Affinage

NBR1

Next to BRCA1 gene 1 protein · UniProt Q14596

Length
966 aa
Mass
107.4 kDa
Annotated
2026-06-10
97 papers in source corpus 41 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NBR1 is an evolutionarily conserved, multidomain selective autophagy receptor that delivers ubiquitinated and specific protein cargo to autophagosomes for lysosomal degradation, while also acting as a non-autophagic scaffold in signaling and trafficking (PMID:19250911, PMID:19398892, PMID:19502794, PMID:19427866). Cargo engagement is achieved through a modular domain architecture: a high-affinity UBA domain that binds mono- and polyubiquitin without linkage-type specificity, structurally distinguished from p62 by a tilted, extended helix α-3 that blocks self-dimerization (PMID:19427866, PMID:24692539); a non-canonical Tyr/Ile LIR motif that engages ATG8/LC3-family proteins as resolved by NMR (PMID:21620860); an N-terminal type-A PB1 domain mediating homo- and hetero-oligomerization with p62 and binding to titin kinase (PMID:16376336); and dedicated cargo-recognition modules including a J/amphipathic-helix and coiled-coil for pexophagy and an FW (and ZZ) domain that recognizes substrate N-termini such as the mannosidase Ams1 (PMID:23239026, PMID:34169534, PMID:35752625). The LIR functions as a multivalent interaction hub where ATG8 proteins, FIP200, and TAX1BP1 bind overlapping determinants, and LIR-mediated TAX1BP1 recruitment optimizes autophagic flux (PMID:39928048). NBR1 and p62 act cooperatively but separably: p62 drives ubiquitin condensate formation while NBR1 equips the heterooligomeric complex with its high-affinity UBA domain and recruits TAX1BP1 (PMID:19250911, PMID:19398892, PMID:19502794, PMID:34471133), and NBR1 promotes p62 liquid-like body formation required for Nrf2 activation under oxidative stress (PMID:31916398). Its receptor activity mediates pexophagy, where ubiquitinated peroxisomal signals such as PXMP4 recruit NBR1 (PMID:23239026, PMID:41267209), focal adhesion turnover and cell migration (PMID:26903539, PMID:27484104), and clearance of aggregation-prone substrates including tau—with BAG3 gating NBR1's preference for monomeric tau—and α-synuclein inclusions (PMID:37899687, PMID:40818508, PMID:22484440). NBR1 activity is regulated by GSK3-mediated phosphorylation at Thr586, which suppresses ubiquitinated-protein aggregate formation and is reduced in inclusion body myositis muscle (PMID:24879152). Beyond autophagy, NBR1 is a PB1-domain signaling adapter that complexes with activated p38 MAPK to restrain osteoblast differentiation and bone formation (PMID:20616007) and with MEKK3 to drive JNK signaling in myeloid cells and Th2 differentiation (PMID:25043814, PMID:20808283), functions as a late-endosomal regulator of receptor tyrosine kinase trafficking via Spred2 (PMID:19822672, PMID:20937771), and degrades innate immune signaling molecules including ubiquitinated MAVS and IRF3, as well as STING in hepatic stellate cells through a non-autophagic endolysosomal route (PMID:33577621, PMID:35914352, PMID:39423823). Accumulation of NBR1 when autophagy is impaired drives pro-metastatic basal differentiation in mammary tumors by sequestering the ubiquitin ligase ITCH to stabilize p63 (PMID:32084360, PMID:32267786, PMID:40579454).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2005 High

    Establishing the structural basis of NBR1's oligomerization module showed how it physically couples to p62 and to titin kinase, defining the PB1 domain as its core protein-interaction hub before its autophagy role was known.

    Evidence X-ray crystallography of the PB1 domain at 1.55 Å

    PMID:16376336

    Open questions at the time
    • Did not establish autophagy function
    • Functional consequence of titin kinase binding not resolved
  2. 2009 High

    Identifying NBR1 as a bona fide autophagy receptor with both a LIR and a UBA domain answered whether it could bridge ubiquitinated cargo to autophagosomes, and showed it acts independently of p62.

    Evidence Reciprocal Co-IP, LIR/UBA mutagenesis, autophagy assays in p62-null cells; UBA binding to K48/K63 chains

    PMID:19250911 PMID:19398892 PMID:19427866 PMID:19502794

    Open questions at the time
    • Cargo repertoire beyond aggregates undefined
    • Structural basis of LIR and UBA binding not yet resolved
  3. 2011 High

    Solving the GABARAPL-1/NBR1-LIR complex defined how a non-canonical Tyr/Ile LIR engages ATG8-family proteins, explaining the molecular determinants of autophagosome recruitment.

    Evidence NMR structure, ITC, and mutagenesis

    PMID:21620860

    Open questions at the time
    • Selectivity among ATG8 paralogs not fully mapped
    • In vivo affinity tuning unknown
  4. 2014 High

    The UBA domain structure explained why NBR1 binds ubiquitin with high affinity and without linkage specificity, distinguishing it mechanistically from p62 and clarifying its role in heterooligomeric cargo capture.

    Evidence Solution NMR structure with ITC and mutagenesis

    PMID:24692539

    Open questions at the time
    • Consequences of lacking dimerization in vivo not fully tested
    • Does not address cargo other than ubiquitin
  5. 2012 High

    Demonstrating that NBR1 is necessary and sufficient for pexophagy, requiring coincident J- and UBA-domain binding to peroxisomes, defined a substrate-selectivity logic distinct from generic ubiquitin recognition.

    Evidence Domain mutagenesis with pexophagy reporter assays and microscopy

    PMID:23239026

    Open questions at the time
    • Peroxisomal ubiquitin signal identity not defined at the time
    • Role of upstream ligases unknown
  6. 2010 High

    Genetic and signaling studies revealed NBR1's non-autophagic scaffold functions—restraining p38-driven osteoblast differentiation and enabling PB1-dependent Th2 differentiation—establishing it as a signaling adapter beyond autophagy.

