Affinage

STT3A

Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit STT3A · UniProt P46977

Length
705 aa
Mass
80.5 kDa
Annotated
2026-06-10
100 papers in source corpus 13 papers cited in narrative 13 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

STT3A encodes the catalytic subunit of an oligosaccharyltransferase (OST) complex that catalyzes N-linked glycosylation of nascent polypeptides at NxS/T sequons, a function conserved from yeast, where loss of the STT3 ortholog abolishes transferase activity and OST complex assembly (PMID:7588624), to the trypanosome single-subunit enzyme, whose reconstituted activity established that sequon flanking residues, polyprenyl tail length, and lipid-linked oligosaccharide structure govern catalysis (PMID:28204532). The STT3A-OST isoform operates cotranslationally by direct interaction with the protein translocation channel, and quantitative glycoproteomics of ~1,000 acceptor sites defined its preference for sites with suboptimal flanking sequences and sites within cysteine-rich domains; its loss provokes hyperglycosylation of the ER chaperone GRP94 and activates the unfolded protein response through ATF6 and PERK (PMID:31296534, PMID:36139350). STT3A is the primary isoform glycosylating substrates including HSV-1 envelope glycoproteins gC and gD, with STT3B-OST providing partial compensation (PMID:30811219), and it N-glycosylates and stabilizes the immune checkpoint ligand PD-L1, a reaction enhanced in tumor cells by TGF-β1/c-Jun-driven STT3A induction and by GMPS, which bridges the Sec61 translocon to STT3A to facilitate cotranslational PD-L1 modification (PMID:35311117, PMID:39690246). Both recessive active-site missense mutations and dominant-negative heterozygous active-site variants in STT3A cause congenital disorders of glycosylation with neurological and skeletal manifestations (PMID:23842455, PMID:34653363).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1995 High

    Established that STT3 is the essential determinant of oligosaccharyltransferase activity and complex assembly, and that it dictates substrate specificity toward lipid-linked oligosaccharides.

    Evidence Genetic screen, in vitro OTase assays, and depletion experiments in S. cerevisiae; pulse-chase glycosylation assays linking it to the PKC1/STT1 pathway

    PMID:7588624 PMID:7590309

    Open questions at the time
    • Did not define the catalytic residues or structural basis of transfer
    • Mammalian isoform-specific roles not addressed
  2. 1996 Medium

    Identified the human STT3A protein (ITM1) as a highly hydrophobic conserved multipass membrane protein, providing the molecular entity for downstream functional work.

    Evidence cDNA cloning, sequence analysis, cross-species similarity searches, and genetic mapping

    PMID:8838310

    Open questions at the time
    • No functional or enzymatic assay performed
    • Membrane topology only predicted, not experimentally resolved
  3. 2013 High

    Demonstrated that recessive active-site missense mutation causes a congenital disorder of glycosylation and defined STT3A-specific acceptor substrate defects distinct from STT3B-CDG.

    Evidence Patient fibroblast glycosylation assays, GFP biomarker rescue, and STT3A-deficient HeLa cell complementation

    PMID:23842455

    Open questions at the time
    • Mechanism by which the mutation impairs catalysis not structurally resolved
    • Tissue-specific basis of neurological phenotype unexplained
  4. 2017 High

    Resolved sequon and lipid-substrate determinants of catalysis using a reconstituted single-subunit ortholog, defining +1 and -2 sequon effects and LLO analog requirements.

    Evidence Recombinant TbSTT3A expression with synthetic fluorescent peptide and LLO analog kinetics and competitive inhibition

    PMID:28204532

    Open questions at the time
    • Trypanosome enzyme differs from mammalian multi-subunit OST
    • Does not address cotranslational coupling to the translocon
  5. 2019 High

    Mapped the genome-wide acceptor repertoire of STT3A, establishing its preference for suboptimal-sequon and cysteine-rich cotranslational sites and revealing GRP94 hyperglycosylation as a marker of its loss and of ER stress.

