Affinage

TFG

Protein TFG · UniProt Q92734

Length
400 aa
Mass
43.4 kDa
Annotated
2026-04-28
100 papers in source corpus 32 papers cited in narrative 32 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TFG is a self-assembling scaffolding protein that forms octameric ring complexes and hollow condensates at the ER–ERGIC interface, where it organizes COPII-coated transport carriers, regulates inner coat (Sec23) dynamics, and spatially compartmentalizes anterograde from retrograde trafficking to control ER-to-Golgi cargo export including procollagen (PMID:25586378, PMID:28851831, PMID:38985515, PMID:40253417). TFG binds SEC-16 to maintain ER exit site architecture, interacts with LC3C via a LIR motif to coordinate autophagosome biogenesis through ULK1 regulation, and associates with TRAF3 to promote TBK1–IRF3 antiviral signaling and stabilize ULK1 against proteasomal degradation (PMID:21478858, PMID:33932238, PMID:33411856, PMID:35091545). Disease-associated mutations in the PB1 or coiled-coil domains (e.g., R106C, G269V, P285L) disrupt oligomerization or promote amyloid fibril formation, impairing ER secretory and endosomal trafficking in a neuron-autonomous manner and causing hereditary spastic paraplegia and related axonopathies (PMID:23479643, PMID:36161950, PMID:38077690, PMID:39527745).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1998 High

    Establishing that TFG possesses a coiled-coil domain that drives oligomerization, and that this self-assembly is essential for constitutive activation of oncogenic TRK-T3, defined TFG's core biochemical property — homo-oligomerization — and its first known functional consequence.

    Evidence Deletion mutagenesis, NIH3T3 transformation assay, and biochemical oligomerization analysis

    PMID:9488046

    Open questions at the time
    • Native cellular function of TFG oligomerization unknown
    • Whether oligomerization serves any non-oncogenic role unresolved
  2. 2003 High

    Identification of the PB1 domain and SH2-binding motif as additional determinants of TFG complex formation and signaling showed that TFG uses multiple domains beyond the coiled-coil for oligomerization and protein interactions.

    Evidence Site-specific and deletion mutagenesis with biological and biochemical assays in mammalian cells

    PMID:10861999 PMID:12584559

    Open questions at the time
    • Endogenous binding partners of the PB1 domain in non-oncogenic context not identified
    • Structural basis of PB1-mediated oligomerization unresolved
  3. 2006 Medium

    Discovery that TFG interacts with NEMO and TANK and enhances NF-κB signaling provided the first evidence of a native TFG signaling function outside oncogenic fusions.

    Evidence Yeast two-hybrid screen, co-immunoprecipitation, NF-κB reporter assay

    PMID:16547966

    Open questions at the time
    • Mechanism by which TFG enhances NF-κB not resolved
    • Physiological relevance in vivo not tested
    • Single-lab finding without independent replication
  4. 2011 High

    Demonstration that C. elegans TFG-1 directly binds SEC-16 and is required for COPII and SEC-16 levels at ER exit sites established TFG's primary physiological role: organizing COPII-dependent ER export.

    Evidence Co-immunoprecipitation, sedimentation analysis showing hexamers, RNAi depletion with cargo secretion assay in C. elegans

    PMID:21478858

    Open questions at the time
    • Mammalian validation needed
    • Whether TFG directly contacts COPII subunits unknown
    • Mechanism of SEC-16 stabilization unclear
  5. 2013 High

    Linking the TFG p.R106C mutation to impaired oligomerization, slowed ER secretion, disrupted ER morphology, and hereditary axon degeneration established TFG as a disease gene for hereditary spastic paraplegia and connected its oligomeric assembly to neuronal health.

    Evidence Biochemical self-assembly assays, cell-based secretion assays, fluorescence microscopy of ER morphology in patient-derived and manipulated cells

    PMID:23479643

    Open questions at the time
    • Whether defect is cell-autonomous to neurons not established
    • Downstream neurotoxic mechanism (ER stress vs. trafficking defect) not resolved
  6. 2015 High

    Structural and functional studies revealing that mammalian TFG forms octameric cup-like structures that polymerize and concentrate COPII carriers at the ER–ERGIC interface defined the architecture by which TFG organizes early secretory trafficking.

    Evidence 3D electron microscopy, in vitro polymerization, siRNA knockdown with electron tomography and secretion assay

    PMID:25586378

    Open questions at the time
    • Direct COPII coat subunit binding interface not mapped
    • How TFG polymers spatially segregate coated carriers unresolved
  7. 2016 High

    Showing that TFG is specifically required for procollagen but not small soluble cargo export revealed cargo-selective roles, while ALG-2 was identified as a calcium-dependent regulator of TFG polymerization at ER exit sites.

