Affinage

UNC93B1

Protein unc-93 homolog B1 · UniProt Q9H1C4

Length
597 aa
Mass
66.6 kDa
Annotated
2026-06-10
60 papers in source corpus 28 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

UNC93B1 is a polytopic ER membrane protein that serves as the master chaperone and trafficking regulator for nucleic-acid-sensing and select other Toll-like receptors, and is essential for TLR3/7/9-dependent type I/III interferon antiviral immunity in humans (PMID:16973841, PMID:16415873). It physically binds nascent TLRs in the ER—engaging acidic juxtamembrane residues of TLR9 and TLR3 and contacting the transmembrane and luminal juxtamembrane regions of TLR3 and TLR7 through its N-terminal six-helix bundle, with an overall fold resembling major facilitator superfamily transporters (PMID:23585677, PMID:33432245)—and stabilizes TLR protein, such that its loss causes near-complete depletion of TLR3 and TLR7 even before trafficking (PMID:29768176). UNC93B1 then escorts these receptors out of the ER by packaging them into COPII vesicles and directing them through the secretory pathway to distinct destinations: endolysosomes for TLR7/9/11/13 and the plasma membrane for the flagellin receptor TLR5, using receptor-specific routes including AP-2 recruitment for TLR9 and a C-terminal Yxxϕ sorting motif (PMID:23426999, PMID:24778236, PMID:25187660). Beyond delivery, UNC93B1 sets the balance and intensity of TLR signaling: residue D34 represses TLR7 while favoring TLR9, and disruption of this balance toward TLR7 drives systemic autoimmune inflammation in mice (PMID:19451267, PMID:21683627). It terminates TLR7 signaling by recruiting syntenin-1 in a phosphorylation-dependent manner to sort TLR7 into multivesicular-body intralumenal vesicles, whereas TLR9 (and TLR3) must be released from UNC93B1 within endosomes to bind ligand and signal, enforcing receptor-specific, compartmentalized activation (PMID:31546246, PMID:31546247). A spectrum of human UNC93B1 variants that selectively enhance TLR7 and/or TLR8 activity cause systemic lupus erythematosus and chilblain lupus, establishing UNC93B1 as a TLR-subtype-specific gatekeeper of autoimmunity (PMID:38207055, PMID:38869500, PMID:38780621, PMID:38831104). UNC93B1 additionally interacts with the ER calcium sensor STIM1 to prime its activation and support store-operated calcium entry and antigen cross-presentation (PMID:29158474, PMID:35065962), and negatively regulates cGAS-STING signaling by delivering STING for lysosomal degradation (PMID:35577759, PMID:33837956).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2006 High

    Established that UNC93B1 is non-redundantly required for intracellular TLR-driven antiviral immunity, converting a then-unknown gene into a central node of innate nucleic-acid sensing.

    Evidence Human loss-of-function mutations with interferon-response assays in patient cells, and an ENU 3d (H412R) mouse mutation abolishing TLR3/7/9 signaling and antigen presentation

    PMID:16415873 PMID:16973841

    Open questions at the time
    • Did not define the molecular mechanism by which UNC93B1 acts on TLRs
    • Localization as a 12-TM ER protein noted but interaction partners not yet mapped
  2. 2008 High

    Resolved how UNC93B1 acts mechanistically by showing it physically binds TLR7/9 in the ER and is required for their ER exit and endolysosomal delivery.

    Evidence Reciprocal Co-IP, subcellular fractionation, live imaging, and genetic complementation of 3d dendritic cells

    PMID:18305481

    Open questions at the time
    • Did not identify the TLR binding interface
    • Did not explain receptor-specific differences in trafficking
  3. 2009 High

    Showed UNC93B1 not only traffics but biases TLR usage, identifying residue D34 as a switch repressing TLR7 in favor of TLR9.

    Evidence Complementation cloning, Co-IP, endolysosomal trafficking and TLR-ligand signaling assays of D34A mutant

    PMID:19451267

    Open questions at the time
    • Physiological consequence of altered balance not yet shown in vivo
    • Structural basis of D34-mediated selectivity unknown
  4. 2011 High

    Demonstrated the in vivo pathological stakes of the TLR7/9 balance and broadened the client repertoire beyond nucleic-acid sensors.

