| 1996 |
UFE1 (STX18 ortholog in S. cerevisiae) is an essential gene required for both spore germination and vegetative growth, with sequence similarity to SED5 and the coiled-coil region of USO1, suggesting involvement in the secretory pathway. |
Gene disruption experiments, sequence analysis |
Current genetics |
Medium |
8929391
|
| 1997 |
Ufe1p (yeast STX18 ortholog) functions as an ER t-SNARE mediating retrograde transport from the Golgi to the ER. It forms a functional SNARE complex with Sec20p, Tip20p, and the v-SNARE Sec22p. A growth-inhibiting mutation in Ufe1p is compensated by a mutation in Sec20p, and SEC22 acts as an allele-specific multicopy suppressor of a temperature-sensitive ufe1 mutation. |
Co-precipitation, genetic suppressor analysis, allele-specific multicopy suppressor screen |
The EMBO journal |
High |
9214619
|
| 1998 |
Ufe1p (yeast STX18 ortholog) is required for ER membrane fusion in a process that does not require Sec18p/NSF or Sec17p but instead requires the NSF-related ATPase Cdc48p. Ufe1p acts as a t-SNARE undergoing direct t-t-SNARE and Cdc48p interactions during organelle (ER) membrane fusion, in addition to its role as a t-SNARE for vesicular traffic. |
In vitro ER membrane fusion assay, protein interaction studies, genetic analysis |
Cell |
High |
9506516
|
| 1998 |
The v-SNARE Sec22p recycles from the Golgi back to the ER via retrograde COPI vesicles, and this recycling requires functional Ufe1p (yeast STX18 ortholog) as well as Sec20p, Sec21p, and Sec27p. Ufe1-1 mutant cells show mislocalization of Sec22p to Golgi structures rather than ER. |
Immunofluorescence microscopy, subcellular fractionation, alpha-factor-tagged Sec22 reporter assay in yeast mutants |
Journal of cell science |
Medium |
9580559
|
| 1998 |
Temperature-sensitive tip20 mutants are synthetic lethal with ufe1-1 and ret2-1 (delta-COP), indicating Tip20p and Ufe1p (yeast STX18 ortholog) function together in ER-Golgi retrograde transport, likely as part of the docking complex for Golgi-derived retrograde transport vesicles. |
Synthetic lethality / genetic epistasis analysis |
Yeast (Chichester, England) |
Medium |
9639310
|
| 2002 |
Candida albicans Ufe1p (ortholog of STX18) functionally complements a thermosensitive ufe1 mutation in S. cerevisiae, demonstrating functional conservation of the ER t-SNARE activity across fungal species. CaUfe1p interacts with CaSec20p and CaTip20p as part of an ER-tSNARE complex. |
Complementation assay, two-hybrid analysis, co-immunoprecipitation |
Molecular genetics and genomics |
Medium |
12471444
|
| 2003 |
Slt1 (a previously uncharacterized ER-localized SNARE) forms a SNARE complex with Sec22 and the ER syntaxin Ufe1 (yeast STX18 ortholog) and is required for retrograde traffic to the ER. Down-regulation of Slt1 leads to improper secretion of proteins normally resident in the ER. Sec20 likely contributes the fourth SNARE to this SNAREpin. |
Sequence analysis, localization studies, functional knockdown, complex assembly assay |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
12893879
|
| 2007 |
Yeast Ufe1 (STX18 ortholog) is subject to ERAD-like degradation by the ubiquitin-proteasome system, and is protected from this degradation by binding to the SM protein Sly1. This SM-protein-controlled stabilization is specific to Ufe1 and does not apply to the Golgi Qa-SNARE Sed5, despite both being Sly1 partners. |
Protein stability assays, genetic manipulation of ERAD components, interaction studies |
EMBO reports |
Medium |
18007658
|
| 2011 |
The Dsl1 tethering complex (Dsl1, Dsl3/Sec39, Tip20) forms a stable complex with the ER SNAREs Ufe1, Use1, and Sec20 to mediate fusion of COPI vesicles with the ER. Among R-SNAREs, Sec22 is preferred over Ykt6 in the Dsl-SNARE complex. NSF/Sec18 can displace Ykt6 but not Sec22, suggesting a regulatory role for Ykt6. Ufe1 and Sec20 are ER-resident proteins that do not enter COPII vesicles. |
