Affinage

TFG

Protein TFG · UniProt Q92734

Length
400 aa
Mass
43.4 kDa
Annotated
2026-06-10
100 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TFG is a self-assembling scaffold protein that organizes the early secretory pathway by structuring the ER/ERGIC interface and tuning COPII coat dynamics (PMID:25586378, PMID:21478858). It oligomerizes through its PB1 and coiled-coil domains into octameric, cup-like ring complexes that further polymerize and, at physiological conditions, self-organize into a hollow condensate matching the dimensions of the ER-Golgi interface; regularly spaced hydrophobic residues render this condensate a molecular sieve that admits the anterograde COPII coat while excluding retrograde COPI, spatially segregating the two carrier populations (PMID:39574627, PMID:40253417). Functionally, TFG binds the inner COPII coat protein Sec23 through a C-terminal interface shared with the outer coat and the cargo receptor Tango1/cTAGE5, competing with these associations to promote outer coat dissociation and to control the rate of Sec23 recruitment to ER budding sites; it also tethers and clusters inner-coated carriers at the ER/ERGIC interface (PMID:28851831, PMID:38985515). Through these activities TFG organizes transitional ER and ER exit sites, supports anterograde protein secretion (including the specialized export of large cargo such as procollagen), and maintains ER network morphology, with its localization and polymerization promoted in a Ca2+-dependent manner by ALG-2 (PMID:21478858, PMID:27184855, PMID:25586378, PMID:27813252). Disease-causing mutations act on its assembly: PB1-domain (R22W) and coiled-coil (R106C) variants disrupt oligomerization and ring-complex compaction, impairing ER secretion and causing axonopathy and hereditary spastic paraplegia, while low-complexity-domain mutations (G269V, P285L) drive amyloid fibril formation that sequesters wild-type TFG and underlies CMT2-type neurodegeneration (PMID:27601211, PMID:30157421, PMID:38077690, PMID:39574627, PMID:25098539). Beyond the secretory pathway, TFG promotes autophagosome biogenesis by binding LC3C through a LIR motif to favor LC3C-ULK1 engagement and stabilizes ULK1 by competing with TRAF3-mediated K48-linked ubiquitination, and it modulates antiviral innate immunity by recruiting TRAF3 to MAVS and engaging the TBK1-IRF3 axis (PMID:33932238, PMID:35091545, PMID:33411856). TFG was originally identified as the N-terminal fusion partner in oncogenic chimeras (TFG-ALK, TRK-T3/TFG-NTRK1, TFG-RET), where its oligomerization domains mediate constitutive kinase activation and transformation (PMID:10556217, PMID:9488046, PMID:32345963).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1999 High

    Established TFG as a recurrent fusion partner whose oligomerization domains confer constitutive activity on chimeric tyrosine kinases, the founding observation that revealed TFG's self-association capacity.

    Evidence cDNA cloning and in vitro tyrosine kinase assay of TFG-ALK chimeras; deletion mutagenesis and NIH3T3 transformation of TRK-T3 mapping the coiled-coil requirement

    PMID:10556217 PMID:11943732 PMID:9488046

    Open questions at the time
    • Did not address the normal cellular function of full-length TFG
    • Role of N-terminal/PB1 region in transformation only partly resolved
  2. 2003 High

    Refined the structural determinants of TFG-driven transformation, showing that the PB1 domain and an SH2-binding motif beyond the coiled-coil contribute to complex formation, while parallel work mapped TFG's engagement of SH2/SH3-bearing signaling proteins.

    Evidence Deletion/site-specific mutagenesis and transformation assays; reciprocal co-IP with Grb2/Shc/PLC-gamma and SHP-1; SH3 pulldowns in Xenopus

    PMID:10861999 PMID:12584559 PMID:15557341 PMID:30157421

    Open questions at the time
    • Most signaling associations defined in the fusion-protein context, not endogenous TFG
    • Functional consequence of SH3/SH2 binding for native TFG undefined
  3. 2006 Medium

    First linked TFG to inflammatory signaling, placing it within NF-kappaB-modulating complexes.

    Evidence Yeast two-hybrid, co-IP, and NF-kappaB reporter assays identifying NEMO and TANK interactions

    PMID:16547966

    Open questions at the time
    • Mechanism of NF-kappaB enhancement not resolved
    • Stoichiometry within the NEMO complex unknown
  4. 2011 High

    Defined TFG's core cellular function in ER export, showing the conserved ortholog directly couples SEC-16 with the COPII machinery at ER exit sites via oligomerization.

    Evidence C. elegans TFG-1 co-IP with SEC-16, hydrodynamic oligomer characterization, and RNAi depletion phenotypes

    PMID:21478858

    Open questions at the time
    • Hexamer model later revised to octamer in mammals
    • Direct cargo selectivity not yet addressed
  5. 2015 High

    Provided the structural and functional framework for TFG as an ER/ERGIC scaffold, demonstrating self-assembling octameric cup-like polymers that cluster COPII carriers.

