Affinage

NLRC5

Protein NLRC5 · UniProt Q86WI3

Length
1866 aa
Mass
204.6 kDa
Annotated
2026-06-10
100 papers in source corpus 30 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/9 claims corpus-supported (89%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NLRC5 is a multifunctional NLR protein that serves as the master transcriptional coactivator of MHC class I antigen-presentation genes while also tuning innate immune signaling and inflammatory cell death (PMID:20639463, PMID:22412192, PMID:25811463). As an IFN-γ-inducible nuclear protein whose own expression depends on STAT1-mediated signaling, NLRC5 occupies the proximal promoters of MHC class I genes and coordinately drives β2-microglobulin, TAP, and LMP expression (PMID:20639463, PMID:22412192, PMID:22473004); its specificity arises from binding a distinct SXY enhancer module (notably the S-box) through the RFX5-containing enhanceosome, and Rfx5-knockout mice phenocopy Nlrc5 deficiency in MHC class I expression (PMID:25811463). This transactivation requires an intact nucleotide-binding domain and nuclear localization signal for nuclear import as well as the CARD and LRR domains (PMID:22412192, PMID:22310711), and extends to non-classical MHC class I and butyrophilin (BTN3A) genes that license γδ T-cell killing (PMID:25811463, PMID:33364588). Genetic ablation in mice profoundly reduces MHC class I, especially in lymphocytes, and cripples CD8+ T-cell responses to Listeria (PMID:22412192, PMID:22711889, PMID:22491475). NLRC5 expression is itself a regulatory node controlled by PRMT5-mediated transcriptional repression, METTL3/YTHDF2 m6A-dependent mRNA stability, and miR-34a, and is targeted by viral immune evasion proteins including SARS-CoV-2 ORF6, which blocks both STAT1-driven induction and karyopherin-dependent nuclear import (PMID:32641491, PMID:37085864, PMID:30872089, PMID:34782627). In parallel, NLRC5 negatively regulates NF-κB by directly binding IKKα/β to block their phosphorylation, an inhibitory interaction released by TRAF2/6-mediated K63-ubiquitination at K1178 and restored by USP14-mediated deubiquitination (PMID:20434986, PMID:26620909, PMID:36372300). NLRC5 also functions in inflammatory cell death, cooperating with NLRP3 to support caspase-1/IL-1β processing and acting as an innate sensor that assembles with NLRP12 and PANoptosome components to drive PANoptosis in response to heme/PAMP stimuli (PMID:21191067, PMID:38878777). Beyond immunity, NLRC5 restricts dengue virus by recruiting the E3 ligase CUL2 to K48-ubiquitinate the viral NS3 protease for TOLLIP-mediated selective autophagic degradation (PMID:36126167). Reports of NLRC5 as a positive regulator of type I interferon responses conflict with knockout studies showing it is dispensable or inhibitory for type I IFN induction (PMID:20434986, PMID:20538593, PMID:22491475, PMID:22473004).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2010 High

    Establishing whether NLRC5 functions as a brake on inflammatory signaling, the first studies showed it directly engages the IKK and RLR machinery to dampen NF-κB and type I interferon responses.

    Evidence Co-IP, siRNA knockdown, reporter and phosphorylation assays in HEK293T and other lines

    PMID:20434986

    Open questions at the time
    • Did not reconcile with reports of NLRC5 as a positive antiviral regulator
    • Mechanism of IKK phosphorylation block not structurally defined
  2. 2010 High

    Defining NLRC5's nuclear function, it was identified as an IFN-γ-inducible nuclear factor that occupies MHC class I promoters and coordinately drives β2m, TAP, and LMP expression, establishing it as a transcriptional activator of antigen presentation.

    Evidence ChIP, reporter assays, siRNA knockdown and overexpression in lymphoid and epithelial lines

    PMID:20639463

    Open questions at the time
    • Cis-element specificity not yet mapped
    • Co-factors mediating promoter recruitment unknown
  3. 2010 Medium

    Addressing whether NLRC5 also acts cytosolically in inflammasomes and antiviral sensing, studies reported cooperativity with NLRP3 for caspase-1/IL-1β processing and conflicting positive roles in type I IFN induction.

    Evidence Reconstitution, Co-IP, caspase-1 cleavage and qPCR/ELISA in monocytic cells, THP-1, and fibroblasts

    PMID:20061403 PMID:20538593 PMID:20610642 PMID:21191067

    Open questions at the time
    • Positive versus negative roles in interferon signaling unresolved across cell types
    • Inflammasome contribution single-lab
  4. 2012 High

    To distinguish in vivo physiological function, knockout mice demonstrated NLRC5 is specifically required for MHC class I (not class II) expression and CD8+ T-cell responses, with lymphocytes most affected, while remaining largely dispensable for NF-κB and type I IFN.

    Evidence Multiple independent Nlrc5-deficient mouse lines, ChIP, domain mutagenesis, flow cytometry, Listeria infection

    PMID:22412192 PMID:22473004 PMID:22491475 PMID:22711889

    Open questions at the time
    • Cell-type basis of differential MHC I dependence unexplained
    • KO data contradicted earlier positive IFN role reports
  5. 2012 Medium

    Mapping the domains required for activity, the NBD and an intact NLS were shown to be essential for nuclear import and MHC class I transactivation.