    Evidence Nbr1-truncation and T-cell conditional knockout mice, Co-IP, pharmacological p38 inhibition

    PMID:20616007 PMID:20808283

    Open questions at the time
    • Mechanism linking PB1 scaffolding to transcription factor activation incompletely defined
    • Whether autophagy contributes was not dissected
  7. 2010 Medium

    Mapping a C-terminal amphipathic helix to late-endosomal localization and showing NBR1 regulates RTK degradation via Spred2 separated its endocytic trafficking role from its autophagy role.

    Evidence Truncation mutagenesis, colocalization, siRNA, RTK degradation assays; Spred2 EVH1 Co-IP

    PMID:19822672 PMID:20937771

    Open questions at the time
    • RTK internalization mechanism partly inferred
    • Relationship between endosomal and autophagic pools needs further definition
  8. 2014 High

    Identifying GSK3 phosphorylation at Thr586 as a switch that prevents ubiquitinated-protein aggregation, with reduced phosphorylation in sIBM muscle, established post-translational control of NBR1 aggregate-handling activity and a human disease link.

    Evidence In vitro kinase assay, site mutagenesis, Atg7 KO mice, patient biopsy immunohistochemistry

    PMID:24879152

    Open questions at the time
    • Kinase regulation in disease context not resolved
    • How phosphorylation alters domain conformation unknown
  9. 2014 High

    Defining the MEKK3–NBR1 PB1 complex and FW-domain MAP1B interaction extended the catalogue of NBR1 partner interfaces and connected NBR1 to JNK signaling and microtubule-associated trafficking.

    Evidence PB1 Co-IP and myeloid-specific knockout mice (MEKK3); Co-IP and microtubule depolymerization (MAP1B)

    PMID:22654911 PMID:25043814

    Open questions at the time
    • Functional consequence of MAP1B interaction not fully defined
    • Whether JNK and autophagy roles are coupled unknown
  10. 2016 High

    Live-cell demonstration that autophagy-competent NBR1 promotes focal adhesion disassembly tied its receptor activity to cell migration, broadening cargo beyond aggregates and organelles.

    Evidence Live-cell imaging, siRNA, autophagy-competent vs defective NBR1 rescue, FA turnover assays

    PMID:26903539 PMID:27484104

    Open questions at the time
    • Which FA components are ubiquitinated cargo not fully defined
    • Recruitment signal at FAs unknown
  11. 2021 High

    In vitro reconstitution dissected the division of labor in p62–NBR1 condensates, showing NBR1 contributes its high-affinity UBA domain and recruits TAX1BP1, while TAX1BP1 drives FIP200 recruitment and degradation.

    Evidence In vitro reconstitution with cell biology assays and Co-IP

    PMID:34471133

    Open questions at the time
    • Stoichiometry of the heterooligomeric complex in cells not resolved
    • Regulation of TAX1BP1 hand-off unknown
  12. 2021 High

    Cryo-EM of fungal Nbr1 ZZ and FW domains defined single-domain bispecific and quaternary-structure cargo recognition via N-terminal di-glycine pockets, revealing how NBR1 selects specific protein substrates independently of ubiquitin.

    Evidence Cryo-EM structures (ZZ1, FW), competitive binding and mutagenesis in fission yeast and C. thermophilum

    PMID:34169534 PMID:35752625

    Open questions at the time
    • Human FW/ZZ cargo not identified by structure
    • Conservation of these cargo modes in mammals untested
  13. 2020 High

    Showing NBR1 promotes p62 liquid-body formation required for Nrf2 activation, and that autophagic clearance of NBR1 restrains pro-metastatic differentiation, established NBR1 abundance as a node coupling autophagy flux to stress signaling and tumor progression.

    Evidence NBR1 gain/loss, p62 droplet imaging, Nrf2 reporters; autophagy-deficient mammary cancer models with NBR1 epistasis and transcriptomics

    PMID:31916398 PMID:32084360 PMID:32267786

    Open questions at the time
    • Direct structural basis of droplet promotion not defined
    • Identity of the basal differentiation effector resolved only later
  14. 2025 High

    Identifying ITCH sequestration by accumulated NBR1–p62 condensates as the mechanism stabilizing p63 closed the loop on how impaired autophagy converts NBR1 into a pro-metastatic driver.

    Evidence Co-IP, condensate imaging, NBR1 ITCH-binding mutants, in vivo mammary tumor models

    PMID:40579454

    Open questions at the time
    • Whether other ligases are sequestered unknown
    • Generality across tumor types untested
  15. 2025 High

    Systematic LIR-array analysis recast the NBR1 LIR as a multivalent hub for ATG8, FIP200, and TAX1BP1 binding to overlapping determinants, with phosphorylation tuning ATG8/FIP200 but not TAX1BP1 engagement.

    Evidence Peptide binding arrays of >100 LIRs, mutagenesis, in vivo flux assays, phosphomimetics

    PMID:39928048

    Open questions at the time
    • Kinase responsible for LIR phosphorylation in cells unidentified
    • Temporal ordering of competing binders unresolved
  16. 2023 High

    BAG3-dependent partitioning of NBR1 toward monomeric tau, with NBR1 depletion raising phospho-tau in neurons, defined a co-chaperone-gated specificity that distinguishes NBR1 from SQSTM1 in tauopathy-relevant clearance.

    Evidence In vitro binding with purified proteins, Co-IP, neuronal NBR1 depletion, BAG3 KO mice

    PMID:37899687

    Open questions at the time
    • How BAG3 alters NBR1 cargo preference structurally unknown
    • Relevance to in vivo aggregate clearance not fully tested
  17. 2025 Medium

    Direct NBR1 binding to phosphorylated tau and tau aggregates in iPSC neurons and human AD brain, with knockdown raising aggregate levels, linked NBR1 to Alzheimer's disease pathology.

