ACH1 encodes a conserved fungal acetyl-CoA hydrolase/transferase family enzyme that interconverts acetate and short-chain acyl-CoA species, with the best fungal enzymology favoring acetate CoA-transferase as the dominant activity. In Candida albicans, ACH1 supports mitochondrial acetate metabolism, growth on acetate and ethanol as alternative carbon sources, and efficient amino-acid-driven extracellular alkalinization.
Definition: A biological process in which a fungal cell catabolizes extracellular amino acids as carbon sources and releases alkaline nitrogenous waste, thereby increasing the pH of the extracellular environment.
Justification: Vylkova et al. identified Candida albicans mutants, including ach1, that are defective in raising extracellular pH from acidic amino-acid-containing medium. The local GO cache has terms for cellular responses to acidic, neutral, and alkaline pH. The GO pH-change branch has a broad pH elevation term and intracellular/vacuolar/lysosomal descendants, but no term for the organism-driven environmental alkalinization phenotype these mutants affect.
Parent term: pH elevation
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003986 acetyl-CoA hydrolase activity | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: The PTN000484586 placement correctly connects C. albicans ACH1 to fungal Ach1 acetate metabolism, but the specific hydrolase term is secondary to the later CoA-transferase recharacterization of fungal Ach1 enzymes. Reason: C. albicans ACH1 complements Saccharomyces ach1 loss and is induced by acetate, ethanol, and glycerol, supporting conserved acetate/acetyl-CoA metabolism. The specific GO:0003986 assertion should be flagged rather than removed: S. cerevisiae Ach1p retains minor acetyl-CoA hydrolase activity, but Fleck and Brock showed that the fungal enzyme has its highest activity as a succinyl-CoA:acetate CoA-transferase and concluded that fungal Ach1 functions in mitochondrial acetate detoxification by CoA transfer. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000484586 SUPPORTS TRANSFER This node correctly scopes the fungal Ach1 acetate-metabolism enzyme family onto C. albicans ACH1 and supports acetyl-CoA hydrolase as a minor retained side activity. Supporting Evidence: PMID:18689527 Both ACH1 and ACS2 complement mutations in their S. cerevisiae homolog. PMID:18689527 ACH1 was present at low levels in glucose-containing medium and was highly induced when acetate, ethanol, or glycerol was the carbon source. PMID:19298859 Ach1p showed highest specific activity for the CoASH transfer from succinyl-CoA to acetate and only a minor acetyl-CoA-hydrolase activity. |
| GO:0003986 acetyl-CoA hydrolase activity | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: The automated hydrolase assignment captures the historical EC 3.1.2.1 annotation, but later fungal Ach1 enzymology favors CoA transfer as the dominant reaction. Reason: The C. albicans enzyme is a conserved fungal Ach1-family protein and is experimentally tied to acetate/acetyl-CoA metabolism by interspecies complementation. GO:0003986 is retained as a non-core minor activity because S. cerevisiae Ach1p was re-characterized as a succinyl-CoA:acetate CoA-transferase while still showing minor acetyl-CoA hydrolase activity. Supporting Evidence: PMID:18689527 Both ACH1 and ACS2 complement mutations in their S. cerevisiae homolog. PMID:19298859 Ach1p showed highest specific activity for the CoASH transfer from succinyl-CoA to acetate and only a minor acetyl-CoA-hydrolase activity. |
| GO:0003986 acetyl-CoA hydrolase activity | IGI PMID:18689527 Role of acetyl coenzyme A synthesis and breakdown in alterna... | KEEP AS NON CORE | Summary: C. albicans ACH1 functionally complements S. cerevisiae ach1, but the historically named hydrolase activity is no longer the best description of the fungal enzyme. Reason: The complementation in PMID:18689527 supports conserved Ach1-family acetate metabolism, not specifically acetyl-CoA hydrolysis. The later re-characterization of S. cerevisiae Ach1p showed predominant succinyl-CoA:acetate CoA-transferase activity while retaining minor hydrolase activity, so GO:0003986 is a secondary activity rather than the best description of fungal Ach1 function. Supporting Evidence: PMID:18689527 the C. albicans genes complement the S. cerevisiae deletions, indicating conservation of function. PMID:19298859 Ach1p showed highest specific activity for the CoASH transfer from succinyl-CoA to acetate and only a minor acetyl-CoA-hydrolase activity. |
