Affinage

UNC93B1

Protein unc-93 homolog B1 · UniProt Q9H1C4

Length
597 aa
Mass
66.6 kDa
Annotated
2026-04-28
60 papers in source corpus 26 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

UNC93B1 is a 12-transmembrane ER-resident chaperone that controls the stability, trafficking, and signaling of nucleic acid-sensing Toll-like receptors (TLR3, TLR7, TLR8, TLR9, TLR11, TLR12, TLR13) and the cell-surface receptor TLR5. UNC93B1 stabilizes TLR proteins in the ER, loads them into COPII vesicles for ER exit, and directs post-Golgi sorting to endolysosomes via AP-2-dependent (TLR9) or alternative pathways, while TLR5 is routed to the plasma membrane (PMID:18305481, PMID:23426999, PMID:24778236, PMID:29768176). Within endosomes, UNC93B1 releases TLR9 to permit ligand binding while retaining TLR7, and it terminates TLR7 signaling by recruiting syntenin-1 to sort TLR7 into multivesicular bodies; the balance of TLR7 versus TLR9 activation—governed by residue D34, N-glycosylation at N272, and negative regulatory residues—prevents autoimmunity, as loss-of-function mutations cause susceptibility to herpes simplex encephalitis while gain-of-function variants cause systemic lupus erythematosus and chilblain lupus (PMID:16973841, PMID:31546246, PMID:31546247, PMID:38780621, PMID:38869500). UNC93B1 also interacts with STIM1 to prime store-operated Ca²⁺ entry for antigen cross-presentation and negatively regulates cGAS-STING signaling by directing STING to autophagy-lysosomal degradation (PMID:29158474, PMID:35065962, PMID:33837956).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2006 High

    Before the genetic identification of UNC93B1, the mechanism by which endosomal TLRs reach their signaling compartment was unknown; ENU mutagenesis revealed that the 3d (H412R) mutation in Unc93b1 abolished TLR3, TLR7, and TLR9 signaling and antigen cross-presentation, establishing UNC93B1 as a master regulator of intracellular TLR function.

    Evidence ENU mutagenesis screen with positional cloning and functional TLR assays in mouse dendritic cells; concurrent human genetic study identifying autosomal recessive UNC93B1 deficiency causing impaired antiviral IFN responses

    PMID:16415873 PMID:16973841

    Open questions at the time
    • Mechanism of UNC93B1 action (chaperone vs. transport vs. signaling adapter) was not determined
    • Whether UNC93B1 physically contacts TLRs was not shown
  2. 2008 High

    The question of whether UNC93B1 directly binds TLRs or acts indirectly was resolved when co-immunoprecipitation and imaging demonstrated physical interaction with TLR7 and TLR9 in the ER and showed that the 3d mutation traps these TLRs in the ER, establishing UNC93B1 as a direct ER-to-endosome trafficking chaperone.

    Evidence Co-immunoprecipitation, subcellular fractionation, confocal microscopy, and complementation in 3d dendritic cells

    PMID:18305481

    Open questions at the time
    • The molecular mechanism of ER exit was not defined
    • Whether UNC93B1 remains associated with TLRs in endosomes was unclear
  3. 2009 High

    How UNC93B1 differentially regulates TLR7 versus TLR9 was unclear until the D34A mutation was shown to shift UNC93B1 affinity toward TLR7 and away from TLR9, revealing a competitive binding mechanism that balances TLR7/TLR9 activation and, when disrupted, causes lethal TLR7-dependent inflammation.

    Evidence D34A knock-in mice, co-IP of endogenous proteins, TLR signaling assays, B-cell depletion rescue experiments

    PMID:19451267 PMID:21683627

    Open questions at the time
    • Structural basis for D34-mediated selectivity was not resolved
    • Whether additional residues participate in TLR selectivity was unknown
  4. 2013 High

    The pathway by which UNC93B1 moves TLRs out of the ER was defined when reconstituted COPII vesicle budding assays showed UNC93B1 loads TLRs into COPII vesicles, and post-Golgi sorting studies revealed that TLR9 requires UNC93B1-mediated AP-2 recruitment for endolysosomal delivery whereas TLR7/11/12/13 use alternative routes; separately, acidic residues in TLR9 and TLR3 juxtamembrane regions were identified as the UNC93B1 binding determinants.