    Evidence siRNA in iPSC-derived neurons, Co-IP, HEK biosensor assays, human AD brain Co-IP

    PMID:40818508

    Open questions at the time
    • Causality in disease progression not established
    • Whether NBR1 is protective or contributory in vivo unresolved
  18. 2021 Medium

    Demonstrating NBR1-mediated autophagic degradation of ubiquitinated MAVS and of IRF3 defined NBR1 as a negative regulator of innate antiviral signaling co-opted by viruses.

    Evidence Co-IP, ubiquitination site mapping, NBR1 knockdown, IFN reporters (MAVS); Co-IP, ATG3/ATG7 KO, IRF3 degradation (IRF3)

    PMID:33577621 PMID:35914352

    Open questions at the time
    • Single-lab findings without reciprocal independent validation
    • Endogenous regulation outside infection unclear
  19. 2024 Medium

    Showing NBR1 antagonizes STING via non-autophagic endolysosomal trafficking and by displacing p62 from STING expanded NBR1's roles into autophagy-independent immune control with tumor consequences.

    Evidence Co-IP, NBR1 KO, STING trafficking assays, HCC tumor models in hepatic stellate cells

    PMID:39423823

    Open questions at the time
    • Single-lab mechanism
    • How NBR1 routes STING to lysosomes molecularly undefined
  20. 2025 Medium

    Identifying the MARCHF7–PXMP4 ubiquitination signal that recruits NBR1 to peroxisomes provided the upstream cargo-marking mechanism for NBR1-dependent pexophagy.

    Evidence Functional screening, Co-IP, ubiquitination assays, recruitment assays with ubiquitination-defective PXMP4

    PMID:41267209

    Open questions at the time
    • Single-lab finding
    • Generality beyond PEX1-deficient context untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NBR1's autophagic and non-autophagic functions, its competing LIR-hub binders, and its post-translational regulation are coordinated to dictate cargo choice in different tissues remains unresolved.
  • No unified model integrating endosomal, condensate, and signaling pools
  • Kinases/regulators directing cargo selection in vivo unidentified
  • Human structural data for FW/ZZ cargo recognition lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 4 GO:0005198 structural molecule activity 2 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005768 endosome 3 GO:0005829 cytosol 3 GO:0005777 peroxisome 2
Pathway
R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 4 R-HSA-9612973 Autophagy 4 R-HSA-162582 Signal Transduction 3
Partners
BAG3FIP200ITCHMAP1BMEKK3SPRED2SQSTM1TAX1BP1
Complex memberships
NBR1-MEKK3 PB1 complexp62/SQSTM1-NBR1 heterooligomer

