Affinage

TEX10

Testis-expressed protein 10 · UniProt Q9NXF1

Round 2 corrected
Length
929 aa
Mass
105.7 kDa
Annotated
2026-04-28
46 papers in source corpus 10 papers cited in narrative 10 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TEX10 is a chromatin-associated transcriptional co-activator that coordinates histone acetylation and DNA demethylation to regulate pluripotency, germ cell development, and context-dependent gene expression programs. In embryonic stem cells, TEX10 localizes to super-enhancers in a Sox2-dependent manner and recruits p300 and Tet1 to sustain self-renewal, acting downstream of the non-canonical PRC1 components Pcgf3/5 (PMID:25936917, PMID:29054931). TEX10 also binds H3K4me3-marked promoters of Wnt-pathway negative regulators (Psmd3/Psmd7) to restrain Wnt signaling during primordial germ cell-like cell specification and spermatogenesis, and conditional knockout in mice causes spermatocyte arrest at metaphase I (PMID:39988597). In cancer contexts, TEX10 co-opts its transcriptional co-activator function to enhance NF-κB signaling by promoting RELA nuclear localization and to augment STAT3 transcriptional activity via p300-mediated STAT3 acetylation (PMID:32995120, PMID:37792308).

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 2015 High

    The first mechanistic question—how TEX10 functions in stem cells—was answered by showing it is recruited to super-enhancers by Sox2 and coordinates p300-mediated histone acetylation and Tet1-mediated DNA demethylation to sustain pluripotency.

    Evidence Co-IP/MS, ChIP-seq, bisulfite sequencing, and knockdown/knockout phenotypic assays in mouse ESCs and reprogramming systems

    PMID:25936917

    Open questions at the time
    • Structural basis for TEX10–Sox2 interaction undefined
    • Whether TEX10 has intrinsic enzymatic activity or functions purely as a scaffold unknown
    • Genome-wide target selectivity beyond super-enhancers not characterized
  2. 2017 High

    The upstream dependency of TEX10 chromatin recruitment was established: Pcgf3/5 (non-canonical PRC1 subunits) are required for TEX10 and p300 occupancy at target gene promoters, positioning TEX10 within a Pcgf3/5→TEX10→p300 activation axis for mesoderm differentiation genes.

    Evidence AP-MS interactomics, ChIP-seq occupancy changes upon CRISPR-Cas9 Pcgf3/5 double knockout, RNA-seq in mouse ESCs

    PMID:29054931

    Open questions at the time
    • Direct versus bridged interaction between TEX10 and Pcgf3/5 not resolved
    • Whether TEX10 is a stable subunit of a defined Pcgf3/5-containing complex or transiently recruited unknown
  3. 2018 Low

    TEX10 was implicated in cancer stemness for the first time, with knockdown reducing stem cell markers and chemoresistance in hepatocellular carcinoma, linked to decreased STAT3 pathway activity.

    Evidence shRNA/siRNA knockdown, sphere formation, drug resistance assays, and xenograft models in HCC cell lines

    PMID:30045663

    Open questions at the time
    • No direct TEX10–STAT3 physical interaction demonstrated in this study
    • Mechanism connecting TEX10 to STAT3 activation not biochemically defined
    • Single-lab finding without independent replication
  4. 2020 Medium

    A direct mechanism for TEX10 in NF-κB signaling was established: TEX10 physically interacts with RELA (p65) and enhances its nuclear localization and promoter occupancy, driving expression of pro-tumorigenic targets in colorectal cancer.

    Evidence Co-IP, ChIP, nuclear/cytoplasmic fractionation, shRNA library screen, in vivo xenograft in CRC models

    PMID:32995120

    Open questions at the time
    • Domain mapping of TEX10–RELA interaction not performed
    • Whether TEX10's role in NF-κB activation is independent of its chromatin remodeling function unclear
    • Single-lab study
  5. 2023 Medium

    The earlier STAT3 link was mechanistically resolved: TEX10 physically interacts with STAT3 and promotes its p300-mediated acetylation, enhancing STAT3 transcriptional activity; p300 silencing abolishes TEX10-driven STAT3 activation, establishing an epistatic TEX10→p300→STAT3 axis in HCC metastasis.