    Evidence COPII vesicle budding reconstitution, AP-2 depletion, site-directed mutagenesis of TLR juxtamembrane residues, co-IP and trafficking assays

    PMID:23426999 PMID:23585677

    Open questions at the time
    • Precise post-Golgi sorting machinery for TLR7/11 was not identified
    • Whether UNC93B1 acts catalytically or stoichiometrically in COPII loading was unclear
  5. 2014 High

    UNC93B1 was previously thought to regulate only endosomal TLRs; the discovery that UNC93B1 binds TLR5 and is required for its plasma membrane localization and flagellin responses expanded UNC93B1's role to cell-surface TLR trafficking, while identification of a C-terminal YxxΦ sorting motif in UNC93B1 showed that AP-1/AP-2-dependent pathways fine-tune subcellular routing of TLR7/8/9.

    Evidence Co-IP, surface biotinylation, flow cytometry in 3d and UNC93B1-KO mice; mutagenesis of YxxΦ motif with AP knockdown in primary human cells

    PMID:24778236 PMID:25187660

    Open questions at the time
    • How TLR5 is sorted to the plasma membrane rather than endosomes via UNC93B1 was not mechanistically resolved
  6. 2017 High

    The impaired antigen cross-presentation in 3d mice had no mechanistic explanation beyond TLR defects until UNC93B1 was shown to bind STIM1 in the ER, promote STIM1 oligomerization and store-operated Ca²⁺ entry, and thereby enable cross-presentation through a TLR-independent mechanism rescued by constitutively active STIM1.

    Evidence Co-immunoprecipitation, calcium imaging, cross-presentation assays, rescue with constitutively active STIM1

    PMID:29158474

    Open questions at the time
    • The structural basis for UNC93B1-STIM1 interaction was not resolved at this point
    • Whether STIM1 and TLR binding are mutually exclusive on UNC93B1 was unknown
  7. 2018 High

    Whether UNC93B1 merely traffics TLRs or also stabilizes them was ambiguous until UNC93B1 knockout was shown to cause near-complete loss of TLR3 and TLR7 protein, and an ER-retained UNC93B1 mutant was sufficient to restore TLR stability and largely rescue signaling, demonstrating a chaperone-like stabilization function independent of forward trafficking.

    Evidence Western blot of TLR protein in UNC93B1-KO primary cells, ER-retained UNC93B1 mutant rescue

    PMID:29768176

    Open questions at the time
    • Whether UNC93B1 prevents proteasomal vs. lysosomal TLR degradation was not determined
    • The stoichiometry of stabilization was not addressed
  8. 2019 High

    Two companion studies resolved the endosomal fate of TLR7 versus TLR9: TLR9 is released from UNC93B1 in endosomes to enable ligand binding and signaling, whereas TLR7 remains UNC93B1-bound and is negatively regulated by UNC93B1-mediated recruitment of syntenin-1, which sorts TLR7 into multivesicular body intralumenal vesicles; disruption of either mechanism causes autoimmunity.

    Evidence UNC93B1 mutagenesis, artificial TLR9-UNC93B1 tethering, syntenin-1 KO mice, exosome isolation, phospho-mutant analysis

    PMID:31546246 PMID:31546247

    Open questions at the time
    • The signal triggering TLR9 release from UNC93B1 was not identified
    • Whether syntenin-1-dependent sorting applies to TLR8 was not tested
  9. 2021 High

    Cryo-EM structures of TLR3–UNC93B1 and TLR7–UNC93B1 complexes revealed that UNC93B1 adopts a major facilitator superfamily fold and contacts TLR transmembrane and juxtamembrane regions via its N-terminal six-helix bundle, providing the first structural framework for understanding TLR-selective binding.

    Evidence Cryo-EM structure determination of human and mouse complexes

    PMID:33432245

    Open questions at the time
    • No TLR9–UNC93B1 structure was solved
    • How D34 or glycosylation sites modulate the interface was not structurally resolved
  10. 2021 Medium

    UNC93B1 was found to negatively regulate cGAS-STING signaling by binding STING and directing it to autophagy-lysosomal degradation, extending UNC93B1's function beyond TLR regulation to cytosolic DNA sensing pathway control.