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 NBR1 is an autophagy receptor containing both an LC3-interacting region (LIR) and a ubiquitin-binding UBA domain; it is recruited to ubiquitin-positive protein aggregates and degraded by autophagy in a LIR-dependent manner. NBR1 and p62 form oligomers but can function independently, as NBR1 undergoes autophagosomal clearance in p62-deficient cells. Co-immunoprecipitation, domain mutagenesis, cell-based autophagy assays, immunofluorescence, p62-knockout cells Molecular cell High 19250911 19398892 19502794
2009 NBR1 UBA domain binds K48- and K63-linked polyubiquitin chains. NBR1 also binds LC3-A via a novel LIR binding site. Ubiquitin-binding (but not PB1-mediated p62 interaction) is required to target NBR1 to LC3- and polyubiquitin-positive bodies. UBA domain binding assays, co-immunoprecipitation, mutagenesis, fluorescence microscopy FEBS letters High 19427866
2011 NMR structure determination of the GABARAPL-1/NBR1-LIR complex revealed that the NBR1 LIR motif (containing Tyr and Ile rather than canonical Trp/Leu) interacts with ATG8-family proteins. A Trp substitution increases binding affinity; increasing N-terminal negative charges has little effect due to enthalpy-entropy compensation. NMR structure determination, isothermal titration calorimetry, mutagenesis Journal of molecular biology High 21620860
2012 NBR1 is necessary and sufficient for pexophagy (selective autophagic degradation of peroxisomes). The amphipathic α-helical J domain, UBA domain, LIR, and coiled-coil domain are all required. Substrate selectivity is partly achieved by coincident binding of the J and UBA domains to peroxisomes. p62 binding to NBR1 increases pexophagy efficiency but is not required when NBR1 is in excess. Loss-of-function/gain-of-function cell assays, domain mutagenesis, fluorescence microscopy, pexophagy reporter assays Journal of cell science High 23239026
2014 Solution NMR structure of the NBR1 UBA domain reveals helix α-3 is tilted farther from helix α-2 and extended by ~one turn compared to p62 UBA. This structural difference inhibits p62-type self-dimerization of NBR1 UBA and results in significantly higher affinity for monoubiquitin. NBR1 UBA lacks polyubiquitin linkage-type specificity, binding each monomeric unit of polyubiquitin with similar affinity via the same surface as monoubiquitin. NMR structure determination, isothermal titration calorimetry, mutagenesis The Journal of biological chemistry High 24692539
2005 Crystal structure of the NBR1 PB1 domain at 1.55 Å resolution reveals a type-A PB1 domain with two negatively charged residue clusters. This domain mediates protein–protein interactions with titin kinase and with p62. X-ray crystallography FEBS letters High 16376336
2021 In vitro reconstitution defined that p62 is the major driver of ubiquitin condensate formation, while NBR1 promotes condensate formation by equipping the p62-NBR1 heterooligomeric complex with a high-affinity UBA domain. NBR1 also recruits TAX1BP1 to p62-formed ubiquitin condensates. TAX1BP1 (not NBR1) is the main driver of FIP200 recruitment and autophagic degradation of p62-ubiquitin condensates. In vitro reconstitution, cell biology assays, Co-immunoprecipitation Nature communications High 34471133
2016 NBR1 is required for autophagy-dependent focal adhesion (FA) turnover and cell migration. Autophagosomes associate with FAs primarily during disassembly. NBR1 depletion impairs FA turnover and decreases targeting of autophagosomes to FAs. Ectopic expression of autophagy-competent but not autophagy-defective NBR1 enhances FA disassembly and reduces FA lifetime. Live-cell imaging, siRNA knockdown, NBR1 mutagenesis (autophagy-competent vs defective), FA turnover assays The Journal of cell biology High 26903539 27484104
2010 NBR1 functions as a negative regulator of osteoblastic bone formation. Genetic truncation of murine Nbr1 leads to increased bone mass through increased osteoblast differentiation. Truncated Nbr1 fails to complex with activated p38 MAPK, leading to hyperactivation of p38 MAPK in osteoblasts. Pharmacological p38 MAPK inhibition abrogates the increased osteoblast differentiation in Nbr1 mutant cells. Murine genetic model (Nbr1 truncation), Co-immunoprecipitation, pharmacological p38 inhibition, osteoblast differentiation assays Proceedings of the National Academy of Sciences of the United States of America High 20616007
2009 Spred2 attenuation of FGF receptor signaling is dependent on its interaction with NBR1. NBR1 is a late endosomal protein that directly binds the EVH1 domain of Spred2 and colocalizes with it in vivo. The Spred2-NBR1 interaction redirects trafficking of activated FGF receptors to the lysosomal degradation pathway. Co-immunoprecipitation, colocalization fluorescence microscopy, FGF signaling assays, siRNA knockdown The Journal of cell biology High 19822672
2010 Nbr1 C-terminus contains a novel membrane-interacting amphipathic α-helix essential for late endosomal localization. Ectopic Nbr1 expression inhibits ligand-mediated lysosomal degradation of receptor tyrosine kinases (RTKs) likely via inhibition of receptor internalization; depletion of endogenous NBR1 enhances RTK degradation. Autophagic and late endocytic localizations of Nbr1 are independent of one another. Truncation mutagenesis, fluorescence microscopy, siRNA depletion, RTK degradation assays Molecular and cellular biology Medium 20937771
2014 NBR1 forms a signaling complex with MEKK3 via PB1 domain interaction, enabling activation of JNK signaling. NBR1 inactivation in myeloid cells impairs macrophage M1 polarization and chemotactic activity, prevents adipose tissue inflammation, and improves glucose tolerance in obese mice. PB1 domain interaction assays (Co-IP), myeloid-specific NBR1 knockout mouse model, JNK activation assays Cell metabolism High 25043814
