Vtc4 is the catalytic subunit of the vacuolar transporter chaperone (VTC) complex, the membrane-integral polyphosphate (polyP) polymerase of S. cerevisiae. It has an N-terminal SPX domain, a central cytosolic triphosphate tunnel metalloenzyme (TTM/VTC) domain and three C-terminal transmembrane helices. The central domain transfers the gamma-phosphate of ATP to a growing polyP chain (Mn2+-dependent; active-site Lys458), and the nascent chain is threaded through a channel formed by the transmembrane helices of Vtc4, Vtc3 (or Vtc2) and three Vtc1 subunits, so that synthesis is obligatorily coupled to polyP import into the vacuole lumen. Binding of inositol (pyro)phosphates to the Vtc4 SPX domain activates the enzyme, linking polyP storage to cellular phosphate status. Vtc4 is required for polyP accumulation and resides mainly on the vacuolar membrane, with a pool on the ER and cell periphery. The VTC complex also contributes to homotypic vacuole fusion and to microautophagic vesicle scission, and Vtc4 binds calmodulin; these roles are less well understood. Delivery of Vtc4 to the vacuolar membrane depends partly on the AP-3 adaptor pathway; in AP-3 mutants part of Vtc4 mislocalizes to the cytoplasm.
Definition: The process in which inorganic polyphosphate is transported across a membrane, as when a nascent polyphosphate chain is translocated from the cytosol into the vacuole lumen.
Justification: The VTC complex forms a polyP-selective transmembrane channel that couples synthesis with import into the vacuole; no GO term describes polyP transport.
Parent term: transmembrane transport
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000329 fungal-type vacuole membrane | HDA PMID:26928762 One library to make them all: streamlining the creation of y... | ACCEPT | Summary: Genome-wide SWAT-GFP localization places Vtc4 at the vacuolar membrane, consistent with low-throughput data. Reason: Vacuolar membrane is the principal, functionally relevant location of the catalytic VTC complex, where synthesis is coupled to polyP import into the vacuole lumen. This is the precise fungal term and is core. Supporting Evidence: PMID:25315834 the VTC complex obligatorily couples synthesis of polyP to its import in order to avoid toxic intermediates in the cytosol PMID:36759618 Fifteen trans-membrane helices form a novel membrane channel enabling the transport of newly synthesized polyP into the vacuolar lumen. |
| GO:0000329 fungal-type vacuole membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of vacuolar membrane localization at PTN000845986; supported directly by yeast experimental data. Reason: Vacuolar membrane location of Vtc4 is experimentally established in S. cerevisiae and Vtc4 orthologs in other fungi (e.g. N. crassa VTC-4) also localize to vacuolar membranes. The IBA is consistent and core. Supporting Evidence: PMID:25315834 the VTC complex obligatorily couples synthesis of polyP to its import in order to avoid toxic intermediates in the cytosol |
| GO:0000421 autophagosome membrane | IEA GO_REF:0000044 | MODIFY | Summary: UniProt SubCell 'autophagosome membrane' mapping, derived from the microautophagy study. Reason: The supporting study (PMID:17079729) concerns microautophagy, in which the vacuolar membrane itself invaginates into an autophagic tube that pinches off vesicles into the lumen; Vtc4 is enriched on these vacuolar-membrane invaginations, not on double-membrane autophagosomes of macroautophagy. The correct location is vacuolar membrane (fungal-type vacuole membrane), which the gene already carries. Proposed replacements: fungal-type vacuole membrane Supporting Evidence: PMID:17079729 This occurs by an autophagic tube, a specialized vacuolar membrane invagination that pinches off vesicles into the vacuolar lumen. PMID:17079729 Our data suggest that the VTC complex is an important constituent of autophagic tubes and that it is required for scission of microautophagic vesicles from these tubes. |