    Evidence Quantitative glycoproteomics of ~1,000 sites in STT3A-KO vs wild-type HEK cells with ER stress induction

    PMID:31296534

    Open questions at the time
    • Structural basis of translocon docking not defined
    • Causal link between GRP94 hyperglycosylation and downstream physiology unclear
  6. 2019 High

    Demonstrated STT3A as the primary OST isoform glycosylating viral envelope glycoproteins required for HSV-1 infectivity, with partial STT3B compensation.

    Evidence STT3A/STT3B knockout HEK293 cells, NGI-1 inhibition, plaque assays, and Western blotting of viral glycoproteins

    PMID:30811219

    Open questions at the time
    • Cell-type dependence of compensation not mechanistically explained
    • Specific viral glycosites not enumerated
  7. 2022 Medium

    Linked STT3A loss to broad glycoproteome remodeling, altered glycan processing, and unfolded protein response activation, extending its physiological footprint beyond direct acceptor sites.

    Evidence CRISPR KO with quantitative proteomics, glycoproteomics, and UPR marker Western blotting

    PMID:36139350

    Open questions at the time
    • Single lab, corroborates but does not independently extend prior glycoproteomics
    • Causal ordering of UPR activation vs glycan changes unresolved
  8. 2022 Medium

    Connected STT3A to cancer signaling and immune evasion by showing TGF-β1/c-Jun-driven STT3A induction glycosylates and stabilizes PD-L1, and that STT3A supports MAPK and PI3K/AKT signaling and EMT in lung adenocarcinoma.

    Evidence ChIP, co-IP, glycosylation and T-cell cytotoxicity assays in NPC cells; CRISPR KO, NGI-1 inhibition, MS pathway screening, and xenografts in lung adenocarcinoma

    PMID:35311117 PMID:35832442

    Open questions at the time
    • Direct PD-L1 acceptor sites not mapped in these studies
    • Single-lab mechanistic chains not independently replicated
  9. 2024 Medium

    Identified GMPS as an accessory module bridging the Sec61 translocon to STT3A to enhance cotranslational PD-L1 glycosylation, refining the architecture of substrate delivery to the catalytic subunit.

    Evidence Proteomics, scRNA-seq, co-IP of the GMPS–Sec61–STT3A complex, and GMPS knockdown PD-L1 glycosylation assays in HCC

    PMID:39690246

    Open questions at the time
    • Stoichiometry and structural basis of the GMPS–Sec61–STT3A interaction undefined
    • Single Co-IP-based complex, generality beyond PD-L1 untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structural model of the human STT3A-OST complex docked to the Sec61 translocon, and the basis for its isoform-specific acceptor selection in vivo, remain to be established.
  • No human STT3A-OST/Sec61 structure in the corpus
  • Determinants partitioning substrates between STT3A and STT3B not fully resolved at residue level

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 3 GO:0140096 catalytic activity, acting on a protein 3
Localization
GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-392499 Metabolism of proteins 3 R-HSA-8953897 Cellular responses to stimuli 2
Partners
GMPSPD-L1SEC61STT3B
Complex memberships
STT3A-OST (oligosaccharyltransferase) complexSec61 translocon channel