2014 NBR1 is phosphorylated by GSK3 at Thr586. This phosphorylation prevents aggregation of ubiquitinated proteins by inhibiting formation of protein aggregates (not their degradation), as confirmed in Atg7 knockout mice. Reduced NBR1 Thr586 phosphorylation was found in sporadic inclusion body myositis (sIBM) muscle and correlated with severity of protein aggregation. In vitro kinase assay, phosphorylation site mutagenesis, Atg7 KO mice, immunohistochemistry of patient biopsies Autophagy High 24879152
2002 NBR1 interacts with FEZ1 (a PKCζ-interacting protein) and CIB (calcium and integrin binding protein) by yeast two-hybrid. Co-expression of NBR1 and CIB shifts CIB from nuclear to perinuclear localization, while co-expression of FEZ1 and NBR1 shows overlapping cytoplasmic localization. Yeast two-hybrid, co-transfection/colocalization microscopy European journal of biochemistry Low 11856312
2012 NBR1 FW domain interacts with microtubule-associated protein MAP1B. Upon autophagy induction, MAP1B colocalizes with NBR1 in discrete vesicles dependent on an intact microtubule network. MAP1B is not recruited to autophagosomes for degradation, but phospho-MAP1B levels increase upon blockage of autophagic degradation. Co-immunoprecipitation, fluorescence colocalization, nocodazole microtubule depolymerization, lysosomal inhibition assays International journal of cell biology Medium 22654911
2020 NBR1 mediates the formation of p62 liquid-like bodies/condensates. Overexpression of NBR1 blocks selective degradation of p62 by autophagy and promotes p62 accumulation and phosphorylation in liquid bodies required for Nrf2 activation. Loss of Nbr1 suppresses both p62/SQSTM1 liquid droplet formation and p62-dependent Nrf2 activation during oxidative stress. NBR1 overexpression/knockout, p62 liquid droplet imaging, Nrf2 pathway reporter assays, oxidative stress induction EMBO reports High 31916398
2020 Autophagic degradation of NBR1 restricts metastatic progression in mammary tumors. Genetic ablation of autophagy leads to NBR1 accumulation, which drives a pro-metastatic basal epithelial differentiation program in otherwise luminal tumor cells. This pro-metastatic differentiation and metastatic outgrowth are reversed by preventing NBR1 accumulation. Conditional knockout of autophagy regulators, transcriptomics, genetic NBR1 rescue in mammary cancer models Developmental cell High 32084360 32267786
2025 NBR1-p62/SQSTM1 complexes accumulate as biomolecular condensates when autophagy is inhibited, and sequester ITCH (a ubiquitin ligase that degrades p63), thereby stabilizing and activating p63 to drive pro-metastatic basal differentiation. NBR1 mutants unable to sequester ITCH do not promote basal differentiation or metastasis in vivo. Co-immunoprecipitation, condensate imaging, NBR1 ITCH-binding mutants, in vivo mouse mammary tumor models Nature cell biology High 40579454
2021 IAV PB1 protein promotes RNF5-catalyzed K27-linked polyubiquitination of MAVS at Lys362 and Lys461, then recruits NBR1 to recognize ubiquitinated MAVS and deliver it to autophagosomes for degradation, thereby suppressing RIG-I-MAVS innate immune signaling. Co-immunoprecipitation, ubiquitination assays, NBR1 knockdown, autophagy flux assays, reporter gene assays PLoS pathogens Medium 33577621
2022 NBR1 mediates autophagic degradation of IRF3 to negatively regulate type I interferon production. NBR1 binds both unphosphorylated and phosphorylated IRF3 through its UBA domain. Viral infection elevates NBR1 expression, forming a negative feedback loop promoting IRF3 degradation. Co-immunoprecipitation, ATG3/ATG7 knockout, NBR1 knockdown, IFN reporter assays, Sendai virus infection Biochemical and biophysical research communications Medium 35914352
2023 BAG3 regulates specificity of NBR1 vs SQSTM1 in recognizing MAPT (tau) species: NBR1 preferentially binds monomeric tau in a BAG3-dependent manner (BAG3 promotes NBR1-monomeric tau interaction), while SQSTM1 binds oligomeric tau when BAG3 is present. In primary neurons, depletion of NBR1 (but not SQSTM1) significantly increases phosphorylated MAPT levels. In vitro binding assays with purified proteins, Co-IP, neuronal NBR1 depletion, BAG3 knockout mouse model Autophagy High 37899687
2010 NBR1 is a new PB1 signaling adapter required for Th2 differentiation. T-cell-specific NBR1-deficient mice show impaired lung inflammation and defective Th2 differentiation ex vivo, with alterations in T-cell polarity and selective inhibition of Gata3 and NFATc1 activation. T-cell conditional NBR1 knockout mice, in vivo lung inflammation model, ex vivo Th2 differentiation assays The EMBO journal High 20808283
2014 The viral protease 2Apro and 3Cpro of coxsackievirus cleave NBR1 at two sites, generating C-terminal fragments that exhibit dominant-negative effects against native NBR1 by competing for LC3 and ubiquitin chain binding. SQSTM1 and NBR1 have a positive mutual regulatory relationship: knockdown of SQSTM1 reduces NBR1 expression and vice versa. Viral protease cleavage assays, dominant-negative mutant overexpression, siRNA knockdown, Co-immunoprecipitation Cell death and differentiation Medium 24769734
2021 The ZZ1 domain of fission yeast Nbr1 (an evolutionarily conserved domain) binds two distinct cargo proteins (Ams1 mannosidase and Ape4 aminopeptidase) that compete for the same site. Cryo-EM structure at high resolution reveals the ZZ domain recognizes cargo N-termini via a conserved acidic pocket and engages additional cargo-specific contacts. This defines a single-domain bispecific cargo recognition mechanism. Cryo-EM structure determination, competitive binding assays, domain mutagenesis The EMBO journal High 34169534
