Affinage

TUFM

Elongation factor Tu, mitochondrial · UniProt P49411

Round 2 corrected
Length
455 aa
Mass
49.9 kDa
Annotated
2026-04-28
130 papers in source corpus 22 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TUFM is the mitochondrial elongation factor Tu, a GTPase that delivers aminoacyl-tRNAs to the mitochondrial ribosome during translation elongation and is essential for oxidative phosphorylation complex assembly (PMID:10715211, PMID:17160893). Beyond its canonical translation role, TUFM functions as a dual-localized (mitochondrial and cytosolic) regulator of autophagy and mitophagy by interacting with the ATG5–ATG12–ATG16L1 complex, Beclin-1, and NLRX1, and it suppresses RIG-I-mediated type I interferon signaling during viral infection (PMID:22749352, PMID:33113344). TUFM's autophagy-promoting activity is tuned by multiple post-translational modifications: PINK1 phosphorylation at Ser222 converts TUFM from a mitophagy activator to a cytosolic suppressor, MRG15-mediated deacetylation at K82/K91 targets it for ClpXP degradation, RNF185-catalyzed K27-linked ubiquitination enables SQSTM1–LC3-dependent mitophagy, and lactylation at K286 impairs TOMM40-mediated mitochondrial import (PMID:33113344, PMID:35985547, PMID:38084826, PMID:39496783). Loss-of-function mutations in TUFM cause combined oxidative phosphorylation deficiency 4 (COXPD4), presenting as severe lactic acidosis with leukodystrophy or dilated cardiomyopathy (PMID:17160893, PMID:30903008).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1993 High

    Structural determination of EF-Tu in both GTP and GDP states revealed how a large interdomain rotation (~90°) upon GTP binding exposes the aminoacyl-tRNA binding cleft, establishing the conformational switch mechanism underlying translational GTPase function.

    Evidence X-ray crystallography of Thermus aquaticus EF-Tu in GTP vs. GDP forms

    PMID:8069622

    Open questions at the time
    • Mitochondrial EF-Tu structure not yet solved
    • Ribosome-bound conformation unknown
  2. 1995 High

    The crystal structure of the EF-Tu·GTP·aminoacyl-tRNA ternary complex resolved how EF-Tu simultaneously contacts the aminoacylated CCA end and the T-stem of tRNA across all three domains, and revealed molecular mimicry with EF-G, explaining their shared ribosomal binding site.

    Evidence 2.7 Å X-ray crystallography of Thermus aquaticus EF-Tu·GDPNP·aa-tRNA complex

    PMID:7491491

    Open questions at the time
    • Ribosome context not included
    • Mitochondrial-specific features not addressed
  3. 1997 High

    Cloning and characterization of the human TUFM gene defined its genomic organization (9 introns, chromosome 16p11.2) and encoded a 455-residue protein with an N-terminal mitochondrial targeting sequence, establishing the molecular identity of the human mitochondrial translation factor.

    Evidence cDNA cloning, Northern blot, FISH chromosomal mapping

    PMID:9332382

    Open questions at the time
    • No functional assays performed
    • Protein localization beyond mitochondria not examined
  4. 2000 High

    The crystal structure of bovine mitochondrial EF-Tu·GDP revealed conserved three-domain architecture but altered domain orientations and reduced nucleotide affinity compared to bacterial orthologs, explaining the requirement for the dedicated mitochondrial guanine nucleotide exchange factor EF-Ts.

    Evidence 1.94 Å X-ray crystallography of bovine mitochondrial EF-Tu·GDP

    PMID:10715211

    Open questions at the time
    • GTP-bound mitochondrial structure not solved
    • C-terminal zinc-finger-like extension function not tested
  5. 2003 Medium

    Overexpression of EF-Tu in yeast corrected respiratory defects, mitochondrial morphology, and mtDNA instability caused by MELAS-equivalent tRNA mutations, providing the first functional evidence that EF-Tu abundance can compensate for defective mitochondrial tRNAs.

    Evidence Multicopy suppression in yeast mitochondrial transformation with respiratory growth assays

    PMID:12524521

    Open questions at the time
    • Yeast system; relevance to mammalian TUFM assumed but not directly shown
    • Mechanism of suppression (tRNA stabilization vs. enhanced decoding) not distinguished
  6. 2006 High

    Identification of pathogenic TUFM mutations in patients with fatal infantile leukodystrophy and lactic acidosis, validated by functional complementation in yeast and mammalian cells, established TUFM as essential for human mitochondrial translation and linked it to Mendelian disease (COXPD4).

    Evidence Patient genetic analysis, structural modeling, functional complementation in yeast and human cells

    PMID:17160893

    Open questions at the time
    • Precise impact on ternary complex formation not biochemically resolved
    • Phenotypic spectrum incompletely defined
  7. 2008 Medium

    TUFM overexpression partially rescued mitochondrial translation and respiratory chain assembly defects in human MELAS patient myoblasts, demonstrating therapeutic potential of TUFM dosage compensation for mitochondrial tRNA disorders.