    Evidence Domain deletion/mutagenesis with localization imaging and reporter assays

    PMID:22310711

    Open questions at the time
    • Karyopherin partners mediating import not identified
    • Single lab
  6. 2014 High

    Resolving the structural basis of NLRC5's effector domain and its antiviral engagement, NMR revealed an atypical CARD that binds the tandem CARD of RIG-I, an interaction targeted by influenza NS1.

    Evidence Solution NMR structure, in vitro binding, Co-IP and domain mapping in airway epithelial cells

    PMID:24815518 PMID:25404059

    Open questions at the time
    • Functional consequence of RIG-I binding conflicts with negative regulation reports
    • Stoichiometry of NLRC5-RIG-I complex undefined
  7. 2015 High

    Determining the molecular basis of NLRC5 promoter specificity, ChIP-seq with genetic epistasis established that NLRC5 transactivates MHC class I exclusively via a distinct SXY/S-box module requiring the RFX5 enhanceosome.

    Evidence ChIP-seq, Rfx5-KO and Nlrc5/CIIta double-KO mice, motif discovery, reporter assays

    PMID:25811463

    Open questions at the time
    • Direct DNA-binding versus enhanceosome-bridged recruitment not fully distinguished
    • Full enhanceosome subunit composition for NLRC5 not enumerated
  8. 2015 High

    Explaining how NLRC5's inhibitory activity is dynamically switched, K63-ubiquitination by TRAF2/6 at K1178 was shown to dissociate the NLRC5-IKK complex and sensitize NF-κB, with USP14 deubiquitination restoring inhibition.

    Evidence Site-directed mutagenesis, ubiquitination assays, Co-IP, mathematical modeling

    PMID:26620909

    Open questions at the time
    • Spatial regulation of ubiquitination relative to nuclear pool unknown
    • Crosstalk with transcriptional function not addressed
  9. 2016 Medium

    Extending the transactivation program beyond classical MHC I, NLRC5 was shown to drive BTN3A1-3 expression and BTN3A-dependent Vγ9Vδ2 T-cell killing of tumor cells.

    Evidence ChIP, reporter assays, overexpression and γδ T-cell killing assays in tumor cells

    PMID:33364588

    Open questions at the time
    • Whether BTN3A regulation uses the same S-box determinant not confirmed
    • Single lab
  10. 2024 Medium

    Establishing how NLRC5 protein and transcript levels are set, multiple regulatory inputs were defined: PRMT5 transcriptional repression, METTL3/YTHDF2 m6A-dependent mRNA stability, miR-34a targeting, and USP14-mediated proteasomal stabilization, the latter feeding NF-κB and Smad2/3 outputs in vascular disease.

    Evidence Knockdown/inhibition, RIP/meRIP, Argonaute IP, ChIP, ubiquitination assays in melanoma, endometrial cancer, microglia and ApoE-/- models

    PMID:30872089 PMID:32641491 PMID:36372300 PMID:37085864 PMID:38424494

    Open questions at the time
    • Most regulatory axes shown in single disease contexts
    • Hierarchy among these inputs unknown
  11. 2024 High

    Defining NLRC5's roles in inflammatory cell death and viral restriction, it was shown to assemble with NLRP12/PANoptosome to sense heme/PAMP and drive PANoptosis, and to recruit CUL2 to K48-ubiquitinate dengue NS3 for TOLLIP-mediated autophagic degradation.

    Evidence CRISPR KO and reconstitution, Co-IP, cell death/ROS assays, ubiquitination assays, in vivo models

    PMID:34095138 PMID:36126167 PMID:38878777

    Open questions at the time
    • How NLRC5 switches between nuclear transactivator and cytosolic sensor/scaffold roles is unresolved
    • Sensor ligand-binding mechanism for heme not structurally defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how a single protein integrates its nuclear MHC class I transactivation, cytosolic NF-κB/RLR regulation, inflammasome/PANoptosome assembly, and antiviral ubiquitin-autophagy functions, and what governs the switch between these mutually exclusive activities.
  • No unified structural model of full-length NLRC5
  • Signal-dependent partitioning between nucleus and cytosol mechanistically undefined
  • Contradictory roles in type I IFN signaling unreconciled

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 3 GO:0140110 transcription regulator activity 3 GO:0098772 molecular function regulator activity 2 GO:0140299 molecular sensor activity 1
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 2
Pathway
R-HSA-168256 Immune System 3 R-HSA-162582 Signal Transduction 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-9612973 Autophagy 1
Partners
CUL2IKKAIKKBNLRP12NLRP3RFX5RIG-IUSP14
Complex memberships
NLRP3 inflammasomePANoptosome (with NLRP12)RFX5 enhanceosome (SXY module)