2022 The FW domain of Nbr1 from Chaetomium thermophilum binds the α-mannosidase Ams1 (a selective autophagy cargo). Cryo-EM structure at 2.2 Å resolution shows FW domain adopts an immunoglobulin-like β-sandwich structure; it recognizes the quaternary structure of the Ams1 tetramer and specifically recognizes the N-terminal di-glycine of Ams1 via a conserved pocket. Cryo-EM structure determination, domain binding assays Nature communications High 35752625
2015 NBR1 is dispensable for PARK2-mediated mitophagy. Deletion of NBR1 alone or in combination with SQSTM1 does not prevent degradation of damaged mitochondria following mitochondrial depolarization. NBR1 knockout, SQSTM1/NBR1 double knockout, mitophagy flux assays Cell death & disease Medium 26512954
2023 In Arabidopsis, upon intense light exposure, NBR1 associates with photodamaged chloroplasts independently of ATG7. NBR1 coats both the surface and interior of chloroplasts, followed by direct engulfment into the central vacuole via microautophagy. NBR1 relocalization into chloroplasts is greatly enhanced by removing the self-oligomerization mPB1 domain. Delivery depends on the UBA2 domain of NBR1 but not on E3 ligases SP1 or PUB4. Live-cell imaging, NBR1 domain deletion mutants (mPB1, UBA2), atg7 mutants, fluorescence microscopy eLife High 37070813
2025 The LIR motif of NBR1 functions as a protein interaction hub where ATG8-family proteins, FIP200, and TAX1BP1 each bind to distinct overlapping determinants within the same short linear motif. LIR-mediated TAX1BP1 interaction promotes optimal NBR1 autophagic flux. Phosphorylation generally enhances FIP200 and ATG8-family binding but not TAX1BP1 binding. Peptide binding arrays (>100 LIRs), mutagenesis, in vivo NBR1 flux assays, phosphomimetic peptide analysis The Journal of cell biology High 39928048
2025 NBR1 interacts with the PDCoV envelope (E) protein independently of ubiquitination and directs E protein to phagophores for autophagic degradation, limiting viral replication. PDCoV NSP5 (3C-like protease) cleaves porcine NBR1 at Gln353, impairing its selective autophagy function. NSP5 proteases from PEDV, TGEV, and SARS-CoV-2 also cleave NBR1 at the same site. Co-immunoprecipitation, NBR1 overexpression/knockdown, protease cleavage mapping (Q353A mutant), viral titer assays Autophagy Medium 40047225
2024 In hepatic stellate cells (HSCs), NBR1 antagonizes STING signaling by promoting STING trafficking to the endosome-lysosomal compartment for degradation independent of autophagy. NBR1 also prevents interaction of the E3 ligase TRIM32 with STING by displacing p62 from STING. NBR1 deletion in p62-deficient HSCs rescues inhibited STING-IFN pathway and reduces hepatocellular carcinoma progression. Co-immunoprecipitation, NBR1 knockout, STING trafficking assays, HCC tumor models Molecular cell Medium 39423823
2025 NBR1 directly interacts with phosphorylated tau and tau aggregates. NBR1 knockdown in iPSC-derived neurons significantly increases tau aggregate levels. NBR1 expression is increased in Alzheimer's disease patients and NBR1 specifically interacts with tau in human AD brain. siRNA knockdown in iPSC-derived neurons, Co-immunoprecipitation, HEK biosensor autophagy assays, human AD brain Co-IP Neurobiology of disease Medium 40818508
2025 TBK1-MARCHF7-PXMP4-NBR1 axis regulates pexophagy: MARCHF7 promotes ubiquitination of PXMP4 at Lys20 in PEX1-deficient cells; ubiquitinated PXMP4 acts as recognition signal for NBR1 recruitment to peroxisomes. Downregulation of MARCHF7 or PXMP4 impairs NBR1 recruitment and pexophagic flux. Functional screening, Co-IP, ubiquitination assays, NBR1 recruitment assays, knockdown/reconstitution with ubiquitination-defective PXMP4 mutant Autophagy Medium 41267209
2024 NBR1 directs autophagic degradation of SRBD1 in nucleus pulposus cells. NBR1 knockdown leads to accumulation of SRBD1, triggering cellular senescence via AKT1/p53 and RB/p16 pathways and SASP via NF-κB pathway. Proteomics, immunoprecipitation/mass spectrometry, NBR1 knockdown, in vivo and in vitro validation International journal of biological sciences Medium 38169523
2024 VDAC2 lactylation at Lys75 disrupts its interaction with NBR1, suppressing cardiomyocyte autophagy and exacerbating myocardial injury in septic cardiomyopathy. PDK4-driven lactate accumulation is the upstream driver of this VDAC2 modification. Co-immunoprecipitation, site-directed mutagenesis (K75), proteomics, murine sepsis model bioRxivpreprint Low bio_10.1101_2025.09.22.25336402
2016 NBR1 localizes to Lewy bodies and glial cytoplasmic inclusions in α-synucleinopathies (Parkinson's disease, DLB, MSA). In cultured cells bearing LB-like inclusions, NBR1 knockdown represses formation of α-synuclein aggregates, establishing a role for NBR1 in cytoplasmic inclusion formation in α-synucleinopathy. Immunohistochemistry, NBR1 knockdown in cell model of LB inclusions, Western blot Acta neuropathologica Medium 22484440
2022 NBR1 plays a non-autophagy role in unconventional secretion of IL-12 in intestinal myeloid cells. In Atg5-deficient cells, accumulated NBR1 delivers IL-12 to late endosomes, contributing to excess IL-12 secretion that promotes intestinal inflammation. Atg5 conditional KO mice, NBR1 genetic analysis, late endosome trafficking assays, IL-12 secretion assays Journal of Crohn's & colitis Medium 34374750
2024 NBR1 facilitates autophagic degradation of caspase 8 in vascular endothelial cells exposed to arsenite: NBR1 recruits caspase 8 to autophagosomes. Overexpression of NBR1 facilitates caspase 8 degradation and reduces apoptosis; protective effect is abolished by autophagy inhibition. Co-immunoprecipitation (NBR1-caspase 8), NBR1 overexpression/knockdown, autophagy inhibitor/genetic knockdown, apoptosis assays Biochemical and biophysical research communications Low 38678786