    Evidence D34A knock-in mice with cell-depletion dissection showing TLR7-driven lethal inflammation; Co-IP and infection studies establishing TLR11 and TLR8 as UNC93B1-dependent

    PMID:21097503 PMID:21683627 PMID:22164301

    Open questions at the time
    • Mechanism of TLR competition for UNC93B1 not defined biochemically
    • TLR8 finding was Medium-confidence single-lab
  5. 2013 High

    Defined the secretory-pathway logic of UNC93B1 action: COPII packaging of TLRs and receptor-specific sorting machinery, plus the TLR binding determinants.

    Evidence In vitro COPII budding reconstitution, AP-complex interaction assays, and site-directed mutagenesis of TLR9/TLR3 juxtamembrane acidic residues

    PMID:23426999 PMID:23585677

    Open questions at the time
    • Alternative trafficking pathways for TLR7/11/12/13 not molecularly defined
    • How UNC93B1 selects AP-2 for TLR9 specifically unresolved
  6. 2014 High

    Extended UNC93B1's chaperone role to a cell-surface TLR and dissected its own sorting-motif requirements.

    Evidence Co-IP and surface-localization assays for TLR5 in 3d/KO cells; Yxxϕ motif mutagenesis with AP1/AP2 knockdown in human primary cells

    PMID:24778236 PMID:25187660

    Open questions at the time
    • AP-independent functions of Yxxϕ implied but unidentified
    • How UNC93B1 distinguishes plasma-membrane vs endosomal destinations unclear
  7. 2015 Medium

    Identified an ER co-factor coupling ligand sensing to TLR translocation.

    Evidence Ligand-induced Co-IP, LRRC59 knockdown, and TLR3 localization/signaling assays

    PMID:26466955

    Open questions at the time
    • Single-lab finding without reciprocal in vivo validation
    • Mechanism linking ligand internalization to LRRC59-UNC93B1 association unknown
  8. 2017 High

    Revealed a TLR-independent function: UNC93B1 partners with STIM1 to enable calcium signaling and antigen cross-presentation.

    Evidence Co-IP plus constitutively active STIM1 rescue, calcium flux and cross-presentation assays in 3d DCs

    PMID:29158474

    Open questions at the time
    • Structural basis of STIM1 priming not yet resolved at this stage
    • Relationship between calcium role and TLR trafficking role unclear
  9. 2018 High

    Distinguished UNC93B1's stabilization function from its trafficking function, showing protein stability is the upstream requirement.

    Evidence Quantitative TLR protein measurement in KO vs WT primary cells and ER-retained UNC93B1 mutant rescue

    PMID:29768176

    Open questions at the time
    • How an ER-retained mutant restores endosomal trafficking not fully explained
    • Stabilization mechanism at the molecular level undefined
  10. 2019 High

    Established opposing receptor-specific regulatory logic: UNC93B1 actively terminates TLR7 via syntenin-1 sorting, while it must release TLR9 in endosomes to permit signaling.

    Evidence Co-IP, exosome fractionation, phosphorylation analysis and autoimmunity knock-in mice for TLR7; pH/compartment Co-IP, affinity mutations and engineered tethers for TLR9

    PMID:31546246 PMID:31546247

    Open questions at the time
    • Kinase phosphorylating UNC93B1 not identified
    • Trigger for TLR9 release within endosomes not defined
  11. 2021 High

    Provided atomic-resolution interaction interfaces and revealed UNC93B1's MFS-transporter-like architecture, and uncovered its negative regulation of cGAS-STING.

    Evidence Cryo-EM of TLR3- and TLR7-UNC93B1 complexes; Co-IP and KO functional assays showing STING degradation; CNS expression and let-7b neurodegeneration studies

    PMID:33432245 PMID:33837956 PMID:34589086

    Open questions at the time
    • STING regulation findings were Medium-confidence single-lab studies
    • Functional consequence of MFS-like fold (potential transport activity) untested
  12. 2022 High

    Mechanistically detailed UNC93B1 control over STIM1 conformation and added a post-translational requirement for TLR9 signaling.

    Evidence Cysteine crosslinking, Co-IP and calcium/Orai1 assays for STIM1 helix zipping; N-glycosylation mutagenesis (N272Q) with MyD88-recruitment assays; STING-degradation confirmation

    PMID:35065962 PMID:35577759 PMID:35874766

    Open questions at the time
    • Why Asn272 glycosylation specifically gates MyD88 recruitment unclear
    • Integration of calcium and TLR functions in one protein not unified
  13. 2024 High

    Comprehensively mapped UNC93B1 regulatory regions and connected a spectrum of human variants to TLR-subtype-specific autoimmune disease.