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 NLRC5 inhibits NF-κB-dependent responses by directly interacting with IKKα and IKKβ and blocking their phosphorylation. It also interacts with RIG-I and MDA5 (but not MAVS) to inhibit RLR-mediated type I interferon responses. siRNA knockdown of NLRC5 enhanced NF-κB activation and type I interferon signaling. Co-immunoprecipitation, siRNA knockdown, reporter assays, phosphorylation assays in HEK293T and other cell lines Cell High 20434986
2010 NLRC5 is an IFN-γ-inducible nuclear protein that associates with and activates the proximal promoters of MHC class I genes (chromatin immunoprecipitation). NLRC5 expression drives enhanced MHC class I expression and also induces β2-microglobulin, TAP, and LMP gene expression. Knockdown of NLRC5 specifically impaired IFN-γ-induced MHC class I upregulation. Chromatin immunoprecipitation (ChIP), reporter gene assays, siRNA knockdown, overexpression in lymphoid and epithelial cell lines Proceedings of the National Academy of Sciences of the United States of America High 20639463
2010 NLRC5 overexpression broadly dampens NF-κB-, AP-1-, and type I IFN-dependent signaling, most likely through transcriptional repression. NLRC5 shuttles between cytosol and nucleus in a CrmA-dependent manner. Knockdown in RAW264.7 macrophages potently upregulated proinflammatory responses and was also critical for LPS-induced IL-10 production. Overexpression and siRNA knockdown, reporter assays, subcellular fractionation/localization, cytokine ELISA in RAW264.7 macrophages Journal of immunology (Baltimore, Md. : 1950) Medium 20610642
2010 NLRC5 is a cytosolic protein predominantly expressed in hematopoietic cells. Knockdown of endogenous NLRC5 reduced Sendai virus- and poly(I:C)-mediated type I interferon pathway responses in THP-1 cells and primary dermal fibroblasts, demonstrating a positive role in antiviral innate immunity. Overexpression alone did not trigger NF-κB or interferon pathways in HEK293T cells. siRNA knockdown, overexpression, qPCR, ELISA in THP-1 cells and primary fibroblasts The Journal of biological chemistry Medium 20538593
2010 NLRC5 is upregulated by IFN-γ via a JAK/STAT-mediated autocrine signaling loop in human fibroblasts post-CMV infection. Overexpression and enforced oligomerization of NLRC5 activates IFN-γ activation sequence (GAS) and IFN-specific response element (ISRE) promoter elements and upregulates antiviral target genes (IFN-α, OAS1, PRKRIR). Reporter assays, siRNA knockdown, promoter analysis, overexpression/oligomerization experiments in human fibroblasts Journal of immunology (Baltimore, Md. : 1950) Medium 20061403
2010 NLRC5 knockdown nearly eliminated caspase-1, IL-1β, and IL-18 processing in response to bacterial infection, PAMPs, and DAMPs. NLRC5 reconstituted inflammasome activity with procaspase-1, pro-IL-1β, and ASC, showing cooperativity with NLRP3. NLRC5 biochemically associates with NLRP3 in a nucleotide-binding domain-dependent but LRR-inhibitory fashion. siRNA knockdown, reconstitution experiments, Co-immunoprecipitation, caspase-1 cleavage assays in human monocytic cells Journal of immunology (Baltimore, Md. : 1950) Medium 21191067
2012 NLRC5 deficiency in mice dramatically impaired basal MHC class I expression specifically in T, NKT, and NK lymphocytes (but only mildly affected APCs). Endogenous NLRC5 localized to the nucleus and occupied the proximal promoter region of H-2 genes by ChIP. NLRC5-mediated MHC I induction required both CARD and LRR domains. Nlrc5-deficient lymphocytes showed markedly reduced elimination by cytotoxic T cells. Nlrc5-deficient mouse generation, ChIP, domain mutagenesis, flow cytometry, cytotoxicity assays Journal of immunology (Baltimore, Md. : 1950) High 22412192
2012 NLRC5 knockout mice show severe reduction in MHC class I and related genes (β2m, Tap1, Lmp2) but unaffected MHC class II. IFN-γ stimulation cannot overcome impaired MHC class I expression in Nlrc5-deficient cells. Upon Listeria monocytogenes infection, Nlrc5-deficient mice displayed impaired CD8+ T cell activation and increased bacterial loads. NLRC5 knockout mouse, qPCR, flow cytometry, infection models, CD8+ T cell activation assays Journal of immunology (Baltimore, Md. : 1950) High 22711889
2012 NLRC5 is specifically required in vivo for MHC class I gene expression and CD8+ T cell activation. NLRC5-deficient mice showed profound defects in MHC class I expression and failed to mount Listeria-specific CD8+ T cell responses. NLRP3-mediated inflammasome activation was also partially impaired in NLRC5-deficient mice. However, NLRC5 was dispensable for NF-κB-dependent proinflammatory genes and type I interferon induction. NLRC5-deficient mouse generation, infection models, flow cytometry, cytokine measurement, CD8+ T cell functional assays Cell research High 22491475
