VPS45

id: P38932
gene_symbol: VPS45
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:559292
  label: Saccharomyces cerevisiae
description: >-
  VPS45 encodes a Sec1/Munc18 (SM) family protein essential for vacuolar
  protein sorting and membrane traffic between the late Golgi and the
  prevacuolar compartment/endosome. Vps45p binds and regulates the syntaxin
  t-SNAREs Pep12p (a prevacuolar/endosomal t-SNARE) and Tlg2p (a late
  Golgi/early endosome t-SNARE), forming distinct Vps45p-Tlg2p and
  Vps45p-Pep12p complexes. Acting as an active SM chaperone rather than a
  passive syntaxin binder, Vps45p stabilizes Tlg2p (preventing its rapid
  proteasomal degradation) and positively regulates productive SNARE complex
  assembly, thereby enabling docking/fusion of Golgi-derived transport vesicles
  with the prevacuolar compartment. It defines a VPS45-dependent intracellular
  (biosynthetic) route into the PVC distinct from the VPS45-independent
  endocytic route, and is also required for the constitutive cytoplasm-to-vacuole
  targeting (Cvt) pathway of aminopeptidase I. Vps45p is recruited to endosomal
  membranes through the Vac1p adaptor, which integrates Vps21p (Rab5-like) and
  Vps34-generated PI(3)P signals; it cycles between the cytosol and the
  cytoplasmic face of intracellular (vacuolar/endosomal) membranes. Mutations in
  human VPS45 cause severe congenital neutropenia, underscoring the conserved
  importance of this trafficking regulator. Orthologous to human VPS45.
existing_annotations:
- term:
    id: GO:0016192
    label: vesicle-mediated transport
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      Vesicle-mediated transport is consistent with the core biology of VPS45 as
      an SM-family protein that drives SNARE-dependent docking and fusion of
      transport vesicles in the endosomal/Golgi-to-vacuole system.
    action: ACCEPT
    reason: >-
      Well-supported high-level process; Vps45p is required for fusion of
      Golgi-derived vesicles with the prevacuolar compartment.
    supported_by:
    - reference_id: file:yeast/VPS45/VPS45-deep-research-falcon.md
      reference_section_type: OTHER
      supporting_text: >-
        Vps45 is an endosomal SM protein
- term:
    id: GO:0000139
    label: Golgi membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      Golgi membrane localization is consistent with the role of Vps45p in
      Golgi(TGN)-to-prevacuolar transport and with its association with the late
      Golgi/early endosome syntaxin Tlg2p.
    action: ACCEPT
    reason: >-
      Supported by IDA evidence (PMID:7720726) on this same term and by the
      VPS45-dependent Golgi-to-PVC trafficking step.
    supported_by:
    - reference_id: file:yeast/VPS45/VPS45-deep-research-falcon.md
      reference_section_type: OTHER
      supporting_text: |-
        Sec1/Munc18-family SM protein required for docking/fusion of Golgi-derived vesicles with the prevacuolar compartment
- term:
    id: GO:0006886
    label: intracellular protein transport
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      Intracellular protein transport is consistent with the role of Vps45p in
      moving biosynthetic cargo from the Golgi/TGN into the prevacuolar
      compartment.
    action: ACCEPT
    reason: >-
      High-level but accurate; Vps45p defines an intracellular route for
      biosynthetic cargo into the PVC.
    supported_by:
    - reference_id: file:yeast/VPS45/VPS45-deep-research-falcon.md
      reference_section_type: OTHER
      supporting_text: |-
        A **VPS45-dependent intracellular route** (Golgi/TGN → PVC) for biosynthetic cargo
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      Cytoplasm localization is consistent with the cycling behavior of Vps45p,
      a peripheral membrane SM protein that exchanges between the cytosol and the
      cytoplasmic face of intracellular membranes. The vacuolar/Golgi membrane
      annotations capture the more specific membrane-associated compartments.
    action: ACCEPT
    reason: >-
      Consistent with UniProt subcellular location and falcon synthesis; Vps45p
      becomes more cytosolic when its Tlg2 membrane anchor is removed.