Evidence

Reading pass · 13 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 STT3 (yeast ortholog of STT3A) is required for oligosaccharyltransferase (OTase) activity in vivo and in vitro; depletion of STT3 results in loss of transferase activity and deficiency in assembly of the OTase complex. A mutation in STT3 alters substrate specificity such that glycosyl transfer from incomplete lipid-linked oligosaccharides is greatly reduced, while transfer of full-length Glc3Man9GlcNAc2 is relatively unaffected. Genetic screen in S. cerevisiae, in vitro OTase activity assays, STT3 depletion experiments, synthetic lethal analysis The EMBO journal High 7588624
1995 STT3 (yeast, encoding a protein ~60% identical to its human homolog) is essential for protein glycosylation and functions in the PKC1/STT1 pathway; stt3 mutants are defective in protein glycosylation as shown by pulse-chase experiments. Pulse-chase glycosylation assays, genetic epistasis with PKC1/STT1 pathway, staurosporine/temperature sensitivity phenotyping in S. cerevisiae Gene Medium 7590309
1996 The human STT3A protein (then designated ITM1/B5) is a highly hydrophobic integral membrane protein of ~80.5 kDa with 10–14 predicted transmembrane domains; it is 60% similar to yeast STT3 and 58% similar to C. elegans T12A2.2, establishing it as part of a conserved transmembrane protein family. The gene (Itm1) maps to mouse chromosome 9. cDNA cloning from fetal mouse mandibular condyle and human testis libraries, sequence analysis, database similarity searches, genetic mapping Genomics Medium 8838310
2013 Homozygous missense mutation p.Val626Ala in STT3A causes a congenital disorder of glycosylation (CDG) characterized by neurologic abnormalities, hypotonia, intellectual disability, and failure to thrive. The mutation impairs glycosylation of a GFP biomarker, reduces glycosylation of STT3A-specific acceptor substrates in patient fibroblasts, and expression of the mutant allele in STT3A-deficient HeLa cells fails to rescue glycosylation. STT3A-CDG preferentially affects transferrin glycosylation, distinguishing it from STT3B-CDG. Patient fibroblast glycosylation assays, GFP biomarker glycosylation rescue experiments, STT3A-deficient HeLa cell complementation, biochemical analysis of acceptor substrate specificity Human molecular genetics High 23842455
2019 Quantitative glycoproteomics of ~1,000 acceptor sites in wild-type versus STT3A-deficient cells revealed that STT3A-dependent sites include those with suboptimal flanking sequences, sites in cysteine-rich domains, and sites requiring cotranslational glycosylation via direct interaction with the protein translocation channel. STT3A deficiency causes hyperglycosylation of the ER chaperone GRP94 at five otherwise-silent sites; this hyperglycosylation also occurs in wild-type cells treated with ER stress inducers. Quantitative glycoproteomics in STT3A knockout and wild-type HEK cells, site-occupancy analysis, ER stress induction experiments The Journal of cell biology High 31296534
2017 The single-subunit STT3A ortholog from Trypanosoma brucei (TbSTT3A) was recombinantly expressed and characterized: charged residues at the +1 position of the NxS/T sequon inhibit glycan transfer; an acidic residue at -2 increases catalytic turnover but is not essential (unlike bacterial OST); polyprenyl tail length but not double-bond stereochemistry determines lipid-linked oligosaccharide (LLO) analog affinity; phosphonate LLO analogs act as competitive inhibitors. Recombinant protein expression and purification, in vitro activity assays with synthetic fluorescent acceptor peptides and synthetic LLO analogs, kinetic analysis Glycobiology High 28204532