| GO:0000421 autophagosome membrane | NAS PMID:17079729 The vacuolar transporter chaperone (VTC) complex is required... | MODIFY | Summary: Author-statement annotation of autophagosome membrane based on Vtc localization to autophagic tubes. Reason: The supporting study (PMID:17079729) concerns microautophagy, in which the vacuolar membrane itself invaginates into an autophagic tube that pinches off vesicles into the lumen; Vtc4 is enriched on these vacuolar-membrane invaginations, not on double-membrane autophagosomes of macroautophagy. The correct location is vacuolar membrane (fungal-type vacuole membrane), which the gene already carries. Proposed replacements: fungal-type vacuole membrane Supporting Evidence: PMID:17079729 This occurs by an autophagic tube, a specialized vacuolar membrane invagination that pinches off vesicles into the vacuolar lumen. PMID:17079729 Our data suggest that the VTC complex is an important constituent of autophagic tubes and that it is required for scission of microautophagic vesicles from these tubes. |
| GO:0000822 inositol hexakisphosphate binding | IDA PMID:27080106 Control of eukaryotic phosphate homeostasis by inositol poly... | ACCEPT | Summary: SPX domain of Vtc4 binds InsP6 and related inositol (pyro)phosphates; crystal structures of SPX-Vtc4 with InsP6 and binding-surface mutants. Reason: Direct binding is shown for the Vtc4 SPX domain, and binding-surface mutations impair both InsP binding and polyP synthesis in yeast. In the assembled complex the Vtc4 SPX (not Vtc3) is the PP-InsP sensor. InsP6 is the experimentally used ligand; the physiological activator is probably 5-InsP7/1,5-InsP8, but this term is precise for what was measured. Core regulatory input. Supporting Evidence: PMID:27080106 Substitutions of critical binding surface residues impair InsP binding in vitro, inorganic polyphosphate synthesis in yeast PMID:36759618 Together, these findings reveal that it is the SPX domain of Vtc4, rather than that of Vtc3, which acts as the PP-InsP nutrient sensor in fully assembled VTC complex. |
| GO:0005515 protein binding | IPI PMID:19841731 Bayesian modeling of the yeast SH3 domain interactome predic... | REMOVE | Summary: High-throughput SH3-domain interactome hit with PIN3 (Q06449). Reason: Bare protein binding is uninformative, and the SH3 interactome screen gives no functional context for a Vtc4-Pin3 association. Removal does not mean the interaction is false. |
| GO:0005516 calmodulin binding | IDA PMID:17079729 The vacuolar transporter chaperone (VTC) complex is required... | KEEP AS NON CORE | Summary: The central cytosolic domain of Vtc4 binds calmodulin (Cmd1p-Sepharose) and Vtc4 co-immunoprecipitates with Cmd1p. Reason: Direct binding shown in the full text of PMID:17079729 (quoted in the notes file; the cached record is abstract-only). The functional significance for polyP synthesis or vacuole fusion is not established, so this is retained as non-core. Supporting Evidence: file:yeast/VTC4/VTC4-notes.md bound to Cmd1p-Sepharose in the presence and in absence of free Ca2+ |
| GO:0005774 vacuolar membrane | EXP PMID:19390046 Catalytic core of a membrane-associated eukaryotic polyphosp... | MODIFY | Summary: Vacuolar membrane localization from the structural/biochemical study of the VTC polymerase. Reason: Vacuolar membrane localization is well established, but in S. cerevisiae the precise term is GO:0000329 fungal-type vacuole membrane, which this gene already carries (HDA, IBA). Proposed replacements: fungal-type vacuole membrane Supporting Evidence: PMID:25315834 the VTC complex obligatorily couples synthesis of polyP to its import in order to avoid toxic intermediates in the cytosol |