    Evidence TUFM overexpression in patient-derived A3243G myoblasts with BN-PAGE and pulse-chase labeling

    PMID:18753147

    Open questions at the time
    • Partial rescue only; mechanism of compensation not fully defined
    • Long-term or in vivo efficacy not tested
  8. 2009 High

    The ribosome-bound EF-Tu·aa-tRNA structure delineated a conformational communication pathway from the 30S decoding center to the GTPase center, revealing how codon–anticodon recognition at the A site triggers GTP hydrolysis in EF-Tu to ensure translational accuracy.

    Evidence 3.6 Å X-ray crystallography of the full ribosome–EF-Tu–aa-tRNA complex

    PMID:19833920

    Open questions at the time
    • Bacterial ribosome used; mitochondrial ribosome context not resolved
    • Kinetic proofreading steps not directly observed
  9. 2012 High

    Discovery that TUFM forms an endogenous complex with NLRX1 and the ATG5–ATG12–ATG16L1 autophagy machinery, and that TUFM suppresses RIG-I-mediated interferon responses while promoting autophagy during viral infection, revealed a major non-translational function for a mitochondrial translation factor.

    Evidence Quantitative mass spectrometry, reciprocal co-IP, knockdown/overexpression with IFN-β and autophagy readouts

    PMID:22749352

    Open questions at the time
    • How TUFM accesses the cytosolic autophagy machinery from mitochondria not explained
    • Whether autophagy and translation functions are independent not resolved
  10. 2016 Medium

    Two studies expanded TUFM's non-translational roles: TUFM loss induced EMT via the AMPK–GSK3β–β-catenin axis in lung cancer cells, while the NLRX1–TUFM complex was shown to recruit Beclin-1 to mitochondria to promote autophagy in response to EGFR inhibition, positioning TUFM as a metabolic and autophagy hub in cancer.

    Evidence siRNA knockdown with EMT/metabolic assays (A549/MCF7); co-IP with Beclin-1 recruitment and autophagy flux assays in HNSCC

    PMID:26781467 PMID:26876213

    Open questions at the time
    • Direct vs. indirect effects on EMT not distinguished
    • Beclin-1 ubiquitination mechanism at mitochondria not fully defined
  11. 2019 Medium

    A novel TUFM missense variant (p.His115Pro) causing COXPD4 with dilated cardiomyopathy expanded the disease phenotype beyond leukodystrophy, indicating tissue-specific vulnerability to TUFM deficiency.

    Evidence Whole exome sequencing and OXPHOS biochemical analysis in patient

    PMID:30903008

    Open questions at the time
    • Limited mechanistic follow-up on how this variant disrupts EF-Tu function
    • No functional complementation performed
  12. 2020 High

    PINK1 was shown to phosphorylate TUFM at Ser222, creating a phosphoswitch that converts cytosolic TUFM from a mitophagy activator (via ATG5–ATG12 promotion) to a mitophagy suppressor, establishing a self-antagonizing feedback loop that ensures robust mitophagy control.

    Evidence Co-IP, genetic epistasis, subcellular fractionation, phosphorylation assays, Atg5–Atg12 conjugation assays in PINK1 KO/KI cells

    PMID:33113344

    Open questions at the time
    • Structural basis of how pS222 inhibits ATG12–ATG5 conjugation not resolved
    • Whether this pathway operates in neurons in vivo not shown
  13. 2021 Medium

    Multiple studies defined additional TUFM functions: OMM-localized TUFM inhibits caspase-8-mediated apoptosis through its autophagic activity (requiring the GxxxG dimerization motif), TUFM activates mtROS–TFEB–autophagy signaling in obesity models, and TUFM regulates BACE1 mRNA stability through ROS, linking it to neurodegeneration-relevant pathways.

    Evidence GxxxG mutagenesis and caspase-8 assays; DARTS/LC-MS target ID with TUFM-KO and TFEB translocation; siRNA/overexpression with BACE1 mRNA stability assays

    PMID:33398033 PMID:33774866 PMID:34511600

    Open questions at the time
    • GxxxG dimerization–autophagy link not structurally characterized
    • BACE1 regulation appears indirect via ROS; direct RNA-binding of TUFM not demonstrated
    • In vivo relevance of TUFM–caspase-8 axis not validated
  14. 2022 High

    Two post-translational regulatory mechanisms were identified: MRG15 deacetylates TUFM at K82/K91, accelerating ClpXP-dependent degradation and thereby reducing mitophagy (promoting NASH via NLRP3 inflammasome activation), while FUNDC1 interacts with TUFM to stabilize mtDNA and prevent cytoplasmic mtDNA release that triggers PANoptosis.

    Evidence IP-MS, acetylation site mutagenesis, ClpXP protease assays, mouse NASH models; FUNDC1 co-IP domain mapping, mtDNA release assays in cardiomyocytes

    PMID:35985547 PMID:36470869

    Open questions at the time
    • Whether acetylation and phosphorylation (S222) modifications cross-regulate each other is unknown
    • FUNDC1–TUFM interaction interface not structurally resolved
  15. 2024 High

    Two further regulatory mechanisms were characterized: RNF185 catalyzes K27-linked ubiquitination of TUFM to enable SQSTM1–LC3-mediated mitophagy during Senecavirus A infection, and lactylation of TUFM at K286 after traumatic brain injury disrupts TOMM40 interaction and mitochondrial import, suppressing mitophagy and promoting neuronal apoptosis.