| GO:0003986 acetyl-CoA hydrolase activity | ISA PMID:18689527 Role of acetyl coenzyme A synthesis and breakdown in alterna... | KEEP AS NON CORE | Summary: Sequence and orthology to S. cerevisiae ACH1 support the Ach1 enzyme family, but the specific hydrolase term is a secondary side activity. Reason: C. albicans ACH1 is close enough to S. cerevisiae ACH1 to complement the yeast ach1 growth defect, so the orthology call is sound. The exact molecular-function term captures a minor retained hydrolase activity; the major Ach1 activity is succinyl-CoA:acetate CoA-transferase. Supporting Evidence: PMID:18689527 Both ACH1 and ACS2 complement mutations in their S. cerevisiae homolog. PMID:19298859 Ach1p showed highest specific activity for the CoASH transfer from succinyl-CoA to acetate and only a minor acetyl-CoA-hydrolase activity. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Retain the broad cytoplasm annotation as non-core localization evidence from UniProt-curated C. albicans proteomics. Reason: The UniProt cytoplasm statement is experimentally anchored to C. albicans peptide detection. It is broader than the fungal mitochondrial functional model and than the cytosol rows propagated from S. cerevisiae, but it remains useful evidence that at least some ACH1 protein is cytoplasmic. Supporting Evidence: file:CANAL/ACH1/ACH1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15378761}. |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: PTN000484602 places the fungal Ach1-family enzyme in mitochondria across Ascomycota and is appropriate for C. albicans ACH1. Reason: The Ascomycota-restricted PTN000484602 placement is consistent with S. cerevisiae Ach1 localization and with later fungal enzymology assigning Ach1 to mitochondrial acetate detoxification. C. albicans ACH1 is inside this fungal Ach1 clade and functionally complements S. cerevisiae ach1. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000484602 SUPPORTS TRANSFER The PTN000484602 mitochondrial placement is confined to Ascomycota and is supported by fungal Ach1 experimental localization and enzymology. Supporting Evidence: PMID:18689527 Both ACH1 and ACS2 complement mutations in their S. cerevisiae homolog. PMID:19298859 Our results imply that Ach1p is involved in mitochondrial acetate detoxification by a CoASH transfer from succinyl-CoA to acetate. |
| GO:0005739 mitochondrion | IEA GO_REF:0000117 | ACCEPT | Summary: The ARBA mitochondrial assignment is consistent with experimental and PAINT support for fungal Ach1 mitochondrial activity. Reason: Although the row itself is electronic, the same mitochondrial placement is supported by the Ascomycota PAINT node and by fungal Ach1 literature placing CoA-transferase-dependent acetate detoxification in mitochondria. Supporting Evidence: PMID:19298859 Our results imply that Ach1p is involved in mitochondrial acetate detoxification by a CoASH transfer from succinyl-CoA to acetate. |
| GO:0005739 mitochondrion | IGI PMID:18689527 Role of acetyl coenzyme A synthesis and breakdown in alterna... | ACCEPT | Summary: C. albicans ACH1 complements the S. cerevisiae mitochondrial/cytosolic Ach1 protein and is accepted as mitochondrial. Reason: PMID:18689527 demonstrated functional conservation between C. albicans and S. cerevisiae ACH1, and the later CoA-transferase model assigns fungal Ach1 to mitochondrial acetate detoxification. The mitochondrion annotation is therefore a sound location for ACH1 activity. Supporting Evidence: PMID:18689527 the C. albicans genes complement the S. cerevisiae deletions, indicating conservation of function. PMID:19298859 Our results imply that Ach1p is involved in mitochondrial acetate detoxification by a CoASH transfer from succinyl-CoA to acetate. |
| GO:0005739 mitochondrion | ISA PMID:18689527 Role of acetyl coenzyme A synthesis and breakdown in alterna... | ACCEPT | Summary: ACH1 orthology supports transfer of the conserved fungal mitochondrial Ach1 placement. Reason: The C. albicans protein belongs to the acetyl-CoA hydrolase/transferase family and functionally complements S. cerevisiae ach1; combined with the Ascomycota PAINT mitochondrial node, this supports ACH1 activity in the mitochondrion. Supporting Evidence: file:CANAL/ACH1/ACH1-uniprot.txt Belongs to the acetyl-CoA hydrolase/transferase family. PMID:18689527 Both ACH1 and ACS2 complement mutations in their S. cerevisiae homolog. |