    Evidence 3D electron microscopy, in vitro self-association, siRNA knockdown with secretion and live-cell imaging assays

    PMID:23479643 PMID:25586378

    Open questions at the time
    • Molecular contacts with COPII components not yet mapped
    • Atomic-resolution interface unresolved
  6. 2016 High

    Resolved cargo selectivity and regulatory inputs, showing TFG is specifically required for large-cargo (procollagen) export and is recruited and polymerized at ERES by Ca2+-dependent ALG-2.

    Evidence siRNA cargo-specific secretion assays for procollagen vs soluble cargo; ALG-2 co-IP, in vitro cross-linking, and live imaging

    PMID:27184855 PMID:27813252

    Open questions at the time
    • How ALG-2/Ca2+ signaling integrates with secretory demand unclear
    • Selectivity mechanism for large cargo not mechanistically defined at this stage
  7. 2017 High

    Identified the direct molecular target of TFG on the COPII coat, establishing it as a regulator of coat dynamics through competition at the Sec23 interface.

    Evidence In vitro binding/competition assays with concentration-dependence, co-IP, and cellular vesicle-clustering assays mapping the Sec23/Tango1/cTAGE5 interface

    PMID:28851831

    Open questions at the time
    • Kinetic consequences for Sar1 GTP hydrolysis not directly measured here
    • Link between Sec23 binding and condensate organization not yet made
  8. 2018 High

    Connected TFG assembly defects to neuronal disease at endogenous expression levels, showing the R106C ring-compaction defect impairs secretion and axon fasciculation.

    Evidence CRISPR-engineered human stem cells, secretion assays, and neuronal differentiation with axon fasciculation readouts

    PMID:25098539 PMID:27601211 PMID:30157421

    Open questions at the time
    • Cell-type basis of neuronal vulnerability incomplete
    • How impaired oligomerization translates to axonal phenotype unresolved
  9. 2021 High

    Expanded TFG's scaffold role into autophagy and ULK1 regulation, showing LC3C-LIR binding promotes autophagosome biogenesis and TFG protects ULK1 from TRAF3-mediated degradation.

    Evidence Co-IP, LIR/ubiquitination assays, autophagy flux measurements, and patient fibroblast analysis

    PMID:32910713 PMID:33932238 PMID:35091545

    Open questions at the time
    • Interplay between ER-export and autophagy roles of TFG unclear
    • Whether ULK1 stabilization is independent of ER scaffolding unknown
  10. 2022 High

    Refined TFG's antiviral and neuronal trafficking roles, showing TRAF3 recruitment to MAVS and TBK1-IRF3/mTOR engagement, and an ER-export-independent role in Rab4A recycling-endosome trafficking in neurons.

    Evidence Knockdown with IRF3/mTOR phosphorylation assays and viral infection; CRISPR rat model with organelle-specific neuronal trafficking assays

    PMID:33411856 PMID:35121777 PMID:36161950

    Open questions at the time
    • How a single scaffold partitions among ER, autophagy, immune, and endosomal functions unresolved
    • Direct biochemical basis for endosomal role not defined
  11. 2024 High

    Delivered atomic-resolution architecture and kinetic mechanism, defining the octameric ring interface disrupted by PB1 mutations and showing TFG sets the rate of Sec23 recruitment.

    Evidence X-ray crystallography and cryo-EM of ring complexes with in vivo axonopathy; live-cell kinetic imaging of Sec23 dynamics; cryo-EM of disease-mutant amyloid fibrils

    PMID:38077690 PMID:38985515 PMID:39574627

    Open questions at the time
    • Octamer ring structure reported in a preprint
    • Direct measurement of Sar1 GTP hydrolysis rate inferred, not shown
  12. 2025 High

    Unified TFG's structural and functional roles into a condensate model, showing it forms a hollow biomolecular condensate acting as a molecular sieve to segregate anterograde from retrograde carriers, while a parallel cancer study defined an FBXO45-TFG-ATF2-NF-kappaB stabilization axis.

    Evidence In vitro condensate reconstitution, diffusion/sieving assays, hydrophobic-residue mutagenesis, cell-cycle manipulation; site-specific ubiquitination and in vivo metastasis assays

    PMID:40253417 PMID:41030651

    Open questions at the time
    • How condensate material properties are regulated in vivo across the cell cycle incompletely defined
    • Relationship between FBXO45-driven stabilization and secretory function unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single self-assembling scaffold mechanistically coordinates its distinct roles in ER export, autophagy, innate immunity, and neuronal endosomal trafficking, and how condensate properties are tuned to physiological state, remains unresolved.
  • No integrated model partitioning TFG among its functions
  • Regulatory inputs governing condensate assembly/disassembly in vivo undefined
  • Mechanism linking endosomal trafficking role to the secretory scaffold unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005783 endoplasmic reticulum 4 GO:0005829 cytosol 2
Pathway
R-HSA-9609507 Protein localization 4 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-168256 Immune System 2 R-HSA-9612973 Autophagy 2
Partners
MAP1LC3CPDCD6/ALG-2SEC16SEC23TANGO1/CTAGE5TRAF3TRIM25ULK1
Complex memberships
COPII coatER/ERGIC interface scaffold (TFG condensate)

