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Showing STX5 — SED5 is a alias.

STX5

Syntaxin-5 · UniProt Q13190

Length
355 aa
Mass
39.7 kDa
Annotated
2026-06-10
12 papers in source corpus 8 papers cited in narrative 8 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

STX5 (yeast Sed5p) is a cis-Golgi-localized t-SNARE of the syntaxin family that mediates anterograde ER-to-Golgi and intra-Golgi vesicular transport, with depletion blocking cargo delivery to the Golgi and driving accumulation of ER membranes and transport vesicles (PMID:1400588, PMID:7929581). Both its transmembrane and cytoplasmic domains independently encode cis-Golgi targeting information (PMID:7929581). SNARE complex assembly by Sed5/STX5 is positively regulated by the Sec1/Munc18 protein Sly1, which binds the N-terminal helix of Sed5—relieving an autoinhibitory intramolecular interaction between the N-terminal region and its own C-terminal helix—and enhances formation of the early Golgi Sed5–Bet1 trans-SNARE complex (PMID:9753609, PMID:12186954). Intra-Golgi SNARE complexes containing the mammalian ortholog Syntaxin5a are further stabilized by the COG tethering complex through direct Cog4 and Cog6 interactions, loss of which leaves Syntaxin5 free and reduces steady-state SNARE complex levels and mobility (PMID:18086915). PKA-site phosphorylation of Sed5 at serine-317 toggles the protein between states controlling ER-Golgi transport, retrograde recycling, and Golgi stacking morphology (PMID:16093353). Beyond core trafficking, STX5 binds the VLDL-receptor C-terminal domain to influence its Golgi maturation, glycosylation, and surface delivery (PMID:23701949), and Sed5 supports autophagy by directing Atg9-containing vesicle trafficking to the phagophore assembly site in concert with Sft1/Sft2 (PMID:28927260).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 1992 High

    Established that Sed5p is an essential integral membrane component of the early secretory pathway, defining the gene's core role before any molecular activity was known.

    Evidence Gene depletion/overexpression with carboxypeptidase Y transport assay, immunofluorescence, and EM in yeast

    PMID:1400588

    Open questions at the time
    • Did not define the protein family or SNARE activity
    • Precise sub-Golgi localization not yet resolved
  2. 1994 High

    Placed Sed5 in the syntaxin family and mapped its cis-Golgi targeting determinants, showing both transmembrane and cytoplasmic domains independently direct localization.

    Evidence Epitope-tagged and chimeric Sed5 expression in COS cells, immuno-EM, domain-swap mutagenesis, in vivo yeast assays

    PMID:7929581

    Open questions at the time
    • Did not identify cognate v-SNAREs or regulators
    • Targeting receptor/machinery for the cytoplasmic-domain signal unknown
  3. 1998 Medium

    Resolved how the regulator Sly1 engages Sed5, localizing binding to the N-terminal helix and linking it to an autoinhibitory intramolecular interaction.

    Evidence In vitro binding/pull-down assays with individual Sed5 helices and truncation fragments

    PMID:9753609

    Open questions at the time
    • In vitro domain-mapping not validated in cells
    • Functional consequence of relieving autoinhibition not demonstrated here
  4. 2002 High

    Demonstrated that Sly1 binding to Sed5 is functionally productive, enhancing assembly of the early Golgi Sed5-Bet1 trans-SNARE complex.

    Evidence Co-IP, in vitro SNARE complex formation with recombinant Sly1 added to yeast lysate, temperature-sensitive sly1 mutant

    PMID:12186954

    Open questions at the time
    • Full reconstituted membrane fusion not shown
    • Quantitative kinetics of Sly1-stimulated assembly not defined
  5. 2005 High

    Identified phosphoregulation of Sed5 at PKA-site S317 as a switch controlling transport directionality and Golgi morphology.

    Evidence S317A/S317D site-directed mutagenesis, transport and morphology readouts, genetic epistasis with sec21-2 in yeast

    PMID:16093353

    Open questions at the time
    • Direct demonstration of PKA as the in vivo kinase incomplete
    • Mechanism by which phosphostate alters SNARE assembly not resolved
  6. 2007 High

    Connected Syntaxin5/Sed5 to the COG tethering complex, showing COG stabilizes intra-Golgi SNARE complexes via Cog4/Cog6 binding.

