| 2000 |
Crystal structure of the human TOM1 VHS domain resolved to 1.5 Å, revealing eight helices in a superhelix with a conserved basic patch on helix 3 (implicated in membrane binding) and a negatively charged ridge on helix 2 (implicated in protein-protein interactions involving helices 2 and 4). |
X-ray crystallography (1.5 Å resolution) |
Biochemistry |
High |
10985773
|
| 1997 |
TOM1 is a direct transcriptional target of v-Myb; the Myb-inducible tom-1 promoter contains a functional Myb binding site and requires a juxtaposed C/EBP binding site for Myb-dependent activation, with C/EBP acting as a cooperation partner. |
Promoter deletion/mutation analysis, reporter gene assay, transcription factor binding site mapping |
The EMBO journal |
High |
9135152
|
| 2003 |
TOM1 directly binds ubiquitin chains and Tollip via its GAT domain; endogenous TOM1 co-fractionates with Tollip in a complex; TOM1 also binds clathrin heavy chain through a canonical clathrin-binding motif; deletion of the clathrin-binding motif alters GFP-TOM1 cytoplasmic distribution. |
Co-immunoprecipitation, gel filtration, Western blot, GFP fluorescence microscopy, GST pulldown |
The Journal of biological chemistry |
High |
14563850
|
| 2004 |
The GAT domain of TOM1 (and TOM1L1) interacts with ubiquitin and Tollip; ubiquitin and Tollip bind overlapping regions of the GAT domain in a mutually exclusive manner. Tollip localizes on early endosomes and recruits cytosolic TOM1 and ubiquitinated proteins to endosomes. |
GST pulldown, Co-immunoprecipitation, fluorescence microscopy, domain mapping |
The Journal of biological chemistry |
High |
15047686
|
| 2003 |
Endofin, a FYVE-domain early endosomal protein, binds specifically to the C-terminal region of TOM1 (not TOM1-L1 or TOM1-L2) and recruits cytosolic TOM1 to early endosomes; confirmed by yeast two-hybrid, GST pulldown, Co-IP, and immunofluorescence with EEA1 co-localization. |
Yeast two-hybrid screen, GST pulldown, Co-immunoprecipitation, immunofluorescence, sucrose density gradient fractionation |
The Journal of biological chemistry |
High |
14613930
|
| 2005 |
TOM1 binds clathrin heavy chain through three sites (residues 300–321, 321–326, and a LEDEF clathrin-binding box at 362–366); endofin overexpression recruits clathrin (but not dynamin, AP1, AP2, or AP3) to endosomes via TOM1; microinjection of anti-TOM1 antibody reduces membrane association of clathrin. |
GST pulldown with deletion/point mutants, overexpression, immunofluorescence, antibody microinjection |
Journal of cell science |
High |
15657082
|
| 2006 |
All TOM1 family members (TOM1, TOM1L1, TOM1L2) bind Tollip via their GAT domains and bind clathrin through their C-terminal regions; when co-expressed with Tollip, all three family members recruit clathrin onto endosomes. |
Co-immunoprecipitation, fluorescence microscopy with Tollip co-expression |
Biochemical and biophysical research communications |
Medium |
16412388
|
| 2004 |
Overexpression of TOM1 suppresses NF-κB and AP-1 activation induced by IL-1β and TNF-α; the VHS domain of TOM1 is required for this suppressive activity. |
Reporter gene assay (NF-κB and AP-1 luciferase), domain deletion analysis |
Biological & pharmaceutical bulletin |
Medium |
15056867
|
| 2008 |
Dictyostelium TOM1 (DdTom1) GAT domain binds ubiquitin; the VHS and GAT domains interact with phospholipids enabling endosomal membrane recruitment; the C-terminal domain recruits clathrin, Eps15, and TSG101 (an ESCRT component), supporting participation in an ancestral ESCRT-0 complex for sorting ubiquitinated proteins to MVBs. |
Domain-binding assays, subcellular fractionation, co-immunoprecipitation, fluorescence microscopy |
Traffic (Copenhagen, Denmark) |
Medium |
19054384
|
| 2010 |
miR-126 directly targets the 3'-UTR of TOM1 mRNA; introduction of synthetic pre-miR-126 in CF bronchial epithelial cells inhibited luciferase activity from a TOM1 3'-UTR reporter and decreased TOM1 protein; TOM1 knockdown increased NF-κB-regulated IL-8 secretion, while TOM1 overexpression downregulated NF-κB activity after LPS or IL-1β stimulation. |