    supported_by:
    - reference_id: file:yeast/VPS45/VPS45-deep-research-falcon.md
      reference_section_type: OTHER
      supporting_text: |-
        becomes more **cytosolic** when Tlg2 lacks its N-terminal Vps45-binding region
- term:
    id: GO:0005774
    label: vacuolar membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      Vacuolar membrane is consistent with the experimentally documented cycling
      of Vps45p on and off the cytoplasmic side of the vacuolar membrane
      (UniProt; PubMed:12756236) and with its membrane association in wild-type
      contexts.
    action: ACCEPT
    reason: >-
      Supported by UniProt subcellular location and falcon membrane-association
      evidence.
    supported_by:
    - reference_id: file:yeast/VPS45/VPS45-deep-research-falcon.md
      reference_section_type: OTHER
      supporting_text: |-
        Vps45p is predominantly **membrane-associated** in wild-type contexts
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      Golgi apparatus localization is consistent with the role of Vps45p at the
      late Golgi/TGN, where it associates with the Tlg2p syntaxin module and
      mediates Golgi-to-PVC transport.
    action: ACCEPT
    reason: >-
      Plausible and corroborated by the more specific Golgi membrane (IDA)
      annotation; Vps45p acts at Tlg2-associated Golgi/endosomal membranes.
    supported_by:
    - reference_id: file:yeast/VPS45/VPS45-deep-research-falcon.md
      reference_section_type: OTHER
      supporting_text: |-
        Golgi (TGN) → prevacuolar compartment/endosome (PVC)** transport in the CPY pathway
- term:
    id: GO:0006886
    label: intracellular protein transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      Duplicate of the IBA intracellular protein transport annotation; consistent
      with the biosynthetic Golgi-to-PVC route mediated by Vps45p.
    action: ACCEPT
    reason: >-
      Same well-supported high-level process as the IBA annotation above.
    supported_by:
    - reference_id: file:yeast/VPS45/VPS45-deep-research-falcon.md
      reference_section_type: OTHER
      supporting_text: |-
        A **VPS45-dependent intracellular route** (Golgi/TGN → PVC) for biosynthetic cargo
- term:
    id: GO:0015031
    label: protein transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: >-
      Protein transport is a high-level keyword-derived term consistent with the
      role of Vps45p in vacuolar protein sorting; more specific child terms
      (Golgi to vacuole transport, Cvt pathway) better capture the biology.
    action: ACCEPT
    reason: >-
      Accurate but general; retained as a parent of the specific transport
      processes Vps45p mediates.
    supported_by:
    - reference_id: file:yeast/VPS45/VPS45-deep-research-falcon.md
      reference_section_type: OTHER
      supporting_text: |-
        Sec1/Munc18-family SM protein required for docking/fusion of Golgi-derived vesicles with the prevacuolar compartment
- term:
    id: GO:0016192
    label: vesicle-mediated transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      Duplicate of the IBA vesicle-mediated transport annotation; consistent with
      the SNARE-dependent vesicle docking/fusion role of Vps45p.
    action: ACCEPT
    reason: >-
      Same well-supported high-level process as the IBA annotation above.
    supported_by:
    - reference_id: file:yeast/VPS45/VPS45-deep-research-falcon.md
      reference_section_type: OTHER
      supporting_text: |-
        Vps45 is an endosomal SM protein
- term:
    id: GO:0031201
    label: SNARE complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      SNARE complex localization reflects the engagement of Vps45p with syntaxin
      SNAREs (Tlg2p/Pep12p) and its requirement for productive ternary SNARE
      complex formation (with Tlg1p and Vti1p for the Tlg2 module).
    action: ACCEPT
    reason: >-
      Supported by falcon evidence that Vps45p is required for Tlg2 entry into
      ternary SNARE complexes; also annotated by IPI elsewhere in this file.
    supported_by:
    - reference_id: file:yeast/VPS45/VPS45-deep-research-falcon.md
      reference_section_type: OTHER
      supporting_text: |-
        Vps45p is needed not just for Tlg2 stability but also for Tlg2 entry into ternary SNARE complexes
- term:
    id: GO:0031338
    label: regulation of vesicle fusion
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      Regulation of vesicle fusion is consistent with the SM-protein function of
      Vps45p in controlling SNARE-dependent docking and fusion; the more specific
      child term positive regulation of SNARE complex assembly (GO:0035543) is
      also annotated.
    action: ACCEPT
    reason: >-
      Supported; Vps45p positively regulates productive SNARE complex assembly,
      a key control point for vesicle fusion.