| GO:0005774 vacuolar membrane | EXP PMID:26928762 One library to make them all: streamlining the creation of y... | MODIFY | Summary: Vacuolar membrane localization from the SWAT-GFP library. Reason: Vacuolar membrane localization is well established, but in S. cerevisiae the precise term is GO:0000329 fungal-type vacuole membrane, which this gene already carries (HDA, IBA). Proposed replacements: fungal-type vacuole membrane Supporting Evidence: PMID:25315834 the VTC complex obligatorily couples synthesis of polyP to its import in order to avoid toxic intermediates in the cytosol |
| GO:0005774 vacuolar membrane | IDA PMID:12584253 Role of the Vtc proteins in V-ATPase stability and membrane ... | MODIFY | Summary: Vtc proteins on purified vacuoles; topology analysis with cytoplasmic N-terminal region. Reason: Vacuolar membrane localization is well established, but in S. cerevisiae the precise term is GO:0000329 fungal-type vacuole membrane, which this gene already carries (HDA, IBA). Proposed replacements: fungal-type vacuole membrane Supporting Evidence: PMID:25315834 the VTC complex obligatorily couples synthesis of polyP to its import in order to avoid toxic intermediates in the cytosol |
| GO:0005774 vacuolar membrane | IEA GO_REF:0000120 | MODIFY | Summary: Combined automated annotation (ARBA/SubCell) of vacuolar membrane. Reason: Vacuolar membrane localization is well established, but in S. cerevisiae the precise term is GO:0000329 fungal-type vacuole membrane, which this gene already carries (HDA, IBA). Proposed replacements: fungal-type vacuole membrane Supporting Evidence: PMID:25315834 the VTC complex obligatorily couples synthesis of polyP to its import in order to avoid toxic intermediates in the cytosol |
| GO:0005783 endoplasmic reticulum | IBA GO_REF:0000033 | MODIFY | Summary: Phylogenetic inference of ER localization at PTN001646574. Reason: Vtc4 is found on the ER/nuclear envelope (notably in the Vtc1-Vtc2-Vtc4 subcomplex, which relocates to the vacuole under starvation). The precise term is GO:0005789 endoplasmic reticulum membrane, already carried by the gene (Vtc4 is a 3-TM integral membrane protein). ER localization is secondary to the vacuolar site of polyP synthesis and is not core. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN001646574 Β· PANTHER node PTN001646574 SUPPORTS TRANSFER Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: PMID:17079729 The VTC complex is present on the ER and vacuoles and at the cell periphery. |
| GO:0005783 endoplasmic reticulum | IDA PMID:17079729 The vacuolar transporter chaperone (VTC) complex is required... | MODIFY | Summary: GFP-Vtc fusions localize to the ER, marking the nuclear rim. Reason: Vtc4 is found on the ER/nuclear envelope (notably in the Vtc1-Vtc2-Vtc4 subcomplex, which relocates to the vacuole under starvation). The precise term is GO:0005789 endoplasmic reticulum membrane, already carried by the gene (Vtc4 is a 3-TM integral membrane protein). ER localization is secondary to the vacuolar site of polyP synthesis and is not core. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: PMID:17079729 The VTC complex is present on the ER and vacuoles and at the cell periphery. file:yeast/VTC4/VTC4-notes.md All GFP-Vtc fusions localized to the ER, marking the nuclear rim. |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:17079729 The vacuolar transporter chaperone (VTC) complex is required... | KEEP AS NON CORE | Summary: ER membrane localization of Vtc4 (GFP fusion, nuclear rim). Reason: Correct and as precise as warranted; the ER pool (largely Vtc1-Vtc2-Vtc4) is a secondary location, not the site of the core activity. Supporting Evidence: PMID:17079729 The VTC complex is present on the ER and vacuoles and at the cell periphery. file:yeast/VTC4/VTC4-notes.md All GFP-Vtc fusions localized to the ER, marking the nuclear rim. |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt SubCell mapping of ER membrane. Reason: Consistent with experimental ER localization; non-core secondary location. Supporting Evidence: PMID:17079729 The VTC complex is present on the ER and vacuoles and at the cell periphery. |