| GO:0005829 cytosol | IGI PMID:18689527 Role of acetyl coenzyme A synthesis and breakdown in alterna... | UNDECIDED | Summary: The cytosol transfer from S. cerevisiae is not resolvable from the cached Candida complementation paper; mitochondrion and broad cytoplasm have clearer evidence. Reason: The CGD row transfers an SGD cytosol annotation by IGI to C. albicans ACH1. PMID:18689527 supports C. albicans/S. cerevisiae ACH1 functional conservation, and the C. albicans UniProt record has a direct broad cytoplasm call from proteomics, but neither cached source directly verifies the more specific cytosol location. Leave this row unresolved until the underlying SGD cytosol evidence is reviewed. Supporting Evidence: PMID:18689527 Both ACH1 and ACS2 complement mutations in their S. cerevisiae homolog. file:CANAL/ACH1/ACH1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15378761}. |
| GO:0005829 cytosol | ISA PMID:18689527 Role of acetyl coenzyme A synthesis and breakdown in alterna... | UNDECIDED | Summary: The sequence-based cytosol transfer from S. cerevisiae is plausible but cannot be confirmed from the cached Candida paper and UniProt broad cytoplasm call. Reason: ACH1 is a conserved fungal Ach1-family protein and C. albicans ACH1 complements S. cerevisiae ach1, which supports transfer of the fungal Ach1 enzyme function. That does not by itself verify transfer to cytosol, and the Candida-specific localization evidence available here is only the parent cytoplasm term, so this more specific cytosol row should remain unresolved until the SGD cytosol evidence is checked directly. Supporting Evidence: PMID:18689527 Both ACH1 and ACS2 complement mutations in their S. cerevisiae homolog. file:CANAL/ACH1/ACH1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15378761}. |
| GO:0006083 acetate metabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: PTN000484586 correctly propagates acetate metabolic process across the fungal Ach1 clade. Reason: ACH1 directly acts on acetate/acetyl-CoA interconversion in fungi. The C. albicans enzyme complements S. cerevisiae ach1, deletion of C. albicans ACH1 causes growth defects on acetate and ethanol, and S. cerevisiae Ach1p was re-characterized as an acetate-using CoA-transferase. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000484586 SUPPORTS TRANSFER PTN000484586 captures the fungal Ach1-family acetate-metabolism node; C. albicans ACH1 has direct mutant and complementation evidence for the same conserved acetate/acetyl-CoA metabolic role. Supporting Evidence: PMID:18689527 loss of ACH1 conferred a mild retardation of growth in the presence of ethanol and acetate, phenotypes that were complemented by the restoration of a single copy of ACH1 PMID:19298859 Ach1p showed highest specific activity for the CoASH transfer from succinyl-CoA to acetate and only a minor acetyl-CoA-hydrolase activity. |
| GO:0006083 acetate metabolic process | IEA GO_REF:0000120 | ACCEPT | Summary: Automated acetate metabolic process annotation is consistent with Candida-specific ACH1 mutant phenotypes and fungal Ach1 enzymology. Reason: This IEA row agrees with direct CGD and PAINT evidence: C. albicans ACH1 deletion impairs growth on acetate and ethanol, and fungal Ach1 enzymes catalyze CoA transfer to acetate. ACH1 therefore directly participates in acetate metabolism. Supporting Evidence: PMID:18689527 loss of ACH1 conferred a mild retardation of growth in the presence of ethanol and acetate, phenotypes that were complemented by the restoration of a single copy of ACH1 PMID:19298859 Complementation of an ach1 mutant with the coaT gene reversed the growth defect on acetate confirming the in vivo function of Ach1p as a CoA-transferase. |
| GO:0006083 acetate metabolic process | IGI PMID:18689527 Role of acetyl coenzyme A synthesis and breakdown in alterna... | ACCEPT | Summary: Functional complementation with S. cerevisiae ach1 supports conserved involvement in acetate metabolism. Reason: C. albicans ACH1 restores the growth of S. cerevisiae ach1 on acetate medium, and C. albicans ach1 deletion itself mildly retards growth on acetate and ethanol. This directly supports an acetate metabolic role. Supporting Evidence: PMID:18689527 loss of ACH1 conferred a mild retardation of growth in the presence of ethanol and acetate, phenotypes that were complemented by the restoration of a single copy of ACH1 PMID:18689527 the C. albicans genes complement the S. cerevisiae deletions, indicating conservation of function. |
