophagy receptor that bridges ubiquitinated cargo to autophagosomes through ubiquitin binding plus ATG8-family binding.	Ubiquitinated cargos broadly	Rasmussen et al., 2022, Journal of Cell Biology; Vargas et al., 2023, Nature Reviews Molecular Cell Biology (rasmussen2022nbr1thearchetypal pages 1-2, vargas2023themechanismsand pages 1-6)	https://doi.org/10.1083/jcb.202208092 ; https://doi.org/10.1038/s41580-022-00542-2
Aggrephagy / p62-body organization	NBR1 is recruited to p62 bodies, enhances p62 phase separation with ubiquitin, and promotes clustering of ubiquitinated aggregates; however, receptor requirements can be cell-type dependent, with redundancy in mouse ESCs/neurons.	p62 condensates; ubiquitinated aggregates	Rasmussen et al., 2022, Journal of Cell Biology; Trapannone et al., 2023, Life Science Alliance (rasmussen2022nbr1thearchetypal pages 6-8, trapannone2023p62andnbr1 pages 7-9, trapannone2023p62andnbr1 pages 9-12)	https://doi.org/10.1083/jcb.202208092 ; https://doi.org/10.26508/lsa.202301936
Pexophagy	NBR1 mediates selective degradation of ubiquitinated peroxisomes; AH, UBA, LIR, and CC regions are required, and p62 can enhance but is not strictly required.	Ubiquitinated peroxisomes; p62	Rasmussen et al., 2022, Journal of Cell Biology (rasmussen2022nbr1thearchetypal pages 10-11)	https://doi.org/10.1083/jcb.202208092
Xenophagy / antiviral defense	NBR1 participates in xenophagy, including recruitment to intracellular pathogens and turnover during HSV-1 infection; HSV-1 infection significantly lowers NBR1 protein in H4 and HaCaT cells, consistent with active xenophagic receptor clearance.	HSV-1-associated cargo; ubiquitinated pathogens	Pino-Belmar et al., 2024, Cells; Rasmussen et al., 2022, Journal of Cell Biology (pinobelmar2024anintrinsichost pages 1-2, pinobelmar2024anintrinsichost pages 2-3, rasmussen2022nbr1thearchetypal pages 8-10, pinobelmar2024anintrinsichost pages 8-10)	https://doi.org/10.3390/cells13151256 ; https://doi.org/10.1083/jcb.202208092
Focal-adhesion turnover / migration	NBR1 binds ubiquitylated focal-adhesion proteins and mediates their selective autophagic turnover, promoting focal-adhesion turnover and cell migration/metastatic outgrowth in some cancer models.	Ubiquitylated focal-adhesion components	Cerda-Troncoso et al., 2021, Frontiers in Oncology; Rasmussen et al., 2022, Journal of Cell Biology (cerdatroncoso2021protumoralfunctionsof pages 6-7, rasmussen2022nbr1thearchetypal pages 10-11)	https://doi.org/10.3389/fonc.2020.619727 ; https://doi.org/10.1083/jcb.202208092
Disease-linked selective cargo clearance	In human nucleus pulposus cells, NBR1 directs autophagic-lysosomal clearance of SRBD1; NBR1 knockdown caused a proteomic shift with 1,082 differentially expressed proteins and ~50.6-fold SRBD1 upregulation, linking NBR1 to suppression of senescence/SASP pathways.	SRBD1	Song et al., 2024, International Journal of Biological Sciences (song2024selectiveautophagyreceptor pages 1-2, song2024selectiveautophagyreceptor pages 8-10)	https://doi.org/10.7150/ijbs.90186
Immune evasion / MHC-I regulation	NBR1-mediated selective autophagy can reduce MHC class I abundance in pancreatic ductal adenocarcinoma cells, linking cargo selection to tumor immune evasion.	Ubiquitylated MHC-I	Rasmussen et al., 2022, Journal of Cell Biology; Cerda-Troncoso et al., 2021, Frontiers in Oncology (cerdatroncoso2021protumoralfunctionsof pages 7-8, rasmussen2022nbr1thearchetypal pages 11-12)	https://doi.org/10.1083/jcb.202208092 ; https://doi.org/10.3389/fonc.2020.619727

Table: This table summarizes the validated domain architecture of human NBR1 (UniProt Q14596) and its best-supported molecular interactions and selective-autophagy functions. It is useful as a compact functional annotation reference grounded only in the provided source contexts.

