Affinage

TBL1X

F-box-like/WD repeat-containing protein TBL1X · UniProt O60907

Length
577 aa
Mass
62.5 kDa
Annotated
2026-06-10
61 papers in source corpus 21 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/7 claims corpus-supported (86%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TBL1X is a WD40-repeat scaffold/adaptor subunit of the NCoR/SMRT-HDAC3 transcriptional co-repressor complex that controls developmental and metabolic gene programs by coupling sequence-specific transcription factors to histone deacetylation and to the ubiquitin-proteasome system (PMID:18309295, PMID:42020373). In its corepressor role it is recruited to target promoters by transcription factors such as Snail, where it bridges to HDAC3 and drives histone hypoacetylation (PMID:18309295), and it functions as a corepressor/coactivator exchange factor for nuclear receptors and transcription factors (PMID:15834507). Studies of the Drosophila ortholog Ebi established a parallel function as a substrate-recognition component of SCF-like (Skp1/Cul1/F-box) ubiquitin-ligase complexes that target proteins for degradation, including beta-catenin and the neuronal repressor Tramtrack88 (Ttk88) via Sina/phyllopod, thereby controlling EGFR-dependent photoreceptor differentiation and cell-cycle entry (PMID:11389839, PMID:11032805, PMID:10215623). Through these dual scaffolding activities TBL1X integrates Notch, EGFR, and AP-1 signaling to maintain correct patterns of gene expression and neuronal survival (PMID:12230979, PMID:16763555, PMID:22666340). In mammalian disease contexts the same SCF/TBL1X supercomplex promotes proteasomal degradation of oncoproteins, and TBL1X controls the stability of cyclin D1, RAD51, and TP53 and the transcriptional output of TCF4 and ZEB1 in several cancers (PMID:36206873, PMID:40009753, PMID:35173544, PMID:39462759). Genetically, TBL1X serves as a co-factor for the PAX6-HDAC3 network governing insulin promoter activity and beta-cell identity (PMID:42020373) and restrains pro-inflammatory CD4+ T cell activity (PMID:41539423). Loss-of-function mutations truncating or destabilizing the WD40-repeat domain cause central hypothyroidism through impaired thyroid hormone receptor-corepressor signaling in the pituitary and hypothalamus (PMID:27603907).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1999 Medium

    Established that the TBL1X ortholog Ebi is a conserved WD40/F-box-like protein acting in EGFR signaling to downregulate a transcriptional repressor, framing TBL1X-family proteins as candidate degradation adaptors.

    Evidence Loss-of-function genetics and Egfr genetic interaction in Drosophila, with domain analysis showing six WD40 repeats and an F-box-like motif

    PMID:10215623

    Open questions at the time
    • Biochemical mechanism of Ttk88 downregulation not reconstituted
    • Direct physical partners not identified in this study
  2. 2000 High

    Defined Ebi as a substrate-recognition adaptor that promotes ubiquitin-dependent degradation, resolving how it links signaling to protein turnover and neuronal differentiation.

    Evidence Co-IP with Sina and phyllopod, in vitro and S2-cell Ttk88 degradation assays, and loss-of-function genetics in Drosophila

    PMID:11032805

    Open questions at the time
    • Mechanism of the separate S-phase-limiting function unresolved
    • E3 composition not fully defined
  3. 2001 Medium

    Extended the degradation-adaptor role to the mammalian context by showing the Ebi/TBL1X homolog targets beta-catenin via an SCF-like Siah/SIP/Skp1 complex downstream of p53.

    Evidence Co-IP, interaction mapping, and beta-catenin degradation assays with p53/Siah epistasis

    PMID:11389839

    Open questions at the time
    • Direct demonstration with human TBL1X protein limited
    • Phosphorylation-independence of beta-catenin recognition not structurally explained
  4. 2002 High

    Connected Ebi to corepressor biology by showing it complexes with Su(H) and SMRTER and that EGFR signaling drives proteasome-dependent SMRTER relocalization to derepress targets.

    Evidence Co-IP, genetic epistasis, proteasome inhibition, and subcellular localization in Drosophila photoreceptors

    PMID:12230979

    Open questions at the time
    • Mammalian equivalence of the Su(H)/SMRTER step not tested
    • Whether TBL1X mediates SMRTER turnover directly unclear
  5. 2006 Medium

    Showed the Ebi/SMRTER corepressor complex competes with Notch activation at a specific promoter, establishing TBL1X-family proteins in promoter-level repression logic during patterning.