2019 STT3A-OST complex mediates cotranslational N-glycosylation of HSV-1 envelope glycoproteins gC and gD as the primary OST isoform; STT3B-OST can partially compensate. Cells lacking STT3B activity and treated with the OST inhibitor NGI-1 (which targets STT3A) show cell-type-dependent HSV-1 dysfunction, demonstrating the essentiality of STT3A-mediated cotranslational N-glycosylation for HSV-1 infectivity. STT3A/STT3B subunit knockout HEK293 cell lines, NGI-1 pharmacological inhibition, plaque-forming unit assays, Western blotting of viral envelope glycoproteins FASEB journal High 30811219
2021 Heterozygous missense variants in STT3A located in the active/catalytic site cause an autosomal-dominant CDG with skeletal anomalies, short stature, macrocephaly, intellectual disability, and increased muscle tone. Expression of homologous variants in yeast STT3 in wild-type background induces glycosylation defects of carboxypeptidase Y and worsens glycosylation in stt3-7 hypomorphic yeast, supporting a dominant-negative mechanism. Patient fibroblasts show normal STT3A mRNA/protein but abnormal glycosylation. Clinical genetics, 3D structural modeling of OST complex, yeast complementation assays with CPY glycosylation readout, patient fibroblast biochemical analysis American journal of human genetics High 34653363
2022 TGF-β1 upregulates STT3A expression through c-Jun binding to the STT3A promoter; STT3A transfers N-linked glycans to PD-L1 in NPC cells, stabilizing PD-L1 and enabling immune evasion. Inhibition of TGF-β1 reduces glycosylated PD-L1 and enhances cytotoxic T-cell function against NPC cells. ChIP assay (c-Jun binding to STT3A promoter), co-immunoprecipitation, glycosylation assays, TGF-β1 inhibition functional assays, T-cell cytotoxicity assays Frontiers in oncology Medium 35311117
2022 Proteomics and glycoproteomics in STT3A-KO HEK293 cells revealed that STT3A deletion has greater impact on glycoprotein expression than STT3B deletion, reduces total mannosylated N-glycans and increases fucosylated N-glycans (via differential expression of glycan-processing enzymes), causes hyperglycosylation of ENPL (GRP94) via ER stress, and activates the unfolded protein response (ATF6 and PERK pathways). CRISPR/Cas9 KO, quantitative proteomics, glycoproteomics, Western blotting for UPR markers Cells Medium 36139350
2024 GMPS (guanine monophosphate synthase) promotes PD-L1 N-glycosylation in hepatocellular carcinoma by acting as an additional module connecting the Sec61 translocon channel complex to STT3A, thereby enhancing the interaction between PD-L1 and the STT3A catalytic subunit and facilitating cotranslational modification and translocation of the nascent PD-L1 peptide. Proteomic and scRNA-seq analyses, co-immunoprecipitation (GMPS–Sec61–STT3A complex), PD-L1 glycosylation assays, GMPS knockdown/inhibition functional experiments Cell death and differentiation Medium 39690246
2022 STT3A knockout or NGI-1 inhibition in lung adenocarcinoma cell lines suppresses proliferation, migration, invasion, and tumor growth in vivo; downstream, STT3A-dependent glycosylation supports activation of MAPK and PI3K/AKT signaling pathways and promotes epithelial-mesenchymal transition as identified by mass spectrometry and validated by Western blotting. CRISPR/Cas9 KO, NGI-1 pharmacological inhibition, mass spectrometry-based downstream pathway screening, Western blotting, xenograft mouse model Translational lung cancer research Medium 35832442
2015 In Arabidopsis, loss of function of STT3a (plant ortholog) suppresses spontaneous cell death and constitutive defense responses in bir1-1 mutants without affecting SOBIR1 accumulation, suggesting STT3a-dependent ER quality control glycosylation is required for additional signaling components beyond SOBIR1 that activate immunity. Arabidopsis genetic epistasis (stt3a loss-of-function in bir1-1 background), Western blotting for SOBIR1 protein levels PloS one Low 25775181