References

(rasmussen2022nbr1thearchetypal pages 1-2): Nikoline Lander Rasmussen, Athanasios Kournoutis, Trond Lamark, and Terje Johansen. Nbr1: the archetypal selective autophagy receptor. The Journal of Cell Biology, Oct 2022. URL: https://doi.org/10.1083/jcb.202208092, doi:10.1083/jcb.202208092. This article has 110 citations.
(rasmussen2022nbr1thearchetypal pages 4-6): Nikoline Lander Rasmussen, Athanasios Kournoutis, Trond Lamark, and Terje Johansen. Nbr1: the archetypal selective autophagy receptor. The Journal of Cell Biology, Oct 2022. URL: https://doi.org/10.1083/jcb.202208092, doi:10.1083/jcb.202208092. This article has 110 citations.
(vargas2023themechanismsand pages 1-6): Jose Norberto S. Vargas, Maho Hamasaki, Tsuyoshi Kawabata, Richard J. Youle, and Tamotsu Yoshimori. The mechanisms and roles of selective autophagy in mammals. Nature Reviews Molecular Cell Biology, 24:167-185, Oct 2023. URL: https://doi.org/10.1038/s41580-022-00542-2, doi:10.1038/s41580-022-00542-2. This article has 1079 citations and is from a domain leading peer-reviewed journal.
(rasmussen2022nbr1thearchetypal pages 6-8): Nikoline Lander Rasmussen, Athanasios Kournoutis, Trond Lamark, and Terje Johansen. Nbr1: the archetypal selective autophagy receptor. The Journal of Cell Biology, Oct 2022. URL: https://doi.org/10.1083/jcb.202208092, doi:10.1083/jcb.202208092. This article has 110 citations.
(cerdatroncoso2021protumoralfunctionsof pages 7-8): Cristóbal Cerda-Troncoso, Manuel Varas-Godoy, and Patricia V. Burgos. Pro-tumoral functions of autophagy receptors in the modulation of cancer progression. Frontiers in Oncology, Feb 2021. URL: https://doi.org/10.3389/fonc.2020.619727, doi:10.3389/fonc.2020.619727. This article has 19 citations.
(rasmussen2022nbr1thearchetypal pages 2-4): Nikoline Lander Rasmussen, Athanasios Kournoutis, Trond Lamark, and Terje Johansen. Nbr1: the archetypal selective autophagy receptor. The Journal of Cell Biology, Oct 2022. URL: https://doi.org/10.1083/jcb.202208092, doi:10.1083/jcb.202208092. This article has 110 citations.
(rasmussen2022nbr1thearchetypal pages 10-11): Nikoline Lander Rasmussen, Athanasios Kournoutis, Trond Lamark, and Terje Johansen. Nbr1: the archetypal selective autophagy receptor. The Journal of Cell Biology, Oct 2022. URL: https://doi.org/10.1083/jcb.202208092, doi:10.1083/jcb.202208092. This article has 110 citations.
(rasmussen2022nbr1thearchetypal media 2c6d1299): Nikoline Lander Rasmussen, Athanasios Kournoutis, Trond Lamark, and Terje Johansen. Nbr1: the archetypal selective autophagy receptor. The Journal of Cell Biology, Oct 2022. URL: https://doi.org/10.1083/jcb.202208092, doi:10.1083/jcb.202208092. This article has 110 citations.
(north2025thelc3interactingregion pages 1-4): Brian J North, Amelia E Ohnstad, Michael J Ragusa, and Christopher J Shoemaker. The lc3-interacting region of nbr1 is a protein interaction hub enabling optimal flux. bioRxiv, May 2025. URL: https://doi.org/10.1101/2024.05.09.593318, doi:10.1101/2024.05.09.593318. This article has 9 citations.
(song2024selectiveautophagyreceptor pages 8-10): Honghai Song, Yutao Zhu, Chuan Hu, Qianyu Liu, Yang Jin, Pan Tang, Jiechao Xia, Dingqi Xie, Sicheng Jiang, Geliang Yao, Zhili Liu, and Zhijun Hu. Selective autophagy receptor nbr1 retards nucleus pulposus cell senescence by directing the clearance of srbd1. International Journal of Biological Sciences, 20:701-717, Jan 2024. URL: https://doi.org/10.7150/ijbs.90186, doi:10.7150/ijbs.90186. This article has 17 citations and is from a peer-reviewed journal.
(song2024selectiveautophagyreceptor pages 1-2): Honghai Song, Yutao Zhu, Chuan Hu, Qianyu Liu, Yang Jin, Pan Tang, Jiechao Xia, Dingqi Xie, Sicheng Jiang, Geliang Yao, Zhili Liu, and Zhijun Hu. Selective autophagy receptor nbr1 retards nucleus pulposus cell senescence by directing the clearance of srbd1. International Journal of Biological Sciences, 20:701-717, Jan 2024. URL: https://doi.org/10.7150/ijbs.90186, doi:10.7150/ijbs.90186. This article has 17 citations and is from a peer-reviewed journal.
(song2024selectiveautophagyreceptor pages 5-8): Honghai Song, Yutao Zhu, Chuan Hu, Qianyu Liu, Yang Jin, Pan Tang, Jiechao Xia, Dingqi Xie, Sicheng Jiang, Geliang Yao, Zhili Liu, and Zhijun Hu. Selective autophagy receptor nbr1 retards nucleus pulposus cell senescence by directing the clearance of srbd1. International Journal of Biological Sciences, 20:701-717, Jan 2024. URL: https://doi.org/10.7150/ijbs.90186, doi:10.7150/ijbs.90186. This article has 17 citations and is from a peer-reviewed journal.
(pinobelmar2024anintrinsichost pages 6-8): Camila Pino-Belmar, Rayén Aguilar, Guillermo E. Valenzuela-Nieto, Viviana A. Cavieres, Cristóbal Cerda-Troncoso, Valentina C. Navarrete, Paula Salazar, Patricia V. Burgos, Carola Otth, and Hianara A. Bustamante. An intrinsic host defense against hsv-1 relies on the activation of xenophagy with the active clearance of autophagic receptors. Cells, 13:1256, Jul 2024. URL: https://doi.org/10.3390/cells13151256, doi:10.3390/cells13151256. This article has 12 citations.
(pinobelmar2024anintrinsichost pages 8-10): Camila Pino-Belmar, Rayén Aguilar, Guillermo E. Valenzuela-Nieto, Viviana A. Cavieres, Cristóbal Cerda-Troncoso, Valentina C. Navarrete, Paula Salazar, Patricia V. Burgos, Carola Otth, and Hianara A. Bustamante. An intrinsic host defense against hsv-1 relies on the activation of xenophagy with the active clearance of autophagic receptors. Cells, 13:1256, Jul 2024. URL: https://doi.org/10.3390/cells13151256, doi:10.3390/cells13151256. This article has 12 citations.
(pinobelmar2024anintrinsichost pages 1-2): Camila Pino-Belmar, Rayén Aguilar, Guillermo E. Valenzuela-Nieto, Viviana A. Cavieres, Cristóbal Cerda-Troncoso, Valentina C. Navarrete, Paula Salazar, Patricia V. Burgos, Carola Otth, and Hianara A. Bustamante. An intrinsic host defense against hsv-1 relies on the activation of xenophagy with the active clearance of autophagic receptors. Cells, 13:1256, Jul 2024. URL: https://doi.org/10.3390/cells13151256, doi:10.3390/cells13151256. This article has 12 citations.
(rasmussen2022nbr1thearchetypal pages 11-12): Nikoline Lander Rasmussen, Athanasios Kournoutis, Trond Lamark, and Terje Johansen. Nbr1: the archetypal selective autophagy receptor. The Journal of Cell Biology, Oct 2022. URL: https://doi.org/10.1083/jcb.202208092, doi:10.1083/jcb.202208092. This article has 110 citations.
(cerdatroncoso2021protumoralfunctionsof pages 6-7): Cristóbal Cerda-Troncoso, Manuel Varas-Godoy, and Patricia V. Burgos. Pro-tumoral functions of autophagy receptors in the modulation of cancer progression. Frontiers in Oncology, Feb 2021. URL: https://doi.org/10.3389/fonc.2020.619727, doi:10.3389/fonc.2020.619727. This article has 19 citations.
(trapannone2023p62andnbr1 pages 7-9): Riccardo Trapannone, Julia Romanov, and Sascha Martens. P62 and nbr1 functions are dispensable for aggrephagy in mouse escs and esc-derived neurons. Life Science Alliance, 6:e202301936, Aug 2023. URL: https://doi.org/10.26508/lsa.202301936, doi:10.26508/lsa.202301936. This article has 6 citations and is from a peer-reviewed journal.
(OpenTargets Search: -NBR1): Open Targets Query (-NBR1, 13 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.
(rasmussen2022nbr1thearchetypal media 47b06603): Nikoline Lander Rasmussen, Athanasios Kournoutis, Trond Lamark, and Terje Johansen. Nbr1: the archetypal selective autophagy receptor. The Journal of Cell Biology, Oct 2022. URL: https://doi.org/10.1083/jcb.202208092, doi:10.1083/jcb.202208092. This article has 110 citations.
(rasmussen2022nbr1thearchetypal media 07b5ca64): Nikoline Lander Rasmussen, Athanasios Kournoutis, Trond Lamark, and Terje Johansen. Nbr1: the archetypal selective autophagy receptor. The Journal of Cell Biology, Oct 2022. URL: https://doi.org/10.1083/jcb.202208092, doi:10.1083/jcb.202208092. This article has 110 citations.
(trapannone2023p62andnbr1 pages 9-12): Riccardo Trapannone, Julia Romanov, and Sascha Martens. P62 and nbr1 functions are dispensable for aggrephagy in mouse escs and esc-derived neurons. Life Science Alliance, 6:e202301936, Aug 2023. URL: https://doi.org/10.26508/lsa.202301936, doi:10.26508/lsa.202301936. This article has 6 citations and is from a peer-reviewed journal.
(pinobelmar2024anintrinsichost pages 2-3): Camila Pino-Belmar, Rayén Aguilar, Guillermo E. Valenzuela-Nieto, Viviana A. Cavieres, Cristóbal Cerda-Troncoso, Valentina C. Navarrete, Paula Salazar, Patricia V. Burgos, Carola Otth, and Hianara A. Bustamante. An intrinsic host defense against hsv-1 relies on the activation of xenophagy with the active clearance of autophagic receptors. Cells, 13:1256, Jul 2024. URL: https://doi.org/10.3390/cells13151256, doi:10.3390/cells13151256. This article has 12 citations.
(rasmussen2022nbr1thearchetypal pages 8-10): Nikoline Lander Rasmussen, Athanasios Kournoutis, Trond Lamark, and Terje Johansen. Nbr1: the archetypal selective autophagy receptor. The Journal of Cell Biology, Oct 2022. URL: https://doi.org/10.1083/jcb.202208092, doi:10.1083/jcb.202208092. This article has 110 citations.

Artifacts

Edison artifact artifact-00

Citations

vargas2023themechanismsand pages 1-6
song2024selectiveautophagyreceptor pages 8-10
song2024selectiveautophagyreceptor pages 1-2
song2024selectiveautophagyreceptor pages 5-8
pinobelmar2024anintrinsichost pages 6-8
pinobelmar2024anintrinsichost pages 8-10
cerdatroncoso2021protumoralfunctionsof pages 6-7
cerdatroncoso2021protumoralfunctionsof pages 7-8
pinobelmar2024anintrinsichost pages 1-2
pinobelmar2024anintrinsichost pages 2-3
https://doi.org/10.1083/jcb.202208092
https://doi.org/10.3389/fonc.2020.619727
https://doi.org/10.1101/2024.05.09.593318
https://doi.org/10.1038/s41580-022-00542-2
https://doi.org/10.26508/lsa.202301936
https://doi.org/10.3390/cells13151256
https://doi.org/10.7150/ijbs.90186
https://doi.org/10.1083/jcb.202208092,
https://doi.org/10.1038/s41580-022-00542-2,
https://doi.org/10.3389/fonc.2020.619727,
https://doi.org/10.1101/2024.05.09.593318,
https://doi.org/10.7150/ijbs.90186,
https://doi.org/10.3390/cells13151256,
https://doi.org/10.26508/lsa.202301936,

📚 Additional Documentation

Notes

(NBR1-notes.md)

NBR1 (Next to BRCA1 gene 1 protein) — review notes

UniProt: Q14596 (NBR1_HUMAN), 966 aa. HGNC:6746. Located head-to-head with BRCA1 at 17q21.

Domain architecture (UniProt features)

PB1 domain (4–85): mediates self-oligomerization and heterodimerization with SQSTM1/p62 [PMID:12813044; PMID:19250911]. Asp-50 is required for p62 interaction.
ZZ-type zinc finger (212–264): binds two Zn2+ ions (8 coordinating residues). Basis of GO:0008270 zinc ion binding.
ATG8/LIR regions (542–636 and 727–738): LC3-interacting regions; Tyr-732 mutation abolishes ATG8-family binding PMID:19250911.
UBA domain (913–957): binds K48- and K63-linked polyubiquitin; F929A abolishes ubiquitin binding [PMID:24692539, PMID:19427866].
An Ig-like / FW region (Nbr1_FW, ~365–485; PDB 4OLE).

Core function: ubiquitin-binding selective autophagy receptor

NBR1 is a ubiquitin-binding autophagy cargo receptor that, like its functional partner SQSTM1/p62, bridges ubiquitinated cargo to ATG8/LC3 on the forming autophagosome.
- PMID:19250911 — NBR1 contains PB1, ZZ, two LIR/ATG8-binding regions, and a UBA domain; interacts with SQSTM1, MAP1LC3A/B/C, GABARAP, GABARAPL1, GABARAPL2; required for autophagosomal degradation of ubiquitinated substrates; Asp-50 (p62 binding) and Tyr-732 (ATG8 binding) mutants characterized.
- PMID:19427866. Also binds USP8 and p14/Robld3 (endosomal trafficking).
- PMID:24692539 — F929A complete loss of ubiquitin binding; structural basis of UBA-Ub binding. (Not cached; verified via PubMed and UniProt features.)
- PMID:34471133 — in vitro reconstitution; NBR1 (with p62/TAX1BP1) drives ubiquitin condensate formation and autophagy initiation. Interacts with TAX1BP1. full_text_available: true.
- PMID:33226137 — receptor-mediated clustering of FIP200; NBR1 flux used as a selective-autophagy readout; NBR1 interacts with TAX1BP1.