    Evidence Co-IP, FRET, RNAi knockdown, FRAP, dominant-negative overexpression in yeast and mammalian cells

    PMID:18086915

    Open questions at the time
    • Structural basis of Cog4/Cog6-Syntaxin5 interface unknown
    • Whether COG acts on assembly versus disassembly not distinguished
  7. 2013 Medium

    Extended STX5 function to cargo-specific trafficking by showing direct interaction with the VLDL-receptor influencing its glycosylation and surface delivery.

    Evidence Co-IP, in vitro binding, glycosylation maturation assays, overexpression, BFA treatment, trafficking assays

    PMID:23701949

    Open questions at the time
    • Single-lab characterization without reciprocal in vivo validation
    • Physiological role of the STX5-VLDLR interaction not established
  8. 2017 Medium

    Implicated Sed5 in autophagy by linking it to anterograde trafficking of Atg9 vesicles to the phagophore assembly site.

    Evidence Temperature-sensitive sed5-1 mutant, fluorescence microscopy of Atg8/Atg9/Atg23/Atg27, genetic suppression by SFT1/SFT2 overexpression in yeast

    PMID:28927260

    Open questions at the time
    • Direct physical role of Sed5 in Atg9 vesicle fusion not shown
    • Conservation of this autophagy role in mammalian STX5 untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How phosphoregulation, Sly1 binding, and COG tethering are integrated to coordinate the directionality and fidelity of STX5-mediated fusion remains unresolved.
  • No high-resolution structure of STX5 in an assembled trans-SNARE complex
  • Crosstalk between S317 phosphostate and Sly1/COG regulation undefined
  • Mammalian autophagy and cargo-selective roles not mechanistically unified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4
Localization
GO:0005794 Golgi apparatus 3
Pathway
R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-9612973 Autophagy 1
Partners
BET1COG4COG6SFT1SFT2SLY1/SCFD1VLDLR
Complex memberships
cis-Golgi SNARE complex

Evidence

Reading pass · 8 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 Sed5p (yeast ortholog of STX5) is an integral membrane protein required for ER-to-Golgi vesicular transport; depletion blocks carboxypeptidase Y transport to the Golgi and causes dramatic accumulation of ER membranes and vesicles; overexpression reduces ER-to-Golgi transport efficiency and causes vesicle accumulation. Immunofluorescence shows Sed5p localizes to punctate cytoplasmic structures, not ER membranes. Gene depletion/overexpression with cargo transport assay (carboxypeptidase Y), immunofluorescence, electron microscopy The Journal of cell biology High 1400588
1994 Sed5p is a member of the syntaxin family and localizes to the cis-Golgi network (tubulo-vesicular compartment on the cis side of the Golgi). Both its transmembrane domain and cytoplasmic domain contribute independently to its Golgi localization; the transmembrane domain contains targeting information, but cytoplasmic domain provides an additional targeting mechanism sufficient when the transmembrane domain is altered. Expression of epitope-tagged Sed5 and chimeric molecules in COS cells, immuno-EM, domain-swap mutagenesis, in vivo yeast functional assays The Journal of cell biology High 7929581
1998 The N-terminal helix of Sed5 is responsible for binding Sly1 protein, whereas Sly1 binding to syntaxin 1 requires almost the entire molecule. The N-terminal region of Sed5 also binds to its own C-terminal helix (intramolecular interaction), and Sly1 binding interferes with this intramolecular interaction. Protein-protein interaction assays dissecting individual helices of Sed5; pull-down/binding assays with truncation/domain fragments Biochemical and biophysical research communications Medium 9753609
2002 Sly1 (Sec1/Munc18 family protein) binds to the t-SNARE Sed5 and enhances formation of the early Golgi SNARE complex (Sed5–Bet1 trans-SNARE complex). A temperature-sensitive sly1 mutant with reduced Sed5 binding fails to promote SNARE complex formation; addition of recombinant Sly1 to yeast lysate enhances in vitro SNARE complex formation. Co-immunoprecipitation, in vitro SNARE complex formation assay with recombinant Sly1 added to yeast lysate, temperature-sensitive mutant analysis Journal of cell science High 12186954
2005 Phosphorylation of Sed5 at a conserved PKA consensus site (serine-317) regulates ER-Golgi transport and Golgi morphology. A phosphomimetic (S317D) substitution causes ER elaboration, defects in retrograde Golgi-to-ER transport, accumulation of small transport vesicles, and growth inhibition. A non-phosphorylatable (S317A) substitution has no transport defects but causes ordering of the Golgi into a mammalian-like stacked structure dependent on Sed5 retrograde recycling (absent in sec21-2 retrograde transport mutants). Site-directed mutagenesis (S317A and S317D), phosphoprotein analysis, intracellular transport assays, fluorescence microscopy, genetic epistasis with sec21-2 Molecular biology of the cell High 16093353
2007 The COG (conserved oligomeric Golgi) tethering complex colocalizes and co-immunoprecipitates with intra-Golgi SNARE molecules. In mammalian cells, hCog4p and hCog6p interact with Syntaxin5a (the mammalian ortholog of Sed5p), as confirmed by FRET. COG complex knockdown decreases Golgi SNARE mobility, causes accumulation of free Syntaxin5, and decreases steady-state levels of intra-Golgi SNARE complexes. Overexpression of the hCog4p N-terminal Syntaxin5a-binding domain destabilizes intra-Golgi SNARE complexes. Co-immunoprecipitation, FRET (in vivo interaction), RNAi knockdown, FRAP, dominant-negative overexpression The Journal of cell biology High 18086915
2013 STX5 physically interacts with the C-terminal domain of the VLDL-receptor (VLDL-R). Overexpression of Stx5 prevents advanced Golgi-maturation of VLDL-R without causing ER accumulation, instead translocating ER-/N-glycosylated VLDL-R to the plasma membrane via a BFA-insensitive and low-temperature-insensitive pathway, and interferes with VLDL-R reaching the trans-Golgi network. Co-immunoprecipitation, in vitro binding assays, glycosylation maturation assays, overexpression, BFA treatment, subcellular fractionation/trafficking assays Experimental cell research Medium 23701949
2017 Yeast Sed5 (cis-Golgi t-SNARE) plays a role in autophagy by regulating anterograde trafficking of Atg9-containing vesicles to the phagophore assembly site (PAS). In sed5-1 mutant cells, Atg8 is not properly transported to the PAS (multiple Atg8 dots dispersed in cytoplasm or trapped in Golgi), and Atg23 and Atg27 fail to localize properly to the Golgi. Overexpression of SFT1 or SFT2 (suppressors of sed5-ts) rescues these autophagy defects, indicating genetic interaction between Sft1/2 and Sed5 is required for autophagy. Temperature-sensitive sed5-1 mutant analysis, fluorescence microscopy of Atg8/Atg9/Atg23/Atg27 localization, genetic suppression by SFT1/SFT2 overexpression Molecules and cells Medium 28927260