2012 NLRC5 knockout mice showed enhanced IKK and IRF3 phosphorylation in response to TLR stimulation or viral infection, with elevated IL-6 and IFN-β production in MEFs, macrophages, and in vivo. NLRC5 induction by TLR ligands or cytokines requires STAT1-mediated signaling. NLRC5 knockout mice, LPS/VSV challenge, phosphorylation assays, ELISA, STAT1 pathway inhibition Cell research High 22473004
2012 NLRC5 knockdown in chicken HD11 macrophages reduced IFN-α and IFN-β expression after LPS or poly(I:C) stimulation, indicating a positive regulatory role for NLRC5 in type I interferon responses. No direct relationship was found between NLRC5 knockdown and IL-6 or MHC class I expression in this avian model. siRNA knockdown, qPCR in chicken HD11 macrophage cell line BMC veterinary research Low 22401171
2012 The nucleotide-binding domain (NBD) of NLRC5 is critical for both nuclear translocation and transactivation of MHC class I genes. An intact nuclear localization signal is required for NLRC5 nuclear import and MHC class I gene induction. Domain deletion/mutagenesis, subcellular localization imaging, MHC class I reporter assays Biochemical and biophysical research communications Medium 22310711
2013 Rhinovirus ion channel protein 2B targets the ER and Golgi to trigger Ca2+ flux, which activates NLRP3 and NLRC5 inflammasomes cooperatively, leading to IL-1β secretion in bronchial cells. Virus deletion mutants, siRNA knockdown, Ca2+ flux measurements, IL-1β secretion assays in primary bronchial cells American journal of respiratory cell and molecular biology Medium 23815151
2014 NLRC5 binds RIG-I via its N-terminal death domain (atypical CARD). This interaction is critical for robust antiviral responses against influenza virus, as NLRC5 extends and stabilizes RIG-I expression. The influenza NS1 protein binds to NLRC5 to suppress its function. NLRC5's antiviral activity is LRR-domain independent. Co-immunoprecipitation, interaction domain mapping, overexpression in A549 and human bronchial epithelial cells, viral replication assays European journal of immunology Medium 25404059
2014 The solution NMR structure of the N-terminal effector domain of NLRC5 reveals a six α-helix bundle with a death fold. It is an atypical CARD (α-helix 3 replaced by a loop; α-helix 1 lacks characteristic interruption) with a distinct electrostatic surface. In vitro interaction experiments showed interaction with the tandem CARD of RIG-I. Solution NMR structure determination, in vitro interaction experiments Biochemistry High 24815518
2015 NLRC5 exclusively transactivates classical and non-classical MHC class I genes through binding to a specific SXY enhancer module distinct from that occupied by CIITA. NLRC5 chromatin recruitment requires the enhanceosome factor RFX5; Rfx5-knockout mice phenocopy Nlrc5 deficiency in MHC class I expression. The S-box sequence within the SXY module is the essential feature conferring NLRC5 specificity. ChIP-sequencing, Rfx5-knockout mice and cells, Nlrc5/CIIta double-knockout mice, de novo motif discovery, reporter assays PLoS genetics High 25811463
2015 NLRC5 undergoes K63-linked ubiquitination by TRAF2/6 at lysine 1,178 following LPS stimulation, leading to dissociation of the NLRC5-IKK complex and creating a coherent feedforward loop to sensitize NF-κB activation. The deubiquitinase USP14 removes polyubiquitin chains from NLRC5, restoring NLRC5-mediated inhibition of NF-κB signaling. Ubiquitination assays, site-directed mutagenesis (K1178), Co-immunoprecipitation, mathematical modeling, USP14 overexpression/knockdown The Journal of cell biology High 26620909
2016 NLRC5 promotes transcription of BTN3A1-3 genes through an atypical regulatory motif in their promoters, similar to MHC class I genes. Forced NLRC5 expression promotes BTN3A-dependent Vγ9Vδ2 T-cell-mediated killing of tumor cells. ChIP, reporter assays, NLRC5 overexpression in tumor cells, Vγ9Vδ2 T cell killing assays, BTN3A gene correlation analysis iScience Medium 33364588
2019 HIV-1 Tat-induced miRNA-34a targets NLRC5 mRNA (validated by Argonaute immunoprecipitation), downregulating NLRC5 protein and resulting in increased NF-κB p65 expression and microglial activation. miR-34a mimic downregulated NLRC5; miR-34a inhibitor upregulated NLRC5. Argonaute immunoprecipitation, bioinformatics, miRNA mimic/inhibitor transfection, in vivo validation in HIV-1 transgenic rats and SIV-infected macaques Brain, behavior, and immunity Medium 30872089