    Evidence Co-IP with ubiquitin linkage analysis and RNF185 domain mapping; lactylation proteomics with K286R knockin mice and TUFM–TOMM40 co-IP in TBI model

    PMID:38084826 PMID:39496783

    Open questions at the time
    • Whether K27-ubiquitination occurs under physiological (non-viral) conditions unknown
    • Interplay between lactylation, acetylation, and phosphorylation on TUFM not examined
    • Structural basis for how K286 lactylation disrupts TOMM40 binding not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • A unified structural and kinetic model of how TUFM's multiple post-translational modifications (phosphorylation, acetylation, ubiquitination, lactylation) are integrated to partition TUFM between its mitochondrial translation function and its extra-translational autophagy/mitophagy roles remains to be established.
  • No cryo-EM structure of TUFM on the human mitochondrial ribosome
  • PTM crosstalk and hierarchical regulation not studied
  • Whether cytosolic TUFM pool is translationally active or exclusively autophagy-related is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003924 GTPase activity 4 GO:0045182 translation regulator activity 4 GO:0003723 RNA binding 3 GO:0060090 molecular adaptor activity 3
Localization
GO:0005739 mitochondrion 6 GO:0005840 ribosome 2 GO:0005829 cytosol 1
Pathway
R-HSA-9612973 Autophagy 9 R-HSA-392499 Metabolism of proteins 6 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3 R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-5357801 Programmed Cell Death 3
Partners
ATG12ATG16L1ATG5BECN1FUNDC1NLRX1PINK1RNF185
Complex memberships
Mitochondrial EF-Tu·EF-Ts complexMitochondrial ribosome (mitoribsome)NLRX1–TUFM complex