Aggrephagy / protein aggregation

PMID:24879152 — NBR1 promotes formation of ubiquitinated protein aggregates; GSK3A phosphorylation at Thr-586 inhibits this; relevant to inclusion body myositis. Supports aggrephagy (GO:0035973) and the dual aggregate-formation function noted in UniProt.
PMID:20417604 — Alfy/WDFY3 scaffolds selective macroautophagy of aggregated proteins with p62/NBR1-positive proteins (NBR1 contextually a cargo partner). Background/context, NBR1 named in network.

Pexophagy (peroxisome turnover)

Reactome R-HSA-9664873 "Pexophagy"; reactions R-HSA-9664867/9664880/9664881 (NBR1 binds MAP1LC3B; MAP1LC3B binds ATM:Ub-p-PEX5:SQSTM1:NBR1; NBR1 binds ATM:Ub-p-PEX5:SQSTM1). NBR1 (with p62) is the receptor for ubiquitinated PEX5 / peroxisomal membrane proteins → peroxisomal membrane localization (GO:0005778) is functionally grounded.

Innate immunity / antiviral selective autophagy

PMID:35914352 — NBR1 binds IRF3 (both unphosphorylated and phosphorylated) and targets it for autophagic degradation; negatively regulates type I IFN. Interacts with IRF3; induced upon viral infection.
PMID:33577621 — NBR1 recognizes ubiquitinated MAVS (K27-linked) and delivers it to autophagosomes; influenza PB1 hijacks this; NBR1 deficiency impairs MAVS degradation. Verified via PubMed (not cached). Supports antiviral innate immune response / selective autophagy roles.

SRBD1 clearance / cellular senescence

PMID:38169523 — NBR1 interacts with SRBD1 and clears it via the autophagic-lysosomal pathway, retarding nucleus pulposus cell senescence. full_text_available: true.

FGFR / endosomal signaling

PMID:19822672 — NBR1 as late endosomal protein in FGFR down-regulation. Supports late endosome (GO:0005770) localization.

Bone / osteoblast / MAPK (mouse-derived, ISS/IEA from Ensembl Compara to mouse ortholog P97432/Q501R9)

The negative regulation of osteoblast differentiation (GO:0045668), regulation of bone mineralization (GO:0030500), regulation of stress-activated MAPK cascade (GO:0032872) and MAPK binding (GO:0051019) annotations originate from BHF-UCL ISS and Ensembl Compara IEA, ultimately tracing to mouse Nbr1 work (Whitehouse et al.; p38 MAPK scaffold / osteoblast studies). NBR1 functions as a p38/MAPK scaffold and a truncated-NBR1 transgenic mouse shows increased bone mass via osteoblast effects. These are real but secondary/pleiotropic roles, supported only by ISS/IEA in human → KEEP_AS_NON_CORE.

Th2 / PB1 signalling adapter

PMID:20808283 — T-cell-specific NBR1-deficient mice; impaired Th2 differentiation. PB1-domain adapter role; pleiotropic/immune developmental role (no GO term currently annotated from it; it is one of the IPI protein-binding sources).

Sarcomere / M band / titin

UniProt: Cytoplasm, myofibril, sarcomere, M line (by similarity to mouse Q501R9). Interacts with titin/TTN and TRIM55 PMID:15802564. Basis of M band (GO:0031430) IEA-SubCell. Real but tissue-specific (cardiac/skeletal muscle) → KEEP_AS_NON_CORE.

Localization summary

Cytoplasm/cytosol (core), autophagosome/phagophore assembly site, lysosome (degraded there), late endosome, peroxisomal membrane (pexophagy), M band (muscle). Mitochondrion colocalization (GO:0005739, PMID:21296869) reflects Parkin-mitophagy context. Mitochondrial intermembrane space (GO:0005758, Ensembl IEA) and membrane (GO:0016020, HDA from NK-cell membrane proteome PMID:19946888) are low-confidence/generic.

Protein binding (IPI) sources

Many GO:0005515 protein binding annotations from interactome/specific studies: PMID:19250911 (SQSTM1, ATG8s), 19427866 (USP8, ubiquitin), 20010802 (Nix mitophagy context), 20368287 (PI3K-mTOR interactome), 20417604 (Alfy), 20562859 (autophagy network), 20808283 (Th2 PB1 adapter), 24879152 (GSK3), 25416956/33961781 (HuRI/BioPlex interactomes), 29568061 (MAC-tag), 30824926 (GSK3A/sperm), 34524948 (macroautophagy proximity interactome), 19822672 (Spred2/FGFR). All KEEP_AS_NON_CORE per "avoid bare protein binding" guideline; informative partners noted in reasons.

Key GO terms verified via QuickGO API

GO:0035973 aggrephagy = "selective degradation of protein aggregates by macroautophagy"
GO:0000425 pexophagy
GO:0160247 autophagy cargo adaptor activity = "binding activity of a molecule that brings together a cargo, targeted for degradation via autophagy, to a phagophore" (the precise MF for an autophagy receptor)
GO:0061753 substrate localization to autophagosome
GO:0032480 negative regulation of type I interferon production
GO:0140374 antiviral innate immune response

Pn Notes

(NBR1-pn-notes.md)

NBR1 PN Consistency Notes

Generated: 2026-06-18
Project: PROTEOSTASIS
Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
UniProt: Q14596
AIGR review status: COMPLETE
Review batch: proteostasis-batch-2026-06-14
Batch change status: added

Source Files Checked

AIGR review YAML: present - genes/human/NBR1/NBR1-ai-review.yaml
AIGR review HTML: missing - genes/human/NBR1/NBR1-ai-review.html
Gene notes: present - genes/human/NBR1/NBR1-notes.md
GOA TSV: present - genes/human/NBR1/NBR1-goa.tsv
UniProt record: present - genes/human/NBR1/NBR1-uniprot.txt
PN dossier: projects/PROTEOSTASIS/reports/phase1_dossiers/NBR1.md
PN consistency section: projects/PROTEOSTASIS/reports/phase1_dossiers/_sections/NBR1.md
PN projection report: projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv
PN mapping audit: projects/PROTEOSTASIS/reports/pn_mapping_audit/current_mapping_scrutiny.tsv

Deep Research Files

genes/human/NBR1/NBR1-deep-research-falcon.md

AIGR Review Snapshot

Description: 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.
Existing/core annotation action counts: ACCEPT: 10; KEEP_AS_NON_CORE: 38; NEW: 3; REMOVE: 1; UNDECIDED: 1

PN Consistency Summary

Consistency: Highly consistent. Deep research (Rasmussen 2022 JCB; Vargas 2023 NRMCB) confirms archetypal SLR — UBA polyUb binding, LIR, AH+UBA peroxisome targeting, p62-body recruitment. Review and PN both center the cargo-adaptor/receptor MF. Notable nuance both capture: NBR1/p62 can be dispensable for aggrephagy in some cell types (Trapannone 2023) — receptor redundancy, not a contradiction. Review REMOVEs GO:0005758 mito intermembrane space (no support; only colocalizes with mitochondria during mitophagy) — well-justified.
PN story / NEW pressure: Review proactively adds the same receptor MF the PN elevates: GO:0160247 autophagy cargo adaptor activity as NEW (action: NEW), plus GO:0035973 aggrephagy NEW and GO:0032480 negative regulation of type I IFN production NEW. Review also proposes a child term pexophagy receptor activity under GO:0160247. So PN's GO:0000425 pexophagy (process) is captured by review only at the MF/locational level, not as the BP term GO:0000425 — a minor gap (review has peroxisomal-membrane locations + proposed pexophagy-receptor MF but no GO:0000425 BP annotation).
Evidence alignment: Strong ALP-branch overlap (Kirkin 2009 "A Role for NBR1...", TRAF6/midbody, CEP55, peroxisome receptor). Review adds Rasmussen 2022 reconstitution not in PN refs.
Verdict: CONSISTENT and convergent — review already adds GO:0160247 NEW. Minor: consider adding GO:0000425 pexophagy BP to match PN projection. Recommended edits: consider [YAML] add existing/new GO:0000425 pexophagy (involved_in) to NBR1 review to mirror PN projection and SQSTM1 co-receptor evidence.