2020 PRMT5 inhibits transcription of the NLRC5 gene in melanoma cells, thereby suppressing MHC class I antigen presentation. PRMT5 knockdown augmented NLRC5 expression and increased MHC class I abundance. PRMT5 knockdown/pharmacological inhibition (GSK3326595), gene expression analysis, MHC class I flow cytometry in melanoma cells Science translational medicine Medium 32641491
2021 SARS-CoV-2 ORF6 protein suppresses NLRC5 both transcriptionally (by blocking STAT1 signaling, reducing IRF1 and NLRC5 gene expression) and functionally (by blocking karyopherin complex-dependent nuclear import of NLRC5), thereby inhibiting MHC class I pathway induction. SARS-CoV-2 ORF6 overexpression, gene expression profiling in COVID-19 patients and infected cell lines, nuclear import assays, STAT1 signaling analysis Nature communications High 34782627
2021 LC3 (autophagy protein) directly interacts with NLRC5 and inhibits NLRC5-mediated MHC class I antigen presentation pathway in endometrial cancer cells in vitro and in vivo. Autophagy upregulation correlates negatively with NLRC5 and MHC class I expression in endometrial cancer. Co-immunoprecipitation, autophagy modulation, MHC class I reporter assays, in vivo tumor model Cancer letters Medium 34974132
2022 NLRC5 interacts with the dengue virus NS3 protease domain and recruits E3 ubiquitin ligase CUL2 to catalyze K48-linked poly-ubiquitination of NS3, which is then recognized by cargo receptor TOLLIP for selective autophagic degradation. This NLRC5-CUL2-NS3-TOLLIP axis restricts dengue virus infection. Co-immunoprecipitation, ubiquitination assays, autophagy inhibitors, NLRC5 knockout, overexpression, viral replication assays Autophagy High 36126167
2022 METTL3-mediated m6A modification of NLRC5 mRNA inhibits its YTHDF2-dependent degradation, thereby stabilizing NLRC5 and promoting MHC class I-mediated immunosurveillance in endometrial cancer. METTL3 depletion increased YTHDF2-dependent NLRC5 mRNA degradation. RNA immunoprecipitation (RIP), methylated RIP, RNA stability assays, METTL3 overexpression/depletion, YTHDF2 functional experiments, tumor mouse model Biomarker research Medium 37085864
2022 NLRC5 regulates IFNα-induced alternative splicing and expression of HLA class I and antigen presentation genes in human pancreatic β cells, indicating a role beyond transcriptional activation of MHC class I to include regulation of alternative splicing events. Bulk and single-cell RNA sequencing, NLRC5 gain/loss-of-function in EndoC-βH1 and human islet cells Science advances Medium 36103539
2023 NLRC5 directly bound to NLRP3 and NLRC4 in inflammasomes (Co-IP) to cooperatively drive microglial pyroptosis (gasdermin D cleavage) and apoptosis. NLRC5 knockdown suppressed GSDMD cleavage, IL-1β and caspase-3 activation in a retinal ischemia model. Co-immunoprecipitation, NLRC5 knockdown, GSDMD/caspase-3/IL-1β assays in retinal ischemia model (in vivo and primary microglia) Frontiers in cell and developmental biology Medium 34095138
2023 NLRC5 interacts with HSPA8 in macrophages and suppresses the NF-κB pathway. Myeloid-specific deletion of NLRC5 aggravated pressure overload-induced cardiac remodeling and promoted IL-6 secretion, affecting cardiomyocyte hypertrophy and cardiac fibroblast activation. Co-immunoprecipitation (NLRC5-HSPA8), myeloid-specific Nlrc5 conditional KO mice, pressure overload model, NF-κB pathway analysis, IL-6 ELISA JACC. Basic to translational science Medium 37325412
2024 NLRC5 acts as an innate immune sensor driving PANoptosis (inflammatory cell death) in response to heme/PAMP and heme/cytokine combinations. NLRC5 interacted with NLRP12 and PANoptosome components to form a cell death complex. TLR signaling and NAD+ depletion regulated NLRC5 expression and ROS production to control PANoptosis. NLRC5-deficient mice were protected in hemolytic and inflammatory models. CRISPR-based NLRC5 knockout and reconstitution, Co-immunoprecipitation (NLRP12 and PANoptosome), cell death assays, ROS measurement, NLRC5-deficient mouse models Cell High 38878777
2022 USP14, a deubiquitinase, stabilizes NLRC5 by preventing its proteasomal degradation, thereby enhancing NLRC5-mediated inhibition of NF-κB signaling in endothelial cells. USP14 overexpression in ApoE-/- mice reduced atherosclerotic lesions. USP14 overexpression/knockdown, Co-immunoprecipitation, ubiquitination assays, NF-κB pathway analysis, ApoE-/- mouse model Biochimica et biophysica acta. Molecular and cell biology of lipids Medium 36372300
2024 USP14 promotes de-ubiquitination and stabilization of NLRC5, leading to Smad2/3 pathway activation and EndMT progression in atherosclerosis. USF1 transcriptionally activates USP14 to drive this USF1/USP14/NLRC5/Smad2/3 axis. Dual-luciferase reporter assay, ChIP, Co-immunoprecipitation, ubiquitination assays, shRNA knockdown, ApoE-/- mouse atherosclerosis model Molecular medicine (Cambridge, Mass.) Medium 38424494