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 Crystal structure of the ternary complex of aminoacyl-tRNA, EF-Tu (Thermus aquaticus), and GTP analog (GDPNP) at 2.7 Å resolution revealed that EF-Tu-GTP binds one side of the acceptor helix of tRNA involving all three domains, with binding sites for the aminoacylated CCA end and phosphorylated 5' end at domain interfaces and the T-stem interacting with domain 3; the overall shape mimics EF-G-GDP, suggesting molecular mimicry in the translational apparatus. X-ray crystallography Science High 7491491
1993 Crystal structure of Thermus aquaticus EF-Tu in GTP conformation (2.5 Å) compared to E. coli EF-Tu-GDP revealed that GTP binding causes dramatic conformational changes: internal rearrangements in the GTP-binding domain similar to ras-p21, plus a ~90.8° rotation of domain 1 relative to domains 2 and 3, exposing the tRNA binding site located at the domain interface cleft. X-ray crystallography, structural comparison Structure High 8069622
2000 Crystal structure of bovine mitochondrial EF-Tu (the direct ortholog of human TUFM) in complex with GDP at 1.94 Å resolution showed three-domain architecture similar to bacterial EF-Tu-GDP but with altered orientation of domain 1 relative to domains 2 and 3; mitochondrial EF-Tu binds nucleotides less tightly than prokaryotic EF-Tu, possibly due to increased mobility near the GDP-binding site; the C-terminal extension has structural similarities to DNA-recognizing zinc fingers, suggesting involvement in RNA recognition. X-ray crystallography Journal of Molecular Biology High 10715211
2006 Mutations in the human mitochondrial elongation factor Tu (EFTu/TUFM) gene cause defective mitochondrial DNA translation leading to severe infantile macrocystic leukodystrophy with micropolygyria and fatal lactic acidosis; functional complementation in yeast and mammalian cell systems confirmed the pathogenic role of TUFM mutant alleles, establishing TUFM as essential for mitochondrial translation in humans. Patient genetic analysis, structural modeling, functional complementation in yeast and mammalian cells American Journal of Human Genetics High 17160893
2008 Overexpression of EFTu (TUFM) but not EFTs or EFG1 partially suppressed the mitochondrial translation defect and respiratory chain assembly failure caused by the A3243G MELAS tRNA(Leu(UUR)) mutation, demonstrating that increased TUFM levels can compensate for defective mitochondrial tRNA aminoacylation/decoding. Overexpression in patient-derived myoblasts, Blue-Native gel electrophoresis, pulse-chase labeling Human Molecular Genetics Medium 18753147
2012 TUFM forms an endogenous protein complex with the mitochondrial NLR protein NLRX1, identified by high-throughput quantitative mass spectrometry and confirmed by co-immunoprecipitation; TUFM interacts with the autophagy proteins Atg5-Atg12 and Atg16L1; TUFM inhibits RIG-I-like receptor-induced type I interferon production and promotes autophagy during viral infection, paralleling NLRX1 function. Quantitative mass spectrometry, endogenous co-immunoprecipitation, knockdown/overexpression with IFN and autophagy readouts Immunity High 22749352
2013 TUFM reduces DDX58 (RIG-I)-activated type I interferon cytokine production and augments virus-induced autophagy; TUFM interacts with the ATG12-ATG5-ATG16L1 complex to form a molecular complex that modulates autophagy, acting downstream of NLRX1. Co-immunoprecipitation, siRNA knockdown, autophagy and cytokine assays Autophagy Medium 23321557
1997 The human mitochondrial EF-Tu (TUFM) cDNA encodes a 455 amino acid protein (~49.8 kDa) with an N-terminal mitochondrial leader sequence of ~50 residues; the gene contains 9 introns, maps to chromosome 16p11.2, and an intronless pseudogene maps to chromosome 17q11.2; single ~1.7 kb mRNA transcript detected in human liver. cDNA cloning, sequencing, Northern blot, chromosomal mapping (FISH/somatic cell hybrid) Gene High 9332382
2016 TUFM downregulation in lung cancer cells induces epithelial-mesenchymal transition (EMT) via activation of AMPK, phosphorylation of GSK3β, and increased nuclear accumulation of β-catenin; TUFM knockdown also reduced mitochondrial respiratory chain activity, increased glycolytic function, and elevated reactive oxygen species (ROS) production. siRNA knockdown, western blot, migration/invasion assays, metabolic assays in A549 and MCF7 cells Cellular and Molecular Life Sciences Medium 26781467
2016 In head and neck squamous cell carcinoma (HNSCC), TUFM serves as an anchorage site recruiting Beclin-1 to mitochondria, promoting Beclin-1 polyubiquitination and interfering with its interaction with Rubicon; the NLRX1-TUFM complex promotes autophagic flux in response to EGFR inhibition by cetuximab; defects in either NLRX1 or TUFM compromise autophagy upon EGFR blockade. Co-immunoprecipitation, siRNA knockdown, autophagy flux assays, tumor specimens from clinical trial Oncogene Medium 26876213
2017 TUFM acts as a host restriction factor for avian-signature influenza A viruses (PB2627E) in human cells; TUFM shows higher binding affinity for PB2627E than PB2627K; TUFM-deficient cells show increased replication of PB2627E virus; TUFM-dependent autophagy is reduced in TUFM-deficient cells infected with PB2627E virus but not PB2627K virus, suggesting that autophagy mediates the restriction. Immunoprecipitation, differential proteomics, overexpression/knockdown, viral replication assays, autophagy assays mBio Medium 28611246
2020 TUFM has dual mitochondrial and cytosolic localization; TUFM interacts biochemically and genetically with PINK1; PINK1 phosphorylates TUFM at Ser222, creating a phosphoswitch that converts TUFM from an activator to a suppressor of mitophagy; p-S222-TUFM is predominantly cytosolic where it inhibits mitophagy by impeding Atg5-Atg12 conjugate formation; this PINK1/TUFm self-antagonizing feedback is critical for robustness of mitophagy regulation. Co-immunoprecipitation, genetic epistasis, subcellular fractionation, phosphorylation assays, Atg5-Atg12 formation assays, PINK1 knockout/knockin Molecular Cell High 33113344