    supported_by:
    - reference_id: file:yeast/VPS45/VPS45-deep-research-falcon.md
      reference_section_type: OTHER
      supporting_text: |-
        Directly binds Tlg2p and positively regulates productive SNARE complex assembly
- term:
    id: GO:0098588
    label: bounding membrane of organelle
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      Bounding membrane of organelle is a high-level location term consistent
      with the peripheral association of Vps45p with the vacuolar/endosomal
      bounding membranes; more specific terms (vacuolar membrane, Golgi membrane)
      capture the biology.
    action: ACCEPT
    reason: >-
      Plausible high-level location; Vps45p is membrane-associated on the
      cytoplasmic face of intracellular organelle membranes.
    supported_by:
    - reference_id: file:yeast/VPS45/VPS45-deep-research-falcon.md
      reference_section_type: OTHER
      supporting_text: |-
        Vps45p is membrane-associated when full-length Tlg2p is present
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10397773
  review:
    summary: >-
      Generic protein binding is uninformative. The biologically meaningful
      interactions of Vps45p are with its cognate syntaxin SNAREs (Tlg2p,
      Pep12p) and the Vac1p adaptor; these are better captured by SNARE binding
      (GO:0000149) and the SNARE/trafficking process terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Avoid GO:0005515; specific SNARE binding and SNARE-assembly terms more
      accurately represent the function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10978279
  review:
    summary: >-
      Generic protein binding is uninformative; the specific Vps45p-syntaxin and
      Vps45p-Vac1p interactions are better captured by SNARE binding and the
      docking/fusion process terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Avoid GO:0005515; more specific terms capture the biology more accurately.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12553664
  review:
    summary: >-
      Generic protein binding is uninformative for Vps45p; its functional
      partnerships (syntaxins, Vac1p) are represented by more specific terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Avoid GO:0005515; more specific terms capture the biology more accurately.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16429126
  review:
    summary: >-
      Generic protein binding from a high-throughput proteome survey; not
      informative about the specific molecular function of Vps45p.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Avoid GO:0005515; high-throughput interaction without a specific
      functional term.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18719252
  review:
    summary: >-
      Generic protein binding from a binary interactome map; not informative
      about the specific molecular function of Vps45p.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Avoid GO:0005515; high-throughput interaction without a specific
      functional term.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19667197
  review:
    summary: >-
      This study characterizes how the N-terminal peptide of Tlg2p modulates
      binding of its closed conformation to Vps45p — a SNARE-binding interaction.
      Generic protein binding is over-annotated; SNARE binding (GO:0000149)
      captures it specifically.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Avoid GO:0005515; the interaction is syntaxin (SNARE) binding, captured by
      GO:0000149.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27107014
  review:
    summary: >-
      Generic protein binding from a large-scale inter-species interaction
      network; not informative about Vps45p molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Avoid GO:0005515; high-throughput interaction without a specific
      functional term.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:37968396
  review:
    summary: >-
      Generic protein binding from a global interactome study; not informative
      about Vps45p molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Avoid GO:0005515; high-throughput interaction without a specific
      functional term.
- term:
    id: GO:0000011
    label: vacuole inheritance
  evidence_type: IMP
  original_reference_id: PMID:1493335
  review:
    summary: >-
      Vacuole inheritance defects are part of the broad class-D/class-E vps
      mutant phenotype rather than a direct molecular function of Vps45p. The
      core role of Vps45p is SNARE-dependent vesicle docking/fusion in the
      Golgi-to-vacuole/endosomal system; defective vacuole inheritance is an
      indirect downstream consequence of impaired trafficking.
    action: KEEP_AS_NON_CORE
    reason: >-
      Pleiotropic/indirect phenotype of disrupted vacuolar trafficking, not the
      core direct function; retained as non-core.
    supported_by:
    - reference_id: file:yeast/VPS45/VPS45-deep-research-falcon.md
      reference_section_type: OTHER
      supporting_text: |-
        Vps45 is an endosomal SM protein that couples signaling-defined membrane identity (Vac1–Vps21–PI3P) to the formation and maintenance of a fusion-competent syntaxin/SNARE state
- term:
    id: GO:0000139
    label: Golgi membrane
  evidence_type: IDA
  original_reference_id: PMID:7720726
  review:
    summary: >-
      Direct evidence places Vps45p at Golgi membranes, consistent with its role
      in the consumption (fusion) of vacuole-targeted, post-Golgi transport
      vesicles and its association with the Tlg2p syntaxin at late Golgi/early
      endosome membranes.