Full Consistency Review

UniProt: Q14596 · batch: proteostasis-batch-2026-06-14 · review status: COMPLETE (~1021 lines)
PN placement: ALP Autophagy substrate selection|Selective autophagy receptor|{Pexophagy,Aggrephagy,Midbody autophagy} + UPS Ubiquitin and UBL binding|trafficking|selective autophagy|UBA ; PN-node mapping: Pexophagy→GO:0000425, Aggrephagy→GO:0035973, Midbody→GO:0160247 cargo adaptor; ancestors no_mapping/context_only.
Consistency: Highly consistent. Deep research (Rasmussen 2022 JCB; Vargas 2023 NRMCB) confirms archetypal SLR — UBA polyUb binding, LIR, AH+UBA peroxisome targeting, p62-body recruitment. Review and PN both center the cargo-adaptor/receptor MF. Notable nuance both capture: NBR1/p62 can be dispensable for aggrephagy in some cell types (Trapannone 2023) — receptor redundancy, not a contradiction. Review REMOVEs GO:0005758 mito intermembrane space (no support; only colocalizes with mitochondria during mitophagy) — well-justified.
PN story / NEW pressure: Review proactively adds the same receptor MF the PN elevates: GO:0160247 autophagy cargo adaptor activity as NEW (action: NEW), plus GO:0035973 aggrephagy NEW and GO:0032480 negative regulation of type I IFN production NEW. Review also proposes a child term pexophagy receptor activity under GO:0160247. So PN's GO:0000425 pexophagy (process) is captured by review only at the MF/locational level, not as the BP term GO:0000425 — a minor gap (review has peroxisomal-membrane locations + proposed pexophagy-receptor MF but no GO:0000425 BP annotation).
Mapping strategy: Mappings sound. KEY PATTERN fully realized: review independently elevated GO:0160247 over bare protein binding (~12 IPI kept non-core). PN GO:0160247 (more_specific_than_existing_goa) matches the review's NEW exactly.
Evidence alignment: Strong ALP-branch overlap (Kirkin 2009 "A Role for NBR1...", TRAF6/midbody, CEP55, peroxisome receptor). Review adds Rasmussen 2022 reconstitution not in PN refs.
Verdict: CONSISTENT and convergent — review already adds GO:0160247 NEW. Minor: consider adding GO:0000425 pexophagy BP to match PN projection. Recommended edits: consider [YAML] add existing/new GO:0000425 pexophagy (involved_in) to NBR1 review to mirror PN projection and SQSTM1 co-receptor evidence.

PN Dossier Context

review_batch: proteostasis-batch-2026-06-14
review_yaml: genes/human/NBR1/NBR1-ai-review.yaml
PN workbook rows: 4

PN row 1: Autophagy-Lysosome Pathway | Autophagy substrate selection | Selective autophagy receptor | Pexophagy

UniProt: Q14596
In branches: ALP, UPS
Notes: Receptor for selective autophagy. Binds to ATG8 and ubiquitinated or degron-contaning substrates. Active in aggrephagy, Ub-dependent pexophagy, midbody autophagy. Its amphipathic α-helical J domain, the ubiquitin-associated (UBA) domain, the LC3-interacting region and the coiled-coil domain are necessary to mediate pexophagy. Interacts with adaptor protein WDFY3/ALFY form a complex with the ubiquitin E3 ligase TRAF6, important for efficient clearance of midbody ring derivatives by autophagy. Binds to midbody protein CEP55 to facilitate midbody clearance.
PN references (titles):
- Selective Autophagy: ATG8 Family Proteins, LIR Motifs and Cargo Receptors - ScienceDirect
- NBR1 acts as an autophagy receptor for peroxisomes
- A Role for NBR1 in Autophagosomal Degradation of Ubiquitinated Substrates
- TRAF6 mediates ubiquitination of KIF23/MKLP1 and is required for midbody ring degradation by selective autophagy
- Midbody accumulation through evasion of autophagy contributes to cellular reprogramming and tumorigenicity
PN-node mapping records (path + ancestors):
- [type] Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor|Pexophagy
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0000425 pexophagy]
  rationale: This PN path groups receptors for selective autophagic turnover of peroxisomes. The role is part of, but not equivalent to, the full GO pexophagy process, so propagation scope is appropriate.
- [group] Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad PN taxonomy container. The descendants mix components, regulators, context labels, and mechanistic leaves, so propagation should come only from narrower curated nodes.
- [class] Autophagy-Lysosome Pathway|Autophagy substrate selection
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad substrate-selection container. GO has useful targets for specific receptor, cargo-adaptor, and selective-autophagy leaves, but this class mixes marking, recognition, receptor regulation, and unknown roles and should not propagate as one term.
- [branch] Autophagy-Lysosome Pathway
  status=no_mapping scope= GO=[]
  rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

PN row 2: Autophagy-Lysosome Pathway | Autophagy substrate selection | Selective autophagy receptor | Aggrephagy

UniProt: Q14596
In branches: ALP, UPS
Notes: Receptor for selective autophagy. Binds to ATG8 and ubiquitinated or degron-contaning substrates. Active in aggrephagy, Ub-dependent pexophagy, midbody autophagy. Its amphipathic α-helical J domain, the ubiquitin-associated (UBA) domain, the LC3-interacting region and the coiled-coil domain are necessary to mediate pexophagy. Interacts with adaptor protein WDFY3/ALFY form a complex with the ubiquitin E3 ligase TRAF6, important for efficient clearance of midbody ring derivatives by autophagy. Binds to midbody protein CEP55 to facilitate midbody clearance.
PN references (titles):
- Selective Autophagy: ATG8 Family Proteins, LIR Motifs and Cargo Receptors - ScienceDirect
- NBR1 acts as an autophagy receptor for peroxisomes
- A Role for NBR1 in Autophagosomal Degradation of Ubiquitinated Substrates
- TRAF6 mediates ubiquitination of KIF23/MKLP1 and is required for midbody ring degradation by selective autophagy
- Midbody accumulation through evasion of autophagy contributes to cellular reprogramming and tumorigenicity
PN-node mapping records (path + ancestors):
- [type] Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor|Aggrephagy
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0035973 aggrephagy]
  rationale: This PN path denotes receptors that recognize aggregation cargo for the aggrephagy pathway. The category is not identical to the GO process term, but propagation to aggrephagy is appropriate because membership in this receptor class implies direct participation in that process.
- [group] Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad PN taxonomy container. The descendants mix components, regulators, context labels, and mechanistic leaves, so propagation should come only from narrower curated nodes.
- [class] Autophagy-Lysosome Pathway|Autophagy substrate selection
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad substrate-selection container. GO has useful targets for specific receptor, cargo-adaptor, and selective-autophagy leaves, but this class mixes marking, recognition, receptor regulation, and unknown roles and should not propagate as one term.
- [branch] Autophagy-Lysosome Pathway
  status=no_mapping scope= GO=[]
  rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

PN row 3: Autophagy-Lysosome Pathway | Autophagy substrate selection | Selective autophagy receptor | Midbody autophagy

UniProt: Q14596
In branches: ALP, UPS
Notes: Receptor for selective autophagy. Binds to ATG8 and ubiquitinated or degron-contaning substrates. Active in aggrephagy, Ub-dependent pexophagy, midbody autophagy. Its amphipathic α-helical J domain, the ubiquitin-associated (UBA) domain, the LC3-interacting region and the coiled-coil domain are necessary to mediate pexophagy. Interacts with adaptor protein WDFY3/ALFY form a complex with the ubiquitin E3 ligase TRAF6, important for efficient clearance of midbody ring derivatives by autophagy. Binds to midbody protein CEP55 to facilitate midbody clearance.
PN references (titles):
- Selective Autophagy: ATG8 Family Proteins, LIR Motifs and Cargo Receptors - ScienceDirect
- NBR1 acts as an autophagy receptor for peroxisomes
- A Role for NBR1 in Autophagosomal Degradation of Ubiquitinated Substrates
- TRAF6 mediates ubiquitination of KIF23/MKLP1 and is required for midbody ring degradation by selective autophagy
- Midbody accumulation through evasion of autophagy contributes to cellular reprogramming and tumorigenicity
PN-node mapping records (path + ancestors):
- [type] Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor|Midbody autophagy
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0160247 autophagy cargo adaptor activity]
  rationale: Midbody-autophagy receptors such as SQSTM1 link ubiquitinated midbody material to the autophagy machinery. GO does not currently expose a dedicated midbody-autophagy process term in the local ontology cache, so the receptor activity term is the best available mapping target.
- [group] Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad PN taxonomy container. The descendants mix components, regulators, context labels, and mechanistic leaves, so propagation should come only from narrower curated nodes.
- [class] Autophagy-Lysosome Pathway|Autophagy substrate selection
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad substrate-selection container. GO has useful targets for specific receptor, cargo-adaptor, and selective-autophagy leaves, but this class mixes marking, recognition, receptor regulation, and unknown roles and should not propagate as one term.
- [branch] Autophagy-Lysosome Pathway
  status=no_mapping scope= GO=[]
  rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

PN row 4: Ubiquitin Proteasome System | Ubiquitin and UBL binding | trafficking | selective autophagy | UBA

UniProt: Q14596
In branches: ALP, UPS
Signature domains: IPR015940
Auxiliary domains: (none)
PN-node mapping records (path + ancestors):
- [subtype] Ubiquitin Proteasome System|Ubiquitin and UBL binding|trafficking|selective autophagy|UBA
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a selective-autophagy or trafficking subdivision under a UPS binding context. The autophagy context is real, but this node is too indirect for automatic GO propagation.
- [type] Ubiquitin Proteasome System|Ubiquitin and UBL binding|trafficking|selective autophagy
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a UPS taxonomy container. Its descendants mix catalytic roles, complex membership, binding domains, regulators, adaptors, and substrate-context labels, so a single propagating GO assertion would overstate the shared biology.
- [group] Ubiquitin Proteasome System|Ubiquitin and UBL binding|trafficking
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a UPS taxonomy container. Its descendants mix catalytic roles, complex membership, binding domains, regulators, adaptors, and substrate-context labels, so a single propagating GO assertion would overstate the shared biology.
- [class] Ubiquitin Proteasome System|Ubiquitin and UBL binding
  status=context_only scope=too_broad_to_propagate GO=[GO:0140036 ubiquitin-modified protein reader activity]
  rationale: This class records ubiquitin/UBL-reader context, but the subtree mixes ubiquitin, SUMO, UBL-domain, domain-architecture, catalytic, signaling, trafficking, and nucleic-acid process buckets. It is useful context, not a safe direct propagation.
- [branch] Ubiquitin Proteasome System
  status=no_mapping scope= GO=[]
  rationale: Reviewed as the top-level UPS branch. It is a project taxonomy umbrella rather than a direct GO assertion; UPS propagation must come from manually curated child nodes.