| GO:0005938 cell cortex | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt SubCell 'cell cortex' mapping derived from cell-periphery GFP signal. Reason: A Vtc pool is seen at the cell periphery (probably cortical ER of the Vtc1-Vtc2-Vtc4 subcomplex). Plausible but peripheral and of unclear functional significance. Supporting Evidence: PMID:17079729 The VTC complex is present on the ER and vacuoles and at the cell periphery. |
| GO:0006797 polyphosphate metabolic process | IMP PMID:11102525 New components of a system for phosphate accumulation and po... | MODIFY | Summary: phm3 (vtc4) deletion mutants lack detectable polyP. Reason: The phenotype (loss of detectable polyP in phm3/vtc4 deletion) and the enzymology establish that Vtc4 synthesizes polyP. The more precise term is GO:0006799 polyphosphate biosynthetic process, which the gene carries. Proposed replacements: polyphosphate biosynthetic process Supporting Evidence: PMID:11102525 Both the phm3 Ξ and phm4 Ξ mutants lacked detectable polyP. |
| GO:0006797 polyphosphate metabolic process | IMP PMID:19390046 Catalytic core of a membrane-associated eukaryotic polyphosp... | MODIFY | Summary: Catalytic-site mutants of Vtc4 abolish polyP synthesis. Reason: The phenotype (loss of detectable polyP in phm3/vtc4 deletion) and the enzymology establish that Vtc4 synthesizes polyP. The more precise term is GO:0006799 polyphosphate biosynthetic process, which the gene carries. Proposed replacements: polyphosphate biosynthetic process Supporting Evidence: PMID:19390046 Nucleotide- and phosphate-bound structures suggest that the enzyme functions by metal-assisted cleavage of the ATP gamma-phosphate, which is then in-line transferred to an acceptor phosphate to form polyP chains. |
| GO:0006799 polyphosphate biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference at PTN001646574; S. cerevisiae Vtc4 is itself an experimental donor. Reason: Vtc4 is the catalytic subunit of the only known eukaryotic polyP polymerase, so it directly carries out polyP biosynthesis. Core. The target appearing in WITH/FROM reflects its own experimental grounding. Supporting Evidence: PMID:19390046 Nucleotide- and phosphate-bound structures suggest that the enzyme functions by metal-assisted cleavage of the ATP gamma-phosphate, which is then in-line transferred to an acceptor phosphate to form polyP chains. |
| GO:0006799 polyphosphate biosynthetic process | IDA PMID:25315834 Coupled synthesis and translocation restrains polyphosphate ... | ACCEPT | Summary: Reconstitution with purified vacuoles: VTC synthesizes polyP and imports it. Reason: Vtc4 is the catalytic subunit of the only known eukaryotic polyP polymerase, so it directly carries out polyP biosynthesis. Core. Supporting Evidence: PMID:25315834 the VTC complex obligatorily couples synthesis of polyP to its import in order to avoid toxic intermediates in the cytosol |
| GO:0006799 polyphosphate biosynthetic process | IDA PMID:37066886 Cryo-EM structure of the polyphosphate polymerase VTC reveal... | ACCEPT | Summary: Purified endogenous Vtc4/Vtc3/Vtc1 complex synthesizes polyP; structure-function analysis. Reason: Vtc4 is the catalytic subunit of the only known eukaryotic polyP polymerase, so it directly carries out polyP biosynthesis. Core. Supporting Evidence: PMID:37066886 The catalytic Vtc4 central domain is located on top of the pseudo-symmetric polyP channel, creating a strongly electropositive pathway for nascent polyP that can couple synthesis to translocation. |