    action: ACCEPT
    reason: >-
      IDA-supported localization concordant with the Golgi-to-PVC trafficking
      function of Vps45p.
    supported_by:
    - reference_id: file:yeast/VPS45/VPS45-deep-research-falcon.md
      reference_section_type: OTHER
      supporting_text: |-
        Sec1/Munc18-family SM protein required for docking/fusion of Golgi-derived vesicles with the prevacuolar compartment
- term:
    id: GO:0000149
    label: SNARE binding
  evidence_type: IPI
  original_reference_id: PMID:16769821
  review:
    summary: >-
      SNARE binding is a core molecular function of Vps45p. As an SM protein it
      binds its cognate syntaxin SNAREs Tlg2p and Pep12p (via two distinct
      binding modes), forming distinct Vps45p-Tlg2p and Vps45p-Pep12p complexes,
      and is required for productive ternary SNARE complex assembly. Notably,
      PMID:16769821 (Carpp et al. 2006) shows that the Vps45pL117R mutant, which
      abolishes the Sly1p-Sed5p-type binding of Vps45p to the Tlg2p N-terminal
      peptide, still rescues CPY sorting; the essential, fusion-relevant
      interaction is therefore the second mode, in which Vps45p engages the
      assembled SNARE complex (and the v-SNARE Snc2p) rather than only the
      uncomplexed syntaxin N-terminus.
    action: ACCEPT
    reason: >-
      Direct interaction (IPI) with cognate syntaxins; this is the defining
      molecular activity of the SM protein and is strongly corroborated by the
      falcon synthesis.
    supported_by:
    - reference_id: file:yeast/VPS45/VPS45-deep-research-falcon.md
      reference_section_type: OTHER
      supporting_text: |-
        physically associates with the syntaxin-like t-SNARE **Tlg2p** and also forms a separate complex with the endosomal t-SNARE **Pep12p**
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:9624182
  review:
    summary: >-
      Cytosol localization is plausible for Vps45p, a peripheral SM protein that
      cycles between the cytosol and the cytoplasmic face of intracellular
      membranes. However, the cited reference PMID:9624182 (Gerhardt et al.
      1998) is titled and abstracted as a study of the SM protein Vps33p, not
      Vps45p; its cytosol/membrane cycling data concern Vps33p. The full text is
      not available in the publication cache, so it cannot be confirmed whether
      the paper contains a direct IDA observation of Vps45p cytosol
      localization, and the GOA IDA attribution may be a mis-annotation
      conflating two SM-family proteins.
    action: UNDECIDED
    reason: >-
      Cannot verify the IDA: the cited PMID:9624182 is a Vps33p study (Vps45p
      does not appear in the abstract) and the full text is not accessible to
      confirm any direct Vps45p cytosol observation. Per curation guidelines,
      mark UNDECIDED when the relevant publication cannot be accessed/verified
      rather than ACCEPT.
- term:
    id: GO:0006623
    label: protein targeting to vacuole
  evidence_type: IMP
  original_reference_id: PMID:7628704
  review:
    summary: >-
      Protein targeting to the vacuole is a core process for Vps45p; vps45/stt10
      mutants show a class-D vacuolar protein sorting defect, mis-sorting
      biosynthetic cargo (e.g., CPY) that depends on the VPS45-mediated
      Golgi-to-PVC route.
    action: ACCEPT
    reason: >-
      Core vacuolar protein sorting function; strong CPY mis-sorting in vps45
      mutants.
    supported_by:
    - reference_id: file:yeast/VPS45/VPS45-deep-research-falcon.md
      reference_section_type: OTHER
      supporting_text: |-
        strong CPY mis-sorting, with **~70% CPY secretion** versus **~2–4%** in wild type
- term:
    id: GO:0006895
    label: Golgi to endosome transport
  evidence_type: IGI
  original_reference_id: PMID:9335586
  review:
    summary: >-
      Golgi to endosome transport captures the VPS45-dependent intracellular
      route by which biosynthetic cargo moves from the Golgi/TGN to the
      prevacuolar/endosomal compartment (PVC). Genetic interactions with PEP12
      and PEP7 place Vps45p in this Golgi-to-endosome SNARE module.