    Evidence Co-immunoprecipitation, lysosome inhibitor rescue, UNC93B1-KO cell lines and Unc93b1−/− mice with HSV-1 infection

    PMID:33837956 PMID:35577759

    Open questions at the time
    • The domain of UNC93B1 mediating STING interaction was not mapped
    • Whether STING degradation requires UNC93B1 trafficking or only ER interaction was not fully resolved
    • Independent replication beyond two related studies is limited
  11. 2022 High

    The UNC93B1-STIM1 interaction was mechanistically refined: UNC93B1 binds near the STIM1 transmembrane domain and promotes zipping of transmembrane and proximal cytosolic helices within resting STIM1 dimers, priming STIM1 for cortical ER translocation and Orai1 coupling; separately, N-glycosylation at N272 was shown to be specifically required for TLR9 signaling via MyD88 recruitment.

    Evidence In vivo cysteine crosslinking, Ca²⁺ imaging, STIM1-Orai1 interaction assays; glycosylation-site mutagenesis with MyD88 co-IP

    PMID:35065962 PMID:35874766

    Open questions at the time
    • Whether N272 glycosylation affects TLR9 release from UNC93B1 in endosomes was not tested
    • Structural view of UNC93B1-STIM1 complex is lacking
  12. 2024 High

    Systematic mutagenesis of all UNC93B1 cytosolic/luminal residues combined with patient genetics identified both negative and positive regulatory regions for TLR3/7/8/9, establishing that specific gain-of-function UNC93B1 variants (T93I, R336C, E92G, R336L, G325C, I317M) cause selective TLR7 or TLR8 hyperactivation leading to SLE and chilblain lupus, mechanistically linking UNC93B1 to monogenic autoimmune disease.

    Evidence Saturation alanine-scanning mutagenesis screen, genome-edited knock-in mice, patient family genetics, co-IP of UNC93B1-TLR interactions, TLR-specific agonist assays

    PMID:38207055 PMID:38780621 PMID:38869500

    Open questions at the time
    • Structural mapping of newly identified regulatory surfaces onto the cryo-EM structure is incomplete
    • Whether therapeutic targeting of UNC93B1-TLR7/8 interface can ameliorate lupus is untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the signal that triggers TLR9 dissociation from UNC93B1 in endosomes, the structural basis for TLR9-selective glycosylation-dependent regulation, how UNC93B1 simultaneously coordinates TLR chaperoning with STIM1 priming and STING degradation, and whether UNC93B1's regulatory surfaces can be pharmacologically targeted to treat autoimmune disease.
  • No endosomal release signal for TLR9 identified
  • No structure of UNC93B1-STIM1 or UNC93B1-STING complexes
  • Therapeutic tractability of UNC93B1 is unexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0044183 protein folding chaperone 3 GO:0060090 molecular adaptor activity 3
Localization
GO:0005783 endoplasmic reticulum 5 GO:0005768 endosome 3
Pathway
R-HSA-168256 Immune System 9 R-HSA-9609507 Protein localization 3 R-HSA-162582 Signal Transduction 2 R-HSA-9612973 Autophagy 2
Partners
SDCBPSTIM1STING1TLR3TLR5TLR7TLR8TLR9