| GO:0006799 polyphosphate biosynthetic process | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA electronic annotation of polyP biosynthesis. Reason: Vtc4 is the catalytic subunit of the only known eukaryotic polyP polymerase, so it directly carries out polyP biosynthesis. Core. Consistent with experimental data. Supporting Evidence: PMID:19390046 Nucleotide- and phosphate-bound structures suggest that the enzyme functions by metal-assisted cleavage of the ATP gamma-phosphate, which is then in-line transferred to an acceptor phosphate to form polyP chains. |
| GO:0006799 polyphosphate biosynthetic process | IMP PMID:27080106 Control of eukaryotic phosphate homeostasis by inositol poly... | ACCEPT | Summary: SPX-domain binding-surface mutants of Vtc4 reduce polyP synthesis in yeast. Reason: Vtc4 is the catalytic subunit of the only known eukaryotic polyP polymerase, so it directly carries out polyP biosynthesis. Core. Supporting Evidence: PMID:27080106 Substitutions of critical binding surface residues impair InsP binding in vitro, inorganic polyphosphate synthesis in yeast |
| GO:0006799 polyphosphate biosynthetic process | IMP PMID:27252384 Organelle size control - increasing vacuole content activate... | ACCEPT | Summary: Vacuole size-control study using VTC mutants defective in polyP synthesis. Reason: Vtc4 is the catalytic subunit of the only known eukaryotic polyP polymerase, so it directly carries out polyP biosynthesis. Core. The cached record is abstract-only; the curator's IMP is consistent with all other evidence. Supporting Evidence: PMID:27252384 Synthesis of the dominant compound stored inside vacuoles, polyphosphate, stimulates binding of the chaperone Sec18/NSF to vacuolar SNAREs |
| GO:0007034 vacuolar transport | IDA PMID:17079729 The vacuolar transporter chaperone (VTC) complex is required... | KEEP AS NON CORE | Summary: Antibodies to Vtc proteins inhibit microautophagic uptake in vitro. Reason: Vacuolar transport is true in two senses: VTC translocates the polyP it synthesizes into the vacuole lumen, and the VTC complex is required for microautophagic uptake into the vacuole. The term is broad; polyP import is captured more precisely by the proposed NEW GO:0034486 vacuolar transmembrane transport (not a GO descendant of GO:0007034, so not proposed as a replacement), and the microautophagy role by GO:0016237. Retained as non-core. Supporting Evidence: PMID:17079729 Deletion of the VTC complex blocks microautophagic uptake into vacuoles. |
| GO:0007034 vacuolar transport | IMP PMID:17079729 The vacuolar transporter chaperone (VTC) complex is required... | KEEP AS NON CORE | Summary: vtc deletions block microautophagic uptake into vacuoles. Reason: Vacuolar transport is true in two senses: VTC translocates the polyP it synthesizes into the vacuole lumen, and the VTC complex is required for microautophagic uptake into the vacuole. The term is broad; polyP import is captured more precisely by the proposed NEW GO:0034486 vacuolar transmembrane transport (not a GO descendant of GO:0007034, so not proposed as a replacement), and the microautophagy role by GO:0016237. Retained as non-core. Supporting Evidence: PMID:17079729 Deletion of the VTC complex blocks microautophagic uptake into vacuoles. |
| GO:0007034 vacuolar transport | IMP PMID:37066886 Cryo-EM structure of the polyphosphate polymerase VTC reveal... | KEEP AS NON CORE | Summary: Channel mutations block polyP translocation into the vacuole. Reason: Vacuolar transport is true in two senses: VTC translocates the polyP it synthesizes into the vacuole lumen, and the VTC complex is required for microautophagic uptake into the vacuole. The term is broad; polyP import is captured more precisely by the proposed NEW GO:0034486 vacuolar transmembrane transport (not a GO descendant of GO:0007034, so not proposed as a replacement), and the microautophagy role by GO:0016237. Retained as non-core. Supporting Evidence: PMID:37066886 The catalytic Vtc4 central domain is located on top of the pseudo-symmetric polyP channel, creating a strongly electropositive pathway for nascent polyP that can couple synthesis to translocation. |