    Evidence Scanning alanine mutagenesis with CRISPR knock-in mice; multiple patient-derived variants (E92G, R336L, I317M, G325C, L330R, R466S, R525P, T93I, R336C, V117L, T314A) with TLR-specific signaling, Co-IP and lupus-like mouse models

    PMID:38207055 PMID:38780621 PMID:38831104 PMID:38869500

    Open questions at the time
    • Distinct molecular mechanisms among variants (instability vs enhanced TLR binding) not unified into a single model
    • Therapeutic targeting of variant-specific hyperactivation untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Whether UNC93B1's MFS-transporter-like fold confers an actual transport activity, the identity of the kinase phosphorylating UNC93B1 for syntenin-1 recruitment, and the trigger for endosomal TLR release remain unresolved.
  • No demonstrated substrate or transport function despite MFS-like architecture
  • UNC93B1 kinase unidentified
  • PANK4 as a negative-regulatory partner rests only on a preprint single Co-IP

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 3 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005783 endoplasmic reticulum 4 GO:0005768 endosome 3 GO:0005764 lysosome 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 4 R-HSA-9609507 Protein localization 3 R-HSA-5653656 Vesicle-mediated transport 2
Partners
SDCBPSTIM1STING1TLR3TLR5TLR7TLR8TLR9