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 UNC93B1 is required for signaling via intracellular TLR3, TLR7, and TLR9; the 3d missense allele (H412R) of Unc93b1 abolishes all three intracellular TLR pathways, impairs cross-presentation of exogenous antigen, and causes hypersusceptibility to MCMV infection. ENU mutagenesis screen, positional cloning, genetic complementation, functional TLR signaling assays in dendritic cells Nature immunology High 16415873
2006 Human UNC93B1 deficiency (autosomal recessive) results in impaired TLR3/7/9-dependent interferon-alpha/beta and -lambda antiviral responses, establishing UNC93B1 as essential for nucleic acid-sensing TLR signaling in humans. Genetic mapping in patients, functional cellular assays of IFN responses Science High 16973841
2008 UNC93B1 physically interacts with TLR7 and TLR9 in the ER and delivers them to endolysosomes; in 3d (H412R) dendritic cells, neither TLR7 nor TLR9 exits the ER, and this trafficking and signaling defect is rescued by wild-type UNC93B1 expression. Co-immunoprecipitation, subcellular fractionation, confocal microscopy, complementation in 3d dendritic cells Nature High 18305481
2009 UNC93B1 residue D34 biases trafficking between TLR7 and TLR9: the D34A mutation increases UNC93B1 association with TLR7 (upregulating TLR7 trafficking and responses) while decreasing association with TLR9 (downregulating TLR9 trafficking and responses), with TLR3 unaffected. Complementation cloning, Co-IP of endogenous proteins, ligand-induced trafficking assays, TLR signaling assays in DCs The Journal of experimental medicine High 19451267
2010 UNC93B1 directly interacts with TLR11 in the ER, and functional UNC93B1 is required for TLR11-dependent IL-12 secretion by dendritic cells in response to Toxoplasma gondii profilin; loss of UNC93B1 abolishes TLR11-dependent Th1 responses and host resistance. Co-immunoprecipitation, genetic loss-of-function (3d mice), IL-12 secretion assays, in vivo infection model The Journal of biological chemistry High 21097503
2011 TLR9 competes with TLR7 for UNC93B1-dependent trafficking and normally predominates; D34A mutation reverses this balance toward TLR7, causing TLR7-dependent systemic lethal inflammation driven by B-cell-dependent CD4+ T cell differentiation into Th1/Th17 subsets. Knock-in mice with D34A mutation, B-cell depletion experiments, T-cell subset analysis, signaling assays Immunity High 21683627
2011 UNC93B1 physically associates with human TLR8 and is required for TLR8-mediated signaling; TLR8 localizes to early endosomes/ER in human monocytes, distinct from TLR7/TLR9 late endosomal localization. Co-immunoprecipitation, subcellular localization by immunofluorescence in human monocytes and HeLa transfectants PloS one Medium 22164301
2013 UNC93B1 enters the secretory pathway and controls loading of TLRs into COPII vesicles at the ER exit; UNC93B1 remains associated with TLRs through post-Golgi sorting. TLR9 specifically requires UNC93B1-mediated recruitment of adaptor protein complex 2 (AP-2) for endolysosomal delivery, while TLR7, TLR11, TLR12, and TLR13 use alternative pathways. COPII vesicle budding assays, subcellular fractionation, AP-2 depletion, Co-IP, trafficking assays in dendritic cells eLife High 23426999
2013 Acidic residues (D812, E813) in the juxtamembrane region of TLR9 and (D699, E704) of TLR3 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 TLRs, Co-immunoprecipitation, trafficking assays, TLR signaling assays Journal of immunology High 23585677
2014 TLR5, a cell-surface receptor for flagellin, physically interacts with UNC93B1; UNC93B1 is essential for TLR5 plasma membrane localization and flagellin-induced cytokine secretion. 3d or UNC93B1-deficient cells lack TLR5 at the plasma membrane and fail to respond to flagellin. Co-immunoprecipitation, flow cytometry/surface biotinylation for TLR5 localization, cytokine assays in 3d and UNC93B1-KO mice Proceedings of the National Academy of Sciences High 24778236
2014 A C-terminal tyrosine-based sorting motif (YxxΦ) in UNC93B1 differentially regulates TLR7, TLR8, and TLR9 activity in human B cells and monocytes; destruction of YxxΦ abolishes nucleic acid-induced TLR7/8/9 responses but not small-molecule TLR8 responses. YxxΦ influences UNC93B1 subcellular localization via AP1- and AP2-dependent pathways. Site-directed mutagenesis of UNC93B1 YxxΦ motif, AP knockdown, subcellular localization assays, TLR signaling assays in primary human cells Journal of immunology High 25187660
2015 LRRC59, an ER membrane protein, associates with UNC93B1 in a ligand-stimulated, TLR-independent manner and promotes UNC93B1-mediated endosomal translocation of nucleic acid-sensing TLRs (TLR3, TLR8, TLR9) upon infection. Co-immunoprecipitation, LRRC59 knockdown, TLR signaling assays, endosomal localization of TLR3 by imaging Journal of immunology Medium 26466955
2017 UNC93B1 interacts with the ER calcium sensor STIM1, and this interaction is required for STIM1 oligomerization/activation, calcium flux, and antigen cross-presentation in dendritic cells. Expression of constitutively active STIM1 (not requiring UNC93B1 binding) restores cross-presentation in 3d-mutated DCs. Co-immunoprecipitation, calcium imaging, antigen cross-presentation assays, rescue by constitutively active STIM1 mutant Nature communications High 29158474
2018 UNC93B1 regulates TLR stability independently of endosomal trafficking: UNC93B1 deficiency causes near-complete loss of TLR3 and TLR7 protein in primary mouse dendritic cells and macrophages. 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 primary cells, ER-retained UNC93B1 mutant rescue experiments, TLR signaling assays Immunity High 29768176