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 TFG fuses to ALK in anaplastic large cell lymphoma, generating TFG-ALK(S) and TFG-ALK(L) chimeric proteins (85 kDa and 97 kDa) that retain functional tyrosine kinase activity, as demonstrated by in vitro tyrosine kinase assay. In vitro tyrosine kinase assay, RT-PCR, cDNA cloning Blood High 10556217
1998 The TFG coiled-coil domain mediates oligomerization of the TRK-T3 oncoprotein, which is required for constitutive tyrosine kinase activation; deletion of the coiled-coil domain abrogates oligomer formation and constitutive activation, while deletion of the N-terminal region blocks transformation without affecting phosphorylation or complex formation, suggesting a role in cellular localization or substrate interaction. Deletion mutagenesis, NIH3T3 transformation assay, co-immunoprecipitation, biochemical complex analysis Oncogene High 9488046
2002 TFG-ALK fusion proteins (TFG-ALK(S), TFG-ALK(L), TFG-ALK(XL)) have similar transforming efficiency to NPM-ALK in NIH-3T3 fibroblasts and form stable complexes with signaling proteins Grb2, Shc, and PLC-γ. NIH-3T3 transformation assay, co-immunoprecipitation, genomic breakpoint analysis The American journal of pathology High 11943732
2003 Sequences outside the TFG coiled-coil domain in TRK-T3 are required for oncogenic activation; specifically, a PB1 domain and an SH2-binding motif within TFG sequences contribute to protein processing, stable complex formation, and transformation. Deletion mutagenesis, site-specific mutagenesis, NIH3T3 transformation assay, biochemical assays Oncogene High 12584559
2004 TFG interacts with SHP-1 phosphatase; the SHP-1 SH2 domain associates with TFG-derived sequences of TRK-T3 while the SHP-1 catalytic domain associates with the NTRK1-derived portion, and SHP-1 down-regulates TRK-T3 activity. TFG itself is identified as a novel SHP-1-interacting protein. Co-immunoprecipitation, in vitro binding assay The Journal of biological chemistry Medium 15557341
2006 TFG interacts with NEMO and TANK (two NF-κB pathway modulators), identified by yeast two-hybrid screening and confirmed by in vitro and in vivo co-immunoprecipitation. TFG and NEMO form part of the same high molecular weight complex. TFG enhances NF-κB activity induced by TNF-α, TANK, TRAF2, and TRAF6. Yeast two-hybrid, co-immunoprecipitation, NF-κB reporter assay Journal of cellular physiology Medium 16547966
2011 C. elegans TFG-1 (ortholog of human TFG) interacts directly with SEC-16 and controls ER export via COPII-coated vesicles. TFG-1 forms hexamers that facilitate co-assembly of SEC-16 with COPII subunits. TFG-1 depletion leads to marked decline in both SEC-16 and COPII levels at ER exit sites. Co-immunoprecipitation, hydrodynamic (sedimentation) studies, RNAi depletion, immunofluorescence Nature cell biology High 21478858
2013 Loss of TFG function in cell lines slows protein secretion from the ER and alters ER morphology, disrupting organization of peripheral ER tubules and causing collapse of the ER network onto the microtubule cytoskeleton. A disease-causing R106C mutation impairs TFG self-assembly into oligomeric complexes. siRNA knockdown, biochemical oligomerization assay, live-cell imaging, electron microscopy Proceedings of the National Academy of Sciences of the United States of America High 23479643
2013 TFG protein negatively regulates RIG-I-mediated antiviral type-I IFN signaling by binding TRIM25 upon virus infection; TFG knockdown upregulates RIG-I-mediated IFN production and NF-κB signaling, and inhibits VSV replication. TFG also suppresses MAVS-induced signaling. shRNA knockdown, co-immunoprecipitation, IFN reporter assay, VSV replication assay Biochemical and biophysical research communications Medium 23810392
2014 A dominant TFG p.Gly269Val mutation causes CMT2 by increasing the propensity of TFG proteins to form aggregates, sequestering both mutant and wild-type TFG. Loss of endogenous TFG compromises the protein secretion pathway, as demonstrated by secreted Gaussia luciferase reporter assay; this defect is rescued by wild-type but not p.Gly269Val TFG. Cell transfection, aggregate formation assay, secreted Gaussia luciferase reporter assay Neurology Medium 25098539
2015 Mammalian TFG forms flexible, octameric cup-like structures (determined by 3D electron microscopy) that self-associate into larger polymers in vitro. In cells, TFG localizes to the ER/ERGIC interface and clusters COPII-coated transport carriers. Loss of TFG function dramatically slows ER protein export and causes accumulation of COPII-coated carriers throughout the cytoplasm, and disrupts the tight association between ER and ERGIC membranes. 3D electron microscopy, in vitro self-association assay, siRNA knockdown, live-cell imaging, protein secretion assay The EMBO journal High 25586378