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 Loss-of-function UNC93B1 mutations in humans result in impaired cellular IFN-α/β and IFN-λ antiviral responses, establishing UNC93B1 as essential for TLR3/7/9-dependent antiviral signaling in vivo. Human genetic study; functional assays in patient cells (interferon response measurements) Science High 16973841
2006 A missense mutation (H412R) in Unc93b1 ('3d' mutation) abolishes signaling through intracellular TLR3, TLR7, and TLR9, and also impairs cross-presentation and MHC class II presentation of exogenous antigen; UNC93B1 was identified as a 12-transmembrane-spanning ER-resident protein. ENU mutagenesis screen; positional cloning; functional TLR signaling assays; antigen presentation assays in dendritic cells Nature immunology High 16415873
2008 UNC93B1 physically interacts with TLR7 and TLR9 in the ER and delivers them to endolysosomes; the H412R mutation prevents TLR binding and blocks ER exit of TLR7 and TLR9, while wild-type UNC93B1 rescues trafficking and signaling defects in 3d dendritic cells. Co-immunoprecipitation; subcellular fractionation; live-cell imaging; genetic complementation in 3d dendritic cells Nature High 18305481
2009 UNC93B1 residue D34 represses TLR7-mediated responses while favoring TLR9; D34A mutation increases Unc93B1 association with TLR7 and ligand-induced TLR7 trafficking while decreasing TLR9 association and trafficking, biasing nucleic acid sensing toward DNA-sensing in dendritic cells. Complementation cloning; co-immunoprecipitation; endolysosomal trafficking assays; TLR signaling assays with TLR-specific ligands The Journal of experimental medicine High 19451267
2010 UNC93B1 interacts directly with TLR11 in the ER and is required for TLR11-dependent IL-12 secretion and dendritic cell activation in response to Toxoplasma gondii profilin, demonstrating that UNC93B1 interaction and intracellular localization are not unique to nucleic acid-sensing TLRs. Co-immunoprecipitation; subcellular localization; IL-12 secretion assays; in vivo infection model with UNC93B1-deficient mice The Journal of biological chemistry High 21097503
2011 TLR9 competes with TLR7 for UNC93B1-dependent trafficking and predominates; a D34A mutation in UNC93B1 reverses this balance toward TLR7, causing TLR7-dependent systemic lethal inflammation in mice driven by CD4+ T cell Th1/Th17 differentiation and B cell activity. Knock-in mouse model (D34A); TLR competition assays; flow cytometry; B cell depletion experiments Immunity High 21683627
2013 UNC93B1 enters the secretory pathway and directly controls packaging of TLRs into COPII vesicles budding from the ER; it remains associated with TLRs through post-Golgi sorting. TLR9 requires UNC93B1-mediated AP-2 recruitment for endolysosomal delivery, while TLR7, TLR11, TLR12, and TLR13 use alternative trafficking pathways. COPII vesicle budding assays; co-immunoprecipitation; AP complex interaction assays; subcellular trafficking analysis eLife High 23426999
2013 Acidic residues D812/E813 of TLR9 and D699/E704 of TLR3 in the juxtamembrane region are required for UNC93B1 binding; mutation of these residues prevents UNC93B1 interaction, impairs TLR trafficking from the ER, and abolishes TLR signaling. Site-directed mutagenesis of TLR juxtamembrane residues; co-immunoprecipitation; subcellular localization; signaling assays Journal of immunology High 23585677
2014 UNC93B1 is essential for plasma membrane localization and signaling of TLR5 (a flagellin receptor); TLR5 physically interacts with UNC93B1, and cells from 3d or UNC93B1-deficient mice lack TLR5 at the plasma membrane and fail to produce cytokines upon flagellin stimulation. Co-immunoprecipitation; cell surface localization assays; cytokine secretion and costimulatory molecule upregulation in 3d and UNC93B1-KO cells Proceedings of the National Academy of Sciences of the United States of America High 24778236
2014 A C-terminal tyrosine-based sorting motif (YxxΦ) in UNC93B1 differentially regulates TLR7, TLR8, and TLR9 activity toward nucleic acid ligands in human B cells and monocytes; destruction of YxxΦ abolishes these TLR responses. YxxΦ controls UNC93B1 subcellular localization via both AP1- and AP2-dependent pathways, but loss of AP function does not recapitulate altered TLR responses, indicating AP-independent functions. Site-directed mutagenesis of UNC93B1 YxxΦ motif; TLR signaling assays in human primary cells; AP complex knockdown; subcellular localization imaging Journal of immunology High 25187660