    Evidence Genetic epistasis, loss-of-function analysis, and reporter assays identifying the complex at the chn promoter

    PMID:16763555

    Open questions at the time
    • Direct DNA/factor contacts of TBL1X not mapped
    • Mammalian conservation of this regulatory circuit untested
  6. 2005 Medium

    Demonstrated that human TBL1X is a transcriptional repressor and corepressor/coactivator exchange factor, distinguishing it functionally from the non-repressing TBL1Y homolog.

    Evidence GAL4-DBD fusion luciferase reporter assays and RT-PCR expression analysis

    PMID:15834507

    Open questions at the time
    • Single reporter-based assay for the functional claim
    • Endogenous target genes not identified
  7. 2008 High

    Established the canonical mechanism: TBL1X/Ebi is recruited by a sequence-specific repressor (Snail) and acts through the NCoR/SMRT-HDAC3 complex to drive histone deacetylation at target genes.

    Evidence Co-IP, ChIP, HDAC3 RNAi, HDAC inhibitor treatment, and transgenic embryo rescue in Drosophila

    PMID:18309295

    Open questions at the time
    • Whether TBL1X is required for complex assembly versus stability not parsed
    • Direct mammalian Snail-TBL1X recruitment not shown here
  8. 2012 Medium

    Linked Ebi to AP-1-dependent repression controlling apoptotic gene balance, defining a role in neuronal survival and oxidative stress resistance.

    Evidence Co-IP, loss-of-function genetics, survival and oxidative stress assays in Drosophila photoreceptors

    PMID:22666340

    Open questions at the time
    • Direct target apoptotic genes not fully resolved
    • Mammalian AP-1-TBL1X relevance untested
  9. 2013 Medium

    Placed Ebi in cell-cycle control via an RBF/E2F corepressor function antagonistic to Polycomb silencing at the G1/S transition.

    Evidence Co-IP with RBF, genetic epistasis with Polycomb, and gene expression analysis in Drosophila

    PMID:23919509

    Open questions at the time
    • Mechanism of antagonism with Polycomb not biochemically defined
    • Direct target gene set incomplete
  10. 2016 Medium

    Provided the disease anchor: WD40-domain TBL1X mutations cause central hypothyroidism by impairing the thyroid hormone receptor-corepressor complex where TBL1X is expressed in pituitary and hypothalamus.

    Evidence Sanger sequencing across families, in vitro mutant expression/thermal stability assays, and human tissue immunostaining

    PMID:27603907

    Open questions at the time
    • Functional assays limited to protein expression/stability
    • Direct effect on TSH/TH target transcription not measured
  11. 2016 High

    Refined the degradation function with structural detail, mapping specific WD40 repeats (7-8) of Ebi to a ligand domain of the transmembrane substrate Crumbs in ubiquitin-dependent downregulation.

    Evidence Co-IP with domain mapping, ubiquitylation assay, genetic suppression, and in vivo protein-level imaging in Drosophila wing

    PMID:27702784

    Open questions at the time
    • E3 ligase partner for Crb degradation not defined
    • Conservation of WD40-7/8 substrate recognition in mammals untested
  12. 2018 Low

    Reinforced the human loss-of-function model with a WD40-truncating mutation causing central hypothyroidism, consistent with loss of nuclear protein-protein interactions.

    Evidence Next-generation sequencing and clinical/biochemical phenotyping of a patient

    PMID:30591955

    Open questions at the time
    • No direct in vitro mechanistic assay for this specific mutation
    • Causality inferred from genotype-phenotype correlation
  13. 2018 Medium

    Identified post-transcriptional control of TBL1X by miR-138-5p in trophoblasts, linking TBL1X dosage to cell migration and proliferation.

    Evidence 3'-UTR luciferase assay plus migration and proliferation assays in HTR-8/SVneo cells

    PMID:30463081

    Open questions at the time
    • Downstream TBL1X effector genes in trophoblasts not defined
    • In vivo placental relevance not established
  14. 2022 Medium

    Established TBL1X as a druggable degradation hub in lymphoma, where it forms an SCF/TBL1X supercomplex that promotes beta-catenin-independent proteasomal degradation of oncoproteins.