    action: ACCEPT
    reason: >-
      Supported by genetic interaction (IGI) and by the falcon-defined
      VPS45-dependent biosynthetic route into the PVC.
    supported_by:
    - reference_id: file:yeast/VPS45/VPS45-deep-research-falcon.md
      reference_section_type: OTHER
      supporting_text: |-
        A **VPS45-dependent intracellular route** (Golgi/TGN → PVC) for biosynthetic cargo
- term:
    id: GO:0006896
    label: Golgi to vacuole transport
  evidence_type: IMP
  original_reference_id: PMID:7720726
  review:
    summary: >-
      Golgi to vacuole transport is a core biological process for Vps45p, which
      is required for the consumption (docking/fusion) of vacuole-targeted,
      post-Golgi transport vesicles with the prevacuolar compartment en route to
      the vacuole.
    action: ACCEPT
    reason: >-
      IMP-supported core trafficking step; central to the function of this SM
      protein.
    supported_by:
    - reference_id: file:yeast/VPS45/VPS45-deep-research-falcon.md
      reference_section_type: OTHER
      supporting_text: |-
        Sec1/Munc18-family SM protein required for docking/fusion of Golgi-derived vesicles with the prevacuolar compartment
- term:
    id: GO:0007033
    label: vacuole organization
  evidence_type: IMP
  original_reference_id: PMID:9650782
  review:
    summary: >-
      Altered vacuole organization/morphology in vps45 mutants is a downstream
      consequence of impaired delivery of biosynthetic cargo and membrane to the
      vacuole, rather than a direct molecular function. The core role of Vps45p
      is SNARE-mediated docking/fusion at the Golgi-to-PVC step.
    action: KEEP_AS_NON_CORE
    reason: >-
      Indirect/pleiotropic organelle-morphology phenotype of disrupted
      trafficking; retained as non-core.
    supported_by:
    - reference_id: file:yeast/VPS45/VPS45-deep-research-falcon.md
      reference_section_type: OTHER
      supporting_text: |-
        A **VPS45-dependent intracellular route** (Golgi/TGN → PVC) for biosynthetic cargo
- term:
    id: GO:0007035
    label: vacuolar acidification
  evidence_type: IMP
  original_reference_id: PMID:7628704
  review:
    summary: >-
      Defective vacuolar acidification in vps45/stt10 mutants is an indirect
      consequence of the class-D vps trafficking defect; the source paper reports
      vacuoles with normal vacuolar H(+)-ATPase activity but defective
      acidification, indicating mis-delivery of components rather than a direct
      role of Vps45p in acidification.
    action: KEEP_AS_NON_CORE
    reason: >-
      Indirect/pleiotropic phenotype; vacuolar H(+)-ATPase activity is normal, so
      Vps45p does not directly mediate acidification. Retained as non-core.
    supported_by:
    - reference_id: file:yeast/VPS45/VPS45-deep-research-falcon.md
      reference_section_type: OTHER
      supporting_text: |-
        Vps45 is an endosomal SM protein that couples signaling-defined membrane identity (Vac1–Vps21–PI3P) to the formation and maintenance of a fusion-competent syntaxin/SNARE state
- term:
    id: GO:0031201
    label: SNARE complex
  evidence_type: IPI
  original_reference_id: PMID:10397773
  review:
    summary: >-
      Vps45p is part of the SNARE machinery, engaging the Tlg2p syntaxin module
      (with Tlg1p and Vti1p) required for productive SNARE complex formation in
      the Golgi/endosomal system.
    action: ACCEPT
    reason: >-
      Supported by IPI and by falcon evidence that Vps45p is required for Tlg2
      entry into ternary SNARE complexes.
    supported_by:
    - reference_id: file:yeast/VPS45/VPS45-deep-research-falcon.md
      reference_section_type: OTHER
      supporting_text: |-
        Vps45p is needed not just for Tlg2 stability but also for Tlg2 entry into ternary SNARE complexes
- term:
    id: GO:0032258
    label: cytoplasm to vacuole targeting by the Cvt pathway
  evidence_type: IMP
  original_reference_id: PMID:10545112
  review:
    summary: >-
      Vps45p, together with the syntaxin Tlg2p, forms a t-SNARE-Sec1p module
      required for the constitutive cytoplasm-to-vacuole targeting (Cvt) pathway
      of aminopeptidase I. vps45 mutants fail to mature API and phenocopy tlg2
      deletion, while starvation-induced macroautophagy remains intact.