2011 UNC93B1 physically associates with human TLR8 and is required for TLR8-mediated signaling; TLR8 localizes to early endosomes and ER but not late endosomes or lysosomes, and the transmembrane domain and TIR domain of TLR8 are required for proper early endosomal targeting. Co-immunoprecipitation; subcellular localization (confocal microscopy with organelle markers); TLR8 signaling assays; truncation mutant analysis PloS one Medium 22164301
2015 LRRC59, an ER membrane protein, associates with UNC93B1 upon ligand stimulation (in a TLR-independent manner requiring signals from ligand internalization) and promotes UNC93B1-mediated translocation of TLR3, TLR8, and TLR9 from the ER to endosomes. Co-immunoprecipitation (ligand-induced); siRNA knockdown of LRRC59; subcellular localization of endogenous TLR3; TLR signaling assays Journal of immunology Medium 26466955
2017 UNC93B1 interacts with the ER calcium sensor STIM1, and this interaction is required for STIM1 oligomerization and activation; UNC93B1 deficiency impairs endosomal acidification, phagosomal maturation, antigen degradation, antigen export to the cytosol, and STIM1 function, resulting in compromised antigen cross-presentation. Expression of a constitutively active STIM1 mutant that does not bind UNC93B1 restores antigen degradation and cross-presentation in 3d-mutated DCs. Co-immunoprecipitation (UNC93B1-STIM1); constitutively active STIM1 mutant rescue; antigen cross-presentation assays; calcium flux measurements in 3d DCs Nature communications High 29158474
2018 UNC93B1 deficiency causes near-complete loss of TLR3 and TLR7 proteins in primary dendritic cells and macrophages, demonstrating that UNC93B1 is critical for TLR protein stability upstream of trafficking; expression of an ER-retained UNC93B1 version is sufficient to stabilize TLRs and largely restore endosomal TLR trafficking and activity. Western blot of TLR protein levels in UNC93B1-KO vs WT primary cells; ER-retained UNC93B1 mutant rescue experiments; TLR signaling assays Immunity High 29768176
2019 UNC93B1 specifically limits TLR7 (but not TLR9) signaling by recruiting syntenin-1; UNC93B1 mutations that enhance TLR7 signaling disrupt syntenin-1 binding. UNC93B1 and TLR7 are detectable in exosomes, suggesting UNC93B1-syntenin-1 interaction facilitates sorting of TLR7 into intralumenal vesicles of multivesicular bodies to terminate signaling. Phosphorylation of UNC93B1 is required for syntenin-1 binding. Co-immunoprecipitation; exosome fractionation and Western blot; mutagenesis; phosphorylation analysis; TLR7-specific autoimmunity in knock-in mice Nature High 31546246
2019 TLR9 (and TLR3) are released from UNC93B1 within endosomes, and this release is required for ligand binding and signal transduction; UNC93B1 mutations that increase TLR9 affinity or an artificial tether preventing release block TLR9 signaling. TLR7 does not dissociate from UNC93B1 in endosomes and is regulated by distinct mechanisms. Co-immunoprecipitation at different pH/compartments; tethered UNC93B1-TLR9 fusion constructs; affinity-increasing mutations; TLR signaling assays Nature High 31546247
2021 Cryo-EM structures of human and mouse TLR3-UNC93B1 complexes and human TLR7-UNC93B1 complex reveal that UNC93B1 exhibits structural similarity to major facilitator superfamily transporters; both TLRs interact with the UNC93B1 N-terminal six-helix bundle through their transmembrane and luminal juxtamembrane regions; TLR3 and TLR7 complexes differ in their oligomerization state. Cryo-electron microscopy structural determination Nature structural & molecular biology High 33432245
2022 N-glycosylation of UNC93B1 at Asn272 (but not Asn251) is required for TLR9 signaling; the N272Q mutation selectively impairs MyD88 recruitment to TLR9 and downstream signaling without affecting TLR7 signaling, UNC93B1 expression, or TLR9 localization. The two N-glycosylation sites (Asn251 and Asn272) can be glycosylated independently. Site-directed mutagenesis (N251Q, N272Q); TLR9 signaling assays; co-immunoprecipitation of MyD88-TLR9; subcellular localization; TLR7 signaling comparison Frontiers in immunology High 35874766
2022 UNC93B1 attenuates cGAS-STING signaling by directly interacting with STING and delivering it to lysosomes for autophagy-dependent degradation; UNC93B1 knockout enhances STING-dependent IFN-β production and reduces STING protein degradation. This function depends on UNC93B1 trafficking capability. Co-immunoprecipitation (UNC93B1-STING); UNC93B1 overexpression and knockout; lysosome inhibitor rescue; IFN-β promoter assays; IRF3 nuclear translocation; HSV-1 infection in KO mice Journal of medical virology Medium 35577759