2021 TUFM activates autophagy through kaempferide (Kaem)-induced mitochondrial ROS (mtROS), which sequentially promotes lysosomal Ca²⁺ efflux, TFEB translocation, and autophagy induction; TUFM directly binds kaempferide (identified by drug affinity responsive target stability + LC-MS/MS); TUFM absence reverses Kaem-induced autophagy and lipid degradation in vitro and in a diet-induced obesity mouse model. Drug affinity responsive target stability (DARTS), LC-MS/MS target identification, TUFM knockout, mtROS measurement, lysosomal Ca²⁺ assay, TFEB translocation assay, mouse model Communications Biology Medium 33398033
2021 TUFM localizes in part on the outer mitochondrial membrane (OMM) where it inhibits caspase-8-mediated apoptosis through its autophagic function; the GxxxG motif within TUFM's N-terminal mitochondrial targeting sequence is required for self-dimerization and mitophagy; autophagy-competent TUFM is subject to ubiquitin-proteasome-mediated degradation but stabilized upon mitophagy/autophagy activation; TUFM depletion potentiates caspase-8 activation induced by TRAIL. Inducible TUFM depletion, GxxxG motif mutagenesis, subcellular fractionation, caspase-8 activation assays, dimerization assays Cell Death and Differentiation Medium 34511600
2022 FUNDC1 interacts with TUFM via its 96-133 amino acid domain; this FUNDC1-TUFM interaction stabilizes mitochondrial DNA (mtDNA) and prevents cytoplasmic release of mtDNA; FUNDC1 deficiency increases DOX-induced PANoptosis (combined apoptosis/pyroptosis/necroptosis) via PANoptosome activation; TUFM intervention reversed FUNDC1-mediated protection against mtDNA cytosolic release. Co-immunoprecipitation, domain mapping, FUNDC1 knockout, mtDNA cytosolic release assay, PANoptosis markers in cardiomyocytes and mice Cell Death & Disease Medium 36470869
2022 MRG15 interacts with TUFM at the outer mitochondrial membrane and deacetylates TUFM at K82 and K91; deacetylated TUFM undergoes accelerated proteolytic degradation by the mitochondrial ClpXP protease; reduced TUFM levels impair mitophagy, increase oxidative stress, and activate the NLRP3 inflammasome pathway, promoting NASH progression. Immunoprecipitation-mass spectrometry, co-IP, CRISPR depletion, acetylation site mutagenesis (K82/K91), ClpXP protease assays, mitophagy and inflammasome assays, mouse NASH models Journal of Hepatology High 35985547
2024 TUFM is lactylated at K286 following traumatic brain injury (TBI); K286 lactylation inhibits the interaction between TUFM and TOMM40 on mitochondria, reducing mitochondrial import/distribution of TUFM; this suppresses TUFM-mediated mitophagy and increases mitochondria-induced neuronal apoptosis; knockin of lactylation-deficient TufmK286R in mice rescues mitochondrial Tufm distribution and mitophagy and improves functional outcome after TBI. Lactylation proteomics, site-specific mutagenesis (K286R knockin mice), co-immunoprecipitation (TUFM-TOMM40), mitophagy assays, neuronal apoptosis assays, controlled cortical impact mouse model Cell Death and Differentiation High 39496783
2021 TUFM knockdown or overexpression in HEK-APP cells modulates BACE1 protein and mRNA levels by affecting BACE1 mRNA stability (not transcription); TUFM-mediated regulation of BACE1 requires the 5'UTR and is attenuated by ROS scavenger TEMPO, indicating that TUFM regulates BACE1 translation/mRNA stability through mitochondrial ROS; TUFM also modulates apoptosis and Tau phosphorylation in a ROS-dependent manner. siRNA knockdown, overexpression, mRNA stability assay (ActinomycinD), BACE1-5'UTR deletion constructs, ROS measurement and scavenging, Tau phosphorylation assays FASEB Journal Medium 33774866
2024 Senecavirus A (SVA) 2C protein directly interacts with TUFM (at Glu196 and Glu211 of TUFM); E3 ubiquitin ligase RNF185 catalyzes K27-linked polyubiquitination of TUFM through interaction between RNF185's transmembrane domain 1 and TUFM; K27-ubiquitinated TUFM is recognized by SQSTM1/p62, which then interacts with LC3 to link 2C-anchored mitochondria to the phagophore, inducing mitophagy that promotes SVA replication; TUFM also directly interacts with BECN1 and indirectly with the ATG12-ATG5 conjugate. Co-immunoprecipitation, site-directed mutagenesis (TUFM E196/E211), ubiquitination assays, domain mapping (RNF185 TM1), autophagy flux assays, viral replication assays Autophagy Medium 38084826
2009 Crystal structure of the ribosome bound to EF-Tu and aminoacyl-tRNA at 3.6 Å resolution revealed details of tRNA distortion allowing simultaneous interaction with the 30S decoding center and EF-Tu at the factor binding site; a series of conformational changes in EF-Tu and aminoacyl-tRNA delineates a communication pathway between the decoding center and the GTPase center of EF-Tu. X-ray crystallography of ribosome-EF-Tu-aa-tRNA ternary complex Science High 19833920
2019 A novel homozygous TUFM missense variant (c.344A>C; p.His115Pro) causes combined oxidative phosphorylation deficiency 4 (COXPD4) with lactic acidosis and dilated cardiomyopathy without progressive encephalopathy, expanding the phenotypic spectrum of TUFM-related mitochondrial disease. Whole exome sequencing, patient clinical characterization, biochemical analysis of OXPHOS function Journal of Human Genetics Medium 30903008
2003 In yeast, overexpression of the mitochondrial elongation factor EF-Tu (TufM, the yeast ortholog of human TUFM) corrected all defective phenotypes (respiratory growth, mitochondrial morphology, mtDNA deletion accumulation) caused by mitochondrial tRNA(Leu)(UUR) mutations equivalent to human MELAS mutations, demonstrating that EF-Tu can suppress mitochondrial tRNA processing/translation defects. Yeast mitochondrial transformation, multicopy suppression, respiratory growth assays, mitochondrial morphology analysis EMBO Reports Medium 12524521