    action: ACCEPT
    reason: >-
      Directly demonstrated (Abeliovich et al. 1999); a core Vps45p-dependent
      membrane-fusion process.
    supported_by:
    - reference_id: file:yeast/VPS45/VPS45-deep-research-falcon.md
      reference_section_type: OTHER
      supporting_text: |-
        Vps45p and Tlg2p are required for maturation/processing of API via the constitutive Cvt route
- term:
    id: GO:0035543
    label: positive regulation of SNARE complex assembly
  evidence_type: IMP
  original_reference_id: PMID:11432826
  review:
    summary: >-
      Vps45p positively regulates SNARE complex formation: it stabilizes the
      syntaxin homologue Tlg2p (preventing rapid proteasomal degradation) and is
      required for Tlg2p to enter productive ternary SNARE complexes with its
      cognate partners Tlg1p and Vti1p. This is a defining molecular role of the
      SM protein.
    action: ACCEPT
    reason: >-
      Directly demonstrated (Bryant & James 2001); core regulatory function.
    supported_by:
    - reference_id: file:yeast/VPS45/VPS45-deep-research-falcon.md
      reference_section_type: OTHER
      supporting_text: |-
        Directly binds Tlg2p and positively regulates productive SNARE complex assembly
- term:
    id: GO:0048210
    label: Golgi vesicle fusion to target membrane
  evidence_type: IMP
  original_reference_id: PMID:9650782
  review:
    summary: >-
      Golgi vesicle fusion to target membrane reflects the core SM-protein role
      of Vps45p in promoting SNARE-dependent docking and fusion of Golgi-derived
      transport vesicles with the prevacuolar compartment.
    action: ACCEPT
    reason: >-
      Core trafficking function; Vps45p enables docking/fusion of Golgi-derived
      vesicles with the PVC.
    supported_by:
    - reference_id: file:yeast/VPS45/VPS45-deep-research-falcon.md
      reference_section_type: OTHER
      supporting_text: |-
        Sec1/Munc18-family SM protein required for docking/fusion of Golgi-derived vesicles with the prevacuolar compartment
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IMP
  original_reference_id: PMID:11432826
  review:
    summary: >-
      The chaperone-like activity of Vps45p is specific to SNARE complex assembly
      (it stabilizes the Tlg2p syntaxin and promotes productive SNARE pairing),
      not generic binding of unfolded proteins. Modern consensus frames SM
      proteins as active chaperones for productive trans-SNARE complex assembly
      rather than general protein-folding chaperones, so unfolded protein binding
      over-extends the function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The chaperone activity is SNARE-assembly-specific; positive regulation of
      SNARE complex assembly (GO:0035543) and SNARE binding (GO:0000149) capture
      it more accurately than generic unfolded protein binding.
    supported_by:
    - reference_id: file:yeast/VPS45/VPS45-deep-research-falcon.md
      reference_section_type: OTHER
      supporting_text: |-
        SM proteins as **active chaperones for productive trans-SNARE complex assembly**, rather than passive syntaxin binders
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IPI
  original_reference_id: PMID:11432826
  review:
    summary: >-
      Duplicate (IPI) of the unfolded protein binding annotation. As above, the
      chaperone activity of Vps45p is SNARE-assembly-specific rather than generic
      unfolded protein binding.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      SNARE-assembly-specific chaperone activity; better captured by GO:0035543
      and GO:0000149 than by generic unfolded protein binding.
    supported_by:
    - reference_id: file:yeast/VPS45/VPS45-deep-research-falcon.md
      reference_section_type: OTHER
      supporting_text: |-
        SM proteins as **active chaperones for productive trans-SNARE complex assembly**, rather than passive syntaxin binders
core_functions:
- description: >-
    Endosomal Sec1/Munc18 (SM) family protein that binds its cognate syntaxin
    t-SNAREs Tlg2p and Pep12p and acts as an active SNARE-assembly chaperone,
    stabilizing Tlg2p and promoting productive ternary SNARE complex formation
    to drive docking and fusion of Golgi-derived transport vesicles with the
    prevacuolar compartment/endosome (the VPS45-dependent biosynthetic route),
    and the Tlg2-dependent Cvt delivery of aminopeptidase I.