2021 UNC93B1 directly interacts with STING and promotes STING protein degradation; UNC93B1 deficiency blunts TLR3 signaling but augments innate immune responses to cytosolic DNA stimulation by causing STING accumulation, demonstrating a negative regulatory role on STING-mediated signaling. Co-immunoprecipitation (UNC93B1-STING); UNC93B1 knockdown/KO; cytosolic DNA stimulation assays; STING protein level measurement European journal of immunology Medium 33837956
2022 UNC93B1 interacts with STIM1 in the ER lumen near the transmembrane domain; UNC93B1 binding promotes zipping of transmembrane and proximal cytosolic helices within resting STIM1 dimers, priming them for translocation. UNC93B1 deficiency reduces store-operated Ca2+ entry, STIM1-Orai1 interactions, and targets STIM1 to lighter ER domains; UNC93B1 expression accelerates STIM1 recruitment to cortical ER domains. Co-immunoprecipitation; cysteine crosslinking in vivo; calcium flux measurements; STIM1-Orai1 Co-IP; subcellular fractionation; live-cell imaging The Journal of biological chemistry High 35065962
2012 UNC93B1 promotes trafficking of differentially glycosylated TLR3 (but not other NA-sensing TLRs) to the plasma membrane in human epithelial cells; poly(I:C) up-regulates UNC93B1 transcription via TLR3 activation; UNC93B1 increases protein lifetime of TLR3 and TLR9 and augments signaling of all NA-sensing TLRs. Poly(I:C) pretreatment primes B cells to ssDNA activation via UNC93B1 up-regulation. siRNA knockdown; confocal microscopy for TLR3 localization; Western blot for protein stability; TLR signaling assays; UNC93B1 promoter analysis The Journal of biological chemistry Medium 23166319
2003 In C. elegans, UNC-93 colocalizes with SUP-9 (a two-pore K+ channel) and SUP-10 within muscle cells, and genetic evidence suggests these three proteins form a multisubunit complex coordinating muscle contraction; UNC-93 defines a novel multigene family conserved in C. elegans, Drosophila, and humans. Genetic epistasis analysis; cloning of sup-9 and sup-10; colocalization by immunofluorescence in muscle cells The Journal of neuroscience Low 14534247
2024 UNC93B1 variants E92G and R336L cause selective TLR7 hyperactivation; E92G causes UNC93B1 protein instability and reduced interaction with TLR7, leading to constitutive type I IFN signaling, while neither variant affects TLR3 or TLR9 responses, establishing UNC93B1 as a TLR subtype-specific regulator. Patient cell functional assays; mouse macrophage model with variants; co-immunoprecipitation (UNC93B1-TLR7); cytokine measurements; protein stability assays Science immunology High 38207055
2024 UNC93B1 variants I317M, G325C cause gain of TLR7 and TLR8 activity in SLE patients; variants L330R, R466S, R525P cause gain of TLR8 activity in chilblain lupus patients. G325C, L330R, and R466S variants show enhanced interaction with TLR8 by Co-IP, while R525P does not, indicating different disease mechanisms for different mutations. In vitro TLR signaling assays; ex vivo patient cell assays; co-immunoprecipitation (UNC93B1 variants with TLR8) The Journal of experimental medicine High 38869500
2024 Systematic alanine scanning mutagenesis of all cytosolic and luminal UNC93B1 residues identified distinct positive and negative regulatory regions for TLR3, TLR7, and TLR9 responses; human variants UNC93B1-T93I and UNC93B1-R336C in identified negative regulatory regions enhance TLR7/8 responses and cause systemic autoimmune disease when introduced into mice. Scanning alanine mutagenesis screen; TLR signaling assays (TLR3, TLR7/8, TLR9); CRISPR knock-in mouse models; patient variant analysis The Journal of experimental medicine High 38780621
2024 UNC93B1 variant V117L is associated with increased TLR7/8 (but not TLR3/TLR9) responses; variant T314A (proximal to TLR7 transmembrane domain) also causes exaggerated TLR7/8 responses; heterozygous mice expressing Unc93b1 V117L develop spontaneous lupus-like disease. Patient cell functional assays; THP-1 cell TLR stimulation assays; heterozygous knock-in mouse model; cytokine and IFN measurements Nature immunology High 38831104
2021 UNC93B1 is expressed in multiple CNS cell types (microglia, astrocytes, oligodendrocytes, neurons) and is required for microglial activation and neuronal injury induced by extracellular let-7b (a TLR7 activator); intrathecal let-7b causes neurodegeneration in wild-type but not UNC93B1-deficient mice. PCR, immunocytochemistry, flow cytometry for expression; TNF ELISA in UNC93B1-deficient microglia; neuronal injury assays in vitro; intrathecal injection in vivo; neurodegeneration assessment Frontiers in immunology Medium 34589086
2025 PANK4 interacts with UNC93B1 to suppress TLR7 and TLR9-mediated cytokine responses, acting as a negative regulator of nucleic acid-sensing innate immune pathways. Co-immunoprecipitation (PANK4-UNC93B1); TLR7/9 signaling assays with PANK4 loss-of-function bioRxivpreprint Low