    Evidence siRNA/shRNA knockdown, tegavivint (N-terminus-targeting), degradation assays, and Co-IP in DLBCL

    PMID:36206873

    Open questions at the time
    • Specific oncoprotein substrates only partly enumerated
    • Review-format summary of same-group findings
  15. 2022 Medium

    Showed TBL1X can act as a transcriptional trans-activator with TCF4 in a feed-forward circuit promoting carcinoma migration and invasion.

    Evidence Co-IP, Flot2 promoter luciferase, ChIP, knockdown/overexpression migration assays, and in vivo metastasis in NPC

    PMID:35173544

    Open questions at the time
    • Mechanism of corepressor-to-activator switch unresolved
    • Direct TBL1X DNA association not shown
  16. 2023 Medium

    Defined an RNA-guided degradation function: lncRNA MIAT recruits TBL1X to ubiquitinate and downregulate TP53, promoting immune evasion in prostate cancer.

    Evidence RNA pulldown/Co-IP, ubiquitination assay, and in vitro/in vivo knockdown-overexpression rescue

    PMID:37356458

    Open questions at the time
    • E3 ligase mediating TP53 ubiquitination not specified
    • Direct TBL1X-TP53 contact versus complex-mediated not resolved
  17. 2024 Medium

    Revealed isoform-specific function: an exon-6-skipping variant TBL1X-S binds ZEB1 more strongly to drive EMT, showing splicing tunes TBL1X partner selectivity.

    Evidence RNA-seq, mRNA half-life assays, Co-IP for differential ZEB1 binding, CDH1 reporter, and metastasis phenotyping in HCC

    PMID:39462759

    Open questions at the time
    • Structural basis of enhanced ZEB1 binding by TBL1X-S unknown
    • Relative abundance of isoforms in normal tissue unclear
  18. 2024 Medium

    Demonstrated TBL1X is targetable by PROTAC degraders, validating proteasome-dependent ternary-complex-driven removal as a therapeutic strategy.

    Evidence PROTAC synthesis, western blot, proteasome competition, ternary complex and cytotoxicity assays in DLBCL

    PMID:39411529

    Open questions at the time
    • Selectivity over TBL1XR1 not fully characterized
    • In vivo efficacy not established
  19. 2025 Medium

    Connected TBL1X to genomic stability by showing it maintains cyclin D1 and RAD51 levels, making its inhibition synthetically lethal with PARP inhibition in mantle cell lymphoma.

    Evidence shRNA knockdown, tegavivint, protein stability western blots, γH2AX DNA damage, PDX models, and synergy assays

    PMID:40009753

    Open questions at the time
    • Direct mechanism of cyclin D1/RAD51 stabilization not resolved
    • Whether effect is corepressor- or degradation-mediated unclear
  20. 2026 High

    Defined physiological roles in metabolism and immunity: TBL1X (with TBL1XR1) acts through PAX6-HDAC3 to sustain insulin transcription and beta-cell identity, and restrains pro-inflammatory CD4+ T cell activity.

    Evidence Beta-cell and CD4-conditional knockouts, scRNA-seq, ChIP, interactome screens, insulin reporter, bone marrow transplant atherosclerosis model in mice with human validation

    PMID:41539423 PMID:42020373

    Open questions at the time
    • Functional redundancy versus distinct roles of TBL1X and TBL1XR1 not fully separated
    • Whether T cell phenotype is corepressor- or degradation-dependent unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TBL1X switches between histone-deacetylation corepression, transcriptional activation, and SCF-dependent substrate degradation at specific targets, and what governs partner/substrate selectivity, remains unresolved.
  • No structural model explaining context-dependent corepressor-versus-degradation activity
  • Determinants of WD40 substrate/partner selection not mapped across mammalian targets
  • Functional division of labor between TBL1X and TBL1XR1 incompletely defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0140096 catalytic activity, acting on a protein 3 GO:0140110 transcription regulator activity 3
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-168256 Immune System 1 R-HSA-4839726 Chromatin organization 1
Partners
HDAC3PAX6SMRTERSNAILSU(H)TBL1XR1TCF4ZEB1
Complex memberships
NCoR/SMRT-HDAC3 corepressor complexPAX6-HDAC3 complexSCF (Skp1/Cul1/F-box)/TBL1X supercomplex