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nature genetics 2251 20935630
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
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
2006 Perception of the bacterial PAMP EF-Tu by the receptor EFR restricts Agrobacterium-mediated transformation. Cell 1344 16713565
2016 ATPase-Modulated Stress Granules Contain a Diverse Proteome and Substructure. Cell 1233 26777405
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
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2005 Nucleolar proteome dynamics. Nature 934 15635413
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2002 Directed proteomic analysis of the human nucleolus. Current biology : CB 780 11790298
1995 Crystal structure of the ternary complex of Phe-tRNAPhe, EF-Tu, and a GTP analog. Science (New York, N.Y.) 779 7491491
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
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
2003 A proteomics strategy to elucidate functional protein-protein interactions applied to EGF signaling. Nature biotechnology 558 12577067
1985 Structure of the GDP domain of EF-Tu and location of the amino acids homologous to ras oncogene proteins. Science (New York, N.Y.) 554 3898365
2017 Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science (New York, N.Y.) 533 28302793
2003 Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nature biotechnology 485 12665801
2015 Widespread macromolecular interaction perturbations in human genetic disorders. Cell 454 25910212
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2013 The intracellular interactome of tetraspanin-enriched microdomains reveals their function as sorting machineries toward exosomes. The Journal of biological chemistry 413 23463506
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2009 The crystal structure of the ribosome bound to EF-Tu and aminoacyl-tRNA. Science (New York, N.Y.) 402 19833920
1993 The crystal structure of elongation factor EF-Tu from Thermus aquaticus in the GTP conformation. Structure (London, England : 1993) 360 8069622
2007 The layered structure of human mitochondrial DNA nucleoids. The Journal of biological chemistry 340 18063578
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2020 Phosphorylated tau interactome in the human Alzheimer's disease brain. Brain : a journal of neurology 290 32812023
2009 Importin 8 is a gene silencing factor that targets argonaute proteins to distinct mRNAs. Cell 281 19167051
2012 A high-throughput approach for measuring temporal changes in the interactome. Nature methods 273 22863883
2012 The mitochondrial proteins NLRX1 and TUFM form a complex that regulates type I interferon and autophagy. Immunity 257 22749352
1992 Refined structure of elongation factor EF-Tu from Escherichia coli. Journal of molecular biology 257 1542116
2021 Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context. Cell metabolism 239 34800366
2009 An integrated workflow for charting the human interaction proteome: insights into the PP2A system. Molecular systems biology 223 19156129
1998 Chaperone properties of bacterial elongation factor EF-Tu. The Journal of biological chemistry 207 9565560
2021 Activation of mitochondrial TUFM ameliorates metabolic dysregulation through coordinating autophagy induction. Communications biology 189 33398033
1996 An alpha to beta conformational switch in EF-Tu. Structure (London, England : 1993) 176 8939740
2006 Infantile encephalopathy and defective mitochondrial DNA translation in patients with mutations of mitochondrial elongation factors EFG1 and EFTu. American journal of human genetics 162 17160893
2019 The Diverse Functional Roles of Elongation Factor Tu (EF-Tu) in Microbial Pathogenesis. Frontiers in microbiology 152 31708880
2013 The Fic protein Doc uses an inverted substrate to phosphorylate and inactivate EF-Tu. Nature chemical biology 147 24141193
1999 Crystal structure of intact elongation factor EF-Tu from Escherichia coli in GDP conformation at 2.05 A resolution. Journal of molecular biology 127 9918724
2022 FUNDC1 protects against doxorubicin-induced cardiomyocyte PANoptosis through stabilizing mtDNA via interaction with TUFM. Cell death & disease 119 36470869
1997 Crystal structure of the EF-Tu.EF-Ts complex from Thermus thermophilus. Nature structural biology 118 9253415
2008 The A3243G tRNALeu(UUR) MELAS mutation causes amino acid misincorporation and a combined respiratory chain assembly defect partially suppressed by overexpression of EFTu and EFG2. Human molecular genetics 117 18753147
2015 Arabidopsis EF-Tu receptor enhances bacterial disease resistance in transgenic wheat. The New phytologist 114 25760815
2006 The ribosomal stalk binds to translation factors IF2, EF-Tu, EF-G and RF3 via a conserved region of the L12 C-terminal domain. Journal of molecular biology 105 17070545
2001 Conformational change of elongation factor Tu (EF-Tu) induced by antibiotic binding. Crystal structure of the complex between EF-Tu.GDP and aurodox. The Journal of biological chemistry 104 11278992
2002 The tRNA specificity of Thermus thermophilus EF-Tu. Proceedings of the National Academy of Sciences of the United States of America 96 11891293
1984 Homologies in the primary structure of GTP-binding proteins: the nucleotide-binding site of EF-Tu and p21. The EMBO journal 96 6609071
2010 Bacterial translation elongation factor EF-Tu interacts and colocalizes with actin-like MreB protein. Proceedings of the National Academy of Sciences of the United States of America 91 20133608
2000 Structure of an EF-Tu complex with a thiazolyl peptide antibiotic determined at 2.35 A resolution: atomic basis for GE2270A inhibition of EF-Tu. Biochemistry 89 10625477
2009 Elongation in translation as a dynamic interaction among the ribosome, tRNA, and elongation factors EF-G and EF-Tu. Quarterly reviews of biophysics 85 20025795