Source papers

Stage 0 corpus · 60 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Herpes simplex virus encephalitis in human UNC-93B deficiency. Science (New York, N.Y.) 586 16973841
2008 UNC93B1 delivers nucleotide-sensing toll-like receptors to endolysosomes. Nature 549 18305481
2006 The Unc93b1 mutation 3d disrupts exogenous antigen presentation and signaling via Toll-like receptors 3, 7 and 9. Nature immunology 530 16415873
2013 UNC93B1 mediates differential trafficking of endosomal TLRs. eLife 216 23426999
2011 Unc93B1 restricts systemic lethal inflammation by orchestrating Toll-like receptor 7 and 9 trafficking. Immunity 187 21683627
2009 Unc93B1 biases Toll-like receptor responses to nucleic acid in dendritic cells toward DNA- but against RNA-sensing. The Journal of experimental medicine 156 19451267
2018 The Chaperone UNC93B1 Regulates Toll-like Receptor Stability Independently of Endosomal TLR Transport. Immunity 114 29768176
2019 UNC93B1 recruits syntenin-1 to dampen TLR7 signalling and prevent autoimmunity. Nature 112 31546246
2010 UNC93B1 is essential for TLR11 activation and IL-12-dependent host resistance to Toxoplasma gondii. The Journal of biological chemistry 81 21097503
2019 Release from UNC93B1 reinforces the compartmentalized activation of select TLRs. Nature 77 31546247
2021 Cryo-EM structures of Toll-like receptors in complex with UNC93B1. Nature structural & molecular biology 74 33432245
2012 IgM+IgD+CD27+ B cells are markedly reduced in IRAK-4-, MyD88-, and TIRAP- but not UNC-93B-deficient patients. Blood 72 23002119
2024 UNC93B1 variants underlie TLR7-dependent autoimmunity. Science immunology 64 38207055
2003 sup-9, sup-10, and unc-93 may encode components of a two-pore K+ channel that coordinates muscle contraction in Caenorhabditis elegans. The Journal of neuroscience : the official journal of the Society for Neuroscience 64 14534247
2011 Requirement of UNC93B1 reveals a critical role for TLR7 in host resistance to primary infection with Trypanosoma cruzi. Journal of immunology (Baltimore, Md. : 1950) 63 21753151
2014 UNC93B1 is essential for the plasma membrane localization and signaling of Toll-like receptor 5. Proceedings of the National Academy of Sciences of the United States of America 59 24778236
2022 UNC93B1 attenuates the cGAS-STING signaling pathway by targeting STING for autophagy-lysosome degradation. Journal of medical virology 58 35577759
2012 The role of UNC93B1 protein in surface localization of TLR3 receptor and in cell priming to nucleic acid agonists. The Journal of biological chemistry 56 23166319
2011 UNC93B1 physically associates with human TLR8 and regulates TLR8-mediated signaling. PloS one 54 22164301
2010 UNC93B1 mediates host resistance to infection with Toxoplasma gondii. PLoS pathogens 50 20865117
2024 Genetic variants in UNC93B1 predispose to childhood-onset systemic lupus erythematosus. Nature immunology 44 38831104
1992 The Caenorhabditis elegans unc-93 gene encodes a putative transmembrane protein that regulates muscle contraction. The Journal of cell biology 43 1313436
2024 Gain-of-function human UNC93B1 variants cause systemic lupus erythematosus and chilblain lupus. The Journal of experimental medicine 40 38869500
2017 UNC93B1 interacts with the calcium sensor STIM1 for efficient antigen cross-presentation in dendritic cells. Nature communications 39 29158474
2013 Expression of murine Unc93b1 is up-regulated by interferon and estrogen signaling: implications for sex bias in the development of autoimmunity. International immunology 37 23728775
2013 UNC93B1 and nucleic acid-sensing Toll-like receptors mediate host resistance to infection with Leishmania major. The Journal of biological chemistry 36 23325805
2024 Large-scale mutational analysis identifies UNC93B1 variants that drive TLR-mediated autoimmunity in mice and humans. The Journal of experimental medicine 31 38780621
2013 Acidic amino acid residues in the juxtamembrane region of the nucleotide-sensing TLRs are important for UNC93B1 binding and signaling. Journal of immunology (Baltimore, Md. : 1950) 31 23585677
2014 Cutting edge: the UNC93B1 tyrosine-based motif regulates trafficking and TLR responses via separate mechanisms. Journal of immunology (Baltimore, Md. : 1950) 30 25187660
2015 LRRC59 Regulates Trafficking of Nucleic Acid-Sensing TLRs from the Endoplasmic Reticulum via Association with UNC93B1. Journal of immunology (Baltimore, Md. : 1950) 28 26466955
2010 Secretion of the human Toll-like receptor 3 ectodomain is affected by single nucleotide polymorphisms and regulated by Unc93b1. The Journal of biological chemistry 21 20855885