    Evidence Co-IP, ChIP, dual-luciferase reporter, immunofluorescence, xenograft/lung metastasis models in HCC cells

    PMID:37792308

    Open questions at the time
    • Whether TEX10 recruits p300 to STAT3 or stabilizes a pre-existing p300–STAT3 complex not distinguished
    • Relevance of this axis outside HCC not tested
  6. 2025 High

    TEX10's physiological role in germ cell development was defined: it binds H3K4me3-marked promoters of Psmd3 and Psmd7 to activate their expression, restraining Wnt signaling during PGCLC specification and spermatogenesis; conditional knockout mice exhibit metaphase I arrest and reduced sperm number/motility.

    Evidence Conditional knockout mice, dTAG-degron ESCs, ChIP-seq, bulk and single-cell RNA-seq, PGCLC differentiation assays

    PMID:39988597

    Open questions at the time
    • How TEX10 recognizes H3K4me3-marked loci (direct histone binding or via a reader protein) not resolved
    • Whether TEX10's Wnt-restraining function operates in somatic tissues or is germ cell-specific unknown
    • Relationship between the super-enhancer role (Sox2-dependent) and H3K4me3-promoter role (Wnt regulation) not integrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • A unified structural and biochemical understanding of TEX10's molecular activity—whether it possesses intrinsic enzymatic function or acts solely as a scaffold/adaptor—remains unresolved, as does the basis for its context-dependent switching between transcriptional activation in stem/germ cells and oncogenic signaling co-activation in cancer.
  • No crystal/cryo-EM structure of TEX10 or its complexes available
  • No in vitro reconstitution demonstrating direct enzymatic activity
  • Mechanism by which TEX10 switches between super-enhancer, promoter, and NF-κB/STAT3 co-activation modes undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0042393 histone binding 1
Localization
GO:0005634 nucleus 4 GO:0000228 nuclear chromosome 2
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1266738 Developmental Biology 2 GO:0140110 transcription regulator activity 1 R-HSA-1474165 Reproduction 1
Partners
EP300PCGF3PCGF5RELASOX2STAT3TET1XRCC6
Complex memberships
Pcgf3/5–TEX10–p300 transcriptional activation complex