Projected GO annotations (3)

GO:0000425 pexophagy | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor|Pexophagy
GO:0035973 aggrephagy | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor|Aggrephagy
GO:0160247 autophagy cargo adaptor activity | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor|Midbody autophagy

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

id: Q14596
gene_symbol: NBR1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  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.
alternative_products:
- name: '1'
  id: Q14596-1
- name: '2'
  id: Q14596-2
  sequence_note: VSP_004314
existing_annotations:
- term:
    id: GO:0000407
    label: phagophore assembly site
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:34471133
      supporting_text: roles of p62, NBR1 and TAX1BP1 in ubiquitin condensate formation and autophagy initiation
- term:
    id: GO:0016236
    label: macroautophagy
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetic inference of involvement in macroautophagy, the core process in which NBR1 functions as a selective cargo receptor.
    action: ACCEPT
    reason: Core biological process; directly supported by experimental evidence that NBR1 mediates autophagosomal degradation of ubiquitinated substrates.
    supported_by:
    - reference_id: PMID:19250911
      supporting_text: NBR1 and p62 act as receptors for selective autophagosomal degradation of
- term:
    id: GO:0043130
    label: ubiquitin binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Phylogenetic inference of ubiquitin binding, the core molecular function of the UBA domain that recognizes K48/K63 polyubiquitin on cargo.
    action: ACCEPT
    reason: Core molecular function; experimentally demonstrated for the NBR1 UBA domain, redundant with the IDA annotation.
    supported_by:
    - reference_id: PMID:19427866
      supporting_text: the nbr1 UBA domain binds to lysine-48 and -63 linked polyubiquitin-B chains
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic transfer of cytoplasmic localization from the UniProt subcellular location, the dominant compartment where NBR1 operates.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic; the more specific cytosol and autophagosome/phagophore localizations better capture NBR1's site of action.
    supported_by:
    - reference_id: file:human/NBR1/NBR1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005764
    label: lysosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic transfer of lysosomal localization; NBR1 is delivered to lysosomes with its cargo and degraded there.
    action: KEEP_AS_NON_CORE
    reason: Experimentally supported endpoint localization (NBR1 is degraded in lysosomes) but reflects cargo delivery rather than a distinct functional compartment.
    supported_by:
    - reference_id: file:human/NBR1/NBR1-uniprot.txt
      supporting_text: Is targeted to lysosomes for degradation
- term:
    id: GO:0005776
    label: autophagosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: Electronic assignment (multiple IEA methods) of autophagosome localization, where NBR1 is sequestered with cargo via ATG8/LC3 binding.
    action: ACCEPT
    reason: Correct and functionally central localization; NBR1 binds lipidated ATG8 proteins and is incorporated into autophagosomes.
    supported_by:
    - reference_id: file:human/NBR1/NBR1-uniprot.txt
      supporting_text: Cytoplasmic vesicle, autophagosome
- term:
    id: GO:0005778
    label: peroxisomal membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-9664881
      supporting_text: NBR1 binds ATM:Ub-p-PEX5:SQSTM1
- term:
    id: GO:0008270
    label: zinc ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro-based electronic assignment of zinc ion binding, reflecting the ZZ-type zinc finger that coordinates two Zn2+ ions.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:human/NBR1/NBR1-uniprot.txt
      supporting_text: ZN_FING         212..264
- term:
    id: GO:0031430
    label: M band
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic transfer of sarcomeric M-line localization (by similarity to the mouse ortholog), reflecting NBR1's titin-associated role in striated muscle.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:human/NBR1/NBR1-uniprot.txt
      supporting_text: Cytoplasm, myofibril, sarcomere, M line
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19250911
  qualifier: enables
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:human/NBR1/NBR1-uniprot.txt
      supporting_text: Interacts with SQSTM1 (PubMed:19250911)
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19427866
  qualifier: enables
  review:
    summary: Interactions with LC3-A, polyubiquitin, USP8 and p14/Robld3. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records real interactions (LC3, USP8) but bare protein binding is uninformative; the informative content is captured by ubiquitin binding and ATG8 binding.
    supported_by:
    - reference_id: PMID:19427866
      supporting_text: Nbr1 also binds to the autophagic effector protein LC3-A via a novel binding site
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20010802
  qualifier: enables
  review:
    summary: Interaction reported in the Nix/mitophagy receptor study (NBR1 in the LC3/GABARAP receptor network). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-relevance receptor-network context but bare protein binding is uninformative.
    supported_by:
    - reference_id: PMID:20010802
      supporting_text: the mitochondrial protein Nix is a selective autophagy receptor by binding to
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20368287
  qualifier: enables
  review:
    summary: Interaction from a PI3K-mTOR pathway interactome map. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome; bare protein binding is uninformative.
    supported_by:
    - reference_id: PMID:20368287
      supporting_text: Interactome mapping of the phosphatidylinositol 3-kinase
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20417604
  qualifier: enables
  review:
    summary: Interaction in the Alfy/WDFY3 aggrephagy scaffold study (NBR1/p62-positive aggregate clearance). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Relevant aggrephagy context (Alfy bridges p62/NBR1 aggregates to the autophagy machinery) but bare protein binding is uninformative.
    supported_by:
    - reference_id: PMID:20417604
      supporting_text: Alfy is recruited to intracellular inclusions and scaffolds a complex between
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20562859
  qualifier: enables
  review:
    summary: Interaction from a network analysis of the human autophagy system. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Autophagy-network interactome; bare protein binding is uninformative.
    supported_by:
    - reference_id: PMID:20562859
      supporting_text: Network organization of the human autophagy system
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20808283
  qualifier: enables
  review:
    summary: Interaction(s) from the Th2/PB1 signalling adapter study. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Relevant to NBR1's PB1-domain signaling-adapter role in Th2 differentiation but bare protein binding is uninformative.
    supported_by:
    - reference_id: PMID:20808283
      supporting_text: NBR1 is a new PB1 signalling adapter in Th2 differentiation
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24879152
  qualifier: enables
  review:
    summary: Interaction with GSK3 (which phosphorylates NBR1 at Thr-586 to modulate aggregation). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a functionally relevant GSK3 interaction but bare protein binding is uninformative.
    supported_by:
    - reference_id: PMID:24879152
      supporting_text: NBR1 phosphorylation by GSK3 at Thr586 prevents the aggregation of ubiquitinated proteins
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: High-throughput proteome-scale (HuRI) interactome interaction. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome; bare protein binding is uninformative.
    supported_by:
    - reference_id: PMID:25416956
      supporting_text: A proteome-scale map of the human interactome network
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29568061
  qualifier: enables
  review:
    summary: Interaction/localization from a MAC-tag (AP-MS/BioID) study. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput proximity/interaction mapping; bare protein binding is uninformative.
    supported_by:
    - reference_id: PMID:29568061
      supporting_text: MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:30824926
  qualifier: enables
  review:
    summary: GSK3A-related interaction from a sperm-motility study. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a GSK3A interaction context but bare protein binding is uninformative.
    supported_by:
    - reference_id: PMID:30824926
      supporting_text: Isoform-specific GSK3A activity is negatively correlated with human sperm
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: High-throughput cell-specific (BioPlex) interactome interaction. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome; bare protein binding is uninformative.
    supported_by:
    - reference_id: PMID:33961781
      supporting_text: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:34524948
  qualifier: enables
  review:
    summary: Proximity-interactome interaction from a global map of the human macroautophagy pathway. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-relevance macroautophagy proximity interactome but bare protein binding is uninformative.
    supported_by:
    - reference_id: PMID:34524948
      supporting_text: Global Proximity Interactome of the Human Macroautophagy Pathway
- term:
    id: GO:0000407
    label: phagophore assembly site
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Electronic transfer (Ensembl Compara) of phagophore assembly site localization, where NBR1 functions during autophagosome formation.
    action: ACCEPT
    reason: Correct and functionally central localization; redundant with the IBA phagophore assembly site annotation.
    supported_by:
    - reference_id: PMID:34471133
      supporting_text: roles of p62, NBR1 and TAX1BP1 in ubiquitin condensate formation and autophagy initiation
- term:
    id: GO:0005758
    label: mitochondrial intermembrane space
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    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.
    action: REMOVE
    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.
    supported_by:
    - reference_id: file:human/NBR1/NBR1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Functionally grounded secondary localization (FGFR/receptor trafficking) supported by experimental work; not the core autophagy-receptor compartment.
    supported_by:
    - reference_id: PMID:19822672
      supporting_text: a novel late endosomal protein that directly binds to the EVH1 domain of Spred2
- term:
    id: GO:0030500
    label: regulation of bone mineralization
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Electronic transfer (Ensembl Compara) of a regulation-of-bone-mineralization role, derived from mouse Nbr1 osteoblast/bone studies.
    action: KEEP_AS_NON_CORE
    reason: Real but pleiotropic, tissue-specific role inferred from the mouse ortholog (no direct human experimental evidence); secondary to the core autophagy-receptor function.
    supported_by:
    - reference_id: file:human/NBR1/NBR1-uniprot.txt
      supporting_text: 'GO:0030500; P:regulation of bone mineralization; ISS:BHF-UCL'
- term:
    id: GO:0032872
    label: regulation of stress-activated MAPK cascade
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Electronic transfer (Ensembl Compara) of a stress-activated (p38) MAPK regulation role, reflecting NBR1's reported function as a PB1-domain MAPK scaffold.
    action: KEEP_AS_NON_CORE
    reason: Plausible PB1-domain scaffolding role inferred from orthologs; secondary/pleiotropic relative to the core autophagy function.
    supported_by:
    - reference_id: file:human/NBR1/NBR1-uniprot.txt
      supporting_text: 'GO:0032872; P:regulation of stress-activated MAPK cascade; ISS:BHF-UCL'
- term:
    id: GO:0045668