Luciferase 3'-UTR reporter assay, Western blot, siRNA knockdown, cytokine ELISA |
Journal of immunology |
Medium |
20083669
|
| 2012 |
TOM1 is a myosin VI binding partner on endosomes; loss of myosin VI and TOM1 reduces autophagosomal delivery of endocytic cargo and causes a block in autophagosome-lysosome fusion; myosin VI adaptor proteins NDP52, optineurin, and T6BP dock myosin VI to autophagosomes, while TOM1 on endosomes connects endosomal membranes to autophagosomes to promote maturation and lysosomal fusion. |
Co-immunoprecipitation, siRNA knockdown, live-cell fluorescence imaging, autophagy flux assays |
Nature cell biology |
High |
23023224
|
| 2015 |
TOM1 is a direct binding partner of phosphatidylinositol 5-phosphate (PI5P); PI5P recruits TOM1 to signaling endosomes (produced by Shigella IpgD phosphatase), and this recruitment delays EGFR degradation and impairs bulk endocytosis, thereby preventing endosomal maturation. |
Lipid pulldown, Co-immunoprecipitation, domain mapping, cell-based endocytosis/degradation assays |
Journal of cell science |
High |
25588840
|
| 1999 |
Yeast TOM1 encodes a ~380 kDa HECT-domain ubiquitin ligase; site-directed mutagenesis of the conserved active-site cysteine (C3235A) abolishes HECT function and temperature-sensitive growth; overproduction of the HECT domain promotes ubiquitin (but not SUMO/Smt3) conjugation to proteins in vivo. |
Site-directed mutagenesis, in vivo ubiquitin conjugation assay with GST-HECT overproduction, genetic complementation |
Gene |
High |
10395901
|
| 2012 |
Yeast HECT E3 ligase Tom1 and F-box protein Dia2 independently control Cdc6 degradation in G1 phase; both Tom1 and Dia2 immunoprecipitate Cdc6 (binding its C-terminal region) and are required for Cdc6 ubiquitination; Cdc6 and Mcm4 chromatin association is aberrant in tom1Δ cells in G1. |
Co-immunoprecipitation, ubiquitination assay, chromatin fractionation, genetic deletion |
The Journal of biological chemistry |
High |
23129771
|
| 2012 |
Yeast HECT E3 ligase Tom1 ubiquitinates the F-box protein Dia2 for its cell-cycle-dependent degradation in G1 and G2/M (stabilized in S phase); Tom1 binding to Dia2 is enhanced in G1 and reduced in S phase; Tom1 recognizes specific positively charged residues in the Dia2 degradation/NLS domain; loss of Dia2 partially suppresses tom1 temperature-sensitive phenotype; Dia2 degradation is required for G1-to-S phase progression. |
Genetic deletion, Co-immunoprecipitation, ubiquitination assay, cell cycle analysis, domain point mutagenesis |
Molecular biology of the cell |
High |
22933573
|
| 2016 |
Solution NMR structure of the TOM1 GAT domain determined, showing a bundle of three helical elements; structural comparison with Tollip TBD-bound and ubiquitin-bound states reveals conformational differences at the binding interface. |
Solution NMR structural determination |
Data in brief |
Medium |
26977434
|
| 2017 |
Yeast Tom1 E3 ubiquitin ligase interacts with aberrant nascent peptides escorted by the ribosome-bound quality control (RQC) complex to the proteasome; Tom1 limits accumulation and aggregation of stalled peptides in rqc1Δ cells; notably, Tom1's E3 ubiquitin ligase activity is not required for this aggregate-prevention function. |
Co-immunoprecipitation, genetic deletion, protein aggregation assay |
Molecular biology of the cell |
Medium |
28298488
|
| 2018 |
Yeast HECT E3 ligase Tom1 physically interacts with Spo12 (a FEAR network component) and mediates its ubiquitin-dependent turnover in G2/M phase; overexpression of Spo12 is cytotoxic in tom1Δ; Spo12 is still degraded in S phase in the absence of Tom1 and Cdh1, indicating additional E3 ligase(s). |
Co-immunoprecipitation, genetic deletion, protein stability assay |
FEBS letters |
Medium |
29683484
|
| 2018 |
TOM1 binds FcγRIIb2 (a variant Fc receptor) and attenuates its recycling, thereby suppressing neuronal uptake of oligomeric Aβ1-42; TOM1 expression is downregulated in the hippocampus of 3xTg-AD mice and AD patients; lentiviral TOM1 restoration rescues memory deficits in 3xTg-AD mice. |