Evidence

Reading pass · 10 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 TEX10 was identified as a Sox2-interacting protein that is enriched at super-enhancers (SEs) in embryonic stem cells in a Sox2-dependent manner. TEX10 coordinates histone acetylation and DNA demethylation at SEs, functioning together with Tet1 and p300 to sustain pluripotency. Loss of TEX10 impairs ESC self-renewal, early embryo development, and somatic cell reprogramming. Protein interaction network analysis (Co-IP/MS), ChIP-seq, bisulfite sequencing, knockdown/knockout phenotypic assays in ESCs and reprogramming assays Cell stem cell High 25936917
2017 TEX10 interacts with Pcgf3/5 (non-canonical PRC1 components) and the transcriptional co-activator p300 in embryonic stem cells. Pcgf3/5 deletion reduces occupancy of TEX10 and p300 at target gene promoters, placing TEX10 downstream of Pcgf3/5 in a transcriptional activation complex required for mesoderm differentiation genes. Proteomic interactome (AP-MS), ChIP-seq occupancy analysis, CRISPR-Cas9 single/double knockout, RNA-seq The Journal of biological chemistry High 29054931
2020 TEX10 promotes proliferation of colorectal cancer cells by interacting with RELA (NF-κB p65) and increasing its nuclear localization, enhancing RELA occupancy at target gene promoters and driving expression of TNFAIP8, SAT1, and IL6ST. shRNA library screen, Co-IP, ChIP, nuclear/cytoplasmic fractionation, in vitro and in vivo tumor growth assays Advanced science Medium 32995120
2018 TEX10 promotes cancer stem cell properties and chemoresistance in hepatocellular carcinoma through activation of the STAT3 signaling pathway, as shown by decreased stem cell marker expression and drug resistance upon TEX10 knockdown. Knockdown (shRNA/siRNA), Western blot, sphere formation assay, drug resistance assay, xenograft Cell cycle Low 30045663
2023 TEX10 physically interacts with STAT3 and promotes p300-mediated STAT3 acetylation, thereby enhancing STAT3 transcriptional activity and driving HCC cell invasion, EMT, and metastasis. Silencing p300 abolishes TEX10-enhanced STAT3 transcriptional activity. Co-immunoprecipitation, immunofluorescence, ChIP, dual-luciferase reporter assay, xenograft/lung metastasis models Molecular carcinogenesis Medium 37792308
2019 TEX10 promotes stemness and epithelial-mesenchymal transition (EMT) in esophageal squamous cell carcinoma through activation of Wnt/β-catenin signaling; TEX10 knockdown inhibits proliferation, induces apoptosis/cell cycle arrest, and reduces stemness and invasiveness. Knockdown (lentiviral shRNA), Western blot, flow cytometry, Transwell invasion, sphere formation, CCK-8 assay Oncology reports Low 31638260
2021 TEX10 interacts with and stabilizes XRCC6 (Ku70) in bladder carcinoma cells, thereby activating Wnt/β-catenin signaling and DNA repair pathways, promoting tumor growth and radiotherapy resistance; TEX10 knockout reduces radiotherapy resistance. Co-immunoprecipitation, knockdown/knockout, xenograft, irradiation resistance assay Journal of immunology research Low 34966825
2025 TEX10 binds H3K4me3-marked promoters of Psmd3 and Psmd7 (negative regulators of Wnt signaling) and activates their expression, thereby restraining Wnt signaling during ESC-to-PGCLC differentiation and spermatogenesis. Tex10 conditional knockout mice show spermatocyte arrest at metaphase I and reduced sperm number/motility; Tex10 depletion and overexpression respectively compromise and enhance PGCLC differentiation efficiency. Conditional knockout mice, dTAG-degron ESCs, ChIP-seq (H3K4me3 occupancy), bulk and single-cell RNA-seq, ESC-to-PGCLC differentiation assay Nature communications High 39988597
2023 Tex10 binds to Wnt negative regulator gene loci marked by H3K4me3 at the PGCLC stage to restrain Wnt signaling; depletion hyperactivates and overexpression attenuates Wnt signaling, with corresponding effects on PGCLC specification efficiency. Tex10 conditional knockout mice display compromised round spermatid formation associated with aberrant Wnt signaling upregulation. ChIP-seq, conditional knockout mice, single-cell RNA-seq, PGCLC differentiation assay, sperm motility/count analysis bioRxivpreprint Medium 36865339
2022 TEX10 and LINC00624 form a co-regulatory axis that stimulates NF-κB activity to promote proliferation and migration of prostate cancer cells; LINC00624 knockdown decreases TEX10-dependent NF-κB activation. In vitro knockdown, in vivo xenograft, NF-κB reporter/pathway analysis, co-expression analysis Biochemical and biophysical research communications Low 35219000