2016 TFG organizes transitional ER (tER) and ER exit sites into larger structures. TFG depletion disperses tER elements but does not abolish ERES function for small soluble cargoes; however, TFG is specifically required for export of procollagen from the ER, revealing a role in optimizing COPII assembly for large cargo. siRNA knockdown, live-cell imaging, secretion assay for procollagen and soluble cargoes Cell reports High 27184855
2016 ALG-2 (Ca2+-binding protein, PDCD6 product) interacts with TFG through an ALG-2-binding motif on TFG, promotes TFG localization and retention at ER exit sites in a Ca2+-dependent manner, and promotes TFG polymerization in vitro as shown by in vitro cross-linking assays. Co-immunoprecipitation, immunostaining, time-lapse live-cell imaging, in vitro cross-linking assay, deletion mutagenesis The FEBS journal High 27813252
2016 A SPG57-associated TFG variant (p.Arg22Trp) within the PB1 domain impairs TFG oligomerization in vitro, distinct from the coiled-coil domain mutation (p.Arg106Cys), suggesting that both PB1 and coiled-coil domains contribute to TFG complex formation and function. In vitro oligomerization assay, next-generation sequencing, linkage analysis European journal of human genetics Medium 27601211
2017 TFG binds directly to the inner COPII coat protein Sec23 through a C-terminal interaction that shares an interface with the outer COPII coat and cargo receptor Tango1/cTAGE5. TFG binding to Sec23 outcompetes these other associations in a concentration-dependent manner and promotes outer coat dissociation. TFG also tethers vesicles harboring the inner COPII coat, contributing to their clustering at the ER/ERGIC interface. In vitro binding/competition assay, co-immunoprecipitation, cell-based vesicle clustering assay Proceedings of the National Academy of Sciences of the United States of America High 28851831
2017 β-cell-specific TFG knockout mice display glucose intolerance with reduced insulin secretion, smaller β-cell masses due to diminished proliferation, impaired β-cell expansion on high-fat diet, ER dilatation (ER stress), and downregulation of Nrf2 pathway genes. Conditional knockout mice, glucose tolerance test, insulin secretion assay, immunohistochemistry, electron microscopy, microarray gene expression Scientific reports High 29026155
2018 The TFG p.R106C mutation (causing early-onset HSP) alters compaction of TFG ring complexes. CRISPR-engineered human stem cells expressing mutant TFG at endogenous levels exhibit specific defects in ER secretion and axon fasciculation following neuronal differentiation. CRISPR genome editing, protein secretion assay, neuronal differentiation, axon fasciculation assay, biochemical ring complex characterization Cell reports High 30157421
2020 TFG is required for autophagy flux in CH12 B lymphoma cells. Loss of TFG disrupts ER structure (expanded ER), increases ER stress sensitivity, causes accumulation of autophagosomes, and reduces autophagosome-lysosome fusion (lower LC3-II turnover), as demonstrated by tandem-fluorescent-LC3 assay. CRISPR-Cas9 KO, tandem-fluorescent-LC3 assay, LC3 turnover assay, ER stress assay Autophagy High 32910713
2020 TFG maintains the steady-state level of FANCD2-V2 (a specific isoform) through direct protein interaction; the TFG amino acids 5–100 interact with FANCD2-V2 amino acids 1437–1442. Loss of this interaction impairs timely FANCD2-V2 nuclear focus formation upon DNA damage and leads to increased carcinogenicity. Co-immunoprecipitation, deletion mutagenesis, DNA damage focus formation assay, carcinogenicity assay Aging Medium 33099537
2020 TFG-RET fusion in papillary thyroid cancer oligomerizes in a PB1 domain-dependent manner; oligomerization is required for oncogenic transformation of immortalized human thyroid cells. Expression of TFG-RET leads to upregulation of E3 ubiquitin ligase HUWE1; inhibition of HUWE1 reduces RET-mediated oncogenesis. RNA-seq, cell transformation assay, domain mutagenesis, quantitative proteomics, HUWE1 inhibition assay Nature communications High 32345963
2021 TFG interacts with TRAF3 E3 ubiquitin ligase and stabilizes ULK1 by competing with the TRAF3-ULK1 interaction, thereby preventing K48-linked ubiquitination and proteasomal degradation of ULK1. TFG deficiency leads to increased ULK1-TRAF3 interaction, K48-linked ULK1 ubiquitination, and proteasomal degradation, resulting in higher ROS and pyroptotic cell death in macrophages. Co-immunoprecipitation, ubiquitination assay, proteasome inhibition, siRNA/shRNA knockdown, cell death assay Cell death & disease High 35091545