| GO:0008976 polyphosphate kinase activity | EXP PMID:24114837 Trypanosoma brucei vacuolar transporter chaperone 4 (TbVtc4)... | ACCEPT | Summary: Kinetic characterization of polyP kinase activity (Km for ATP); the paper centres on T. brucei Vtc4 but UniProt attributes the yeast kinetics to it. Reason: Vtc4 is the catalytic polyP polymerase (ATP + polyP(n) = ADP + polyP(n+1)); crystal structures, ATP-binding and active-site mutants (R264A/R266A, K458) and reconstituted complexes establish the activity in S. cerevisiae. Core molecular function. The cached record is abstract-only; deferring to the curator on what was assayed. Supporting Evidence: PMID:24114837 Vtc4p (vacuolar transporter chaperone 4) is a long chain polyP kinase that localizes to the yeast vacuole. PMID:19390046 Nucleotide- and phosphate-bound structures suggest that the enzyme functions by metal-assisted cleavage of the ATP gamma-phosphate, which is then in-line transferred to an acceptor phosphate to form polyP chains. |
| GO:0008976 polyphosphate kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference at PTN001646574 with donors S. cerevisiae Vtc4 and T. brucei Vtc4. Reason: Vtc4 is the catalytic polyP polymerase (ATP + polyP(n) = ADP + polyP(n+1)); crystal structures, ATP-binding and active-site mutants (R264A/R266A, K458) and reconstituted complexes establish the activity in S. cerevisiae. Core molecular function. The target being a donor is expected. Supporting Evidence: PMID:19390046 Nucleotide- and phosphate-bound structures suggest that the enzyme functions by metal-assisted cleavage of the ATP gamma-phosphate, which is then in-line transferred to an acceptor phosphate to form polyP chains. |
| GO:0008976 polyphosphate kinase activity | IDA PMID:19390046 Catalytic core of a membrane-associated eukaryotic polyphosp... | ACCEPT | Summary: Crystal structures and activity assays of the Vtc4 catalytic domain identify it as a polyP polymerase. Reason: Vtc4 is the catalytic polyP polymerase (ATP + polyP(n) = ADP + polyP(n+1)); crystal structures, ATP-binding and active-site mutants (R264A/R266A, K458) and reconstituted complexes establish the activity in S. cerevisiae. Core molecular function. Supporting Evidence: PMID:19390046 Nucleotide- and phosphate-bound structures suggest that the enzyme functions by metal-assisted cleavage of the ATP gamma-phosphate, which is then in-line transferred to an acceptor phosphate to form polyP chains. |
| GO:0008976 polyphosphate kinase activity | IEA GO_REF:0000003 | ACCEPT | Summary: EC 2.7.4.1 mapping. Reason: Vtc4 is the catalytic polyP polymerase (ATP + polyP(n) = ADP + polyP(n+1)); crystal structures, ATP-binding and active-site mutants (R264A/R266A, K458) and reconstituted complexes establish the activity in S. cerevisiae. Core molecular function. The EC mapping is correct. Supporting Evidence: PMID:19390046 Nucleotide- and phosphate-bound structures suggest that the enzyme functions by metal-assisted cleavage of the ATP gamma-phosphate, which is then in-line transferred to an acceptor phosphate to form polyP chains. |
| GO:0016237 microautophagy | IDA PMID:17079729 The vacuolar transporter chaperone (VTC) complex is required... | KEEP AS NON CORE | Summary: VTC complex required for microautophagy (vesicle scission from autophagic tubes). Reason: The VTC complex is enriched on autophagic tubes and required for scission of microautophagic vesicles; deletion blocks microautophagic uptake and antibodies inhibit it in vitro. Whether this reflects a direct structural role or an indirect effect of polyP/vacuole membrane state is not resolved, and it is peripheral to the catalytic function, so non-core. Supporting Evidence: PMID:17079729 Our data suggest that the VTC complex is an important constituent of autophagic tubes and that it is required for scission of microautophagic vesicles from these tubes. |