| GO:0006083 acetate metabolic process | ISA PMID:18689527 Role of acetyl coenzyme A synthesis and breakdown in alterna... | ACCEPT | Summary: Orthology to S. cerevisiae ACH1 soundly supports a conserved role in acetate metabolism. Reason: C. albicans ACH1 is an Ach1-family enzyme and functionally complements S. cerevisiae ach1. Its own transcript is induced on acetate and ethanol, and ach1 deletion produces a complemented acetate/ethanol growth defect, so the acetate metabolic process annotation should be retained. Supporting Evidence: PMID:18689527 ACH1 was present at low levels in glucose-containing medium and was highly induced when acetate, ethanol, or glycerol was the carbon source. PMID:18689527 Both ACH1 and ACS2 complement mutations in their S. cerevisiae homolog. |
| GO:0008410 CoA-transferase activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: Correct but broad parent activity for the fungal Ach1-family acetate CoA-transferase. Reason: The fungal Ach1 enzyme family was re-characterized as CoA-transferases and InterPro IPR003702 marks the shared acetyl-CoA hydrolase/transferase N-terminal domain, so this parent term is true. GO:0008775 acetate CoA-transferase activity is more informative for ACH1's molecular function. Supporting Evidence: file:CANAL/ACH1/ACH1-uniprot.txt Belongs to the acetyl-CoA hydrolase/transferase family. PMID:19298859 Complementation of an ach1 mutant with the coaT gene reversed the growth defect on acetate confirming the in vivo function of Ach1p as a CoA-transferase. |
| GO:0008775 acetate CoA-transferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PTN000484586 appropriately propagates acetate CoA-transferase activity to fungal ACH1. Reason: The same PTN000484586 Ach1 node is seeded by S. cerevisiae Ach1p and the Aspergillus nidulans CoaT enzyme; re-characterization of fungal Ach1p showed predominant succinyl-CoA:acetate CoA-transferase activity, and the C. albicans protein complements S. cerevisiae ach1. This supports transfer of GO:0008775 to C. albicans ACH1. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000484586 SUPPORTS TRANSFER The PTN000484586 acetate CoA-transferase assertion is grounded in experimentally characterized fungal Ach1/CoaT enzymes and covers C. albicans ACH1, which complements S. cerevisiae ach1. Supporting Evidence: PMID:18689527 Both ACH1 and ACS2 complement mutations in their S. cerevisiae homolog. PMID:19298859 Ach1p showed highest specific activity for the CoASH transfer from succinyl-CoA to acetate and only a minor acetyl-CoA-hydrolase activity. |
| GO:0008775 acetate CoA-transferase activity | IEA GO_REF:0000002 | ACCEPT | Summary: The InterPro2GO acetate CoA-transferase call is the best current molecular-function assignment for ACH1. Reason: IPR046433 covers the acetyl-CoA hydrolase/transferase family. For fungal Ach1 proteins, later enzymology supports acetate CoA-transferase activity as the dominant reaction, and C. albicans ACH1 complements the S. cerevisiae ach1 defect. Supporting Evidence: PMID:18689527 Both ACH1 and ACS2 complement mutations in their S. cerevisiae homolog. PMID:19298859 Ach1p showed highest specific activity for the CoASH transfer from succinyl-CoA to acetate and only a minor acetyl-CoA-hydrolase activity. |
| GO:0071469 cellular response to alkaline pH | IMP PMID:21586647 The fungal pathogen Candida albicans autoinduces hyphal morp... | MODIFY | Summary: ACH1 is required for efficient amino-acid-driven environmental alkalinization, not for cellular response to alkaline pH; GO currently lacks a precise extracellular pH-elevation term for this phenotype. Reason: PMID:21586647 found ACH1 in a screen for mutants defective in neutralizing acidic amino-acid medium by raising extracellular pH. That is the opposite direction from GO:0071469 cellular response to alkaline pH, which implies a cell responding to an alkaline stimulus. Existing pH elevation terms describe increased internal pH of an organism or cell, not alkalinization of the extracellular medium, so this row should be repaired to an ontology term for amino-acid-catabolism-driven extracellular alkalinization once such a term exists. Proposed replacements: amino acid catabolism-mediated extracellular alkalinization Supporting Evidence: PMID:21586647 Mutations in four genes, STP2, a transcription factor regulating amino acid permeases, ACH1 (acetyl-coenzyme A [acetyl-CoA] hydrolase), DUR1,2 (urea amidolyase), and ATO5, a putative ammonia transporter, abolish or delay neutralization. |
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