Source papers

Stage 0 corpus · 97 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 A role for NBR1 in autophagosomal degradation of ubiquitinated substrates. Molecular cell 935 19250911
2009 NBR1 and p62 as cargo receptors for selective autophagy of ubiquitinated targets. Cell cycle (Georgetown, Tex.) 374 19502794
2012 NBR1 acts as an autophagy receptor for peroxisomes. Journal of cell science 307 23239026
2013 NBR1-mediated selective autophagy targets insoluble ubiquitinated protein aggregates in plant stress responses. PLoS genetics 299 23341779
2011 Plant NBR1 is a selective autophagy substrate and a functional hybrid of the mammalian autophagic adapters NBR1 and p62/SQSTM1. Autophagy 287 21606687
2017 Selective autophagy limits cauliflower mosaic virus infection by NBR1-mediated targeting of viral capsid protein and particles. Proceedings of the National Academy of Sciences of the United States of America 216 28223514
2021 Reconstitution defines the roles of p62, NBR1 and TAX1BP1 in ubiquitin condensate formation and autophagy initiation. Nature communications 185 34471133
2009 NBR1 cooperates with p62 in selective autophagy of ubiquitinated targets. Autophagy 160 19398892
2014 E3 ubiquitin ligase CHIP and NBR1-mediated selective autophagy protect additively against proteotoxicity in plant stress responses. PLoS genetics 135 24497840
2016 NBR1 enables autophagy-dependent focal adhesion turnover. The Journal of cell biology 134 26903539
2021 The PB1 protein of influenza A virus inhibits the innate immune response by targeting MAVS for NBR1-mediated selective autophagic degradation. PLoS pathogens 122 33577621
2020 NBR1-mediated p62-liquid droplets enhance the Keap1-Nrf2 system. EMBO reports 110 31916398
2020 Autophagy suppresses breast cancer metastasis by degrading NBR1. Autophagy 107 32267786
2020 Autophagic Degradation of NBR1 Restricts Metastatic Outgrowth during Mammary Tumor Progression. Developmental cell 105 32084360
2022 NBR1: The archetypal selective autophagy receptor. The Journal of cell biology 84 36255390
2012 Autophagic adapter protein NBR1 is localized in Lewy bodies and glial cytoplasmic inclusions and is involved in aggregate formation in α-synucleinopathy. Acta neuropathologica 83 22484440
2009 Interactions with LC3 and polyubiquitin chains link nbr1 to autophagic protein turnover. FEBS letters 78 19427866
2011 Characterization of the interaction of GABARAPL-1 with the LIR motif of NBR1. Journal of molecular biology 77 21620860
2020 Brassinosteroids act as a positive regulator of NBR1-dependent selective autophagy in response to chilling stress in tomato. Journal of experimental botany 73 31639824
2010 Neighbor of Brca1 gene (Nbr1) functions as a negative regulator of postnatal osteoblastic bone formation and p38 MAPK activity. Proceedings of the National Academy of Sciences of the United States of America 71 20616007
2014 Gambogic acid induced oxidative stress dependent caspase activation regulates both apoptosis and autophagy by targeting various key molecules (NF-κB, Beclin-1, p62 and NBR1) in human bladder cancer cells. Biochimica et biophysica acta 67 25218692
2013 p38(MAPK)-regulated induction of p62 and NBR1 after photodynamic therapy promotes autophagic clearance of ubiquitin aggregates and reduces reactive oxygen species levels by supporting Nrf2-antioxidant signaling. Free radical biology & medicine 64 24269898
2014 Solution structure of the ubiquitin-associated (UBA) domain of human autophagy receptor NBR1 and its interaction with ubiquitin and polyubiquitin. The Journal of biological chemistry 61 24692539
2010 Developmental regulation of MURF ubiquitin ligases and autophagy proteins nbr1, p62/SQSTM1 and LC3 during cardiac myofibril assembly and turnover. Developmental biology 60 21185285
2014 Dominant-negative function of the C-terminal fragments of NBR1 and SQSTM1 generated during enteroviral infection. Cell death and differentiation 51 24769734
2011 Abnormalities of NBR1, a novel autophagy-associated protein, in muscle fibers of sporadic inclusion-body myositis. Acta neuropathologica 50 21935636
2014 Phosphorylation of NBR1 by GSK3 modulates protein aggregation. Autophagy 47 24879152
2013 Brain region- and age-dependent dysregulation of p62 and NBR1 in a mouse model of Huntington's disease. Neurobiology of disease 45 23295856
2014 A macrophage NBR1-MEKK3 complex triggers JNK-mediated adipose tissue inflammation in obesity. Cell metabolism 44 25043814
2009 Spred2 interaction with the late endosomal protein NBR1 down-regulates fibroblast growth factor receptor signaling. The Journal of cell biology 44 19822672
2002 NBR1 interacts with fasciculation and elongation protein zeta-1 (FEZ1) and calcium and integrin binding protein (CIB) and shows developmentally restricted expression in the neural tube. European journal of biochemistry 43 11856312
2010 Nbr1 is a novel inhibitor of ligand-mediated receptor tyrosine kinase degradation. Molecular and cellular biology 42 20937771
2020 Broad and Complex Roles of NBR1-Mediated Selective Autophagy in Plant Stress Responses. Cells 37 33266087
2023 LLPS of SQSTM1/p62 and NBR1 as outcomes of lysosomal stress response limits cancer cell metastasis. Proceedings of the National Academy of Sciences of the United States of America 36 37847732
2015 NBR1 is dispensable for PARK2-mediated mitophagy regardless of the presence or absence of SQSTM1. Cell death & disease 35 26512954
2014 The non-receptor tyrosine kinase Ack1 regulates the fate of activated EGFR by inducing trafficking to the p62/NBR1 pre-autophagosome. Journal of cell science 33 24413169
2012 Autophagy-related proteins (p62, NBR1 and LC3) in intranuclear inclusions in neurodegenerative diseases. Neuroscience letters 32 22728060
2023 The autophagy receptor NBR1 directs the clearance of photodamaged chloroplasts. eLife 31 37070813
2010 NBR1 is a new PB1 signalling adapter in Th2 differentiation and allergic airway inflammation in vivo. The EMBO journal 30 20808283
1996 The BRCA1 and 1A1.3B promoters are parallel elements of a genomic duplication at 17q21. Genomics 30 8954804
2024 Enteric coronavirus nsp2 is a virulence determinant that recruits NBR1 for autophagic targeting of TBK1 to diminish the innate immune response. Autophagy 28 38597182
2021 Poplar Autophagy Receptor NBR1 Enhances Salt Stress Tolerance by Regulating Selective Autophagy and Antioxidant System. Frontiers in plant science 25 33552091
2003 Characterisation of a 161 kb deletion extending from the NBR1 to the BRCA1 genes in a French breast-ovarian cancer family. Human mutation 25 14961556
2023 PSMB1 Inhibits the Replication of Porcine Reproductive and Respiratory Syndrome Virus by Recruiting NBR1 To Degrade Nonstructural Protein 12 by Autophagy. Journal of virology 23 36602366
2017 NBR1-mediated antiviral xenophagy in plant immunity. Autophagy 23 28960115
2018 NBR1 is involved in selective pexophagy in filamentous ascomycetes and can be functionally replaced by a tagged version of its human homolog. Autophagy 21 30081713
1996 Isolation of the murine Nbr1 gene adjacent to the murine Brca1 gene. Genomics 21 8975707
2021 Molecular and structural mechanisms of ZZ domain-mediated cargo selection by Nbr1. The EMBO journal 20 34169534
2020 Overexpression of the Selective Autophagy Cargo Receptor NBR1 Modifies Plant Response to Sulfur Deficit. Cells 20 32164165