2005 Translation elongation factor EF-Tu is a target for Stp, a serine-threonine phosphatase involved in virulence of Listeria monocytogenes. Molecular microbiology 85 15813732
2013 The NLR protein, NLRX1, and its partner, TUFM, reduce type I interferon, and enhance autophagy. Autophagy 73 23321557
1985 Mutants of the elongation factor EF-Tu, a new class of nonsense suppressors. The EMBO journal 73 3926487
1997 Renaturation of rhodanese by translational elongation factor (EF) Tu. Protein refolding by EF-Tu flexing. The Journal of biological chemistry 63 9405422
2014 Two distinct EF-Tu epitopes induce immune responses in rice and Arabidopsis. Molecular plant-microbe interactions : MPMI 62 24200076
1988 Structure-function relationships in the GTP binding domain of EF-Tu: mutation of Val20, the residue homologous to position 12 in p21. The EMBO journal 60 3181143
1994 The structural and functional basis for the kirromycin resistance of mutant EF-Tu species in Escherichia coli. The EMBO journal 59 7525272
2003 The yeast counterparts of human 'MELAS' mutations cause mitochondrial dysfunction that can be rescued by overexpression of the mitochondrial translation factor EF-Tu. EMBO reports 58 12524521
2016 EGFR-targeted mAb therapy modulates autophagy in head and neck squamous cell carcinoma through NLRX1-TUFM protein complex. Oncogene 56 26876213
2012 Association of Acinetobacter baumannii EF-Tu with cell surface, outer membrane vesicles, and fibronectin. TheScientificWorldJournal 55 22666090
2000 High resolution crystal structure of bovine mitochondrial EF-Tu in complex with GDP. Journal of molecular biology 55 10715211
1983 The role of EF-Tu in the expression of tufA and tufB genes. European journal of biochemistry 54 6337847
2020 Paradoxical Mitophagy Regulation by PINK1 and TUFm. Molecular cell 53 33113344
2016 TUFM downregulation induces epithelial-mesenchymal transition and invasion in lung cancer cells via a mechanism involving AMPK-GSK3β signaling. Cellular and molecular life sciences : CMLS 53 26781467
1994 Mutations to kirromycin resistance occur in the interface of domains I and III of EF-Tu.GTP. FEBS letters 53 7925958
1994 The 530 loop of 16S rRNA: a signal to EF-Tu? Trends in genetics : TIG 52 8146911
2002 Mechanisms of EF-Tu, a pioneer GTPase. Progress in nucleic acid research and molecular biology 50 12102560
2018 Elongation Factor Thermo Unstable (EF-Tu) Moonlights as an Adhesin on the Surface of Mycoplasma hyopneumoniae by Binding to Fibronectin. Frontiers in microbiology 49 29867877
2017 Inhibition of Avian Influenza A Virus Replication in Human Cells by Host Restriction Factor TUFM Is Correlated with Autophagy. mBio 49 28611246
2015 A synthetic tRNA for EF-Tu mediated selenocysteine incorporation in vivo and in vitro. FEBS letters 49 26160755
2010 Assembly of Q{beta} viral RNA polymerase with host translational elongation factors EF-Tu and -Ts. Proceedings of the National Academy of Sciences of the United States of America 49 20798060
2010 Cleavage of the sarcin-ricin loop of 23S rRNA differentially affects EF-G and EF-Tu binding. Nucleic acids research 47 20215430
1988 Mutations in ribosomal proteins L7/L12 perturb EF-G and EF-Tu functions. Biochimie 47 3139080
2013 Lysine trimethylation of EF-Tu mimics platelet-activating factor to initiate Pseudomonas aeruginosa pneumonia. mBio 46 23653444
2003 EF-Tu binding peptides identified, dissected, and affinity optimized by phage display. Chemistry & biology 46 12618188
1986 Methylation in vivo of elongation factor EF-Tu at lysine-56 decreases the rate of tRNA-dependent GTP hydrolysis. European journal of biochemistry 45 3096728
1983 Sequence homology between EF-1 alpha, the alpha-chain of elongation factor 1 from Artemia salina and elongation factor EF-Tu from Escherichia coli. FEBS letters 45 6337879
1994 Synergism between the GTPase activities of EF-Tu.GTP and EF-G.GTP on empty ribosomes. Elongation factors as stimulators of the ribosomal oscillation between two conformations. Journal of molecular biology 44 7932721
2021 Autophagy-competent mitochondrial translation elongation factor TUFM inhibits caspase-8-mediated apoptosis. Cell death and differentiation 43 34511600
1979 Polymerization of the bacterial elongation factor for protein synthesis, EF-Tu. European journal of biochemistry 43 467429
2018 Oxidation of Translation Factor EF-Tu Inhibits the Repair of Photosystem II. Plant physiology 42 29439212
2007 Heat-induced accumulation of chloroplast protein synthesis elongation factor, EF-Tu, in winter wheat. Journal of plant physiology 42 17498838
2001 Heat-stress induced synthesis of chloroplast protein synthesis elongation factor (EF-Tu) in a heat-tolerant maize line. Planta 41 11289600
2001 Identification of thermodynamically relevant interactions between EF-Tu and backbone elements of tRNA. Journal of molecular biology 40 11352580
1984 Specific alterations of the EF-Tu polypeptide chain considered in the light of its three-dimensional structure. The EMBO journal 40 6323160
2024 Tufm lactylation regulates neuronal apoptosis by modulating mitophagy in traumatic brain injury. Cell death and differentiation 39 39496783
2020 Anti-vimentin, anti-TUFM, anti-NAP1L1 and anti-DPYSL2 nanobodies display cytotoxic effect and reduce glioblastoma cell migration. Therapeutic advances in medical oncology 38 32426045
2004 Chaperone activity of recombinant maize chloroplast protein synthesis elongation factor, EF-Tu. European journal of biochemistry 38 15355346
1998 Protein-disulfide isomerase activity of elongation factor EF-Tu. Biochemical and biophysical research communications 38 9813162
1990 Functional implications related to the gene structure of the elongation factor EF-Tu from Halobacterium marismortui. Nucleic acids research 37 2155402