Source papers

Stage 0 corpus · 46 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2009 Defining the human deubiquitinating enzyme interaction landscape. Cell 1282 19615732
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2005 Physical association and coordinate function of the H3 K4 methyltransferase MLL1 and the H4 K16 acetyltransferase MOF. Cell 551 15960975
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2002 Functional proteomic analysis of human nucleolus. Molecular biology of the cell 391 12429849
2018 DNA Repair Network Analysis Reveals Shieldin as a Key Regulator of NHEJ and PARP Inhibitor Sensitivity. Cell 379 29656893
2009 Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is required for DNA repair. Cell 375 19596235
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2020 A Genome-wide ER-phagy Screen Highlights Key Roles of Mitochondrial Metabolism and ER-Resident UFMylation. Cell 253 32160526
2004 Functional proteomics mapping of a human signaling pathway. Genome research 247 15231748
2013 PRP19 transforms into a sensor of RPA-ssDNA after DNA damage and drives ATR activation via a ubiquitin-mediated circuitry. Molecular cell 204 24332808
2018 An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. Nature communications 201 29568061
2014 Global mapping of herpesvirus-host protein complexes reveals a transcription strategy for late genes. Molecular cell 173 25544563
2020 UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination. Nature cell biology 168 32807901
2020 Synthetic Lethal and Resistance Interactions with BET Bromodomain Inhibitors in Triple-Negative Breast Cancer. Molecular cell 159 32416067
2018 MYC Protein Interactome Profiling Reveals Functionally Distinct Regions that Cooperate to Drive Tumorigenesis. Molecular cell 152 30415952
2008 Systematic identification of mRNAs recruited to argonaute 2 by specific microRNAs and corresponding changes in transcript abundance. PloS one 148 18461144
2012 Functional proteomics establishes the interaction of SIRT7 with chromatin remodeling complexes and expands its role in regulation of RNA polymerase I transcription. Molecular & cellular proteomics : MCP 145 22586326
2009 Direct binding of CoREST1 to SUMO-2/3 contributes to gene-specific repression by the LSD1/CoREST1/HDAC complex. Molecular cell 140 19394292
2015 Tex10 Coordinates Epigenetic Control of Super-Enhancer Activity in Pluripotency and Reprogramming. Cell stem cell 80 25936917
2017 Polycomb group RING finger proteins 3/5 activate transcription via an interaction with the pluripotency factor Tex10 in embryonic stem cells. The Journal of biological chemistry 41 29054931
2022 LINC00624/TEX10/NF-κB axis promotes proliferation and migration of human prostate cancer cells. Biochemical and biophysical research communications 32 35219000
2024 E3 ubiquitin ligase IPI1 controls rice immunity and flowering via both E3 ligase-dependent and -independent pathways. Developmental cell 23 39025062
2021 LncRNA GATA3‑AS1‑miR‑30b‑5p‑Tex10 axis modulates tumorigenesis in pancreatic cancer. Oncology reports 21 33760161
2020 RNAi Screening Identifies that TEX10 Promotes the Proliferation of Colorectal Cancer Cells by Increasing NF-κB Activation. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 21 32995120
2019 Tex10 promotes stemness and EMT phenotypes in esophageal squamous cell carcinoma via the Wnt/β‑catenin pathway. Oncology reports 21 31638260
2018 Tex10 is upregulated and promotes cancer stem cell properties and chemoresistance in hepatocellular carcinoma. Cell cycle (Georgetown, Tex.) 21 30045663
2021 TEX10 Promotes the Tumorigenesis and Radiotherapy Resistance of Urinary Bladder Carcinoma by Stabilizing XRCC6. Journal of immunology research 11 34966825
2025 Pluripotency factor Tex10 finetunes Wnt signaling for spermatogenesis and primordial germ cell development. Nature communications 6 39988597
2023 Tex10 interacts with STAT3 to regulate hepatocellular carcinoma growth and metastasis. Molecular carcinogenesis 5 37792308
2025 Mechanisms of multidrug resistance caused by an Ipi1 mutation in the fungal pathogen Candida glabrata. Nature communications 4 39863615
2015 Tex10: A New Player in the Core Pluripotency Circuitry. Cell stem cell 4 26046753
2023 The pluripotency factor Tex10 finetunes Wnt signaling for PGC and male germline development. bioRxiv : the preprint server for biology 2 36865339
2025 TEX10: A Novel Drug Target and Potential Therapeutic Direction for Sleep Apnea Syndrome. Nature and science of sleep 1 40330585
2025 Regulatory role of TEX10 gene in proliferation differentiation and apoptosis of bovine myoblasts. The international journal of biochemistry & cell biology 0 40086620