  molecular_function:
    id: GO:0000149
    label: SNARE binding
  directly_involved_in:
  - id: GO:0035543
    label: positive regulation of SNARE complex assembly
  - id: GO:0006896
    label: Golgi to vacuole transport
  - id: GO:0006895
    label: Golgi to endosome transport
  - id: GO:0032258
    label: cytoplasm to vacuole targeting by the Cvt pathway
  locations:
  - id: GO:0000139
    label: Golgi membrane
  - id: GO:0005774
    label: vacuolar membrane
  supported_by:
  - reference_id: file:yeast/VPS45/VPS45-deep-research-falcon.md
    reference_section_type: OTHER
    supporting_text: |-
      Directly binds Tlg2p and positively regulates productive SNARE complex assembly
  - reference_id: file:yeast/VPS45/VPS45-deep-research-falcon.md
    reference_section_type: OTHER
    supporting_text: |-
      Sec1/Munc18-family SM protein required for docking/fusion of Golgi-derived vesicles with the prevacuolar compartment
references:
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10397773
  title: A role for Tlg1p in the transport of proteins within the Golgi apparatus of Saccharomyces cerevisiae.
  findings: []
- id: PMID:10545112
  title: Cytoplasm to vacuole trafficking of aminopeptidase I requires a t-SNARE-Sec1p complex composed of Tlg2p and Vps45p.
  findings: []
- id: PMID:10978279
  title: 'Pep3p/Pep5p complex: a putative docking factor at multiple steps of vesicular transport to the vacuole of Saccharomyces cerevisiae.'
  findings: []
- id: PMID:11432826
  title: Vps45p stabilizes the syntaxin homologue Tlg2p and positively regulates SNARE complex formation.
  findings: []
- id: PMID:12553664
  title: A novel phospholipid-binding protein from the yeast Saccharomyces cerevisiae with dual binding specificities for the transport GTPase Ypt7p and the Sec1-related Vps33p.
  findings: []
- id: PMID:1493335
  title: 'Morphological classification of the yeast vacuolar protein sorting mutants: evidence for a prevacuolar compartment in class E vps mutants.'
  findings: []
- id: PMID:16429126
  title: Proteome survey reveals modularity of the yeast cell machinery.
  findings: []
- id: PMID:16769821
  title: The Sec1p/Munc18 protein Vps45p binds its cognate SNARE proteins via two distinct modes.
  findings: []
- id: PMID:18719252
  title: High-quality binary protein interaction map of the yeast interactome network.
  findings: []
- id: PMID:19667197
  title: The N-terminal peptide of the syntaxin Tlg2p modulates binding of its closed conformation to Vps45p.
  findings: []
- id: PMID:27107014
  title: An inter-species protein-protein interaction network across vast evolutionary distance.
  findings: []
- id: PMID:37968396
  title: The social and structural architecture of the yeast protein interactome.
  findings: []
- id: PMID:7628704
  title: STT10, a novel class-D VPS yeast gene required for osmotic integrity related to the PKC1/STT1 protein kinase pathway.
  findings: []
- id: PMID:7720726
  title: Yeast Vps45p is a Sec1p-like protein required for the consumption of vacuole-targeted, post-Golgi transport vesicles.
  findings: []
- id: PMID:9335586
  title: 'Genetic interactions between a pep7 mutation and the PEP12 and VPS45 genes: evidence for a novel SNARE component in transport between the Saccharomyces cerevisiae Golgi complex and endosome.'
  findings: []
- id: PMID:9624182
  title: The vesicle transport protein Vps33p is an ATP-binding protein that localizes to the cytosol in an energy-dependent manner.
  findings: []
- id: PMID:9650782
  title: 'Traffic into the prevacuolar/endosomal compartment of Saccharomyces cerevisiae: a VPS45-dependent intracellular route and a VPS45-independent, endocytic route.'