    label: negative regulation of osteoblast differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Electronic transfer (Ensembl Compara) of a negative-regulation-of-osteoblast-differentiation role, derived from mouse Nbr1 studies.
    action: KEEP_AS_NON_CORE
    reason: Real but pleiotropic role inferred from the mouse ortholog; secondary to the core autophagy-receptor function.
    supported_by:
    - reference_id: file:human/NBR1/NBR1-uniprot.txt
      supporting_text: 'GO:0045668; P:negative regulation of osteoblast differentiation; ISS:BHF-UCL'
- term:
    id: GO:0051019
    label: mitogen-activated protein kinase binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: Electronic transfer (Ensembl Compara) of MAPK binding, consistent with NBR1's reported p38/MAPK scaffolding activity.
    action: KEEP_AS_NON_CORE
    reason: Plausible scaffolding interaction inferred from orthologs; secondary to the core ubiquitin/ATG8 binding functions.
    supported_by:
    - reference_id: file:human/NBR1/NBR1-uniprot.txt
      supporting_text: 'GO:0051019; F:mitogen-activated protein kinase binding; ISS:BHF-UCL'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Immunofluorescence-curated (HPA) cytosolic localization, the core compartment in which NBR1 operates as a receptor.
    action: ACCEPT
    reason: Correct core localization directly supported by imaging data.
    supported_by:
    - reference_id: file:human/NBR1/NBR1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: EXP
  original_reference_id: PMID:19427866
  qualifier: located_in
  review:
    summary: Experimental cytoplasmic localization from the LC3/polyubiquitin study.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic; the specific cytosol/autophagosome localizations better capture the site of action.
    supported_by:
    - reference_id: PMID:19427866
      supporting_text: Ubiquitin-binding, but not PB1-mediated p62/SQSTM1 interaction, is required to target nbr1 to LC3
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: EXP
  original_reference_id: PMID:35914352
  qualifier: located_in
  review:
    summary: Experimental cytoplasmic localization from the IRF3 autophagic-degradation study.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic; redundant with the more specific cytosol annotation.
    supported_by:
    - reference_id: PMID:35914352
      supporting_text: NBR1 mediates autophagic degradation of IRF3
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: EXP
  original_reference_id: PMID:38169523
  qualifier: located_in
  review:
    summary: Experimental cytoplasmic localization from the SRBD1-clearance study.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic; redundant with the cytosol annotation.
    supported_by:
    - reference_id: PMID:38169523
      supporting_text: Selective Autophagy Receptor NBR1
- term:
    id: GO:0005764
    label: lysosome
  evidence_type: EXP
  original_reference_id: PMID:19250911
  qualifier: located_in
  review:
    summary: Experimental evidence that NBR1 is targeted to lysosomes for degradation along with its cargo.
    action: KEEP_AS_NON_CORE
    reason: Experimentally supported endpoint localization reflecting autophagic delivery and turnover rather than a distinct functional compartment.
    supported_by:
    - reference_id: file:human/NBR1/NBR1-uniprot.txt
      supporting_text: Is targeted to lysosomes for degradation
- term:
    id: GO:0043235
    label: signaling receptor complex
  evidence_type: IDA
  original_reference_id: PMID:19250911
  qualifier: part_of
  review:
    summary: Direct evidence (from the foundational study) placing NBR1 in a receptor complex (GOA renders this term as 'receptor complex').
    action: UNDECIDED
    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.
    supported_by:
    - reference_id: PMID:19250911
      supporting_text: NBR1 and p62 act as receptors for selective autophagosomal degradation of
- term:
    id: GO:0005778
    label: peroxisomal membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9664867
  qualifier: located_in
  review:
    summary: Reactome pexophagy curation (NBR1 binds MAP1LC3B) placing NBR1 at the peroxisomal membrane during peroxisome turnover.
    action: KEEP_AS_NON_CORE
    reason: Functionally grounded localization tied to the pexophagy substrate context; secondary to the general cytosolic receptor function.
    supported_by:
    - reference_id: Reactome:R-HSA-9664867
      supporting_text: NBR1 binds MAP1LC3B
- term:
    id: GO:0005778
    label: peroxisomal membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9664880
  qualifier: located_in
  review:
    summary: Reactome pexophagy curation (MAP1LC3B binds ATM:Ub-p-PEX5:SQSTM1:NBR1).
    action: KEEP_AS_NON_CORE
    reason: Functionally grounded pexophagy localization; secondary to the core receptor function and redundant with the other pexophagy reactions.
    supported_by:
    - reference_id: Reactome:R-HSA-9664880
      supporting_text: MAP1LC3B binds ATM dimer:Ub-p-PEX5:SQSTM1:NBR1
- term:
    id: GO:0005778
    label: peroxisomal membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9664881
  qualifier: located_in
  review:
    summary: Reactome pexophagy curation (NBR1 binds ATM:Ub-p-PEX5:SQSTM1).
    action: KEEP_AS_NON_CORE
    reason: Functionally grounded pexophagy localization; secondary to the core receptor function and redundant with the other pexophagy reactions.
    supported_by:
    - reference_id: Reactome:R-HSA-9664881
      supporting_text: NBR1 binds ATM:Ub-p-PEX5:SQSTM1
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: PMID:21296869
  qualifier: colocalizes_with
  review:
    summary: Direct evidence of NBR1 colocalization with mitochondria in the context of Parkin-mediated mitophagy.
    action: KEEP_AS_NON_CORE
    reason: Correct colocalization (colocalizes_with qualifier) reflecting recruitment to damaged mitochondria during mitophagy; a substrate context rather than a constitutive localization.
    supported_by:
    - reference_id: PMID:21296869
      supporting_text: Broad activation of the ubiquitin-proteasome system by Parkin is critical for
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  qualifier: located_in
  review:
    summary: High-throughput membrane-proteome detection of NBR1 (NK-cell membrane proteome).
    action: KEEP_AS_NON_CORE
    reason: Generic compartment from a high-throughput proteomics survey; consistent with membrane-associated autophagy/peroxisome/endosome pools but uninformative as a standalone term.
    supported_by:
    - reference_id: PMID:19946888
      supporting_text: Defining the membrane proteome of NK cells
- term:
    id: GO:0051019
    label: mitogen-activated protein kinase binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: Sequence-similarity transfer of MAPK binding, consistent with NBR1's reported p38/MAPK scaffolding role.
    action: KEEP_AS_NON_CORE
    reason: Plausible scaffolding interaction inferred by similarity; secondary to the core ubiquitin/ATG8 binding functions and redundant with the IEA MAPK-binding annotation.
    supported_by:
    - reference_id: file:human/NBR1/NBR1-uniprot.txt
      supporting_text: 'GO:0051019; F:mitogen-activated protein kinase binding; ISS:BHF-UCL'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19822672
  qualifier: enables
  review:
    summary: Interaction with Spred2 in the late-endosomal FGFR down-regulation pathway. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real, functionally relevant Spred2 interaction (FGFR trafficking) but bare protein binding is uninformative.
    supported_by:
    - reference_id: PMID:19822672
      supporting_text: NBR1 is a highly conserved multidomain protein that interacts and colocalizes with Spred2
- term:
    id: GO:0005776
    label: autophagosome
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: colocalizes_with
  review:
    summary: Sequence-similarity transfer of autophagosome colocalization.
    action: ACCEPT
    reason: Correct and functionally central localization; redundant with the IEA autophagosome annotation and supported by ATG8/LC3 binding.
    supported_by:
    - reference_id: file:human/NBR1/NBR1-uniprot.txt
      supporting_text: Cytoplasmic vesicle, autophagosome
- term:
    id: GO:0030500
    label: regulation of bone mineralization
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Sequence-similarity (BHF-UCL) transfer of a regulation-of-bone-mineralization role from mouse Nbr1.
    action: KEEP_AS_NON_CORE
    reason: Real but pleiotropic role inferred from the ortholog; secondary to the core autophagy function and redundant with the IEA annotation.
    supported_by:
    - reference_id: file:human/NBR1/NBR1-uniprot.txt
      supporting_text: 'GO:0030500; P:regulation of bone mineralization; ISS:BHF-UCL'
- term:
    id: GO:0032872
    label: regulation of stress-activated MAPK cascade
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Sequence-similarity (BHF-UCL) transfer of stress-activated MAPK regulation.
    action: KEEP_AS_NON_CORE
    reason: Plausible PB1-domain scaffolding role inferred by similarity; secondary/pleiotropic and redundant with the IEA annotation.
    supported_by:
    - reference_id: file:human/NBR1/NBR1-uniprot.txt
      supporting_text: 'GO:0032872; P:regulation of stress-activated MAPK cascade; ISS:BHF-UCL'
- term:
    id: GO:0045668
    label: negative regulation of osteoblast differentiation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Sequence-similarity (BHF-UCL) transfer of negative regulation of osteoblast differentiation from mouse Nbr1.
    action: KEEP_AS_NON_CORE
    reason: Real but pleiotropic role inferred from the ortholog; secondary to the core function and redundant with the IEA annotation.
    supported_by:
    - reference_id: file:human/NBR1/NBR1-uniprot.txt
      supporting_text: 'GO:0045668; P:negative regulation of osteoblast differentiation; ISS:BHF-UCL'
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: Sequence-similarity transfer of late endosome localization, consistent with the experimentally reported FGFR-trafficking role.
    action: KEEP_AS_NON_CORE
    reason: Functionally grounded secondary localization; redundant with the IEA late-endosome annotation.
    supported_by:
    - reference_id: PMID:19822672
      supporting_text: a novel late endosomal protein that directly binds to the EVH1 domain of Spred2
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:19250911
  qualifier: located_in
  review:
    summary: Direct cytosolic localization reported in the foundational autophagy-receptor study.
    action: ACCEPT
    reason: Correct core localization directly demonstrated.
    supported_by:
    - reference_id: file:human/NBR1/NBR1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0016236
    label: macroautophagy
  evidence_type: IDA
  original_reference_id: PMID:19250911
  qualifier: involved_in
  review:
    summary: Direct evidence that NBR1 mediates autophagosomal (macroautophagic) degradation of ubiquitinated substrates. Core biological process.
    action: ACCEPT
    reason: Core biological process directly demonstrated; NBR1 acts as a selective autophagy cargo receptor in macroautophagy.
    supported_by:
    - reference_id: PMID:19250911
      supporting_text: NBR1 and p62 act as receptors for selective autophagosomal degradation of
- term:
    id: GO:0043130
    label: ubiquitin binding
  evidence_type: IDA
  original_reference_id: PMID:19427866
  qualifier: enables
  review:
    summary: Direct evidence that the NBR1 UBA domain binds K48- and K63-linked polyubiquitin chains. Core molecular function.
    action: ACCEPT
    reason: Core molecular function; the UBA domain directly binds polyubiquitin (F929A abolishes binding), enabling recognition of ubiquitinated cargo.
    supported_by:
    - reference_id: PMID:19427866
      supporting_text: the nbr1 UBA domain binds to lysine-48 and -63 linked polyubiquitin-B chains
- term:
    id: GO:0160247
    label: autophagy cargo adaptor activity
  evidence_type: IDA
  original_reference_id: PMID:34471133
  qualifier: enables
  review:
    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.
    action: NEW
    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_replacement_terms:
    - id: GO:0160247
      label: autophagy cargo adaptor activity
    supported_by:
    - reference_id: PMID:34471133