2016 NBR1-dependent selective autophagy is required for efficient cell-matrix adhesion site disassembly. Autophagy 18 27484104
2012 MAP1B Interaction with the FW Domain of the Autophagic Receptor Nbr1 Facilitates Its Association to the Microtubule Network. International journal of cell biology 18 22654911
2005 Crystal structure of the PB1 domain of NBR1. FEBS letters 18 16376336
2010 Autophagic receptors Nbr1 and p62 coregulate skeletal remodeling. Autophagy 17 20814249
2022 Non-autophagy Role of Atg5 and NBR1 in Unconventional Secretion of IL-12 Prevents Gut Dysbiosis and Inflammation. Journal of Crohn's & colitis 16 34374750
2019 Heme acquisition by Shu1 requires Nbr1 and proteins of the ESCRT complex in Schizosaccharomyces pombe. Molecular microbiology 14 31442344
2024 NBR1-mediated selective autophagy of ARF7 modulates root branching. EMBO reports 13 38684906
2024 Selective Autophagy Receptor NBR1 Retards Nucleus Pulposus Cell Senescence by Directing the Clearance of SRBD1. International journal of biological sciences 12 38169523
2023 BAG3 regulates the specificity of the recognition of specific MAPT species by NBR1 and SQSTM1. Autophagy 12 37899687
2022 NBR1 mediates autophagic degradation of IRF3 to negatively regulate type I interferon production. Biochemical and biophysical research communications 12 35914352
2019 Depletion of NBR1 in urothelial carcinoma cells enhances rapamycin-induced apoptosis through impaired autophagy and mitochondrial dysfunction. Journal of cellular biochemistry 12 31297862
2001 Expression of BRCA1, NBR1 and NBR2 genes in human breast cancer cells. Folia biologica 12 11508855
2015 Nbr1, a Receptor for ESCRT-Dependent Endosomal Microautophagy in Fission Yeast. Molecular cell 11 26384663
2022 miR-129-5p targets FEZ1/SCOC/ULK1/NBR1 complex to restore neuronal function in mice with post-stroke depression. Bioengineered 10 35435132
2004 Brca1 expression is regulated by a bidirectional promoter that is shared by the Nbr1 gene in mouse. Gene 10 14729266
2025 Cleavage of the selective autophagy receptor NBR1 by the PDCoV main protease NSP5 impairs autophagic degradation of the viral envelope protein. Autophagy 9 40047225
2025 Autophagy-targeted NBR1-p62/SQSTM1 complexes promote breast cancer metastasis by sequestering ITCH. Nature cell biology 9 40579454
2024 Muscle-derived IL-1β regulates EcSOD expression via the NBR1-p62-Nrf2 pathway in muscle during cancer cachexia. The Journal of physiology 9 39167700
2024 Opposing regulation of the STING pathway in hepatic stellate cells by NBR1 and p62 determines the progression of hepatocellular carcinoma. Molecular cell 9 39423823
2022 Structural mechanism of protein recognition by the FW domain of autophagy receptor Nbr1. Nature communications 9 35752625
2021 Germline mutation in the NBR1 gene involved in autophagy detected in a family with renal tumors. Cancer genetics 9 34488032
2018 An increase in intracellular p62/NBR1 and persistence of Burkholderia mallei and B. pseudomallei in infected mice linked to autophagy deficiency. Immunity, inflammation and disease 9 30569531
2020 Nbr1-regulated autophagy in Lactoferrin-induced osteoblastic differentiation. Bioscience, biotechnology, and biochemistry 8 32141386
2024 NBR1-p62-Nrf2 mediates the anti-pulmonary fibrosis effects of protodioscin. Chinese medicine 7 38589903
2025 The LC3-interacting region of NBR1 is a protein interaction hub enabling optimal flux. The Journal of cell biology 6 39928048
2025 CircRNA GRAMD4 induces NBR1 expression to promote autophagy and immune escape in renal cell carcinoma. Autophagy 6 40373256
2024 NBR1-dependent autophagy activation protects against environmental cadmium-evoked placental trophoblast senescence. Chemosphere 6 38670504
2023 p62 and NBR1 functions are dispensable for aggrephagy in mouse ESCs and ESC-derived neurons. Life science alliance 5 37620146
2025 The alpha-coronavirus E protein inhibits the JAK-STAT pathway signaling by triggering STAT2 degradation through OPTN- and NBR1-mediated selective autophagy. Autophagy 4 40091174
2025 Lumpy skin disease virus ORF142 suppresses the cGAS/STING-mediated IFN-I pathway through NBR1-mediated STING autophagic degradation. Microbial pathogenesis 4 40774565
2021 TRAF3 and NBR1 both influence the effect of the disease-causing CYLD(Arg936X) mutation on NF-κB activity. Experimental dermatology 4 33999445
2008 Sequential barriers and an obligatory metastable intermediate define the apparent two-state folding pathway of the ubiquitin-like PB1 domain of NBR1. Journal of molecular biology 4 18234223
2025 A role for the autophagy receptor NBR1 in the degradation of tau aggregates. Neurobiology of disease 3 40818508
2020 An increase in p62/NBR1 levels in melioidosis patients of Sri Lanka exhibit a characteristic of potential host biomarker. Journal of medical microbiology 3 32815800
2025 Biomolecular condensation of ERC1 recruits ATG8 and NBR1 to drive autophagosome formation for plant heat tolerance. Proceedings of the National Academy of Sciences of the United States of America 2 41213015
2025 E2F2 promotes asthmatic lung injury and airway remodeling by regulating NBR1-mediated epithelial-mesenchymal transition. Naunyn-Schmiedeberg's archives of pharmacology 2 41420736
2024 Biomolecular condensation of ERC1 recruits ATG8 and NBR1 to drive autophagosome formation for plant heat tolerance. bioRxiv : the preprint server for biology 2 39314317
2023 Peroxin 14 tags peroxisomes and interacts with Nbr1 for pexophagy in the filamentous insect pathogenic fungus Beauveria bassiana. Autophagy reports 2 40395302
2025 Regulation of pexophagy by a novel TBK1-MARCHF7-PXMP4-NBR1 axis in PEX1-depleted HeLa cells. Autophagy 1 41267209
2025 A Bacterial Effector Hijacks NBR1 to Modulate Both Autophagy and Ubiquitination-Mediated Degradation That Promotes Bacterial Infection. Plant biotechnology journal 1 41405133
2024 NBR1-mediated autophagic degradation of caspase 8 protects vascular endothelial cells against arsenite-induced apoptotic cell death. Biochemical and biophysical research communications 1 38678786
2023 BAG3 regulates the specificity of the recognition of specific MAPT species by NBR1 and SQSTM1. bioRxiv : the preprint server for biology 1 36798173
2010 Structural insights into the two sequential folding transition states of the PB1 domain of NBR1 from Φ value analysis and biased molecular dynamics simulations. Biochemistry 1 21121670
2026 Glaesserella parasuis serotype 5 disrupts the swine respiratory epithelial barrier via NBR1-mediated selective autophagic degradation of Claudin-1. Veterinary microbiology 0 42000398
2026 NBR1-Regulated Mitochondrial Quality Control in Sertoli Cells Is Involved in the Male Reproductive Damage Induced by Chronic Diquat Poisoning, Which Is Ameliorated by Spermidine. Journal of agricultural and food chemistry 0 42033371
2026 NBR1-Mediated Selective Autophagy in Plant Development and Stress Responses. Plants (Basel, Switzerland) 0 42122842
2025 The predominant role of p62/SQSTM1 over NBR1 in methylmercury-induced cytotoxicity and cellular defense. Biochemical and biophysical research communications 0 39946983
2024 The LC3-interacting region of NBR1 is a protein interaction hub enabling optimal flux. bioRxiv : the preprint server for biology 0 38766171

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