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 NLRC5 negatively regulates the NF-kappaB and type I interferon signaling pathways. Cell 377 20434986
2010 NLR family member NLRC5 is a transcriptional regulator of MHC class I genes. Proceedings of the National Academy of Sciences of the United States of America 367 20639463
2012 NLRC5: a key regulator of MHC class I-dependent immune responses. Nature reviews. Immunology 313 23175229
2016 NLRC5/MHC class I transactivator is a target for immune evasion in cancer. Proceedings of the National Academy of Sciences of the United States of America 227 27162338
2010 NLRC5 limits the activation of inflammatory pathways. Journal of immunology (Baltimore, Md. : 1950) 202 20610642
2020 PRMT5 control of cGAS/STING and NLRC5 pathways defines melanoma response to antitumor immunity. Science translational medicine 199 32641491
2010 Cutting edge: NLRC5-dependent activation of the inflammasome. Journal of immunology (Baltimore, Md. : 1950) 179 21191067
2010 The nucleotide-binding oligomerization domain-like receptor NLRC5 is involved in IFN-dependent antiviral immune responses. Journal of immunology (Baltimore, Md. : 1950) 173 20061403
2024 NLRC5 senses NAD+ depletion, forming a PANoptosome and driving PANoptosis and inflammation. Cell 156 38878777
2010 A role for the human nucleotide-binding domain, leucine-rich repeat-containing family member NLRC5 in antiviral responses. The Journal of biological chemistry 145 20538593
2021 SARS-CoV-2 inhibits induction of the MHC class I pathway by targeting the STAT1-IRF1-NLRC5 axis. Nature communications 135 34782627
2012 NLRC5 deficiency selectively impairs MHC class I- dependent lymphocyte killing by cytotoxic T cells. Journal of immunology (Baltimore, Md. : 1950) 135 22412192
2013 Rhinovirus-induced calcium flux triggers NLRP3 and NLRC5 activation in bronchial cells. American journal of respiratory cell and molecular biology 127 23815151
2012 NLRC5 regulates MHC class I antigen presentation in host defense against intracellular pathogens. Cell research 125 22491475
2012 Enhanced TLR-induced NF-κB signaling and type I interferon responses in NLRC5 deficient mice. Cell research 116 22473004
2010 NLRC5 deficiency does not influence cytokine induction by virus and bacteria infections. Journal of immunology (Baltimore, Md. : 1950) 98 21148033
2012 Cutting edge: impaired MHC class I expression in mice deficient for Nlrc5/class I transactivator. Journal of immunology (Baltimore, Md. : 1950) 91 22711889
2015 NLRC5 exclusively transactivates MHC class I and related genes through a distinctive SXY module. PLoS genetics 83 25811463
2017 NLRC5/CITA: A Key Player in Cancer Immune Surveillance. Trends in cancer 77 28718425
2016 NLRC5 regulates cell proliferation, migration and invasion in hepatocellular carcinoma by targeting the Wnt/β-catenin signaling pathway. Cancer letters 73 26975630
2011 NLRC5: a newly discovered MHC class I transactivator (CITA). Microbes and infection 73 22209772
2016 NLRC5 elicits antitumor immunity by enhancing processing and presentation of tumor antigens to CD8(+) T lymphocytes. Oncoimmunology 71 27471621
2020 Transcriptional Upregulation of NLRC5 by Radiation Drives STING- and Interferon-Independent MHC-I Expression on Cancer Cells and T Cell Cytotoxicity. Scientific reports 66 32355214
2019 HIV-1 Tat-mediated microglial inflammation involves a novel miRNA-34a-NLRC5-NFκB signaling axis. Brain, behavior, and immunity 64 30872089
2017 Dexmedetomidine (DEX) protects against hepatic ischemia/reperfusion (I/R) injury by suppressing inflammation and oxidative stress in NLRC5 deficient mice. Biochemical and biophysical research communications 59 28784305
2019 Knockdown of LncRNA SCAMP1 suppressed malignant biological behaviours of glioma cells via modulating miR-499a-5p/LMX1A/NLRC5 pathway. Journal of cellular and molecular medicine 52 31207033
2014 NLRC5 interacts with RIG-I to induce a robust antiviral response against influenza virus infection. European journal of immunology 52 25404059
2018 NLRC5 deficiency ameliorates diabetic nephropathy through alleviating inflammation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 51 29070585
2015 Reversible ubiquitination shapes NLRC5 function and modulates NF-κB activation switch. The Journal of cell biology 51 26620909
2012 The nucleotide-binding domain of NLRC5 is critical for nuclear import and transactivation activity. Biochemical and biophysical research communications 51 22310711
2013 NLRC5, at the Heart of Antigen Presentation. Frontiers in immunology 50 24319445
2015 NLRC5 regulates TGF-β1-induced proliferation and activation of hepatic stellate cells during hepatic fibrosis. The international journal of biochemistry & cell biology 49 26592197
2017 Insights into the diversity of NOD-like receptors: Identification and expression analysis of NLRC3, NLRC5 and NLRX1 in rainbow trout. Molecular immunology 48 28432942