2019 UNC93B1 limits TLR7 (but not TLR9) signaling by recruiting syntenin-1 (SDCBP) via phosphorylation-dependent binding, which sorts TLR7 into intralumenal vesicles of multivesicular bodies, terminating signaling. Mutations disrupting syntenin-1 binding cause enhanced TLR7 signaling and TLR7-dependent autoimmunity. Co-immunoprecipitation, exosome isolation, UNC93B1 phospho-mutants, syntenin-1 KO mice, autoimmunity phenotype analysis Nature High 31546246
2019 TLR9 is released from UNC93B1 specifically within endosomes, and this release is required for TLR9 ligand binding and signal transduction. Mutations in UNC93B1 that increase TLR9 affinity or artificial tethering of TLR9 to UNC93B1 result in defective signaling. TLR7, unlike TLR9, does not dissociate from UNC93B1 in endosomes and is regulated by distinct mechanisms. UNC93B1 mutagenesis, artificial tethering constructs, ligand binding assays, TLR signaling assays Nature High 31546247
2021 Cryo-EM structures of human TLR3-UNC93B1, mouse TLR3-UNC93B1, and human TLR7-UNC93B1 complexes reveal that UNC93B1 is structurally similar to major facilitator superfamily transporters and interacts with TLR transmembrane and luminal juxtamembrane regions via its N-terminal six-helix bundle. TLR3 and TLR7 complexes differ in oligomerization state. Cryo-EM structure determination Nature structural & molecular biology High 33432245
2021 UNC93B1 interacts with STING and targets it for autophagy-lysosome degradation, thereby suppressing cGAS-STING-mediated IFN-β signaling. This function depends on UNC93B1 trafficking capability; UNC93B1 knockout leads to STING accumulation and augmented cGAS-STING responses. Co-immunoprecipitation, lysosome inhibitor treatment, UNC93B1 KO cell lines, in vivo HSV-1 infection, Western blot of STING levels European journal of immunology Medium 33837956
2022 UNC93B1 interacts with STING and promotes its autophagy-lysosome degradation, reducing STING stability and attenuating IFN-β/IRF3 signaling during DNA virus infection. This interaction requires UNC93B1 trafficking capability and is reversible by lysosome inhibitors. Co-immunoprecipitation, lysosome inhibitor rescue, UNC93B1 KO (HEK293T), primary macrophages from Unc93b1−/− mice, HSV-1 infection assays Journal of medical virology Medium 35577759
2022 N-glycosylation of UNC93B1 at Asn272 (but not Asn251) is specifically required for TLR9 signaling: the N272Q mutation abolishes MyD88 recruitment to TLR9 and downstream signaling without affecting UNC93B1 expression, localization, or TLR7 signaling. Site-directed mutagenesis of glycosylation sites, Co-immunoprecipitation of MyD88, TLR signaling assays Frontiers in immunology Medium 35874766
2022 UNC93B1 binds STIM1 in the ER lumen near the transmembrane domain and promotes zipping of STIM1 transmembrane and proximal cytosolic helices within resting STIM1 dimers, priming STIM1 for translocation to cortical ER. UNC93B1 deficiency reduces store-operated Ca2+ entry and STIM1-Orai1 interactions. Cysteine crosslinking in vivo, Co-immunoprecipitation, STIM1 localization imaging, Ca2+ imaging, STIM1-Orai1 interaction assays The Journal of biological chemistry High 35065962
2024 Systematic scanning-alanine mutagenesis screen of all cytosolic/luminal UNC93B1 residues identified both negative and positive regulatory regions for TLR3, TLR7, and TLR9 responses, revealing that disruption of specific negative regulatory residues (T93I, R336C) leads to enhanced TLR7/8 responses and systemic autoimmune disease in mice. Saturation mutagenesis screen, genome-edited knock-in mice, patient genetics, TLR signaling assays The Journal of experimental medicine High 38780621
2024 UNC93B1 variants (E92G, R336L) cause selective TLR7 hyperactivation with constitutive type I IFN signaling. E92G causes UNC93B1 protein instability and reduced interaction with TLR7, paradoxically leading to TLR7 hyperactivation, establishing that UNC93B1 regulates TLR subtype-specific mechanisms of ligand recognition. Patient genetics, Co-immunoprecipitation (UNC93B1-TLR7 interaction), cytokine assays, TLR-specific agonist stimulation in patient cells and mouse macrophages Science immunology High 38207055
2024 UNC93B1 missense variants (I317M, G325C causing SLE; L330R, R466S, R525P causing chilblain lupus) differentially enhance TLR7/TLR8 activity. G325C, L330R, and R466S show enhanced interaction with TLR8, revealing that distinct UNC93B1 mutations can selectively gain TLR7 or TLR8 function. Patient genetics, Co-immunoprecipitation (UNC93B1-TLR8), TLR-specific functional assays in vitro and ex vivo The Journal of experimental medicine High 38869500
2012 UNC93B1 promotes trafficking of differentially glycosylated TLR3 (but not other nucleic acid-sensing TLRs) to the plasma membrane; UNC93B1 is itself transcriptionally up-regulated by TLR3 activation through poly(I:C), creating a positive feedback loop that primes B cells to respond to subsequent TLR9 activation. siRNA knockdown of UNC93B1, flow cytometry of surface TLR3, TLR signaling assays, reporter assays The Journal of biological chemistry Medium 23166319
2003 In C. elegans, UNC-93 colocalizes with the two-pore K+ channel SUP-9 and the novel transmembrane protein SUP-10 within muscle cells, and genetic evidence indicates these three proteins form a multi-subunit complex that coordinates muscle contraction. Genetic epistasis analysis, protein colocalization by immunofluorescence in C. elegans muscle The Journal of neuroscience Medium 14534247