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 Tmc gene therapy restores auditory function in deaf mice. Science translational medicine 211 26157030
2006 N-trimethyl chitosan (TMC) nanoparticles loaded with influenza subunit antigen for intranasal vaccination: biological properties and immunogenicity in a mouse model. Vaccine 177 16973248
1995 STT3, a highly conserved protein required for yeast oligosaccharyl transferase activity in vivo. The EMBO journal 161 7588624
2001 Crystal structure of the 20 S proteasome:TMC-95A complex: a non-covalent proteasome inhibitor. Journal of molecular biology 144 11493007
2014 Electrospun biomimetic fibrous scaffold from shape memory polymer of PDLLA-co-TMC for bone tissue engineering. ACS applied materials & interfaces 122 24476093
2002 A potent human immunodeficiency virus type 1 protease inhibitor, UIC-94003 (TMC-126), and selection of a novel (A28S) mutation in the protease active site. Journal of virology 118 11773409
2003 Characterization of the transmembrane channel-like (TMC) gene family: functional clues from hearing loss and epidermodysplasia verruciformis. Genomics 117 12906855
2013 tmc-1 encodes a sodium-sensitive channel required for salt chemosensation in C. elegans. Nature 116 23364694
2006 Intravaginal ring delivery of the reverse transcriptase inhibitor TMC 120 as an HIV microbicide. International journal of pharmaceutics 116 16884869
2003 TMC and EVER genes belong to a larger novel family, the TMC gene family encoding transmembrane proteins. BMC genomics 114 12812529
2022 Structures of the TMC-1 complex illuminate mechanosensory transduction. Nature 112 36224384
2008 Mono-N-carboxymethyl chitosan (MCC) and N-trimethyl chitosan (TMC) nanoparticles for non-invasive vaccine delivery. International journal of pharmaceutics 100 18662762
2002 Overcoming drug resistance in HIV-1 chemotherapy: the binding thermodynamics of Amprenavir and TMC-126 to wild-type and drug-resistant mutants of the HIV-1 protease. Protein science : a publication of the Protein Society 91 12142445
2000 N-trimethylated chitosan chloride (TMC) improves the intestinal permeation of the peptide drug buserelin in vitro (Caco-2 cells) and in vivo (rats). Pharmaceutical research 88 10714604
2000 Intestinal absorption of octreotide: N-trimethyl chitosan chloride (TMC) ameliorates the permeability and absorption properties of the somatostatin analogue in vitro and in vivo. Journal of pharmaceutical sciences 83 10861597
2003 An open-label assessment of TMC 125--a new, next-generation NNRTI, for 7 days in HIV-1 infected individuals with NNRTI resistance. AIDS (London, England) 81 14685068
2014 Transmembrane channel-like (TMC) genes are required for auditory and vestibular mechanosensation. Pflugers Archiv : European journal of physiology 79 25074487
2016 Transmembrane channel-like (tmc) gene regulates Drosophila larval locomotion. Proceedings of the National Academy of Sciences of the United States of America 70 27298354
2007 Transport mechanisms of mmePEG750P(CL-co-TMC) polymeric micelles across the intestinal barrier. Journal of controlled release : official journal of the Controlled Release Society 69 17928087
2006 TMC-95-based inhibitor design provides evidence for the catalytic versatility of the proteasome. Chemistry & biology 69 16793518
2013 Mutations in STT3A and STT3B cause two congenital disorders of glycosylation. Human molecular genetics 68 23842455
2011 PLGA, PLGA-TMC and TMC-TPP nanoparticles differentially modulate the outcome of nasal vaccination by inducing tolerance or enhancing humoral immunity. PloS one 67 22073184
2016 TMC-1 Mediates Alkaline Sensation in C. elegans through Nociceptive Neurons. Neuron 64 27321925
2019 Quantitative glycoproteomics reveals new classes of STT3A- and STT3B-dependent N-glycosylation sites. The Journal of cell biology 63 31296534
2015 Modulating Ca²⁺ signals: a common theme for TMEM16, Ist2, and TMC. Pflugers Archiv : European journal of physiology 62 26700940
2015 Femtomolar level detection of RASSF1A tumor suppressor gene methylation by electrochemical nano-genosensor based on Fe3O4/TMC/Au nanocomposite and PT-modified electrode. Biosensors & bioelectronics 59 26562330