1990 Both genes for EF-Tu in Salmonella typhimurium are individually dispensable for growth. Journal of molecular biology 37 2168947
2022 MRG15 aggravates non-alcoholic steatohepatitis progression by regulating the mitochondrial proteolytic degradation of TUFM. Journal of hepatology 35 35985547
2007 The 51-63 base pair of tRNA confers specificity for binding by EF-Tu. RNA (New York, N.Y.) 35 17449728
2006 Expression of chloroplast protein synthesis elongation factor, EF-Tu, in two lines of maize with contrasting tolerance to heat stress during early stages of plant development. Journal of plant physiology 35 16542752
1993 Growth and translation elongation rate are sensitive to the concentration of EF-Tu. Molecular microbiology 34 8332067
2019 Light-inducible expression of translation factor EF-Tu during acclimation to strong light enhances the repair of photosystem II. Proceedings of the National Academy of Sciences of the United States of America 33 31570574
1997 The human mitochondrial elongation factor tu (EF-Tu) gene: cDNA sequence, genomic localization, genomic structure, and identification of a pseudogene. Gene 33 9332382
1990 The role of EF-Tu and other translation components in determining translocation step size. Biochimica et biophysica acta 32 2207156
1997 The ternary complex of EF-Tu and its role in protein biosynthesis. Current opinion in structural biology 31 9032056
1982 The structure of the EF-Tu . GDP . Me2+ complex. European journal of biochemistry 30 7200884
1984 Histidine residues in elongation factor EF-tu from Escherichia coli protected by aminoacyl-tRNA against photo-oxidation. European journal of biochemistry 29 6386466
1996 An elongation factor Tu (EF-Tu) resistant to the EF-Tu inhibitor GE2270 in the producing organism Planobispora rosea. Molecular microbiology 28 8899707
1997 Additional copies of the mitochondrial Ef-Tu and aspartyl-tRNA synthetase genes can compensate for a mutation affecting the maturation of the mitochondrial tRNAAsp. Current genetics 27 9211792
2006 Functional Qbeta replicase genetically fusing essential subunits EF-Ts and EF-Tu with beta-subunit. Journal of bioscience and bioengineering 26 16781472
2004 Triple immunofluorescent labeling of FtsZ, dynamin, and EF-Tu reveals a loose association between the inner and outer membrane mitochondrial division machinery in the red alga Cyanidioschyzon merolae. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 26 15208351
1989 Comparison of the computed structures for the phosphate-binding loop of the p21 protein containing the oncogenic site Gly 12 with the X-ray crystallographic structures for this region in the p21 protein and EFtu. A model for the structure of the p21 protein in its oncogenic form. Journal of biomolecular structure & dynamics 26 2686707
1988 The elongation factor EF-Tu from E. coli binds to the upstream activator region of the tRNA-tufB operon. Nucleic acids research 25 3057439
2021 TUFM is involved in Alzheimer's disease-like pathologies that are associated with ROS. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 24 33774866
2011 Identification and cloning of two immunogenic Clostridium perfringens proteins, elongation factor Tu (EF-Tu) and pyruvate:ferredoxin oxidoreductase (PFO) of C. perfringens. Research in veterinary science 24 21345474
1998 Recognition of the universally conserved 3'-CCA end of tRNA by elongation factor EF-Tu. RNA (New York, N.Y.) 24 9622123
1995 Antibiotic resistance mechanisms of mutant EF-Tu species in Escherichia coli. Biochemistry and cell biology = Biochimie et biologie cellulaire 24 8722034
1994 Why do two EF-Tu molecules act in the elongation cycle of protein biosynthesis? Trends in biochemical sciences 24 8048158
2024 Senecavirus A induces mitophagy to promote self-replication through direct interaction of 2C protein with K27-linked ubiquitinated TUFM catalyzed by RNF185. Autophagy 23 38084826
2019 A novel TUFM homozygous variant in a child with mitochondrial cardiomyopathy expands the phenotype of combined oxidative phosphorylation deficiency 4. Journal of human genetics 23 30903008
2015 EF-Tu dynamics during pre-translocation complex formation: EF-Tu·GDP exits the ribosome via two different pathways. Nucleic acids research 23 26338772
1997 An A to U transversion at position 1067 of 23 S rRNA from Escherichia coli impairs EF-Tu and EF-G function. Journal of molecular biology 23 9325093
1996 Identification of an EF-Tu protein that is periplasm-associated and processed in Neisseria gonorrhoeae. Microbiology (Reading, England) 23 8828215
2011 Is the sequence-specific binding of aminoacyl-tRNAs by EF-Tu universal among bacteria? Nucleic acids research 22 21893586
2010 Identification of Rack1, EF-Tu and Rhodanese as aging-related proteins in human colonic epithelium by proteomic analysis. Journal of proteome research 22 20099848
2008 A signal relay between ribosomal protein S12 and elongation factor EF-Tu during decoding of mRNA. RNA (New York, N.Y.) 22 19095621
2007 Chloroplast protein synthesis elongation factor, EF-Tu, reduces thermal aggregation of rubisco activase. Journal of plant physiology 22 17766005
2000 The effect of mutations in EF-Tu on its affinity for tRNA as measured by two novel and independent methods of general applicability. Journal of biochemical and biophysical methods 22 10647810
1993 Sensitivity of elongation factor Tu (EF-Tu) from different bacterial species to the antibiotics efrotomycin, pulvomycin and MDL 62879. Journal of general microbiology 22 8515234
1991 Error-prone EF-Tu reduces in vivo enzyme activity and cellular growth rate. Molecular microbiology 22 1710757
1984 Modification of amino groups in EF-Tu.GTP and the ternary complex EF-Tu.GTP.valyl-tRNAVal. European journal of biochemistry 22 6430701