Co-immunoprecipitation, Fcgr2b knockout neurons, lentiviral gene delivery, behavioral testing |
The Journal of neuroscience |
Medium |
30185465
|
| 2019 |
TOM1 VHS domain preferentially binds PI5P over other phosphoinositides; PI5P binding destabilizes the VHS domain structure (reduced thermostability, interhelical contacts, and conformational compaction) and binding is endothermic with two non-cooperative binding sites; acyl chains of PI5P contribute to interaction; this structural change may alter downstream effector interactions under Shigella infection. |
Thermal denaturation (DSF), isothermal calorimetry (ITC), NMR spectroscopy |
Scientific reports |
High |
31350523
|
| 2019 |
The TOM1 p.G307D missense variant fails to interact with TOLLIP; patient-derived cells show impaired autophagy and enhanced apoptosis susceptibility; these functional defects are consistent with TOM1's established role in TOLLIP-dependent IL-1 recycling and autophagosome maturation. |
Whole-exome sequencing, Co-immunoprecipitation (mutant vs. WT), autophagy flux assays in patient cells, signaling assays (STAT, ERK1/2) |
NPJ genomic medicine |
Medium |
31263572
|
| 2023 |
SENP1 de-SUMOylates TOM1, promoting its stability and function; CIH induces SUMOylation of TOM1 leading to its destabilization; SENP1 overexpression reduces TOM1 SUMOylation, enhances TOM1 levels and microglial migration, and reduces neuroinflammation; TOM1 knockdown suppresses these SENP1-driven effects, placing TOM1 downstream of SENP1 in this pathway. |
Co-immunoprecipitation, siRNA knockdown, SENP1 overexpression/knockout, SUMO immunoprecipitation, in vitro and in vivo CIH model |
International immunopharmacology |
Medium |
37137262
|
| 2024 |
SIRT5 directly interacts with TOM1 and desuccinylates it at the K48 site, stabilizing TOM1 protein; TOM1 knockdown reverses the pro-autophagy and anti-apoptotic effects of SIRT5 overexpression in an H/R-induced MIRI cell model, placing TOM1 downstream of SIRT5 in regulating autophagy-related cell death. |
Co-immunoprecipitation, succinylation immunoprecipitation, siRNA knockdown rescue assay, overexpression, in vivo MI model |
BMC cardiovascular disorders |
Medium |
39210272
|
| 2024 |
TOM1 contains a DXXLL motif-adjacent region that enhances VHS domain affinity for ubiquitin and is modulated by phosphorylation; TOM1 PI5P binding is pH-dependent—under acidic conditions TOM1 retains TOLLIP complex formation but cannot bind ubiquitin; acidic endosomal pH promotes TOM1 and TOLLIP accumulation at endosomes through this pH-sensing mechanism. |
Biophysical binding assays, phosphorylation analysis, pH-dependent binding assays, Co-immunoprecipitation |
Structure (London, England : 1993) |
Medium |
39208792
|
| 2025 |
Cryo-EM structures of yeast Tom1 during an active ubiquitination cycle reveal that its extended solenoid domain architecture harbors a non-canonical ubiquitin-binding site that coordinates a structural ubiquitin; this structural ubiquitin contributes to the fidelity of K48-linked poly-ubiquitin chain assembly by the HECT domain. |
Cryo-electron microscopy (cryo-EM), in vitro ubiquitination assay, mutagenesis of ubiquitin-binding site |
Cell reports |
High |
40359109
|
| 2025 |
The TOM1 G307D variant impairs TOM1-TOLLIP interaction and reduces TOM1's ability to inhibit TOLLIP binding to PI(3)P; patient cells show autophagosome accumulation due to impaired autophagosome-lysosome fusion and excessive activation of inflammatory pathways. |
Biophysical binding assays, Co-immunoprecipitation, patient cell autophagy/lysosome fusion assays, inflammatory signaling assays |
Disease models & mechanisms |
Medium |
40936361
|
| 2026 |
TOM1 binds the NTF2L domain of the stress granule scaffold protein G3BP1 and promotes stress granule disassembly; TOM1 upregulation during chronic colitis drives SG disassembly, enabling nuclear translocation of FUBP1 and upregulation of c-Myc, thereby contributing to tumorigenesis. |
Co-immunoprecipitation, overexpression, nuclear fractionation, cell-based SG assembly/disassembly assays |
Redox biology |
Medium |
42127552
|