In vitro binding assays, in vivo co-immunoprecipitation, subcellular fractionation (COPII vesicle analysis) |
The Journal of biological chemistry |
High |
21550981
|
| 2016 |
During starvation in yeast, Ufe1 (STX18 ortholog) is increasingly exported from the ER in specific COPII vesicles (dependent on Sec23) and targeted to autophagosome formation sites containing Atg8 and Atg9. Ufe1 interacts with non-ER SNARE proteins implicated in autophagosome formation. Loss of Ufe1 function impairs autophagy, resulting in fewer and smaller autophagosomes. |
Fluorescence microscopy (co-localization with autophagy markers), genetic loss-of-function, COPII mutant analysis (sec23-1), starvation sensitivity assay |
Cell reports |
Medium |
26876173
|
| 2016 |
STX18 (human) is required for ER to Golgi transport of type II collagen during chondrogenesis. Loss of STX18 or its partner SCFD1 (SLY1) severely impairs transport of type II collagen in mammalian chondrocytes, establishing a specific ER export pathway for large ECM proteins during chondrogenesis. |
Loss-of-function (knockdown) in mammalian chondrocytes, co-localization/transport assay for type II collagen |
Developmental biology |
Medium |
27851892
|
| 2016 |
STX18 knockdown in antigen-presenting cells decreases surface translocation of MR1 and impairs MR1-dependent MAIT cell recognition of Mycobacterium tuberculosis-infected cells, indicating STX18 regulates MR1 trafficking and loading of intracellular mycobacterially-derived ligands. |
Lentiviral shRNA screen, surface MR1 quantification, MAIT cell activation assay |
PLoS pathogens |
Medium |
27031111
|
| 2018 |
The ER-resident SNARE Ufe1 (STX18 ortholog) is co-opted by Tomato bushy stunt virus (TBSV) into the viral replication compartment. The viral p33 replication protein physically interacts with both Ufe1p and Use1p, and depletion of Ufe1 causes mislocalization of the p33 protein to the ER membrane, reduces viral RNA accumulation, and impairs formation of membrane contact sites, sterol enrichment at replication sites, and recruitment of pro-viral host factors. |
Co-immunoprecipitation (p33-Ufe1 interaction), cell-free replicase assay, fluorescence microscopy (localization of p33), dominant-negative overexpression, genetic depletion of Ufe1 |
PLoS pathogens |
Medium |
29746582
|
| 2023 |
STX18 is required for cartilage and bone development in vivo. A homozygous p.Arg10Pro substitution in STX18 is associated with severe osteochondrodysplasia in a human fetus. CRISPR/Cas9-mediated Stx18 deficiency in zebrafish causes defects in cartilage and bone development. Stx18 deficiency is accompanied by increased expression of multiple SNARE complex components (Ufe1 complex) and COPI/COPII proteins, suggesting impairment of both anterograde and retrograde vesicular transport. |
Human genetics (homozygous variant identification), CRISPR/Cas9 zebrafish loss-of-function, expression analysis of SNARE and coat proteins |
Journal of bone and mineral research |
Medium |
37718532
|
| 2024 |
STX18 acts as a negative regulator of lipophagy by binding ATG14, disrupting ATG14 interactions with ATG8-family members and subverting PI3KC3-C1 complex formation. Knockdown of STX18 activates ATG14-dependent lipophagy, leading to degradation of lipid droplet-associated anti-viral protein Viperin (RSAD2). Coronavirus M protein binds STX18 and disrupts the STX18-ATG14 interaction to induce lipophagy and degrade Viperin, facilitating virus production. |
Co-immunoprecipitation (STX18-ATG14 interaction), siRNA knockdown, lipid droplet degradation assay, Viperin/RSAD2 protein level measurement, virus production assay |
Nature communications |
High |
38245527
|