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 TBL1X (mammalian homolog of Drosophila Ebi) participates in a novel beta-catenin degradation pathway: Siah binds ubiquitin-conjugating enzymes, and Ebi (an F-box protein homologous to TBL1X) binds beta-catenin independently of the phosphorylation sites recognized by beta-TrCP. Ebi is physically linked to Siah via SIP (an Sgt1 homolog that binds Skp1), forming an SCF-like complex that targets beta-catenin for degradation downstream of p53-induced Siah expression. Co-immunoprecipitation, protein interaction mapping, beta-catenin degradation assay, epistasis with p53/Siah pathway Molecular cell Medium 11389839
2002 Drosophila Ebi (ortholog of TBL1X) forms a complex with Su(H) and the corepressor SMRTER; EGFR signaling promotes transcriptional derepression by causing translocation of SMRTER to the cytoplasm in a proteasome-dependent manner, thereby enabling Delta expression in photoreceptor cells. Co-immunoprecipitation, genetic epistasis (EGFR/ebi/sno pathway), proteasome inhibition, subcellular localization imaging Cell High 12230979
1999 Drosophila Ebi (ortholog of TBL1X) regulates EGFR signaling at multiple steps and promotes EGFR-dependent down-regulation of Tramtrack88 (a repressor of neuronal development). Ebi encodes an evolutionarily conserved protein with an F-box-like domain and six WD40 repeats; proteins with related structures regulate protein degradation. Genetic analysis (loss-of-function mutations, genetic interaction with Egfr), developmental phenotype, protein domain analysis Genes & development Medium 10215623
2000 Drosophila Ebi (ortholog of TBL1X) physically interacts with Sina and phyllopod, and promotes Ttk88 (Tramtrack88) degradation in vitro and in S2 cells. Ebi has two distinct functions: promotion of Ttk88 degradation (enabling neuronal differentiation) and a second independent function limiting S-phase entry in the nervous system. Co-immunoprecipitation (physical interaction with Sina and phyllopod), in vitro degradation assay, S2 cell degradation assay, loss-of-function genetic analysis The EMBO journal High 11032805
2006 The Drosophila Ebi/SMRTER corepressor complex represses transcription of charlatan (chn), an NRSF/REST-like zinc-finger gene, by competing with the Notch intracellular domain (NICD) activation complex at the chn promoter. This double-negative regulation (Ebi/SMRTER represses chn; chn represses Delta) maintains Delta expression and inductive activity in photoreceptor cells under EGF signaling. Genetic epistasis, loss-of-function analysis, transcriptional reporter assays, identification of Ebi/SMRTER complex at chn promoter The EMBO journal Medium 16763555
2008 Drosophila Ebi (ortholog of TBL1X) acts as an essential co-repressor for Snail-mediated transcriptional repression in mesoderm formation. Ebi and Snail interact physically (a conserved Snail domain binds Ebi independently of CtBP). The mammalian Ebi homolog TBL1 is part of the NCoR/SMRT-HDAC3 co-repressor complex, and Ebi interacts with Drosophila HDAC3. Ebi is recruited to Snail target genes in a Snail-dependent manner, correlating with histone hypoacetylation. HDAC3 knockdown or HDAC inhibitor impairs Snail-mediated repression. Co-immunoprecipitation (Ebi-Snail physical interaction), chromatin immunoprecipitation (ChIP), HDAC3 RNAi knockdown, HDAC inhibitor treatment, transgenic embryo rescue, histone acetylation assay The EMBO journal High 18309295
2012 Drosophila Ebi (ortholog of TBL1X) forms a complex with activator protein 1 (AP-1) and is required for repression of pro-apoptotic and anti-apoptotic gene expression in photoreceptor neurons. Loss of ebi causes late-onset neuronal apoptosis and increased sensitivity to oxidative stress. Co-immunoprecipitation (Ebi-AP-1 complex), loss-of-function genetic analysis, survival assay, oxidative stress assay, gene expression analysis PloS one Medium 22666340