2021 TFG binds LC3C through a canonical LIR motif, which enables TFG to favor LC3C-ULK1 binding and thereby promote ULK1 puncta formation, omegasome formation, and autophagosome biogenesis. Fibroblasts from HSP patient with TFG R106C mutation show defects in both autophagy and ULK1 puncta accumulation. Co-immunoprecipitation, LIR motif mutagenesis, immunofluorescence, autophagosome formation assay, patient fibroblast analysis The EMBO journal High 33932238
2021 TFG is required for virus-induced TBK1 activation and IRF3 phosphorylation/dimerization. TFG acts as a TRAF3-interacting protein that facilitates efficient recruitment of TRAF3 to MAVS following Sendai virus infection. TFG-TRAF3 complex also engages mTOR, enabling TBK1 to phosphorylate mTOR on serine 2159 to promote mTORC1 signaling and antiviral gene expression. siRNA/shRNA knockdown, co-immunoprecipitation, IRF3 phosphorylation/dimerization assay, mTOR phosphorylation assay, viral infection assay PLoS pathogens High 33411856
2022 In addition to its role in ER secretory transport, TFG has an unexpected role in trafficking of Rab4A-positive recycling endosomes specifically within axons and dendrites of neurons. Impaired TFG function (R106C) delays biosynthetic secretory protein transport from the ER and compromises transport of endosomal cargoes, resulting in down-regulated inhibitory receptor signaling. Mitochondria and lysosome morphology/trafficking are unaffected. CRISPR-Cas9 rat model, primary cortical neuron culture, live-cell imaging, organelle trafficking assay, cargo-specific transport assay Proceedings of the National Academy of Sciences of the United States of America High 36161950
2022 Loss of TFG in motor neurons (vMNTFG KO mice) is sufficient to cause NMJ degeneration, motor function deterioration, and muscle atrophy. Muscle-specific TFG KO (MUSTFG KO) does not cause apparent motor impairment but elevates a denervation marker and inhibits Agrin-induced AChR clustering in C2C12 myotubes. Tissue-specific conditional knockout mice, motor function testing, NMJ morphology, immunohistochemistry, C2C12 cell assay Scientific reports High 35121777
2023 Disease-related mutations G269V and P285L in the low-complexity domain of TFG cause that domain to form amyloid fibrils. Cryo-EM structures confirm unmistakable amyloid architecture with double-protofilament cores; mutant residues stabilize the fibril structure and mutant sequences show increased amyloid propensity compared to wild-type. Cryo-electron microscopy structure determination, in vitro fibril formation assay PNAS nexus High 38077690
2024 TFG regulates the rate of inner COPII coat (Sec23) recruitment to ER budding sites. In cells lacking TFG, Sec23 accumulates more rapidly at ER subdomains, potentially causing premature GTP hydrolysis on Sar1 and delaying anterograde secretory cargo trafficking regardless of cargo size. siRNA/CRISPR knockdown, live-cell imaging of Sec23 dynamics, secretory cargo trafficking assay Molecular biology of the cell High 38985515
2024 TFG forms octameric ring complexes as determined by X-ray crystallography and cryo-EM. A network of electrostatic and hydrophobic interactions defines the interface between protomers. HSP-associated mutations in the PB1 domain disrupt this interface, destabilize octamers, and lead to axonopathy in vivo. X-ray crystallography, cryo-electron microscopy, in vitro ring complex assay, in vivo axonopathy model bioRxivpreprint High 39574627
2025 At physiological conditions TFG self-organizes into a hollow, anisotropic condensate that matches the dimensions of the ER-Golgi interface and is dynamically regulated across the cell cycle. Regularly spaced hydrophobic residues control the condensation mechanism, producing a porous condensate surface that acts as a molecular sieve: it allows access of COPII (anterograde coat) to the condensate interior while restricting COPI (retrograde coat), spatially compartmentalizing anterograde from retrograde carriers. Live-cell imaging, in vitro condensate reconstitution, size-exclusion/diffusion assay, hydrophobic residue mutagenesis, cell cycle manipulation Nature communications High 40253417
2025 FBXO45 E3 ubiquitin ligase promotes TFG ubiquitination at Lys103, increasing TFG stability. Stabilized TFG facilitates binding of transcription factor ATF2, leading to upregulation of NF-κB p65 expression and promoting migration and invasion in TP53-mutant HCC cells. TFG knockdown abrogates FBXO45-driven metastasis in vivo. Co-immunoprecipitation, ubiquitination assay (Lys103-specific), ATF2 binding assay, NF-κB reporter, in vivo xenograft metastasis model JHEP reports High 41030651
2000 Xenopus TFG (xTFG) selectively interacts with SH3 domains of Src, PLCγ, and the p85 subunit of PI3-kinase, identifying a functional SH3-binding motif in TFG. SH3 domain pulldown assay, transgenic Xenopus overexpression Molecular reproduction and development Medium 10861999