    Evidence siRNA depletion with live-cell imaging and procollagen secretion assays; ALG-2 co-IP and in vitro cross-linking polymerization assays

    PMID:27184855 PMID:27813252

    Open questions at the time
    • How cargo selectivity arises mechanistically unclear
    • Whether ALG-2–TFG regulation is required in vivo untested
  8. 2017 High

    Demonstrating that TFG's C-terminus binds Sec23 on the same interface used by the outer COPII coat and Tango1/cTAGE5, competing for this site in a concentration-dependent manner, provided a molecular mechanism for TFG-driven outer coat disassembly and vesicle tethering at the ER–ERGIC boundary.

    Evidence In vitro binding competition, cryo-EM, vesicle tethering assay, cell-based co-localization

    PMID:28851831

    Open questions at the time
    • Kinetic parameters of competition in live cells not measured
    • Whether Tango1 and TFG act sequentially or in parallel unclear
  9. 2018 High

    CRISPR-engineered iPSC-derived human neurons with endogenous TFG R106C confirmed that the mutation alters ring complex compaction and causes cargo secretion and axon fasciculation defects, validating disease-relevance in a human neuronal model.

    Evidence CRISPR-Cas9 genome editing in iPSCs, biochemical ring analysis, neuronal secretion and fasciculation assays

    PMID:30157421

    Open questions at the time
    • In vivo validation in animal model pending
    • Whether fasciculation defect is primary or secondary to secretion impairment unclear
  10. 2021 High

    Convergent studies established TFG as a dual regulator linking the secretory pathway to autophagy and innate immunity: TFG binds LC3C via a LIR motif to control ULK1 puncta formation and autophagosome biogenesis, interacts with TRAF3 to stabilize ULK1 against K48-ubiquitination, and promotes TBK1–IRF3 antiviral signaling by facilitating TRAF3 recruitment to MAVS.

    Evidence LIR motif mutagenesis and autophagosome quantification; co-IP with ubiquitination linkage assays; IRF3 dimerization and mTOR phosphorylation upon Sendai virus infection

    PMID:33411856 PMID:33932238 PMID:35091545

    Open questions at the time
    • Whether autophagy and innate immune functions are coupled or independent unclear
    • Structural basis of TFG–TRAF3 interaction not resolved
  11. 2022 High

    The TFG R106C mutation in rat primary neurons was shown to impair both biosynthetic ER-to-Golgi transport and Rab4A-positive recycling endosome trafficking specifically in axons and dendrites, broadening disease pathology beyond secretory to endosomal compartments.

    Evidence CRISPR rat model, live-cell cargo trafficking and Rab4A endosome quantification in primary cortical neurons

    PMID:36161950

    Open questions at the time
    • Molecular mechanism linking TFG to Rab4A endosomes unresolved
    • Whether endosomal defect or secretory defect is the primary pathogenic driver unclear
  12. 2023 High

    Cryo-EM structures demonstrated that disease-associated mutations G269V and P285L in TFG's low-complexity domain promote amyloid fibril formation, revealing a gain-of-toxic-function mechanism distinct from loss of oligomerization.

    Evidence Cryo-EM fibril structure determination, in vitro amyloid formation assay

    PMID:38077690

    Open questions at the time
    • Whether amyloid fibrils form in vivo in patient neurons not shown
    • Relative contribution of amyloid gain-of-function vs. loss of ring function to disease unclear
  13. 2024 High

    Multiple studies established that TFG regulates COPII coat dynamics (controlling Sec23 recruitment rate), forms a hollow condensate that acts as a molecular sieve permitting COPII but excluding COPI at the ER–ERGIC interface, and that neuron-specific gene therapy rescues motor neuron disease in R106C rats, confirming cell-autonomous neuronal pathology.