2013 Drosophila Ebi (ortholog of TBL1X) forms a complex with retinoblastoma family protein (RBF) and regulates expression of specific Rbf/E2F pathway target genes, acting as a corepressor to mitigate excess growth signaling. Ebi also sustains expression of Rbf itself. Genetic analysis shows antagonism between Ebi and the Polycomb group silencing complex in regulating the G1/S phase transition. Co-immunoprecipitation (Ebi-RBF complex), genetic epistasis (Polycomb group), gene expression analysis, loss-of-function alleles Genes to cells Medium 23919509
2016 TBL1X mutations (in the conserved WD40-repeat domain) are associated with central hypothyroidism. In vitro studies showed mutations influence TBL1X protein expression and thermal stability. TBL1X mRNA and protein are expressed in human hypothalamus and pituitary, consistent with its role in the thyroid hormone receptor-corepressor complex (NCoR/SMRT) regulating TSH and thyroid hormone signaling. Sanger sequencing, in vitro functional assay (expression and thermal stability of mutant proteins), immunostaining of human hypothalamus and pituitary, mRNA expression analysis The Journal of clinical endocrinology and metabolism Medium 27603907
2016 Drosophila Ebi (TBL1X ortholog) regulates wing growth by ubiquitin-dependent downregulation of the transmembrane protein Crumbs (Crb). Ebi physically binds the extracellular domain of Crb, with the interaction mediated specifically by WD40 repeats 7-8 of Ebi and a laminin G domain of Crb. Ebi knockdown elevates Crb protein levels at the dorsoventral boundary. Co-immunoprecipitation (Ebi-Crb physical interaction, domain mapping), genetic suppression assays, immunofluorescence (Crb protein levels), ubiquitylation assay Development High 27702784
2005 TBL1X (and its homolog TBLR1) acts as a corepressor/coactivator exchanger for nuclear receptors and transcription factors. GAL4-DBD fusion protein experiments showed TBL1X represses promoter activity in luciferase assays, whereas the Y-linked homolog TBL1Y did not repress promoter activity. GAL4-DBD fusion protein expression, dual luciferase reporter assay, RT-PCR expression analysis Journal of human genetics Medium 15834507
2022 TBL1X is required for regulation of major transcriptional programs through the SMRT/NCoR/BCL6 complex, Wnt/β-catenin, and NF-κB signaling. In DLBCL, genetic knockdown of TBL1X and treatment with tegavivint (targeting the TBL1X N-terminus) results in decreased expression of critical oncoproteins in a posttranscriptional/β-catenin-independent manner by promoting proteasomal degradation through a Skp1/Cul1/F-box (SCF)/TBL1X supercomplex. Genetic knockdown (siRNA/shRNA), small molecule treatment (tegavivint), proteasomal degradation assay, co-immunoprecipitation (SCF/TBL1X supercomplex) Experimental hematology Medium 36206873
2023 TBL1X is recruited by lncRNA MIAT to ubiquitinate and downregulate TP53 protein in prostate adenocarcinoma cells, thereby promoting immune evasion. Silencing of TP53 or overexpression of TBL1X abrogated tumor-suppressive effects of MIAT knockdown in vitro and in vivo. RNA pulldown/Co-IP (MIAT-TBL1X interaction), ubiquitination assay, genetic knockdown and overexpression, in vitro and in vivo rescue experiments Biochimica et biophysica acta. Molecular cell research Medium 37356458
2024 PPM1G promotes production of an exon-6-skipping splice variant of TBL1X (TBL1X-S) in hepatocellular carcinoma by prolonging the half-life of the TBL1X-S transcript. TBL1X-S shows significantly enhanced binding affinity for ZEB1 compared to full-length TBL1X, resulting in ZEB1 activation, CDH1 repression, and acceleration of epithelial-mesenchymal transition (EMT). PPM1G-driven metastasis is partially dependent on TBL1X-S. RNA sequencing, mRNA stability assay (half-life measurement), Co-immunoprecipitation (TBL1X variant-ZEB1 interaction), transcriptional reporter (CDH1 promoter), overexpression/knockdown with metastasis phenotype readout Cancer science Medium 39462759