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 TRK-fused gene (TFG) is a new partner of ALK in anaplastic large cell lymphoma producing two structurally different TFG-ALK translocations. Blood 176 10556217
2011 TFG-1 function in protein secretion and oncogenesis. Nature cell biology 159 21478858
1996 TFG/TAF30/ANC1, a component of the yeast SWI/SNF complex that is similar to the leukemogenic proteins ENL and AF-9. Molecular and cellular biology 143 8668146
2008 EML4-ALK fusion transcripts, but no NPM-, TPM3-, CLTC-, ATIC-, or TFG-ALK fusion transcripts, in non-small cell lung carcinomas. Lung cancer (Amsterdam, Netherlands) 135 18242762
2015 TFG clusters COPII-coated transport carriers and promotes early secretory pathway organization. The EMBO journal 105 25586378
2013 Inhibition of TFG function causes hereditary axon degeneration by impairing endoplasmic reticulum structure. Proceedings of the National Academy of Sciences of the United States of America 86 23479643
1991 The synthesis of a family of structurally related proteoglycans in fibroblasts is differently regulated by TFG-beta. Matrix (Stuttgart, Germany) 86 1870448
2004 TFG is a novel fusion partner of NOR1 in extraskeletal myxoid chondrosarcoma. Genes, chromosomes & cancer 83 15188455
2017 TFG facilitates outer coat disassembly on COPII transport carriers to promote tethering and fusion with ER-Golgi intermediate compartments. Proceedings of the National Academy of Sciences of the United States of America 78 28851831
2002 Diversity of genomic breakpoints in TFG-ALK translocations in anaplastic large cell lymphomas: identification of a new TFG-ALK(XL) chimeric gene with transforming activity. The American journal of pathology 77 11943732
2003 Risk of long-term complications after TFG-beta1-guided very-high-dose thoracic radiotherapy. International journal of radiation oncology, biology, physics 71 12829134
1998 Role of the TFG N-terminus and coiled-coil domain in the transforming activity of the thyroid TRK-T3 oncogene. Oncogene 67 9488046
2009 TFG, a target of chromosome translocations in lymphoma and soft tissue tumors, fuses to GPR128 in healthy individuals. Haematologica 63 19797732
2016 TFG Promotes Organization of Transitional ER and Efficient Collagen Secretion. Cell reports 60 27184855
2017 TFG-MET fusion in an infantile spindle cell sarcoma with neural features. Genes, chromosomes & cancer 59 28510278
2017 Resveratrol suppresses melanoma by inhibiting NF-κB/miR-221 and inducing TFG expression. Archives of dermatological research 53 28936555
2014 A novel TFG mutation causes Charcot-Marie-Tooth disease type 2 and impairs TFG function. Neurology 45 25098539
2006 The TFG protein, involved in oncogenic rearrangements, interacts with TANK and NEMO, two proteins involved in the NF-kappaB pathway. Journal of cellular physiology 42 16547966
1997 Characterization and chromosomal mapping of the human TFG gene involved in thyroid carcinoma. Genomics 40 9169129
1991 Cytoskeleton in TFG-beta- and bFGF-modulated endothelial monolayer repair. Experimental cell research 38 2015851
2016 The calcium-binding protein ALG-2 promotes endoplasmic reticulum exit site localization and polymerization of Trk-fused gene (TFG) protein. The FEBS journal 32 27813252
2008 ced-4 and proto-oncogene tfg-1 antagonistically regulate cell size and apoptosis in C. elegans. Current biology : CB 32 18635357
2016 TFG-Related Neurologic Disorders: New Insights Into Relationships Between Endoplasmic Reticulum and Neurodegeneration. Journal of neuropathology and experimental neurology 31 26945032
2020 Proteogenomics analysis unveils a TFG-RET gene fusion and druggable targets in papillary thyroid carcinomas. Nature communications 30 32345963
2016 Hereditary spastic paraplegias: identification of a novel SPG57 variant affecting TFG oligomerization and description of HSP subtypes in Sudan. European journal of human genetics : EJHG 29 27601211
2012 Desferrioxamine attenuates doxorubicin-induced acute cardiotoxicity through TFG-β/Smad p53 pathway in rat model. Oxidative medicine and cellular longevity 29 22619697
2004 Biotransformation of various alkanes using the Escherichia coli expressing an alkane hydroxylase system from Gordonia sp. TF6. Bioscience, biotechnology, and biochemistry 28 15502364
2018 Pathogenic TFG Mutations Underlying Hereditary Spastic Paraplegia Impair Secretory Protein Trafficking and Axon Fasciculation. Cell reports 27 30157421
2012 Identification of TFG (TRK-fused gene) as a putative metastatic melanoma tumor suppressor gene. Genes, chromosomes & cancer 27 22250051
2011 Epithelial to mesenchymal transition (EMT) induced by bleomycin or TFG(b1)/EGF in murine induced pluripotent stem cell-derived alveolar Type II-like cells. Differentiation; research in biological diversity 27 21596473
2003 Role of TFG sequences outside the coiled-coil domain in TRK-T3 oncogenic activation. Oncogene 27 12584559
2016 Novel Genetic, Clinical, and Pathomechanistic Insights into TFG-Associated Hereditary Spastic Paraplegia. Human mutation 23 27492651
2022 TRK-fused gene (TFG) regulates ULK1 stability via TRAF3-mediated ubiquitination and protects macrophages from LPS-induced pyroptosis. Cell death & disease 21 35091545