    Evidence Live-cell TIRF microscopy of coat dynamics; in vitro condensate reconstitution with size-selective exclusion assays; cell type-specific AAV gene therapy in CRISPR rat model

    PMID:38985515 PMID:39527745 PMID:40253417

    Open questions at the time
    • How condensate formation is regulated in vivo (cell cycle, signaling) incompletely understood
    • Whether COPI exclusion is the primary mechanism preventing retrograde coat invasion not formally tested in cells

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include how TFG's secretory, autophagy, and innate immune functions are coordinated or prioritized in different cell types, the structural basis of disease-specific mutations in full-length octameric context, and whether therapeutic intervention can target condensate or oligomer integrity to treat neurodegeneration.
  • Integration of secretory, autophagy, and immune functions into a unified model lacking
  • Full-length octamer structure with disease mutations not yet resolved at atomic resolution in peer-reviewed literature
  • No therapeutic strategy targeting TFG condensate properties validated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4 GO:0060090 molecular adaptor activity 4
Localization
GO:0005783 endoplasmic reticulum 5 GO:0005829 cytosol 3
Pathway
R-HSA-5653656 Vesicle-mediated transport 6 R-HSA-9609507 Protein localization 4 R-HSA-9612973 Autophagy 2 R-HSA-168256 Immune System 1
Partners
ALG2LC3CNEMOSEC16SEC23ATANKTRAF3TRIM25
Complex memberships
COPII coat complex (via Sec23 binding)TFG octameric ring