2025 TBL1X controls the stability of the MCL oncogenic drivers cyclin D1 and RAD51 in mantle cell lymphoma cells. Genetic knockdown of TBL1X or treatment with tegavivint (targeting TBL1X N-terminus) results in significant DNA damage, cell cycle arrest, and cell death in vitro and in vivo. Combining tegavivint with the PARP1/2 inhibitor talazoparib results in synergistic MCL cell death, consistent with TBL1X maintaining genomic stability. Genetic knockdown (shRNA), small molecule treatment (tegavivint), western blot (cyclin D1/RAD51 protein stability), DNA damage assay (γH2AX), cell cycle analysis, in vivo patient-derived xenograft model, synergy assay Blood advances Medium 40009753
2024 TBL1X degraders (PROTACs) targeting TBL1X can selectively reduce TBL1X protein levels via proteasomal degradation in DLBCL cells. TBL1X degradation by the PROTAC TD11 is dependent on ternary complex formation and the proteasome. O-linked PROTACs achieved significant TBL1X degradation while N-linked PROTACs showed minimal degradation, indicating the linker attachment site is critical for effective degradation. PROTAC synthesis, western blot (TBL1X protein levels), proteasome inhibition (competition assay), ternary complex formation assay, cytotoxicity assay ACS medicinal chemistry letters Medium 39411529
2018 miR-138-5p inhibits migration and proliferation of trophoblast cells (HTR-8/SVneo) by directly targeting the 3'-UTR of TBL1X, as confirmed by luciferase assay. TBL1X expression was inversely correlated with miR-138-5p in GDM placentas. Luciferase reporter assay (3'-UTR targeting), wound healing assay, transwell migration assay, CCK8 proliferation assay Cellular physiology and biochemistry Medium 30463081
2022 TBL1X interacts with TCF4 to trans-activate Flotillin-2 (Flot2) expression in nasopharyngeal carcinoma. TBL1X promotes NPC cell migration and invasion through Flot2 both in vitro and in vivo. Flot2 reciprocally increases TBL1X expression by upregulating c-Myc, which was identified as a positive regulatory transcription factor of TBL1X. Co-immunoprecipitation (TBL1X-TCF4 interaction), luciferase reporter (Flot2 promoter), knockdown/overexpression with migration/invasion assays, in vivo metastasis model, ChIP (c-Myc on TBL1X promoter) International journal of biological sciences Medium 35173544
2018 TBL1X is part of the NCoR-SMRT corepressor complex involved in repression of thyroid hormone action in the pituitary and hypothalamus. A hemizygous truncating TBL1X mutation [p.Arg339Ter] largely truncating the WD-40 repeat domain causes central hypothyroidism, consistent with loss of nuclear protein-protein interactions mediated by the WD-40 domain. Next-generation sequencing, clinical biochemistry (FT4/TSH), TRH test, audiometry, brain MRI; loss-of-function mutation characterization Journal of the Endocrine Society Low 30591955
2026 Genetic double deletion of TBL1X/TBL1XR1 in CD4+ T cells leads to a shift from naive to effector and Foxp3+ Treg cells, enhanced cytokine production upon stimulation, and induction of pro-inflammatory transcriptional pathways. Transplantation of TBL1X/TBL1XR1-deficient CD4+ T cell bone marrow doubled atherosclerotic plaque development in LDLR KO recipients compared to wild-type, establishing TBL1X as a co-factor restraining CD4+ T cell pro-inflammatory activity. Conditional knockout (CD4-Cre), bone marrow transplantation, flow cytometry (T cell phenotyping), cytokine stimulation assay (ionomycin/PMA), single-cell RNA sequencing, scRNA-seq of human carotid plaques Molecular metabolism Medium 41539423
2026 TBL1X and TBL1XR1 directly regulate insulin promoter activity through a PAX6-HDAC3 gene regulatory network in pancreatic beta cells. Beta-cell-specific TBL1/R1 knockout in mice leads to progressive hypoinsulinemia, hyperglycemia, loss of beta-cell identity (scRNA-seq shows emergence of polyhormonal cells), and reduced beta-cell maturity. TBL1/R1 interactome screens and ChIP confirm direct association with the insulin promoter and PAX6-HDAC3 complex. Beta-cell-specific conditional knockout (mouse), scRNA-seq, interactome screen (Co-IP/MS), chromatin immunoprecipitation (ChIP), luciferase reporter (insulin promoter), human beta-cell model validation Nature communications High 42020373