2010 Dual role of CpG as immune modulator and physical crosslinker in ovalbumin loaded N-trimethyl chitosan (TMC) nanoparticles for nasal vaccination. Journal of controlled release : official journal of the Controlled Release Society 59 20600405
2005 Self-assembling PEG-p(CL-co-TMC) copolymers for oral delivery of poorly water-soluble drugs: a case study with risperidone. Journal of controlled release : official journal of the Controlled Release Society 58 15681087
2019 Direction Selectivity in Drosophila Proprioceptors Requires the Mechanosensory Channel Tmc. Current biology : CB 56 30853433
2014 Challenges in evaluation of chitosan and trimethylated chitosan (TMC) as mucosal permeation enhancers: From synthesis to in vitro application. Journal of controlled release : official journal of the Controlled Release Society 54 24511609
2009 Enhanced angiogenesis of porous collagen scaffolds by incorporation of TMC/DNA complexes encoding vascular endothelial growth factor. Acta biomaterialia 54 19406694
2011 Studies on adaptability of binding residues and flap region of TMC-114 resistance HIV-1 protease mutants. Journal of biomolecular structure & dynamics 53 21696230
2014 Cohort Profile: The Malaysian Cohort (TMC) project: a prospective study of non-communicable diseases in a multi-ethnic population. International journal of epidemiology 51 24729425
2020 Ankyrin Is An Intracellular Tether for TMC Mechanotransduction Channels. Neuron 50 32325031
2018 TMC Proteins Modulate Egg Laying and Membrane Excitability through a Background Leak Conductance in C. elegans. Neuron 50 29395910
2007 Linear TMC-95-based proteasome inhibitors. Journal of medicinal chemistry 50 17511440
2004 Binding mode of TMC-95A analogues to eukaryotic 20S proteasome. Chembiochem : a European journal of chemical biology 47 15368577
2002 TMC-256A1 and C1, new inhibitors of IL-4 signal transduction produced by Aspergillus niger var niger TC 1629. The Journal of antibiotics 46 12374380
2019 Function and Dysfunction of TMC Channels in Inner Ear Hair Cells. Cold Spring Harbor perspectives in medicine 37 30291150
2009 Resistance-associated mutations to etravirine (TMC-125) in antiretroviral-naïve patients infected with non-B HIV-1 subtypes. Antimicrobial agents and chemotherapy 36 20008779
2006 The Tmc complex from Desulfovibrio vulgaris hildenborough is involved in transmembrane electron transfer from periplasmic hydrogen oxidation. Biochemistry 36 16922512
1995 STT3, a novel essential gene related to the PKC1/STT1 protein kinase pathway, is involved in protein glycosylation in yeast. Gene 32 7590309
2015 TMC-1 attenuates C. elegans development and sexual behaviour in a chemically defined food environment. Nature communications 31 25695879
2024 The structure of the Caenorhabditis elegans TMC-2 complex suggests roles of lipid-mediated subunit contacts in mechanosensory transduction. Proceedings of the National Academy of Sciences of the United States of America 29 38354260
2022 TGF-β1-Mediated PD-L1 Glycosylation Contributes to Immune Escape via c-Jun/STT3A Pathway in Nasopharyngeal Carcinoma. Frontiers in oncology 29 35311117
2017 Characterization of the single-subunit oligosaccharyltransferase STT3A from Trypanosoma brucei using synthetic peptides and lipid-linked oligosaccharide analogs. Glycobiology 28 28204532
2020 PIP/TMC Interfacial Polymerization with Electrospray: Novel Loose Nanofiltration Membrane for Dye Wastewater Treatment. ACS applied materials & interfaces 27 32697565
2009 Insights into drug resistance of mutations D30N and I50V to HIV-1 protease inhibitor TMC-114: free energy calculation and molecular dynamic simulation. Journal of molecular modeling 27 19629548
2003 Simplified synthetic TMC-95A/B analogues retain the potency of proteasome inhibitory activity. Chembiochem : a European journal of chemical biology 27 12794861
2019 Performance of TMC-g-PEG-VAPG/miRNA-145 complexes in electrospun membranes for target-regulating vascular SMCs. Colloids and surfaces. B, Biointerfaces 25 31336282
2014 TMC function in hair cell transduction. Hearing research 25 24423408
2008 Potential prospects of chitosan derivative trimethyl chitosan chloride (TMC) as a polymeric absorption enhancer: synthesis, characterization and applications. The Journal of pharmacy and pharmacology 25 18718113