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 TFG (TRK-fused gene) was identified as a fusion partner of ALK in anaplastic large cell lymphoma, generating TFG-ALK(S) and TFG-ALK(L) chimeric proteins that exhibit constitutive tyrosine kinase activity in vitro. RT-PCR cloning of fusion transcripts; in vitro tyrosine kinase assay Blood High 10556217
1998 The TFG coiled-coil domain mediates oligomerization of the TRK-T3 oncoprotein, which is required for constitutive, ligand-independent tyrosine kinase activation; the TFG N-terminal region is additionally required for full transforming activity, possibly through cellular localization or substrate interaction. Deletion mutagenesis of TFG domains; NIH3T3 transformation assay; biochemical analysis of oligomer formation Oncogene High 9488046
2002 TFG-ALK fusion proteins (TFG-ALK(S), TFG-ALK(L), and the new 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-gamma. Transfection/transformation assay in NIH-3T3 cells; co-immunoprecipitation The American journal of pathology High 11943732
2003 The PB1 domain and an SH2-binding motif within TFG sequences outside the coiled-coil domain are required for TRK-T3 oncogenic activation, contributing to protein processing, stable complex formation, and signaling. Deletion mutagenesis; site-specific mutagenesis; biochemical and biological assays in mammalian cells Oncogene High 12584559
2004 TFG interacts with and modulates the activity of the tyrosine phosphatase SHP-1; the SHP-1 SH2 domain associates with the TFG-derived portion of TRK-T3, while the SHP-1 catalytic domain associates with the NTRK1-derived portion, leading to down-regulation of TRK-T3 signaling. Co-immunoprecipitation; in vitro binding assays; phosphatase activity assays The Journal of biological chemistry High 15557341
2006 TFG interacts with NEMO and TANK, two proteins involved in the NF-κB pathway, identified by yeast two-hybrid screening and confirmed by in vitro and in vivo assays; TFG enhances NF-κB activity induced by TNF-α, TANK, TRAF2, and TRAF6. Yeast two-hybrid screening; co-immunoprecipitation; NF-κB reporter assay Journal of cellular physiology Medium 16547966
2011 TFG-1 (the C. elegans TFG ortholog) interacts directly with SEC-16, the scaffolding protein at ER exit sites, and forms hexamers that facilitate co-assembly of SEC-16 with COPII subunits; TFG-1 depletion causes marked decline in SEC-16 and COPII levels at ER exit sites and reduces protein export from the ER. Co-immunoprecipitation; hydrodynamic (sedimentation) studies; RNAi depletion with cargo secretion assay in C. elegans Nature cell biology High 21478858
2013 A homozygous TFG p.R106C mutation (in the coiled-coil domain) impairs TFG self-assembly into oligomeric complexes; in cells, TFG inhibition slows ER protein secretion and alters ER morphology, disrupting peripheral ER tubule organization and collapsing the ER network onto the microtubule cytoskeleton, leading to hereditary axon degeneration. Biochemical characterization of mutant protein self-assembly; cell line secretion assays; fluorescence microscopy of ER morphology Proceedings of the National Academy of Sciences of the United States of America High 23479643
2013 TFG protein binds TRIM25 upon virus infection and negatively regulates RIG-I-mediated type-I IFN signaling; knockdown of TFG upregulates RIG-I- and MAVS-induced IFN and NF-κB signaling pathways and inhibits VSV replication. shRNA knockdown; reporter assays for IFN and NF-κB; VSV replication assay; co-immunoprecipitation Biochemical and biophysical research communications Medium 23810392
2014 A TFG p.Gly269Val mutation increases propensity of TFG to form aggregates, sequestering both mutant and wild-type TFG and depleting functional TFG; inhibition of endogenous TFG compromises protein secretion, rescuable only by wild-type but not mutant TFG. Cell transfection studies; Gaussia luciferase secretion reporter assay; aggregation analysis Neurology High 25098539
2015 Mammalian TFG forms flexible, octameric cup-like structures that self-associate into larger polymers in vitro; at the ER/ERGIC interface, TFG locally concentrates COPII-coated transport carriers and links ER exit sites to ERGIC membranes; loss of TFG dramatically slows ER protein export and causes accumulation of COPII-coated carriers throughout the cytoplasm. 3D electron microscopy; in vitro polymerization assay; siRNA knockdown with secretion assay and electron tomography The EMBO journal High 25586378
2016 TFG organizes transitional ER (tER) and ER exit sites (ERESs) into larger structures; TFG is required for procollagen export from the ER but not for transport of small soluble cargoes; depletion of TFG disperses tER elements while preserving largely functional individual ERESs associated with ERGICs. siRNA depletion; live-cell imaging; procollagen secretion assay; fluorescence microscopy Cell reports High 27184855
2016 ALG-2 (Ca2+-binding protein) interacts with TFG through a canonical ALG-2-binding motif and promotes TFG polymerization in a Ca2+-dependent manner; ALG-2 concentrates TFG at ER exit sites and extends TFG half-life at ERES. Co-immunoprecipitation; in vitro cross-linking assay; live-cell imaging; ALG-2 overexpression The FEBS journal High 27813252
2016 A TFG p.Arg22Trp variant in the PB1 domain impairs TFG oligomerization in vitro, distinct from the coiled-coil domain R106C variant, suggesting that both PB1 and coiled-coil domains contribute to TFG complex formation and that phenotypic severity may correlate with variant location. In vitro oligomerization assay; biochemical characterization of mutant protein European journal of human genetics : EJHG Medium 27601211