2019 Long noncoding RNA MEG3 regulates rheumatoid arthritis by targeting NLRC5. Journal of cellular physiology 47 30644097
2016 NLRC5 shields T lymphocytes from NK-cell-mediated elimination under inflammatory conditions. Nature communications 47 26861112
2013 Expression regulation and function of NLRC5. Protein & cell 43 23483478
2015 Respiratory Syncytial Virus Infection Upregulates NLRC5 and Major Histocompatibility Complex Class I Expression through RIG-I Induction in Airway Epithelial Cells. Journal of virology 42 25972545
2019 Class I transactivator, NLRC5: a central player in the MHC class I pathway and cancer immune surveillance. Immunogenetics 41 30706093
2019 LncRNA MALAT1 prevents the protective effects of miR-125b-5p against acute myocardial infarction through positive regulation of NLRC5. Experimental and therapeutic medicine 41 32010261
2017 NLRC5 deficiency promotes myocardial damage induced by high fat diet in mice through activating TLR4/NF-κB. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 41 28499247
2020 MHC class I transactivator NLRC5 in host immunity, cancer and beyond. Immunology 39 32633419
2019 The deficiency of miR-214-3p exacerbates cardiac fibrosis via miR-214-3p/NLRC5 axis. Clinical science (London, England : 1979) 39 31434695
2018 NLRC5 mediates cell proliferation, migration, and invasion by regulating the Wnt/β-catenin signalling pathway in clear cell renal cell carcinoma. Cancer letters 39 30543814
2021 The MHC Class-I Transactivator NLRC5: Implications to Cancer Immunology and Potential Applications to Cancer Immunotherapy. International journal of molecular sciences 38 33671123
2011 Regulation of immune pathways by the NOD-like receptor NLRC5. Immunobiology 38 22024701
2022 Transcription and splicing regulation by NLRC5 shape the interferon response in human pancreatic β cells. Science advances 36 36103539
2019 NLRC5: A paradigm for NLRs in immunological and inflammatory reaction. Cancer letters 35 30867141
2021 LC3 and NLRC5 interaction inhibits NLRC5-mediated MHC class I antigen presentation pathway in endometrial cancer. Cancer letters 34 34974132
2018 The Long Non-coding RNA MEG3/miR-let-7c-5p Axis Regulates Ethanol-Induced Hepatic Steatosis and Apoptosis by Targeting NLRC5. Frontiers in pharmacology 34 29692724
2014 NLRC5 mediates cytokine secretion in RAW264.7 macrophages and modulated by the JAK2/STAT3 pathway. Inflammation 34 24445959
2018 NLRC5 deficiency protects against acute kidney injury in mice by mediating carcinoembryonic antigen-related cell adhesion molecule 1 signaling. Kidney international 33 29907459
2012 NLRC5 knockdown in chicken macrophages alters response to LPS and poly (I:C) stimulation. BMC veterinary research 33 22401171
2021 MSCs-Derived Extracellular Vesicles Carrying miR-212-5p Alleviate Myocardial Infarction-Induced Cardiac Fibrosis via NLRC5/VEGF/TGF-β1/SMAD Axis. Journal of cardiovascular translational research 31 34508321
2016 Role of NLRC5 in progression and reversal of hepatic fibrosis. Toxicology and applied pharmacology 31 26806094
2016 NLRC5 promotes cell proliferation via regulating the AKT/VEGF-A signaling pathway in hepatocellular carcinoma. Toxicology 31 27338800
2022 NLRC5 restricts dengue virus infection by promoting the autophagic degradation of viral NS3 through E3 ligase CUL2 (cullin 2). Autophagy 30 36126167
2019 Emerging Roles for NLRC5 in Immune Diseases. Frontiers in pharmacology 30 31824312
2018 Knockdown of NLRC5 attenuates renal I/R injury in vitro through the activation of PI3K/Akt signaling pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 30 29655162
2023 NOD-like receptor NLRC5 promotes neuroinflammation and inhibits neuronal survival in Parkinson's disease models. Journal of neuroinflammation 29 37072793
2021 NLRC5/CITA expression correlates with efficient response to checkpoint blockade immunotherapy. Scientific reports 29 33547395
2020 The lncRNA XIST promotes the progression of breast cancer by sponging miR-125b-5p to modulate NLRC5. American journal of translational research 29 32774715
2017 NLRC5 promotes cell proliferation via regulating the NF-κB signaling pathway in Rheumatoid arthritis. Molecular immunology 29 28865311
2014 Unusual structural features revealed by the solution NMR structure of the NLRC5 caspase recruitment domain. Biochemistry 29 24815518
2023 METTL3 facilitates immunosurveillance by inhibiting YTHDF2-mediated NLRC5 mRNA degradation in endometrial cancer. Biomarker research 27 37085864
2018 Investigation of single and synergic effects of NLRC5 and PD-L1 variants on the risk of colorectal cancer. PloS one 27 29408916
2021 The Regulatory NOD-Like Receptor NLRC5 Promotes Ganglion Cell Death in Ischemic Retinopathy by Inducing Microglial Pyroptosis. Frontiers in cell and developmental biology 26 34095138
2016 Silencing NLRC5 inhibits extracellular matrix expression in keloid fibroblasts via inhibition of transforming growth factor-β1/Smad signaling pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 26 27525969