1999 Characterization of TFG in mus musculus and Caenorhabditis elegans. Biochemical and biophysical research communications 21 10092511
2021 TFG binds LC3C to regulate ULK1 localization and autophagosome formation. The EMBO journal 20 33932238
2004 Analysis of SHP-1-mediated down-regulation of the TRK-T3 oncoprotein identifies Trk-fused gene (TFG) as a novel SHP-1-interacting protein. The Journal of biological chemistry 18 15557341
2021 Spitz nevus with a novel TFG-NTRK2 fusion: The first case report of NTRK2-rearranged Spitz/Reed nevus. Journal of cutaneous pathology 17 33979462
2017 Trk-fused gene (TFG) regulates pancreatic β cell mass and insulin secretory activity. Scientific reports 17 29026155
2014 HMSN-P caused by p.Pro285Leu mutation in TFG is not confined to patients with Far East ancestry. Neurobiology of aging 17 25725944
2020 TFG is required for autophagy flux and to prevent endoplasmic reticulum stress in CH12 B lymphoma cells. Autophagy 16 32910713
2019 Partial Response to Ceritinib in a Patient With Abdominal Inflammatory Myofibroblastic Tumor Carrying a TFG-ROS1 Fusion. Journal of the National Comprehensive Cancer Network : JNCCN 16 31805529
2022 TFG regulates secretory and endosomal sorting pathways in neurons to promote their activity and maintenance. Proceedings of the National Academy of Sciences of the United States of America 15 36161950
2018 High in situ mRNA levels of IL-22, TFG-β, and ARG-1 in keloid scars. Immunobiology 15 30146129
2021 TRK-Fused Gene (TFG), a protein involved in protein secretion pathways, is an essential component of the antiviral innate immune response. PLoS pathogens 13 33411856
2018 R106C TFG variant causes infantile neuroaxonal dystrophy "plus" syndrome. Neurogenetics 13 29971521
2017 Genomic diagnostics leading to the identification of a TFG-ROS1 fusion in a child with possible atypical meningioma. Cancer genetics 13 28449809
2021 Rapid Response to Lorlatinib in a Patient With TFG-ROS1 Fusion Positive Inflammatory Myofibroblastic Tumor of the Chest Wall Metastatic to the Brain and Refractory to First and Second Generation ROS1 Inhibitors. Journal of pediatric hematology/oncology 12 34157012
2021 Deregulation of CLTC interacts with TFG, facilitating osteosarcoma via the TGF-beta and AKT/mTOR signaling pathways. Clinical and translational medicine 12 34185412
2012 The TFG-TEC fusion gene created by the t(3;9) translocation in human extraskeletal myxoid chondrosarcomas encodes a more potent transcriptional activator than TEC. Carcinogenesis 12 22581839
2019 Muscle pathology of hereditary motor and sensory neuropathy with proximal dominant involvement with TFG mutation. Muscle & nerve 11 31449671
2017 TFG associated hereditary spastic paraplegia: an addition to the phenotypic spectrum. Neurogenetics 11 28124177
2016 Identification of novel TFG mutation in HMSN-P pedigree: Emphasis on variable clinical presentations. Journal of the neurological sciences 11 27653917
2015 The TFG-TEC oncoprotein induces transcriptional activation of the human β-enolase gene via chromatin modification of the promoter region. Molecular carcinogenesis 11 26310886
2000 Xenopus laevis TRK-fused gene (TFG) is an SH3 domain binding protein highly expressed in the cement gland. Molecular reproduction and development 11 10861999
2025 A hollow TFG condensate spatially compartmentalizes the early secretory pathway. Nature communications 10 40253417
2024 A Hollow TFG Condensate Spatially Compartmentalizes the Early Secretory Pathway. bioRxiv : the preprint server for biology 9 38585729
2022 TFG::MET-rearranged soft tissue tumor: A rare infantile neoplasm with a distinct low-grade triphasic morphology. Genes, chromosomes & cancer 9 36464850
2021 A Novel TFG Mutation in a Korean Family with α-Synucleinopathy and Amyotrophic Lateral Sclerosis. Movement disorders : official journal of the Movement Disorder Society 9 34779525
2019 Tropomyosin-receptor kinase fused gene (TFG) regulates lipid production in human sebocytes. Scientific reports 9 31036933
2013 Negative regulation of RIG-I-mediated antiviral signaling by TRK-fused gene (TFG) protein. Biochemical and biophysical research communications 9 23810392
2023 Individualized targeted treatment in a case of a rare TFG::ROS1 fusion positive inflammatory myofibroblastic tumor (IMT). Cancer reports (Hoboken, N.J.) 8 37950626
2022 Involvement of neuronal and muscular Trk-fused gene (TFG) defects in the development of neurodegenerative diseases. Scientific reports 8 35121777
2021 Durable response to serial tyrosine kinase inhibitors (TKIs) in an adolescent with metastatic TFG-ROS1 fusion positive Inflammatory Myofibroblastic Tumor (IMT). Lung cancer (Amsterdam, Netherlands) 8 34059352
2022 TFG mutation induces haploinsufficiency and drives axonal Charcot-Marie-Tooth disease by causing neurite degeneration. CNS neuroscience & therapeutics 7 35986567
2022 A Novel CASC15-ALK and TFG-ROS1 Fusion Observed in Uterine Inflammatory Myofibroblastic Tumor. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 7 36730016
2013 [Pathomechanisms of motor neuron death by mutant TFG]. Rinsho shinkeigaku = Clinical neurology 7 24291928
2024 TFG regulates inner COPII coat recruitment to facilitate anterograde secretory protein transport. Molecular biology of the cell 6 38985515