2003 TMC-264, a novel inhibitor of STAT6 activation produced by Phoma sp. TC 1674. The Journal of antibiotics 25 12931859
2022 Green engineering of TMC-CMS nanoparticles decorated graphene sheets for targeting M. tuberculosis. Carbohydrate polymers 24 36657855
2000 Enzyme-catalyzed ring-opening copolymerization of 5-methyl-5-benzyloxycarbonyl-1,3-dioxan-2-one (MBC) with trimethylene carbonate (TMC): synthesis and characterization. Biomacromolecules 24 11710142
1996 TMC-1 A, B, C and D, new antibiotics of the manumycin group produced by Streptomyces sp. Taxonomy, production, isolation, physico-chemical properties, structure elucidation and biological properties. The Journal of antibiotics 24 9031666
2016 Development of an in-process UV-crosslinked, electrospun PCL/aPLA-co-TMC composite polymer for tubular tissue engineering applications. Acta biomaterialia 23 26969522
1996 Novel O-methylated terminal glucuronic acid characterizes the polar glycopeptidolipids of Mycobacterium habana strain TMC 5135. The Journal of biological chemistry 23 8647835
2024 A STT3A-dependent PD-L1 glycosylation modification mediated by GMPS drives tumor immune evasion in hepatocellular carcinoma. Cell death and differentiation 21 39690246
2024 Wide-ranging cellular functions of ion channels and lipid scramblases in the structurally related TMC, TMEM16 and TMEM63 families. Nature structural & molecular biology 21 39715905
2014 The synthetic α-bromo-2',3,4,4'-tetramethoxychalcone (α-Br-TMC) inhibits the JAK/STAT signaling pathway. PloS one 20 24595334
2022 Proteome and Glycoproteome Analyses Reveal the Protein N-Linked Glycosylation Specificity of STT3A and STT3B. Cells 19 36139350
2004 High-dose topotecan, melphalan and cyclophosphamide (TMC) with stem cell support: a new regimen for the treatment of multiple myeloma. Leukemia & lymphoma 19 15160952
2009 TMC-435, an NS3/4A protease inhibitor for the treatment of HCV infection. Current opinion in investigational drugs (London, England : 2000) 18 19649931
1999 TMC-171A,B,C and TMC-154, novel polyketide antibiotics produced by Gliocladium sp. TC 1304 and TC 1282. The Journal of antibiotics 18 10695675
2021 Active site variants in STT3A cause a dominant type I congenital disorder of glycosylation with neuromusculoskeletal findings. American journal of human genetics 16 34653363
1996 Molecular cloning of a highly conserved mouse and human integral membrane protein (Itm1) and genetic mapping to mouse chromosome 9. Genomics 16 8838310
2022 Targeting STT3A produces an anti-tumor effect in lung adenocarcinoma by blocking the MAPK and PI3K/AKT signaling pathway. Translational lung cancer research 15 35832442
2011 The new molecular markers DDIT3, STT3A, ARG2 and FAM129A are not useful in diagnosing thyroid follicular tumors. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 15 22157935
2024 TMC function, dysfunction, and restoration in mouse vestibular organs. Frontiers in neurology 14 38638308
2022 GABA signaling triggered by TMC-1/Tmc delays neuronal aging by inhibiting the PKC pathway in C. elegans. Science advances 14 36542715
2019 Targeting STT3A-oligosaccharyltransferase with NGI-1 causes herpes simplex virus 1 dysfunction. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 14 30811219
2016 Anti-Inflammatory and Cytoprotective Effects of TMC-256C1 from Marine-Derived Fungus Aspergillus sp. SF-6354 via up-Regulation of Heme Oxygenase-1 in Murine Hippocampal and Microglial Cell Lines. International journal of molecular sciences 14 27070586
2015 ER quality control components UGGT and STT3a are required for activation of defense responses in bir1-1. PloS one 14 25775181
2005 Identification of chicken transmembrane channel-like (TMC) genes: expression analysis in the cochlea. Neuroscience 14 15857715
2022 Combined inhibition of EZH2 and CD73 molecules by folic acid-conjugated SPION-TMC nanocarriers loaded with siRNA molecules prevents TNBC progression and restores anti-tumor responses. Life sciences 13 36179812
2021 Tmc Reliance Is Biased by the Hair Cell Subtype and Position Within the Ear. Frontiers in cell and developmental biology 13 33490059
2020 Tmc proteins are essential for zebrafish hearing where Tmc1 is not obligatory. Human molecular genetics 13 32167554