2013 A molecular model of the full-length human NOD-like receptor family CARD domain containing 5 (NLRC5) protein. BMC bioinformatics 26 24044430
2019 NLRC5 negatively regulates LTA-induced inflammation via TLR2/NF-κB and participates in TLR2-mediated allergic airway inflammation. Journal of cellular physiology 25 30945291
2019 The expression of NOD2, NLRP3 and NLRC5 and renal injury in anti-neutrophil cytoplasmic antibody-associated vasculitis. Journal of translational medicine 25 31186034
2024 USF1 transcriptionally activates USP14 to drive atherosclerosis by promoting EndMT through NLRC5/Smad2/3 axis. Molecular medicine (Cambridge, Mass.) 24 38424494
2020 NLRC5 promotes cell migration and invasion by activating the PI3K/AKT signaling pathway in endometrial cancer. The Journal of international medical research 24 32431202
2016 Identification and expressional analysis of NLRC5 inflammasome gene in smolting Atlantic salmon (Salmo salar). Fish & shellfish immunology 24 27640334
2020 NLRC5 negatively regulates inflammatory responses in LPS-induced acute lung injury through NF-κB and p38 MAPK signal pathways. Toxicology and applied pharmacology 23 32710960
2020 NLRC5 promotes transcription of BTN3A1-3 genes and Vγ9Vδ2 T cell-mediated killing. iScience 23 33364588
2018 Knockdown of NLRC5 inhibits renal fibroblast activation via modulating TGF-β1/Smad signaling pathway. European journal of pharmacology 23 29608899
2023 Macrophage-Specific NLRC5 Protects From Cardiac Remodeling Through Interaction With HSPA8. JACC. Basic to translational science 22 37325412
2020 miR-4319 Suppresses the Growth of Esophageal Squamous Cell Carcinoma Via Targeting NLRC5. Current molecular pharmacology 22 31746301
2020 NLRC5 Inhibits Inflammation of Secretory Phase Ectopic Endometrial Stromal Cells by Up-Regulating Autophagy in Ovarian Endometriosis. Frontiers in pharmacology 22 33013364
2012 NLRC5: a NOD-like receptor protein with many faces in immune regulation. Cell research 22 22613950
2020 Innate Immune Molecule NLRC5 Protects Mice From Helicobacter-induced Formation of Gastric Lymphoid Tissue. Gastroenterology 21 32169428
2017 Deficiency of the NOD-Like Receptor NLRC5 Results in Decreased CD8+ T Cell Function and Impaired Viral Clearance. Journal of virology 21 28615208
2016 NLRC5, a promising new entry in tumor immunology. Journal for immunotherapy of cancer 21 27437103
2016 Role of zebrafish NLRC5 in antiviral response and transcriptional regulation of MHC related genes. Developmental and comparative immunology 21 27876605
2015 NLRC5 Mediates IL-6 and IL-1β Secretion in LX-2 Cells and Modulated by the NF-κB/Smad3 Pathway. Inflammation 21 25820389
2020 NLRC5 deficiency ameliorates cardiac fibrosis in diabetic cardiomyopathy by regulating EndMT through Smad2/3 signaling pathway. Biochemical and biophysical research communications 20 32505342
2022 USP14-mediated NLRC5 upregulation inhibits endothelial cell activation and inflammation in atherosclerosis. Biochimica et biophysica acta. Molecular and cell biology of lipids 19 36372300
2019 The Obligate Intracellular Bacterium Orientia tsutsugamushi Targets NLRC5 To Modulate the Major Histocompatibility Complex Class I Pathway. Infection and immunity 19 30559222
2019 Long noncoding RNA FER1L4 regulates rheumatoid arthritis via targeting NLRC5. Clinical and experimental rheumatology 19 31694750
2019 Promotion on NLRC5 upregulating MHC-I expression by IFN-γ in MHC-I-deficient breast cancer cells. Immunologic research 19 31900803
2018 Methylation of the genes ROD1, NLRC5, and HKR1 is associated with aging in Hainan centenarians. BMC medical genomics 19 29394898
2022 Selective autophagy of NLRC5 promotes immune evasion of endometrial cancer. Autophagy 18 35174769
2020 NLRC5: new cancer buster? Molecular biology reports 18 31925644
2020 Arid2-IR promotes NF-κB-mediated renal inflammation by targeting NLRC5 transcription. Cellular and molecular life sciences : CMLS 18 33090288
2017 NLRC5 silencing ameliorates cardiac fibrosis by inhibiting the TGF‑β1/Smad3 signaling pathway. Molecular medicine reports 18 28713900
2020 NLRC5 alleviated OGD/R-induced PC12-cell injury by inhibiting activation of the TLR4/MyD88/NF-κB pathway. The Journal of international medical research 17 32790491
2021 LncRNA MEG3 reverses CCl4-induced liver fibrosis by targeting NLRC5. European journal of pharmacology 16 34536366
2017 NLRC5 polymorphism is associated with susceptibility to chronic periodontitis. Immunobiology 16 28122660
2021 NLRC5 regulates expression of MHC-I and provides a target for anti-tumor immunity in transmissible cancers. Journal of cancer research and clinical oncology 15 33797607
2021 NLRC5: A Potential Target for Central Nervous System Disorders. Frontiers in immunology 15 34220868

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