      supporting_text: roles of p62, NBR1 and TAX1BP1 in ubiquitin condensate formation and autophagy initiation
- term:
    id: GO:0035973
    label: aggrephagy
  evidence_type: IMP
  original_reference_id: PMID:24879152
  qualifier: involved_in
  review:
    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.
    action: NEW
    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_replacement_terms:
    - id: GO:0035973
      label: aggrephagy
    supported_by:
    - reference_id: PMID:24879152
      supporting_text: NBR1 phosphorylation by GSK3 at Thr586 prevents the aggregation of ubiquitinated proteins
- term:
    id: GO:0032480
    label: negative regulation of type I interferon production
  evidence_type: IMP
  original_reference_id: PMID:35914352
  qualifier: involved_in
  review:
    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.
    action: NEW
    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_replacement_terms:
    - id: GO:0032480
      label: negative regulation of type I interferon production
    supported_by:
    - reference_id: PMID:35914352
      supporting_text: NBR1 mediates autophagic degradation of IRF3 to negatively regulate type I
core_functions:
- description: Acts as a ubiquitin-binding selective autophagy cargo receptor that bridges K48/K63-polyubiquitinated cargo (recognized by its UBA domain) to lipidated ATG8/LC3 family proteins (bound by its LIR regions) on the phagophore, delivering ubiquitinated substrates for macroautophagic degradation; functions in parallel with and as a heterooligomer of SQSTM1/p62.
  molecular_function:
    id: GO:0043130
    label: ubiquitin binding
  locations:
  - id: GO:0005829
    label: cytosol
  - id: GO:0000407
    label: phagophore assembly site
  supported_by:
  - reference_id: PMID:19250911
    supporting_text: NBR1 and p62 act as receptors for selective autophagosomal degradation of
  - reference_id: PMID:19427866
    supporting_text: the nbr1 UBA domain binds to lysine-48 and -63 linked polyubiquitin-B chains
  directly_involved_in:
  - id: GO:0016236
    label: macroautophagy
- description: Functions as an autophagy cargo adaptor that simultaneously engages cargo and the phagophore/ATG8 machinery, promoting the formation and clearance of ubiquitinated protein aggregates (aggrephagy); this aggregation-promoting activity is inhibited by GSK3-mediated phosphorylation at Thr-586.
  molecular_function:
    id: GO:0160247
    label: autophagy cargo adaptor activity
  locations:
  - id: GO:0005776
    label: autophagosome
  supported_by:
  - reference_id: PMID:24879152
    supporting_text: NBR1 phosphorylation by GSK3 at Thr586 prevents the aggregation of ubiquitinated proteins
  - reference_id: PMID:34471133
    supporting_text: roles of p62, NBR1 and TAX1BP1 in ubiquitin condensate formation and autophagy initiation
  directly_involved_in:
  - id: GO:0035973
    label: aggrephagy
- description: 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 antiviral-restricting pathway is hijacked by influenza A virus PB1.
  molecular_function:
    id: GO:0160247
    label: autophagy cargo adaptor activity
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: PMID:35914352
    supporting_text: NBR1 mediates autophagic degradation of IRF3 to negatively regulate type I
  directly_involved_in:
  - id: GO:0032480
    label: negative regulation of type I interferon production
proposed_new_terms:
- proposed_name: pexophagy receptor activity
  proposed_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.
  proposed_parent:
    id: GO:0160247
    label: autophagy cargo adaptor activity
  supported_by:
  - reference_id: Reactome:R-HSA-9664881
    supporting_text: NBR1 binds ATM:Ub-p-PEX5:SQSTM1
suggested_questions:
- question: 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?
- question: 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?
suggested_experiments:
- description: 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.
- description: 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.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:19250911
  title: A role for NBR1 in autophagosomal degradation of ubiquitinated substrates.
  findings:
  - statement: NBR1 is a ubiquitin-binding selective autophagy receptor that interacts with SQSTM1 and ATG8-family proteins and mediates autophagosomal degradation of ubiquitinated substrates.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Foundational study establishing NBR1 as an autophagy receptor. Abstract-only in cache; domain/mutagenesis detail corroborated by UniProt features.
- id: PMID:19427866
  title: Interactions with LC3 and polyubiquitin chains link nbr1 to autophagic protein turnover.
  findings:
  - statement: The NBR1 UBA domain binds K48- and K63-linked polyubiquitin; NBR1 binds LC3-A; ubiquitin binding (not PB1/p62 interaction) is required to target NBR1 to LC3/polyubiquitin bodies.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Establishes the core ubiquitin-binding and LC3-binding activities. Abstract available in cache.
- id: PMID:19822672
  title: Spred2 interaction with the late endosomal protein NBR1 down-regulates fibroblast growth factor receptor signaling.
  findings:
  - statement: NBR1 is a late endosomal protein that binds the EVH1 domain of Spred2; Spred2-mediated attenuation of FGF signaling depends on NBR1 and redirects activated receptors to lysosomal degradation.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Supports the late-endosome localization and a receptor-trafficking role.
- id: PMID:19946888
  title: Defining the membrane proteome of NK cells.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput membrane proteome; source of the generic membrane (HDA) annotation.
- id: PMID:20010802
  title: Nix is a selective autophagy receptor for mitochondrial clearance.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Establishes the LC3/GABARAP selective-autophagy receptor paradigm; NBR1 cited in the receptor network; source of a bare protein binding annotation.
- id: PMID:20368287
  title: Interactome mapping of the phosphatidylinositol 3-kinase-mammalian target of rapamycin pathway identifies deformed epidermal autoregulatory factor-1 as a new glycogen synthase kinase-3 interactor.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput interactome; source of a bare protein binding annotation.
- id: PMID:20417604
  title: The selective macroautophagic degradation of aggregated proteins requires the PI3P-binding protein Alfy.
  findings:
  - statement: Alfy/WDFY3 scaffolds selective macroautophagy of aggregated proteins by bridging p62(SQSTM1)/NBR1-positive aggregates to the autophagic machinery.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Supports the aggrephagy context; NBR1 acts as a cargo partner in p62/NBR1-positive inclusions.
- id: PMID:20562859
  title: Network organization of the human autophagy system.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Autophagy interactome network; source of a bare protein binding annotation.
- id: PMID:20808283
  title: NBR1 is a new PB1 signalling adapter in Th2 differentiation and allergic airway inflammation in vivo.
  findings:
  - statement: T-cell-specific NBR1-deficient mice show impaired Th2 differentiation and reduced allergic airway inflammation; NBR1 acts as a PB1-domain signaling adapter.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Establishes a pleiotropic PB1-domain immune signaling-adapter role (mouse in vivo).
- id: PMID:21296869
  title: Broad activation of the ubiquitin-proteasome system by Parkin is critical for mitophagy.
  findings:
  - statement: Parkin-mediated mitochondrial ubiquitination drives mitophagy; NBR1 colocalizes with mitochondria in this context.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Source of the mitochondrion colocalizes_with annotation; reflects recruitment to damaged mitochondria during mitophagy.
- id: PMID:24692539
  title: Solution structure of the ubiquitin-associated (UBA) domain of human autophagy receptor NBR1 and its interaction with ubiquitin and polyubiquitin.
  findings:
  - statement: NMR structure of the NBR1 UBA domain bound to ubiquitin/polyubiquitin; F929A abolishes ubiquitin binding.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Structural basis of the core ubiquitin-binding function. Not in publications cache; verified via PubMed and UniProt mutagenesis features.
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput interactome (HuRI); source of a bare protein binding annotation.
- id: PMID:29568061
  title: An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput interaction/localization mapping; source of a bare protein binding annotation.
- id: PMID:30824926
  title: Isoform-specific GSK3A activity is negatively correlated with human sperm motility.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: GSK3A context; source of a bare protein binding annotation.
- id: PMID:33226137
  title: Receptor-mediated clustering of FIP200 bypasses the role of LC3 lipidation in autophagy.
  findings:
  - statement: NBR1 flux is a selective-autophagy readout; TAX1BP1/TBK1 enforce cargo specificity by clustering FIP200 around NBR1 cargo; NBR1 interacts with TAX1BP1.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Supports the cargo-receptor/autophagy-initiation role and TAX1BP1 interaction. Full text available.
- id: PMID:33577621
  title: The PB1 protein of influenza A virus inhibits the innate immune response by targeting MAVS for NBR1-mediated selective autophagic degradation.
  findings:
  - statement: NBR1 recognizes ubiquitinated MAVS and delivers it to autophagosomes for degradation; influenza A virus PB1 hijacks NBR1; NBR1 deficiency impairs MAVS degradation.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Establishes NBR1-mediated selective autophagy of MAVS and an antiviral-restricting role. Not in cache; verified via PubMed.
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput interactome (BioPlex); source of a bare protein binding annotation.
- id: PMID:34471133
  title: Reconstitution defines the roles of p62, NBR1 and TAX1BP1 in ubiquitin condensate formation and autophagy initiation.
  findings:
  - statement: In vitro reconstitution shows NBR1 (with p62 and TAX1BP1) drives condensation of ubiquitinated proteins and autophagy initiation.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Mechanistic in vitro evidence for the cargo-receptor / condensate-formation function. Full text available.
- id: PMID:34524948
  title: Global Proximity Interactome of the Human Macroautophagy Pathway.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Macroautophagy proximity interactome; source of a bare protein binding annotation.
- id: PMID:24879152
  title: Phosphorylation of NBR1 by GSK3 modulates protein aggregation.
  findings:
  - statement: NBR1 binds ubiquitin and MAP1LC3 to ensure ubiquitinated protein degradation; GSK3 phosphorylation at Thr-586 prevents aggregation of ubiquitinated proteins; reduced NBR1 phosphorylation correlates with aggregation in inclusion body myositis.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Establishes the aggregation-promoting (aggrephagy) function and its GSK3 regulation. Abstract in cache.
- id: PMID:35914352
  title: NBR1 mediates autophagic degradation of IRF3 to negatively regulate type I interferon production.
  findings:
  - statement: NBR1 binds IRF3 and targets it for autophagic-lysosomal degradation, negatively regulating type I IFN production; NBR1 is induced upon viral infection.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Establishes selective autophagy of IRF3 and negative regulation of type I IFN. Abstract in cache.
- id: PMID:38169523
  title: Selective Autophagy Receptor NBR1 Retards Nucleus Pulposus Cell Senescence by Directing the Clearance of SRBD1.
  findings:
  - statement: NBR1 interacts with SRBD1 and clears it via the autophagic-lysosomal pathway, retarding nucleus pulposus cell senescence.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Adds a specific selective-autophagy substrate (SRBD1). Full text available.
- id: Reactome:R-HSA-9664867
  title: NBR1 binds MAP1LC3B
  findings: []
- id: Reactome:R-HSA-9664880
  title: MAP1LC3B binds ATM dimer:Ub-p-PEX5:SQSTM1:NBR1
  findings: []
- id: Reactome:R-HSA-9664881
  title: NBR1 binds ATM:Ub-p-PEX5:SQSTM1
  findings: []