2017 TFG C-terminus binds directly to Sec23 (inner COPII coat subunit) through a shared interface with the outer COPII coat and cargo receptor Tango1/cTAGE5; TFG binding outcompetes these interactions in a concentration-dependent manner, promoting outer coat dissociation; TFG tethers vesicles harboring the inner COPII coat, clustering them at the ER/ERGIC interface. In vitro binding/competition assay; cryo-EM; vesicle tethering assay; cell-based co-localization 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, reduced insulin secretion, smaller β-cell masses due to diminished proliferation, ER dilation (indicative of ER stress), and smaller insulin crystal diameters, demonstrating a role for TFG in maintaining pancreatic β-cell mass and secretory function. Conditional knockout mouse model; glucose tolerance test; immunohistochemistry; electron microscopy; microarray Scientific reports High 29026155
2018 The TFG p.R106C mutation (coiled-coil domain) alters compaction of TFG ring complexes; CRISPR-engineered human iPSC-derived neurons expressing mutant TFG at endogenous levels show specific defects in ER cargo secretion and axon fasciculation. CRISPR-Cas9 genome editing; biochemical analysis of ring complex compaction; iPSC differentiation to neurons; secretion assay; axon fasciculation assay Cell reports High 30157421
2020 TFG interacts with FANCD2-V2 (a specific isoform of FANCD2) through TFG amino acids 5-100 and FANCD2-V2 residues 1437-1442; this interaction maintains the steady-state level of FANCD2-V2 protein and enables timely nuclear focus formation upon DNA damage. Cells lacking TFG aa5-100 fail to show proper FANCD2-V2 focus kinetics and gain carcinogenicity. Co-immunoprecipitation; deletion mutagenesis; nuclear foci assay upon DNA damage; carcinogenicity assay Aging Medium 33099537
2020 TFG is required for autophagy flux in B cells; loss of TFG results in expanded ER, increased ER stress, higher LC3 accumulation, lower LC3-II turnover, and larger autophagosomes, indicating a block in autophagosome-lysosome fusion. CRISPR-Cas9 KO in CH12 B cells; tandem-fluorescent LC3 assay; ER stress gene expression; LC3 turnover assay Autophagy High 32910713
2020 A TFG-RET fusion (exons 1-4 of TFG fused to RET kinase domain) transforms immortalized human thyroid cells in a kinase-dependent manner; TFG-RET oligomerizes in a PB1 domain-dependent manner, and oligomerization is required for oncogenic transformation. RNA-seq fusion detection; transformation assay; kinase inhibition; PB1 domain mutagenesis; oligomerization analysis Nature communications High 32345963
2021 TFG interacts with TRAF3 (E3 ubiquitin ligase) and stabilizes ULK1 by competing with the ULK1-TRAF3 interaction, thereby preventing K48-linked ubiquitination and proteasomal degradation of ULK1; TFG-deficient macrophages show increased ROS, impaired ULK1 stability, and enhanced pyroptotic cell death upon LPS/nigericin stimulation. Co-immunoprecipitation; ubiquitination assay (K48-linkage); siRNA/shRNA knockdown; cell death assay Cell death & disease High 35091545
2021 TFG binds LC3C through a canonical LIR motif; this interaction favors LC3C-ULK1 binding, controls ULK1 puncta number and localization, and is required for proper formation of omegasomes and autophagosomes; patient fibroblasts with R106C-TFG show defects in autophagy and ULK1 puncta. Co-immunoprecipitation; LIR motif mutagenesis; autophagosome/omegasome quantification; patient-derived fibroblast assays The EMBO journal High 33932238
2021 TFG is required for virus-induced TBK1 activation and IRF3 phosphorylation/dimerization via the RIG-I pathway; TFG forms a complex with TRAF3 that enables efficient TRAF3 recruitment to MAVS following Sendai virus infection; TFG also enables the TRAF3-TFG complex to engage mTOR, allowing TBK1 to phosphorylate mTOR-S2159 and promote mTORC1 signaling during antiviral response. siRNA/shRNA knockdown; co-immunoprecipitation; IRF3 dimerization assay; Sendai virus infection; mTOR phosphorylation assay PLoS pathogens High 33411856
2022 In rat primary cortical neurons, the TFG p.R106C variant causes a kinetic delay in biosynthetic ER-to-Golgi secretory protein transport and impairs trafficking of Rab4A-positive recycling endosomes specifically in axons and dendrites, resulting in down-regulated inhibitory receptor signaling; mitochondria and lysosomes are unaffected. CRISPR-Cas9 rat model; primary neuron culture; live-cell cargo trafficking assay; Rab4A endosome quantification; inhibitory receptor signaling assay Proceedings of the National Academy of Sciences of the United States of America High 36161950
2022 Loss of motor neuron-specific TFG (vMNTFG KO mice) causes motor function deterioration, muscle atrophy, and neuromuscular junction (NMJ) denervation in slow-twitch muscles; muscle-specific TFG KO (MUSTFG KO) does not impair movement but shows elevated denervation marker and impaired Agrin-induced AChR clustering. Cell type-specific conditional KO mouse; behavioral testing; NMJ immunostaining; electrophysiology Scientific reports High 35121777
2023 The low-complexity domain of TFG containing disease-related mutations G269V or P285L forms amyloid fibrils; cryo-EM structures confirm an amyloid nature with double-protofilament cores, and mutant sequences show increased amyloid propensity compared to wild-type. Cryo-EM structure determination; in vitro fibril formation assay; bioinformatic amyloid propensity prediction PNAS nexus High 38077690
2024 TFG regulates the rate of inner COPII coat (Sec23) recruitment to ER budding sites; in TFG-deficient cells, Sec23 accumulates more rapidly at ER subdomains, potentially altering GTP hydrolysis timing on Sar1 and delaying anterograde trafficking of secretory cargoes. Live-cell TIRF microscopy of COPII dynamics; siRNA knockdown; secretion assay for multiple cargoes Molecular biology of the cell High 38985515
2024 TFG self-organizes under physiological conditions to form a hollow, anisotropic condensate that matches the dimensions of the ER-Golgi interface; regularly spaced hydrophobic residues control condensation; the condensate acts as a molecular sieve allowing COPII (anterograde) access to the interior while restricting COPI (retrograde) coats, spatially compartmentalizing the early secretory pathway. Biophysical condensate characterization; size-exclusion assay with fluorescent COPII/COPI probes; in vitro reconstitution; cell cycle regulation analysis Nature communications High 40253417