2020 TFG-maintaining stability of overlooked FANCD2 confers early DNA-damage response. Aging 6 33099537
2005 Probable role of spinal purinoceptors in the analgesic effect of Trigonella foenum (TFG) leaves extract. Journal of ethnopharmacology 6 16298092
2004 Altered expression of Tfg and Dap3 in Ikaros-defective T-cell lymphomas induced by X-irradiation in B6C3F1 mice. British journal of haematology 6 14687027
2024 Novel TFG mutation causes autosomal-dominant spastic paraplegia and defects in autophagy. Journal of medical genetics 5 37890998
2021 Non-secretory multiple myeloma with unusual TFG-ALK fusion showed dramatic response to ALK inhibition. NPJ genomic medicine 5 33731690
2021 Homozygous TFG gene variants expanding the mutational and clinical spectrum of hereditary spastic paraplegia 57 and a review of literature. Journal of human genetics 5 33767317
2019 Sural nerve pathology in TFG-associated motor neuron disease with sensory neuropathy. Neuropathology : official journal of the Japanese Society of Neuropathology 5 30957313
2019 Continuum of phenotypes in hereditary motor and sensory neuropathy with proximal predominance and Charcot-Marie-Tooth patients with TFG mutation. American journal of medical genetics. Part A 5 31111683
2018 A novel homozygous mutation of the TFG gene in a patient with early onset spastic paraplegia and later onset sensorimotor polyneuropathy. Journal of human genetics 5 30467354
2025 Dramatic response to crizotinib through MET phosphorylation inhibition in rare TFG-MET fusion advanced squamous cell lung cancer. The oncologist 4 38954846
2023 Fibril structures of TFG protein mutants validate the identification of TFG as a disease-related amyloid protein by the IMPAcT method. PNAS nexus 4 38077690
2022 Mutation Screening of TFG in α-Synucleinopathy and Amyotrophic Lateral Sclerosis. Movement disorders : official journal of the Movement Disorder Society 4 35642252
2024 Remarkable response to capmatinib in a patient with intrahepatic cholangiocarcinoma harboring TFG-MET fusion. International cancer conference journal 3 38962049
2020 A novel TFG c.793C>G mutation in a Chinese pedigree with Charcot-Marie-Tooth disease 2. Brain and behavior 3 32666699
2025 Screening and identification of Theileria annulata proteins interacting with bovine TFG proteins. International journal of biological macromolecules 2 40578648
2024 Reclassification of a spindle cell sarcoma after identification of a TFG-ROS1 fusion: A case demonstrating the clinical benefit of next-generation sequencing in sarcoma. Molecular genetics & genomic medicine 2 38622850
2024 Identification of TFG- and Autophagy-Regulated Proteins and Glycerophospholipids in B Cells. Journal of proteome research 2 38649144
2024 Cell type-specific gene therapy confers protection against motor neuron disease caused by a TFG variant. Proceedings of the National Academy of Sciences of the United States of America 2 39527745
2023 TFG::ALK fusion in ALK positive large B-cell lymphoma: a case report and review of literature. Frontiers in oncology 2 37305584
2022 TFG-β Nuclear Staining as a Potential Relapse Risk Factor in Early-Stage Non-Small-Cell Lung Cancer. International journal of molecular sciences 2 36430262
2013 A TFG-TEC nuclear localization mutant forms complexes with the wild-type TFG-TEC oncoprotein and suppresses its activity. The Biochemical journal 2 24073693
2025 Venetoclax combined with ATRA shows promising therapeutic potential for TFG:: RARA variant APL: a case report. Frontiers in oncology 1 40386562
2025 ALK-positive adult histiocytosis with a TFG-ALKfusion gene. The oncologist 1 40700600
2024 Characterization of a novel TFG variant causing autosomal recessive pure hereditary spastic paraplegia. Annals of clinical and translational neurology 1 38837630
2024 Multiple roles for TFG ring complexes in neuronal cargo trafficking. bioRxiv : the preprint server for biology 1 39574627
2024 First case of acute promyelocytic leukemia with TFG-RARA achieved complete remission treated with venetoclax and all-trans retinoic acid. Hematology (Amsterdam, Netherlands) 1 39606904
2022 Proximal Dominant Hereditary Motor and Sensory Neuropathy with TFG Mutation: First Case Report from India. Neurology India 1 35864671
2022 A novel TFG variant of uncertain significance in amyotrophic lateral sclerosis: A case report and review of literature. Annals of medicine and surgery (2012) 1 36582889
2018 Transforming Growth Factor Beta (TFG-β) Concentration Isoforms are Diminished in Acute Coronary Syndrome. Cell biochemistry and biophysics 1 30003432
2013 [Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) is caused by a mutation in TFG]. Rinsho shinkeigaku = Clinical neurology 1 24291930
2008 [Effect of nebulized TFG on Th1/Th2 imbalance in mouse model with asthma]. Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 1 19007018
2025 Desulfitobacterium elongatum sp. nov. NIT-TF6 Isolated from Trichloroethene-Dechlorinating Culture with Formate. Microorganisms 0 40871367
2025 Elevated FBXO45 promotes TFG ubiquitination and drives lung metastasis of hepatocellular carcinoma. JHEP reports : innovation in hepatology 0 41030651

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