2020 A Missense Variant Affecting the C-Terminal Tail of UNC93B1 in Dogs with Exfoliative Cutaneous Lupus Erythematosus (ECLE). Genes 18 32028618
2018 Toll-like receptor 3 agonist poly I:C reinforces the potency of cytotoxic chemotherapy via the TLR3-UNC93B1-IFN-β signaling axis in paclitaxel-resistant colon cancer. Journal of cellular physiology 18 30387134
2021 UNC93B1 curbs cytosolic DNA signaling by promoting STING degradation. European journal of immunology 17 33837956
2002 The human homologue of unc-93 maps to chromosome 6q27 - characterisation and analysis in sporadic epithelial ovarian cancer. BMC genetics 17 12381271
2023 IRF7 and UNC93B1 variants in an infant with recurrent herpes simplex virus infection. The Journal of clinical investigation 16 37097753
2015 Unc93b1 -Dependent Endosomal Toll-Like Receptor Signaling Regulates Inflammation and Mortality during Coxsackievirus B3 Infection. Journal of innate immunity 15 25675947
2012 UNC93B1 mediates innate inflammation and antiviral defense in the liver during acute murine cytomegalovirus infection. PloS one 15 22723955
2011 Love triangle between Unc93B1, TLR7, and TLR9 prevents fatal attraction. Immunity 14 21777792
2007 Assessing the function of human UNC-93B in Toll-like receptor signaling and major histocompatibility complex II response. Human immunology 14 18082565
2014 An ENU-induced splicing mutation reveals a role for Unc93b1 in early immune cell activation following influenza A H1N1 infection. Genes and immunity 11 24848930
2019 UNC93B1 promotes tumoral growth by controlling the secretion level of granulocyte macrophage colony-stimulating factor in human oral cancer. Biochemical and biophysical research communications 10 30935694
2016 Inhibiting TLR9 and other UNC93B1-dependent TLRs paradoxically increases accumulation of MYD88L265P plasmablasts in vivo. Blood 10 27458005
2007 Immunodeficiency: UNC-93B gets a toll call. Trends in immunology 10 17240194
2005 Isolation of Caenorhabditis elegans genomic DNA and detection of deletions in the unc-93 gene using PCR. Biochemistry and molecular biology education : a bimonthly publication of the International Union of Biochemistry and Molecular Biology 9 21638583
2015 Functional characterisation of a TLR accessory protein, UNC93B1, in Atlantic salmon (Salmo salar). Developmental and comparative immunology 8 25576824
2023 High-expression of the innate-immune related gene UNC93B1 predicts inferior outcomes in acute myeloid leukemia. Frontiers in genetics 7 36741319
2022 N-glycosylation of UNC93B1 at a Specific Asparagine Residue Is Required for TLR9 Signaling. Frontiers in immunology 6 35874766
2017 Unc93b1 is essential for cytokine activation of five PAMPs in the orange-spotted grouper (Epinephelus coioides). Developmental and comparative immunology 6 29097235
2021 Donor UNC-93 Homolog B1 genetic polymorphism predicts survival outcomes after unrelated bone marrow transplantation. Genes and immunity 5 33627833
2021 UNC93B1 Is Widely Expressed in the Murine CNS and Is Required for Neuroinflammation and Neuronal Injury Induced by MicroRNA let-7b. Frontiers in immunology 5 34589086
2023 Investigation of the functional role of UNC93B1 in Nile tilapia (Oreochromis niloticus): mRNA expression, subcellular localization, and physical interaction with fish-specific TLRs. Fish & shellfish immunology 4 37330026
2022 The mammalian trafficking chaperone protein UNC93B1 maintains the ER calcium sensor STIM1 in a dimeric state primed for translocation to the ER cortex. The Journal of biological chemistry 4 35065962
2023 UNC93B1 facilitates TLR18-mediated NF-κB signal activation in Schizothorax prenanti. Fish & shellfish immunology 3 36740083
2024 UNC93B1 Mediates the Effects of cGAS-STING on ER Stress and Iron Death, and Reduces Renal Toxicity in Cadmium-Exposed Rats. Discovery medicine 2 38798261
2021 The Signal Peptide and Chaperone UNC93B1 Both Influence TLR8 Ectodomain Intracellular Endosomal Localization. Vaccines 2 35062674
2026 UNC93B1 promotes pancreatic cancer progression through modulation of cGAS-STING signaling. Frontiers in immunology 0 41716413
2025 Case Report: Novel UNC93B1 variant causes rheumatoid arthritis and interstitial pneumonia. Frontiers in immunology 0 41103438
2023 UNC93B1 facilitates the localization and signaling of TLR5M in Epinephelus coioides. International journal of biological macromolecules 0 38086430
2021 Variants Affecting the C-Terminal Tail of UNC93B1 Are Not a Common Risk Factor for Systemic Lupus Erythematosus. Genes 0 34440442

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