NBR1

Gene Description

Proposed New Ontology Terms

pexophagy receptor activity

Existing Annotations Review

Core Functions

Functions as an autophagy cargo adaptor that simultaneously engages cargo and the phagophore/ATG8 machinery, promoting the formation and clearance of ubiquitinated protein aggregates (aggrephagy); this aggregation-promoting activity is inhibited by GSK3-mediated phosphorylation at Thr-586.

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 antiviral-restricting pathway is hijacked by influenza A virus PB1.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

Research Report: Human NBR1 (UniProt Q14596) — Functional Annotation and Current Understanding

1) Target verification (gene/protein identity)

2) Key concepts and definitions (current understanding)

2.1 Selective autophagy and selective autophagy receptors (SARs)

2.2 NBR1 as an archetypal selective autophagy receptor

3) Molecular architecture, mechanisms, and pathways

3.1 Domain architecture and core molecular interactions

3.2 NBR1 within p62 bodies and autophagy initiation

3.3 Subcellular localization (where NBR1 acts)

4) Recent developments (prioritizing 2023–2024)

4.1 2024: NBR1 in intervertebral disc degeneration via selective clearance of SRBD1 (human cells; disease mechanism)

4.2 2024: NBR1 turnover during HSV-1 infection (xenophagy-linked antiviral defense)

4.3 2023: Updated framing of receptor-based selectivity in mammalian selective autophagy

5) Current applications and real-world implementations

5.1 Cancer and immune evasion (MHC-I degradation)

5.2 Degenerative disease biology (IDD) and selective-autophagy targeting

5.3 Infection biology and host defense

6) Expert opinions and analysis (authoritative sources)

6.1 “Archetypal receptor” framing and cooperation with p62

6.2 Receptor redundancy and context dependence

7) Statistics and data highlights (recent studies)

8) Disease associations from a target–disease knowledgebase (Open Targets)

9) Visual evidence (domain architecture and functional schematic)

10) Summary functional annotation (human NBR1 / UniProt Q14596)

Domain/interactions quick reference

Artifacts

Citations

📚 Additional Documentation

Notes

NBR1 (Next to BRCA1 gene 1 protein) — review notes

Domain architecture (UniProt features)

Core function: ubiquitin-binding selective autophagy receptor

Aggrephagy / protein aggregation

Pexophagy (peroxisome turnover)

Innate immunity / antiviral selective autophagy

SRBD1 clearance / cellular senescence

FGFR / endosomal signaling

Bone / osteoblast / MAPK (mouse-derived, ISS/IEA from Ensembl Compara to mouse ortholog P97432/Q501R9)

Th2 / PB1 signalling adapter

Sarcomere / M band / titin

Localization summary

Protein binding (IPI) sources

Key GO terms verified via QuickGO API

Pn Notes

NBR1 PN Consistency Notes

Source Files Checked

Deep Research Files

AIGR Review Snapshot

PN Consistency Summary

Full Consistency Review

PN Dossier Context

PN row 1: Autophagy-Lysosome Pathway | Autophagy substrate selection | Selective autophagy receptor | Pexophagy

PN row 2: Autophagy-Lysosome Pathway | Autophagy substrate selection | Selective autophagy receptor | Aggrephagy

PN row 3: Autophagy-Lysosome Pathway | Autophagy substrate selection | Selective autophagy receptor | Midbody autophagy

PN row 4: Ubiquitin Proteasome System | Ubiquitin and UBL binding | trafficking | selective autophagy | UBA

Projected GO annotations (3)

Note

📄 View Raw YAML