Source papers

Stage 0 corpus · 12 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1992 SED5 encodes a 39-kD integral membrane protein required for vesicular transport between the ER and the Golgi complex. The Journal of cell biology 269 1400588
1994 Localization of Sed5, a putative vesicle targeting molecule, to the cis-Golgi network involves both its transmembrane and cytoplasmic domains. The Journal of cell biology 151 7929581
2007 Interaction of the conserved oligomeric Golgi complex with t-SNARE Syntaxin5a/Sed5 enhances intra-Golgi SNARE complex stability. The Journal of cell biology 93 18086915
2019 Stx5-Mediated ER-Golgi Transport in Mammals and Yeast. Cells 43 31357511
2005 Immunoisolaton of the yeast Golgi subcompartments and characterization of a novel membrane protein, Svp26, discovered in the Sed5-containing compartments. Molecular and cellular biology 43 16107716
2005 Control of Golgi morphology and function by Sed5 t-SNARE phosphorylation. Molecular biology of the cell 31 16093353
2002 Binding of Sly1 to Sed5 enhances formation of the yeast early Golgi SNARE complex. Journal of cell science 30 12186954
1998 Protein-protein interactions of the yeast Golgi t-SNARE Sed5 protein distinct from its neural plasma membrane cognate syntaxin 1. Biochemical and biophysical research communications 21 9753609
2006 Identification of a Sed5-like SNARE gene LjSYP32-1 that contributes to nodule tissue formation of Lotus japonicus. Plant & cell physiology 13 16699179
2013 Stx5 is a novel interactor of VLDL-R to affect its intracellular trafficking and processing. Experimental cell research 12 23701949
2017 The Roles of the SNARE Protein Sed5 in Autophagy in Saccharomyces cerevisiae. Molecules and cells 7 28927260
2023 STX5 Inhibits Hepatocellular Carcinoma Adhesion and Promotes Metastasis by Regulating the PI3K/mTOR Pathway. Journal of clinical and translational hepatology 4 36969886

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