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.) 584 16973841
2008 UNC93B1 delivers nucleotide-sensing toll-like receptors to endolysosomes. Nature 548 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 215 23426999
2011 Unc93B1 restricts systemic lethal inflammation by orchestrating Toll-like receptor 7 and 9 trafficking. Immunity 185 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 113 29768176
2019 UNC93B1 recruits syntenin-1 to dampen TLR7 signalling and prevent autoimmunity. Nature 109 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 76 31546247
2021 Cryo-EM structures of Toll-like receptors in complex with UNC93B1. Nature structural & molecular biology 73 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
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
2024 UNC93B1 variants underlie TLR7-dependent autoimmunity. Science immunology 59 38207055
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
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
2022 UNC93B1 attenuates the cGAS-STING signaling pathway by targeting STING for autophagy-lysosome degradation. Journal of medical virology 52 35577759
2010 UNC93B1 mediates host resistance to infection with Toxoplasma gondii. PLoS pathogens 50 20865117
1992 The Caenorhabditis elegans unc-93 gene encodes a putative transmembrane protein that regulates muscle contraction. The Journal of cell biology 43 1313436
2024 Genetic variants in UNC93B1 predispose to childhood-onset systemic lupus erythematosus. Nature immunology 40 38831104
2024 Gain-of-function human UNC93B1 variants cause systemic lupus erythematosus and chilblain lupus. The Journal of experimental medicine 39 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
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
2024 Large-scale mutational analysis identifies UNC93B1 variants that drive TLR-mediated autoimmunity in mice and humans. The Journal of experimental medicine 30 38780621
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
2021 UNC93B1 curbs cytosolic DNA signaling by promoting STING degradation. European journal of immunology 17 33837956
2020 A Missense Variant Affecting the C-Terminal Tail of UNC93B1 in Dogs with Exfoliative Cutaneous Lupus Erythematosus (ECLE). Genes 17 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 17 30387134
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 15 37097753
2012 UNC93B1 mediates innate inflammation and antiviral defense in the liver during acute murine cytomegalovirus infection. PloS one 15 22723955
2015 Unc93b1 -Dependent Endosomal Toll-Like Receptor Signaling Regulates Inflammation and Mortality during Coxsackievirus B3 Infection. Journal of innate immunity 14 25675947
2007 Assessing the function of human UNC-93B in Toll-like receptor signaling and major histocompatibility complex II response. Human immunology 14 18082565
2011 Love triangle between Unc93B1, TLR7, and TLR9 prevents fatal attraction. Immunity 13 21777792
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
2015 Functional characterisation of a TLR accessory protein, UNC93B1, in Atlantic salmon (Salmo salar). Developmental and comparative immunology 8 25576824
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 8 21638583
2023 High-expression of the innate-immune related gene UNC93B1 predicts inferior outcomes in acute myeloid leukemia. Frontiers in genetics 7 36741319
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
2022 N-glycosylation of UNC93B1 at a Specific Asparagine Residue Is Required for TLR9 Signaling. Frontiers in immunology 4 35874766
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 1 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