| GO:0016237 microautophagy | IMP PMID:17079729 The vacuolar transporter chaperone (VTC) complex is required... | KEEP AS NON CORE | Summary: VTC complex required for microautophagy (vesicle scission from autophagic tubes). Reason: The VTC complex is enriched on autophagic tubes and required for scission of microautophagic vesicles; deletion blocks microautophagic uptake and antibodies inhibit it in vitro. Whether this reflects a direct structural role or an indirect effect of polyP/vacuole membrane state is not resolved, and it is peripheral to the catalytic function, so non-core. Supporting Evidence: PMID:17079729 Our data suggest that the VTC complex is an important constituent of autophagic tubes and that it is required for scission of microautophagic vesicles from these tubes. |
| GO:0016237 microautophagy | NAS PMID:17079729 The vacuolar transporter chaperone (VTC) complex is required... | KEEP AS NON CORE | Summary: VTC complex required for microautophagy (vesicle scission from autophagic tubes). Reason: The VTC complex is enriched on autophagic tubes and required for scission of microautophagic vesicles; deletion blocks microautophagic uptake and antibodies inhibit it in vitro. Whether this reflects a direct structural role or an indirect effect of polyP/vacuole membrane state is not resolved, and it is peripheral to the catalytic function, so non-core. Supporting Evidence: PMID:17079729 Our data suggest that the VTC complex is an important constituent of autophagic tubes and that it is required for scission of microautophagic vesicles from these tubes. |
| GO:0033254 vacuolar transporter chaperone complex | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of VTC complex membership at PTN001646574. Reason: Vtc4 is the catalytic subunit of the VTC complex: co-immunoprecipitation with Vtc1/2/3 and cryo-EM structures of the Vtc4/Vtc3/Vtc1 (1:1:3) complex. Core. Supporting Evidence: PMID:37066886 The structure reveals a heteropentameric architecture of one Vtc4, one Vtc3, and three Vtc1 subunits. |
| GO:0033254 vacuolar transporter chaperone complex | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA electronic annotation of VTC complex membership. Reason: Vtc4 is the catalytic subunit of the VTC complex: co-immunoprecipitation with Vtc1/2/3 and cryo-EM structures of the Vtc4/Vtc3/Vtc1 (1:1:3) complex. Core. Supporting Evidence: PMID:37066886 The structure reveals a heteropentameric architecture of one Vtc4, one Vtc3, and three Vtc1 subunits. |
| GO:0033254 vacuolar transporter chaperone complex | IPI PMID:11823419 The Vtc proteins in vacuole fusion: coupling NSF activity to... | ACCEPT | Summary: Vtc1 immunoprecipitation co-purifies Vtc2, Vtc3 and Vtc4 in roughly stoichiometric amounts. Reason: Vtc4 is the catalytic subunit of the VTC complex: co-immunoprecipitation with Vtc1/2/3 and cryo-EM structures of the Vtc4/Vtc3/Vtc1 (1:1:3) complex. Core. Supporting Evidence: PMID:11823419 The major co-precipitated bands were identified by MALDI mass spectrometry as Vtc2p, Vtc3p and Vtc4p. |
| GO:0033254 vacuolar transporter chaperone complex | IPI PMID:36759618 The cytoplasmic synthesis and coupled membrane translocation... | ACCEPT | Summary: Cryo-EM of the signal-activated Vtc1/Vtc3/Vtc4 3:1:1 complex. Reason: Vtc4 is the catalytic subunit of the VTC complex: co-immunoprecipitation with Vtc1/2/3 and cryo-EM structures of the Vtc4/Vtc3/Vtc1 (1:1:3) complex. Core. Supporting Evidence: PMID:36759618 Baker's yeast VTC subunits Vtc1, Vtc3, and Vtc4 assemble into a 3:1:1 complex. |
| GO:0033254 vacuolar transporter chaperone complex | IPI PMID:37066886 Cryo-EM structure of the polyphosphate polymerase VTC reveal... | ACCEPT | Summary: Cryo-EM of endogenous Vtc4/Vtc3/Vtc1 heteropentamer. Reason: Vtc4 is the catalytic subunit of the VTC complex: co-immunoprecipitation with Vtc1/2/3 and cryo-EM structures of the Vtc4/Vtc3/Vtc1 (1:1:3) complex. Core. Supporting Evidence: PMID:37066886 The structure reveals a heteropentameric architecture of one Vtc4, one Vtc3, and three Vtc1 subunits. |