Source papers

Stage 0 corpus · 61 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2023 The NHGRI-EBI GWAS Catalog: knowledgebase and deposition resource. Nucleic acids research 1218 36350656
2013 Analysis Tool Web Services from the EMBL-EBI. Nucleic acids research 1210 23671338
2015 The EMBL-EBI bioinformatics web and programmatic tools framework. Nucleic acids research 776 25845596
2001 Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responses. Molecular cell 523 11389839
2022 A joint NCBI and EMBL-EBI transcript set for clinical genomics and research. Nature 435 35388217
2001 Gene duplications at the chemokine locus on mouse chromosome 4: multiple strain-specific haplotypes and the deletion of secondary lymphoid-organ chemokine and EBI-1 ligand chemokine genes in the plt mutation. Journal of immunology (Baltimore, Md. : 1950) 157 11123313
2002 An EGFR/Ebi/Sno pathway promotes delta expression by inactivating Su(H)/SMRTER repression during inductive notch signaling. Cell 147 12230979
2018 EBI Metagenomics in 2017: enriching the analysis of microbial communities, from sequence reads to assemblies. Nucleic acids research 130 29069476
1996 The European Bioinformatics Institute (EBI) databases. Nucleic acids research 79 8594602
1994 The European Bioinformatics Institute (EBI) databases. Nucleic acids research 77 7937043
1999 ebi regulates epidermal growth factor receptor signaling pathways in Drosophila. Genes & development 74 10215623
2016 Mutations in TBL1X Are Associated With Central Hypothyroidism. The Journal of clinical endocrinology and metabolism 66 27603907
2001 Enhancement of anti-tumor immunity by tumor cells transfected with the secondary lymphoid tissue chemokine EBI-1-ligand chemokine and stromal cell-derived factor-1alpha chemokine genes. International journal of cancer 55 11267967
2002 The EBI SRS server--recent developments. Bioinformatics (Oxford, England) 53 11847095
2000 A role for Ebi in neuronal cell cycle control. The EMBO journal 50 11032805
2002 The EBI SRS server-new features. Bioinformatics (Oxford, England) 49 12176845
1994 Induction of G protein-coupled peptide receptor EBI 1 by human herpesvirus 6 and 7 infection in CD4+ T cells. Journal of virology 49 7913511
2006 An NRSF/REST-like repressor downstream of Ebi/SMRTER/Su(H) regulates eye development in Drosophila. The EMBO journal 46 16763555
2018 Integrated Transcriptome Sequencing Analysis Reveals Role of miR-138-5p/ TBL1X in Placenta from Gestational Diabetes Mellitus. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 41 30463081
2008 Drosophila Ebi mediates Snail-dependent transcriptional repression through HDAC3-induced histone deacetylation. The EMBO journal 38 18309295
2018 Melatonin Treatment Regulates SIRT3 Expression in Early Brain Injury (EBI) Due to Reactive Oxygen Species (ROS) in a Mouse Model of Subarachnoid Hemorrhage (SAH). Medical science monitor : international medical journal of experimental and clinical research 37 29872034
2011 An X chromosome-wide association study in autism families identifies TBL1X as a novel autism spectrum disorder candidate gene in males. Molecular autism 31 22050706
2008 Immunosurveillance of lung melanoma metastasis in EBI-3-deficient mice mediated by CD8+ T cells. Journal of immunology (Baltimore, Md. : 1950) 30 18941205
2010 Exacerbation of delayed-type hypersensitivity responses in EBV-induced gene-3 (EBI-3)-deficient mice. Immunology letters 28 20064562
2015 The EBI Search engine: providing search and retrieval functionality for biological data from EMBL-EBI. Nucleic acids research 26 25855807
2017 Effects of electron beam irradiation (EBI) on structure characteristics and thermal properties of walnut protein flour. Food research international (Ottawa, Ont.) 22 28873758
2017 The EBI search engine: EBI search as a service-making biological data accessible for all. Nucleic acids research 20 28472374
2022 TBL1X: At the crossroads of transcriptional and posttranscriptional regulation. Experimental hematology 19 36206873
2005 Molecular analysis of TBL1Y, a Y-linked homologue of TBL1X related with X-linked late-onset sensorineural deafness. Journal of human genetics 19 15834507
2024 Using EMBL-EBI Services via Web Interface and Programmatically via Web Services. Current protocols 18 38857087
2022 TBL1X and Flot2 form a positive feedback loop to promote metastasis in nasopharyngeal carcinoma. International journal of biological sciences 17 35173544
