| Category | Key points | Key recent sources (with year, journal, DOI URL) |
|---|---|---|
| Identity/domains | ATL3 in this report corresponds to human atlastin GTPase 3, an ER-resident dynamin-like large GTPase/atlastin-family protein. Reported architecture includes an N-terminal GTPase domain, a stalk/3-helix bundle, and a C-terminal transmembrane region with membrane-associated helical elements; ATL3 is preferentially associated with ER three-way junctions/tubular ER and differs from ATL1/ATL2 by broader non-CNS expression and distinct disease associations (pqac-00000005, pqac-00000006, pqac-00000008). | Arias 2025, unknown journal, n/a; Greco 2024, unknown journal, n/a; Zlamalova et al. 2024, *Neurobiology of Disease*, https://doi.org/10.1016/j.nbd.2024.106556 |
| Biochemical activity | ATL3 is a membrane-fusion GTPase that uses GTP as substrate; atlastin-family GTPase activity is required for homotypic ER membrane fusion and generation of ER three-way junctions. In ATL3-specific experiments, GTPase-defective ATL3 mutants fail to rescue functional phenotypes, supporting that ATL3’s enzymatic GTPase activity is required for its ER-remodeling function (pqac-00000010, pqac-00000011). | Pletan et al. 2023, *Journal of Virology*, https://doi.org/10.1128/jvi.00756-23 |
| Mechanism of ER fusion | Recent single-molecule work on human atlastin mechanism (performed on ATL1 cytosolic domain, used here as family-mechanistic context) supports a cycle in which GTP binding promotes a loose crossover dimer, GTP hydrolysis tightens the 3HB interface to drive fusion, and Pi/GDP release resets the protein. A membrane-embedded helix between the 3HB and transmembrane region self-associates and is required for fusion; small sequence differences between paralogs can tune this cycle and are relevant to ATL3 interpretation (pqac-00000018, pqac-00000019, pqac-00000020, pqac-00000021, pqac-00000023). | Shi et al. 2024, *Nature Communications*, https://doi.org/10.1038/s41467-024-46919-z |
| ER-phagy role | ATL3 is described as a tubular-ER ER-phagy/reticulophagy receptor or receptor-like factor. Reviews and cited primary work indicate ATL3 promotes degradation of tubular ER during starvation, preferentially targets ER tubules, and contains two GIM motifs in its N-terminal cytosolic region that mediate selective binding to GABARAP rather than LC3, linking tubular ER to the autophagy machinery (pqac-00000013, pqac-00000014, pqac-00000015, pqac-00000016, pqac-00000017, pqac-00000030). | Hill et al. 2023, *Journal of Neuroscience Research*, https://doi.org/10.1002/jnr.25225; Hübner & Dikic 2020, *Cell Death & Differentiation*, https://doi.org/10.1038/s41418-019-0444-0; Yang & Sheng 2026, *Acta Pharmacologica Sinica*, https://doi.org/10.1038/s41401-025-01724-2 |
| Viral infection role | ATL3 has emerging infection-related functions in ER remodeling. During SV40 entry, ATL3 relocalizes to ER foci, forms complexes with LNP/RTN4B and virus-containing penetration machinery, and uses GTPase-dependent fusion activity to help build multi-tubular ER junctions needed for membrane penetration. In coronavirus studies, ATL3 is also reported as an ER-phagy receptor hijacked into ORF8/p62 condensates, suppressing ER-phagy and favoring viral replication/DMV formation (pqac-00000010, pqac-00000011, pqac-00000026, pqac-00000027). | Pletan et al. 2023, *Journal of Virology*, https://doi.org/10.1128/jvi.00756-23; Tan et al. 2023, *Cell Reports*, https://doi.org/10.1016/j.celrep.2023.112286 |
| Disease associations | ATL3 is linked to inherited neuropathies, especially hereditary sensory and autonomic neuropathy type 1F and Charcot-Marie-Tooth disease axonal type 2N in target-disease databases. Human genetic/functional studies also support ATL3 variants causing sensory neuropathy and expanding phenotypes to motor axonopathy; disease-associated variants affect the GTPase/globular domain or later steps of the fusion cycle, with downstream effects on ER architecture, ER-mitochondria contacts, Golgi morphology, and autophagic flux (pqac-00000000, pqac-00000003, pqac-00000004, pqac-00000024, pqac-00000028, pqac-00000029). | Open Targets, ATL3 associations, context pqac-00000000; Arias 2025, unknown journal, n/a |
| Quantitative data | Recent quantitative findings include: in ATL1 family-mechanistic smFRET experiments, crossover dimer states were centered around ~0.28 and ~0.66 FRET, with monomeric states around ~0.18, ~0.41, ~0.63, and ~0.83 depending on nucleotide state; in SV40 studies, ~75% of Bap31+ ER foci colocalized with ATL3 foci, and ATL3 rescue experiments were analyzed over 3 independent experiments with **P ≤ 0.01 or ***P ≤ 0.001; in ATL3 p.Gln170Glu patient fibroblasts, ER-mitochondria contact sites were reduced to 21.5 ± 2.5 and 24.8 ± 3.1 dots/cell versus 118.2 ± 7.7 and 103.5 ± 6.0 in controls/father (pqac-00000020, pqac-00000021, pqac-00000027, pqac-00000028). | Shi et al. 2024, *Nature Communications*, https://doi.org/10.1038/s41467-024-46919-z; Pletan et al. 2023, *Journal of Virology*, https://doi.org/10.1128/jvi.00756-23; Arias 2025, unknown journal, n/a |


*Table: This table summarizes the current functional annotation of human ATL3, including identity, biochemical activity, ER fusion mechanism, ER-phagy, infection-related roles, disease links, and selected quantitative findings. It is useful as a compact evidence map with direct source and context-ID support.*