| GO:0061736 engulfment of target by autophagosome | NAS PMID:17079729 The vacuolar transporter chaperone (VTC) complex is required... | REMOVE | Summary: Author-statement annotation to engulfment of target by autophagosome. Reason: GO:0061736 is defined as the invagination by which an autophagosomal membrane surrounds an object for macroautophagy. PMID:17079729 concerns microautophagy, in which the vacuolar membrane invaginates; Vtc4 is not shown to act on autophagosome formation. The microautophagy role is captured by GO:0016237, which is kept. Supporting Evidence: PMID:17079729 This occurs by an autophagic tube, a specialized vacuolar membrane invagination that pinches off vesicles into the vacuolar lumen. |
| GO:0071944 cell periphery | HDA PMID:26928762 One library to make them all: streamlining the creation of y... | KEEP AS NON CORE | Summary: SWAT-GFP screen reports a cell-periphery signal. Reason: Consistent with the low-throughput observation of a peripheral Vtc pool (likely cortical ER); peripheral to function. Supporting Evidence: PMID:17079729 The VTC complex is present on the ER and vacuoles and at the cell periphery. |
| GO:0034486 vacuolar transmembrane transport | IMP PMID:36759618 The cytoplasmic synthesis and coupled membrane translocation... | NEW | Summary: Vtc4 contributes TM1 to the 15-helix polyP channel and orients its catalytic domain over the channel entrance; channel-residue mutations in any subunit, including Vtc4 K622A/R629A, eliminate the vacuolar polyP store. Reason: Participation test: the VTC transmembrane channel performs polyP translocation across the vacuolar membrane, and Vtc4 is a structural part of that channel (TM1 lines the pore; R629 lines the narrowest point) as well as supplying the nascent chain. This is participation, not mere necessity. No polyP-specific transport term exists, so the general vacuolar transmembrane transport term is used; a specific term is proposed in proposed_new_terms. Supporting Evidence: PMID:36759618 Fifteen trans-membrane helices form a novel membrane channel enabling the transport of newly synthesized polyP into the vacuolar lumen. PMID:36759618 in-cell 31P-NMR measurements showed that mutations targeting on above-mentioned channel residues in any subunit eliminated the VTC-generated vacuolar polyP store in yeast strains PMID:25315834 the VTC complex obligatorily couples synthesis of polyP to its import in order to avoid toxic intermediates in the cytosol |
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Download this section (compressed HTML)Q: Is the requirement of Vtc4 for homotypic vacuole fusion (Sec18/NSF priming, LMA1 binding, V0 trans-complex formation) a direct role of the protein, or an indirect consequence of lumenal polyP signalling to SNAREs?
Q: Does Vtc4 contribute directly to scission of microautophagic vesicles, or does loss of polyP synthesis alter vacuolar membrane properties needed for scission?
Q: Which inositol pyrophosphate (5-InsP7 or 1,5-InsP8) is the physiological activator of the Vtc4 SPX domain in vivo?
Experiment: Test vacuole fusion and microautophagy in strains carrying a catalytically dead Vtc4 (K458A or R264A/R266A) that still assembles the VTC complex, to separate structural from polyP-dependent roles.
Vacuolar membrane polyphosphate polymerase; subunit of vacuolar transporter chaperone (VTC) complex involved in synthesis and transfer of polyP to vacuole; regulates membrane trafficking; role in non-autophagic vacuolar fusion; targeted to vacuole via AP-3 pathway; protein abundance increases in response to DNA replication stress
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