  findings: []
- id: file:yeast/VPS45/VPS45-deep-research-falcon.md
  title: Falcon deep research report for Saccharomyces cerevisiae VPS45 (P38932; YGL095C)
  full_text_unavailable: false
  findings:
  - statement: >-
      Vps45p is an endosomal Sec1/Munc18 (SM) family protein that binds the
      cognate syntaxin t-SNAREs Tlg2p and Pep12p, forming distinct
      Vps45p-Tlg2p and Vps45p-Pep12p complexes.
    reference_section_type: OTHER
    supporting_text: |-
      physically associates with the syntaxin-like t-SNARE **Tlg2p** and also forms a separate complex with the endosomal t-SNARE **Pep12p**; co-immunoprecipitation data support **distinct Vps45p–Tlg2p and Vps45p–Pep12p complexes**
  - statement: >-
      Vps45p positively regulates productive SNARE complex assembly; loss of
      VPS45 prevents Tlg2p from pairing with its cognate partners Tlg1p and
      Vti1p.
    reference_section_type: OTHER
    supporting_text: |-
      Deletion of **VPS45** causes loss of functional Tlg2-dependent SNARE pairing: even when Tlg2 is stabilized, it fails to bind cognate partners **Tlg1p and Vti1p**, indicating Vps45p is required for productive SNARE complex formation
  - statement: >-
      Vps45p stabilizes the syntaxin Tlg2p, protecting it from rapid
      proteasome-dependent degradation; stabilized Tlg2p localizes correctly but
      remains non-functional for SNARE assembly without Vps45p.
    reference_section_type: OTHER
    supporting_text: |-
      Vps45p stabilizes Tlg2p: in **vps45Δ**, Tlg2p is lost through **rapid proteasomal down-regulation**, and proteasome impairment (but not loss of vacuolar proteases) restores Tlg2p levels
  - statement: >-
      Vps45p defines a VPS45-dependent intracellular (biosynthetic) route from
      the Golgi/TGN to the prevacuolar compartment, distinct from a
      VPS45-independent endocytic route from the plasma membrane to the PVC.
    reference_section_type: OTHER
    supporting_text: |-
      A **VPS45-independent endocytic route** (plasma membrane → PVC), demonstrated by delivery of endocytosed cargo (e.g., Ste3p) to the PVC without VPS45 function
  - statement: >-
      Vps45p and Tlg2p are required for the constitutive cytoplasm-to-vacuole
      targeting (Cvt) pathway of aminopeptidase I, but are dispensable for
      starvation-induced macroautophagy.
    reference_section_type: OTHER
    supporting_text: |-
      Vps45p and Tlg2p are required for maturation/processing of API via the constitutive Cvt route: **vps45ts** mutants fail to mature API at non-permissive temperature, phenocopying **tlg2Δ**
  - statement: >-
      Vps45p is recruited to endosomal docking/fusion sites by the Vac1p
      adaptor, which integrates Vps21p (Rab5-like) GTPase activity and
      Vps34-generated PI(3)P.
    reference_section_type: OTHER
    supporting_text: |-
      Vac1p **co-precipitates Vps45p**; this interaction persists without Pep12p, supporting a direct or Pep12-independent association
  - statement: >-
      Vps45p is predominantly membrane-associated in wild-type cells in a
      Tlg2-dependent manner, becoming more cytosolic when the Tlg2 N-terminal
      Vps45-binding region is removed; it cycles on and off membranes.
    reference_section_type: OTHER
    supporting_text: |-
      Vps45p is membrane-associated when full-length Tlg2p is present, but becomes more **cytosolic** when Tlg2 lacks its N-terminal Vps45-binding region (Δ1–230)
  - statement: >-
      Modern consensus frames SM proteins, including the endosomal SM Vps45, as
      active chaperones that template productive trans-SNARE complex assembly
      rather than passive syntaxin binders.
    reference_section_type: OTHER
    supporting_text: |-
      Modern consensus frames SM proteins as **active chaperones for productive trans-SNARE complex assembly**, rather than passive syntaxin binders
  - statement: >-
      Quantitatively, vps45 loss causes strong CPY mis-sorting (~70% CPY
      secretion vs ~2-4% in wild type), underscoring its central role in
      vacuolar protein sorting.
    reference_section_type: OTHER
    supporting_text: |-
      In yeast, vps45Δ causes strong CPY mis-sorting, with **~70% CPY secretion** versus **~2–4%** in wild type