2015 A Phase 2 Exploratory Study of a Novel Interleukin-1 Receptor Inhibitor (EBI-005) in the Treatment of Moderate-to-Severe Allergic Conjunctivitis. Eye & contact lens 16 25915834
2012 Ebi/AP-1 suppresses pro-apoptotic genes expression and permits long-term survival of Drosophila sensory neurons. PloS one 14 22666340
2012 The EBI enzyme portal. Nucleic acids research 13 23175605
2019 Description of Halegenticoccus soli gen. nov., sp. nov., a halophilic archaeon isolated from a soil sample of Ebi lake. Extremophiles : life under extreme conditions 11 31147835
2018 Preclinical Development of EBI-005: An IL-1 Receptor-1 Inhibitor for the Topical Ocular Treatment of Ocular Surface Inflammatory Diseases. Eye & contact lens 11 28727604
2018 Central Hypothyroidism and Novel Clinical Phenotypes in Hemizygous Truncation of TBL1X. Journal of the Endocrine Society 11 30591955
2017 Discovery of EBI-1051: A novel and orally efficacious MEK inhibitor with benzofuran scaffold. Bioorganic & medicinal chemistry 11 29317148
2016 EBI-907, a novel BRAF(V600E) inhibitor, has potent oral anti-tumor activity and a broad kinase selectivity profile. Cancer biology & therapy 11 26810733
2007 Lung CD11c+ cells from mice deficient in Epstein-Barr virus-induced gene 3 (EBI-3) prevent airway hyper-responsiveness in experimental asthma. European journal of immunology 9 17506035
2015 Discovery of EBI-907: A highly potent and orally active B-Raf(V600E) inhibitor for the treatment of melanoma and associated cancers. Bioorganic & medicinal chemistry letters 8 26739779
2021 The IL-27 component EBI-3 and its receptor subunit IL-27Rα are essential for the cytoprotective action of humanin on male germ cells†. Biology of reproduction 7 33330922
2018 Comprehensive identification of pleiotropic loci for body fat distribution using the NHGRI-EBI Catalog of published genome-wide association studies. Obesity reviews : an official journal of the International Association for the Study of Obesity 7 30565845
2023 Long noncoding RNA MIAT regulates TP53 ubiquitination and expedites prostate adenocarcinoma progression by recruiting TBL1X. Biochimica et biophysica acta. Molecular cell research 6 37356458
2013 Ebi alleviates excessive growth signaling through multiple epigenetic functions in Drosophila. Genes to cells : devoted to molecular & cellular mechanisms 6 23919509
2018 Searching and Extracting Data from the EMBL-EBI Complex Portal. Methods in molecular biology (Clifton, N.J.) 5 29605928
2015 Cellular Defense and Sensory Cell Survival Require Distinct Functions of ebi in Drosophila. PloS one 5 26524764
2024 PPM1G-mediated TBL1X mRNA splicing promotes cell migration in hepatocellular carcinoma. Cancer science 4 39462759
2016 Ebi modulates wing growth by ubiquitin-dependent downregulation of Crumbs in Drosophila. Development (Cambridge, England) 4 27702784
2016 Ebi, a Drosophila homologue of TBL1, regulates the balance between cellular defense responses and neuronal survival. American journal of neurodegenerative disease 3 27073743
2011 Genetic characterization of ebi reveals its critical role in Drosophila wing growth. Fly 3 22041576
2016 cMapper: gene-centric connectivity mapper for EBI-RDF platform. Bioinformatics (Oxford, England) 2 27667790
2001 EBI databases and services. Molecular biotechnology 2 11503515
2025 Targeting the DNA damage response through TBL1X in mantle cell lymphoma. Blood advances 1 40009753
2024 Design, Synthesis, and Biological Evaluation of Selective TBL1X Degraders. ACS medicinal chemistry letters 1 39411529
2009 Wellcome Trust/EBI 2009 Meeting Report - Perspectives in Stem Cell Proteomics: 22-23 March 2009, Wellcome Trust Conference Centre, Hinxton, UK. Proteomics 1 19609974
2008 BSPR/EBI 2007 meeting report--Integrative Proteomics: From Molecules to Systems. July 25-27, 2007 Wellcome Trust Conference Centre, Hinxton, UK. Proteomics 1 18203272
2026 Nuclear receptor co-factor TBL1X/TBL1XR1 T cell activity protects against atherosclerosis. Molecular metabolism 0 41539423
2026 TBL1X/TBL1XR1 govern β-cell identity through a PAX6-containing gene regulatory network. Nature communications 0 42020373
2024 Mutant Tbl1x male mice have a short life span and do not breed: unexpected findings. Journal of molecular endocrinology 0 38381448
2022 Verification of an iPSC line (LZUi002-A) from a patient with a novel mutation in the TBL1X gene. Stem cell research 0 35339883

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