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: []