2009 Effect of 3D-microstructure of bioabsorbable PGA:TMC scaffolds on the growth of chondrogenic cells. Journal of biomedical materials research. Part B, Applied biomaterials 13 18546178
2020 Greener approach for synthesis of N,N,N-trimethyl chitosan (TMC) using ternary deep eutectic solvents (TDESs). Carbohydrate research 12 32505997
2016 TMC-SNPdb: an Indian germline variant database derived from whole exome sequences. Database : the journal of biological databases and curation 12 27402678
2015 Synthesis, characterization and in vitro biocompatibility study of Au/TMC/Fe3O4 nanocomposites as a promising, nontoxic system for biomedical applications. Beilstein journal of nanotechnology 12 26425418
2006 Porous hybrid structures based on P(DLLA-co-TMC) and collagen for tissue engineering of small-diameter blood vessels. Journal of biomedical materials research. Part B, Applied biomaterials 12 16649175
2001 High-dose topotecan, melphalan, and cyclophosphamide (TMC) with stem cell support: a new regimen for the treatment of advanced ovarian cancer. Gynecologic oncology 12 11520135
2011 STT3A, C1orf24, TFF3: putative markers for characterization of follicular thyroid neoplasms from fine-needle aspirates. The Laryngoscope 10 21520112
2001 TMC-205 a new transcriptional up-regulator of SV40 promoter produced by an unidentified fungus. Fermentation, isolation, physico-chemical properties, structural determination and biological activities. The Journal of antibiotics 10 11592499
2024 Transmembrane Channel-Like (Tmc) Subunits Contribute to Frequency Sensitivity in the Zebrafish Utricle. The Journal of neuroscience : the official journal of the Society for Neuroscience 9 37952940
2024 Sequence variations and accessory proteins adapt TMC functions to distinct sensory modalities. Neuron 9 38986620
2011 Insights into the structural function of the complex of HIV-1 protease with TMC-126: molecular dynamics simulations and free-energy calculations. Journal of molecular modeling 9 21850570
2011 A step-by-step approach to study the influence of N-acetylation on the adjuvanticity of N,N,N-trimethyl chitosan (TMC) in an intranasal nanoparticulate influenza virus vaccine. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 9 22009112
2023 Toxicity and Estrogenicity of Bisphenol TMC in Oryzias melastigma via In Vivo and In Silico Studies. Environmental science & technology 8 36795899
2021 Intramolecular hydrogen bond interruption and scaffold hopping of TMC-5 led to 2-(4-alkoxy-3-cyanophenyl)pyrimidine-4/5-carboxylic acids and 6-(4-alkoxy-3-cyanophenyl)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-ones as potent pyrimidine-based xanthine oxidase inhibitors. European journal of medicinal chemistry 8 34992040
2015 The Cytoprotective Effects of E-α-(4-Methoxyphenyl)-2',3,4,4'-Tetramethoxychalcone (E-α-p-OMe-C6H4-TMC)--A Novel and Non-Cytotoxic HO-1 Inducer. PloS one 8 26565402
2014 Acceleration of aneurysm healing by P(DLLA-co-TMC)-coated coils enabling the controlled release of vascular endothelial growth factor. Biomedical materials (Bristol, England) 8 24945939
2022 Nasal Administration of M2e/CpG-ODN Encapsulated in N-Trimethyl Chitosan (TMC) Significantly Increases Specific Immune Responses in a Mouse Model. Archives of Razi Institute 7 37274902
2016 Inhibition of interleukin-3- and interferon- α-induced JAK/STAT signaling by the synthetic α-X-2',3,4,4'-tetramethoxychalcones α-Br-TMC and α-CF3-TMC. Biological chemistry 7 27341558
1999 TMC-66, a new endothelin converting enzyme inhibitor produced by Streptomyces sp. A5008. The Journal of antibiotics 7 10513839
2021 Investigating potency of TMC-126 against wild-type and mutant variants of HIV-1 protease: a molecular dynamics and free energy study. SAR and QSAR in environmental research 6 34787532
2020 Antioxidative and Radioprotective Properties of Glycosylated Flavonoid, Xanthorhamnin from Radio-Resistant Bacterium Bacillus indicus Strain TMC-6. Current microbiology 5 32125445
2020 Enhancement of cartilage extracellular matrix synthesis in Poly(PCL-TMC)urethane scaffolds: a study of oriented dynamic flow in bioreactor. Biotechnology letters 5 32785804

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