2024 Reintroduction of wild-type TFG specifically into synapsin 1-positive neurons (but not GFAP-positive glia) via gene therapy provides robust protection against motor neuron disease in TFG p.R106C rats, demonstrating that TFG pathology in HSP is cell-autonomous to neurons. Cell type-specific AAV gene therapy in CRISPR rat model; quantitative gait analysis; astrocyte reactivity assessment Proceedings of the National Academy of Sciences of the United States of America High 39527745
2024 X-ray crystallography and cryo-EM reveal that TFG forms octameric ring complexes through a network of electrostatic and hydrophobic interactions at the protomer interface; HSP-associated PB1 domain mutations disrupt this interface, destabilizing octamers and ultimately causing axonopathy. X-ray crystallography; cryo-EM structure determination; in vivo genetic analysis in disease model bioRxivpreprint High 39574627
2025 FBXO45 E3 ligase promotes TFG Lys103 ubiquitination, increasing TFG stability; stabilized TFG facilitates binding of transcription factor ATF2, which upregulates NF-κB p65, promoting HCC cell migration, invasion, and lung metastasis. Co-immunoprecipitation; ubiquitination site mapping (Lys103); overexpression/knockdown; orthotopic xenograft model; ATF2-NF-κB reporter JHEP reports : innovation in hepatology Medium 41030651
2000 Xenopus TFG (xTFG) interacts with SH3 domains of Src, PLCγ, and the p85 subunit of PI3-kinase through a conserved SH3-binding motif, identifying TFG as an SH3 domain-binding protein. SH3 domain pulldown; mRNA microinjection overexpression in Xenopus embryos 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 156 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 142 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 103 25586378
1991 The synthesis of a family of structurally related proteoglycans in fibroblasts is differently regulated by TFG-beta. Matrix (Stuttgart, Germany) 86 1870448
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 85 23479643
2004 TFG is a novel fusion partner of NOR1 in extraskeletal myxoid chondrosarcoma. Genes, chromosomes & cancer 83 15188455
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
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 74 28851831
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
2017 TFG-MET fusion in an infantile spindle cell sarcoma with neural features. Genes, chromosomes & cancer 58 28510278
2016 TFG Promotes Organization of Transitional ER and Efficient Collagen Secretion. Cell reports 57 27184855
2017 Resveratrol suppresses melanoma by inhibiting NF-κB/miR-221 and inducing TFG expression. Archives of dermatological research 52 28936555
2014 A novel TFG mutation causes Charcot-Marie-Tooth disease type 2 and impairs TFG function. Neurology 44 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
2020 Proteogenomics analysis unveils a TFG-RET gene fusion and druggable targets in papillary thyroid carcinomas. Nature communications 30 32345963
2016 TFG-Related Neurologic Disorders: New Insights Into Relationships Between Endoplasmic Reticulum and Neurodegeneration. Journal of neuropathology and experimental neurology 30 26945032
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 28 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
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
2012 Identification of TFG (TRK-fused gene) as a putative metastatic melanoma tumor suppressor gene. Genes, chromosomes & cancer 26 22250051
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 18 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
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
2021 Spitz nevus with a novel TFG-NTRK2 fusion: The first case report of NTRK2-rearranged Spitz/Reed nevus. Journal of cutaneous pathology 16 33979462
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
2024 A Hollow TFG Condensate Spatially Compartmentalizes the Early Secretory Pathway. bioRxiv : the preprint server for biology 9 38585729
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
2022 Involvement of neuronal and muscular Trk-fused gene (TFG) defects in the development of neurodegenerative diseases. Scientific reports 8 35121777
2022 TFG::MET-rearranged soft tissue tumor: A rare infantile neoplasm with a distinct low-grade triphasic morphology. Genes, chromosomes & cancer 8 36464850
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
2025 A hollow TFG condensate spatially compartmentalizes the early secretory pathway. Nature communications 7 40253417
2023 Individualized targeted treatment in a case of a rare TFG::ROS1 fusion positive inflammatory myofibroblastic tumor (IMT). Cancer reports (Hoboken, N.J.) 7 37950626
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
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
2024 TFG regulates inner COPII coat recruitment to facilitate anterograde secretory protein transport. Molecular biology of the cell 3 38985515
2020 A novel TFG c.793C>G mutation in a Chinese pedigree with Charcot-Marie-Tooth disease 2. Brain and behavior 3 32666699
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 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
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 Screening and identification of Theileria annulata proteins interacting with bovine TFG proteins. International journal of biological macromolecules 1 40578648
2025 ALK-positive adult histiocytosis with a TFG-ALKfusion gene. The oncologist 1 40700600
2024 Identification of TFG- and Autophagy-Regulated Proteins and Glycerophospholipids in B Cells. Journal of proteome research 1 38649144
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 TFG-β Nuclear Staining as a Potential Relapse Risk Factor in Early-Stage Non-Small-Cell Lung Cancer. International journal of molecular sciences 1 36430262
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