VTC-4 is the catalytic polyphosphate-polymerase subunit of the vacuolar transporter chaperone complex. Its SPX regulatory domain, central VTC catalytic domain, and membrane-spanning region support ATP-dependent polyphosphate synthesis coupled to storage in the vacuolar lumen. Tagged Neurospora crassa VTC-4 occurs in prevacuolar compartments and the tubular and spherical vacuolar network. Conserved fungal Vtc4 mechanisms include inositol-phosphate sensing and contributions to vacuolar membrane traffic.
Summary: Tagged target VTC-4 is observed with the vacuolar ATPase in prevacuolar compartments and the tubular and spherical vacuolar network, supporting fungal vacuole membrane residence.
Summary: The target SPX domain and Vtc4 subfamily assignment justify transfer from the InsP6-bound Chaetomium thermophilum Vtc4 SPX structure, PDB 5IJP. Binding to InsP6 is distinct from claiming it is the most potent physiological activator.
Supporting Evidence:
file:NEUCR/vtc-4/vtc-4-PDB-5IJP.json
Crystal structure of the SPX domain of Chaetomium thermophilum Vtc4 in complex with inositol hexakisphosphate (InsP6).
Summary: Budding-yeast Vtc4 central-domain binding to calmodulin was tested directly. The conserved Vtc4 central domain supports this partner-binding inference, which is ancillary to polyphosphate polymerization.
Supporting Evidence:
file:NEUCR/vtc-4/vtc-4-primary-excerpts.md
bound to Cmd1p-Sepharose in the presence and in absence of free Ca2+.
Summary: Budding-yeast VTC occupies the ER and redistributes to vacuoles on autophagy induction. Conserved Vtc4 complex membership supports the IBA/orthology inference as a secondary location; the direct N. crassa experiment establishes vacuolar/PVC localization and does not exclude an ER pool.
The VTC complex is present on the ER and vacuoles and at the cell periphery. On induction of autophagy by nutrient limitation the VTC complex is recruited to and concentrated on vacuoles.
Summary: Budding-yeast VTC occupies the ER and redistributes to vacuoles on autophagy induction. Conserved Vtc4 complex membership supports the IBA/orthology inference as a secondary location; the direct N. crassa experiment establishes vacuolar/PVC localization and does not exclude an ER pool.
The VTC complex is present on the ER and vacuoles and at the cell periphery. On induction of autophagy by nutrient limitation the VTC complex is recruited to and concentrated on vacuoles.
Summary: The catalytic Vtc4 subfamily specifically synthesizes polyphosphate by extending a phosphate chain using ATP, making biosynthesis more precise than metabolism.
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.
Summary: The target has the Vtc4 catalytic subfamily architecture, distinct from the noncatalytic Vtc2/Vtc3 relatives. Primary structural and mutational characterization of fungal Vtc4 establishes ATP-dependent phosphate-chain polymerization and supports conserved polyphosphate synthesis.
Supporting Evidence:
file:NEUCR/vtc-4/vtc-4-uniprot.txt
DR PANTHER; PTHR46140:SF1; VACUOLAR TRANSPORTER CHAPERONE COMPLEX SUBUNIT 4-RELATED; 1.
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.
Summary: The target has the Vtc4 catalytic subfamily architecture, distinct from the noncatalytic Vtc2/Vtc3 relatives. Primary structural and mutational characterization of fungal Vtc4 establishes ATP-dependent phosphate-chain polymerization and supports conserved polyphosphate synthesis.
Supporting Evidence:
file:NEUCR/vtc-4/vtc-4-uniprot.txt
DR PANTHER; PTHR46140:SF1; VACUOLAR TRANSPORTER CHAPERONE COMPLEX SUBUNIT 4-RELATED; 1.
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.
Summary: Vtc4 participates in a membrane complex coupling polymer production to vacuolar delivery; its target vacuolar/PVC localization and conserved VTC polymerase-translocation mechanism support vacuolar transport.
Supporting Evidence:
file:NEUCR/vtc-4/vtc-4-uniprot.txt
DR PANTHER; PTHR46140:SF1; VACUOLAR TRANSPORTER CHAPERONE COMPLEX SUBUNIT 4-RELATED; 1.
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.
Summary: The target has the Vtc4 catalytic subfamily architecture, distinct from the noncatalytic Vtc2/Vtc3 relatives. Primary structural and mutational characterization of fungal Vtc4 establishes ATP-dependent phosphate-chain polymerization and supports conserved polyphosphate synthesis.
Supporting Evidence:
file:NEUCR/vtc-4/vtc-4-uniprot.txt
DR PANTHER; PTHR46140:SF1; VACUOLAR TRANSPORTER CHAPERONE COMPLEX SUBUNIT 4-RELATED; 1.
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.
Summary: The target has the Vtc4 catalytic subfamily architecture, distinct from the noncatalytic Vtc2/Vtc3 relatives. Primary structural and mutational characterization of fungal Vtc4 establishes ATP-dependent phosphate-chain polymerization and supports conserved polyphosphate synthesis.
Supporting Evidence:
file:NEUCR/vtc-4/vtc-4-uniprot.txt
DR PANTHER; PTHR46140:SF1; VACUOLAR TRANSPORTER CHAPERONE COMPLEX SUBUNIT 4-RELATED; 1.
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.
Summary: The characterized yeast VTC complex is required for microautophagic vesicle scission. Conserved Vtc4 complex membership supports transfer of this membrane-traffic contribution as a secondary process, distinct from its primary polymerase activity.
Deletion of the VTC complex blocks microautophagic uptake into vacuoles. The mutants still form autophagic tubes but the production of microautophagic vesicles from their tips is impaired.
Summary: The Vtc4-specific family assignment, SPX-VTC-membrane architecture, and native vacuolar localization support membership in the conserved VTC polymerase/translocation complex.
Supporting Evidence:
file:NEUCR/vtc-4/vtc-4-uniprot.txt
DR PANTHER; PTHR46140:SF1; VACUOLAR TRANSPORTER CHAPERONE COMPLEX SUBUNIT 4-RELATED; 1.
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.
Summary: The Vtc4-specific family assignment, SPX-VTC-membrane architecture, and native vacuolar localization support membership in the conserved VTC polymerase/translocation complex.
Supporting Evidence:
file:NEUCR/vtc-4/vtc-4-uniprot.txt
DR PANTHER; PTHR46140:SF1; VACUOLAR TRANSPORTER CHAPERONE COMPLEX SUBUNIT 4-RELATED; 1.
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.
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.
These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.
Review rationale: Native tagged VTC-4 localizes with vacuolar ATPase to prevacuolar compartments and the vacuolar network (PMID:26453652, full-text localization section). This directly supports membrane residence of the target VTC protein and agrees with characterized fungal VTC architecture. The existing fungal-type vacuole membrane annotation is more precise than generic vacuolar membrane.
Supporting Evidence:
PMID:26453652: "Vacuolar membrane proteins, such as the vacuolar ATPase (VMA-1) and the polyphosphate polymerase (VTC-4), were observed in the PVCs."