Putative phospholipase B homolog of S. cerevisiae LPL1, likely encoding a lipid droplet-associated enzyme with phospholipase activity on glycerophospholipids. Based on homology, predicted to contain GXSXG lipase motif and function in phospholipid metabolism during stationary phase.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0006629
lipid metabolic process
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: This broad biological process term is appropriate for a phospholipase B enzyme. The S. cerevisiae homolog LPL1 is well-characterized as functioning in lipid metabolism, specifically in phospholipid hydrolysis and lipid droplet dynamics. The IBA annotation is based on phylogenetic inference from characterized orthologs.
Reason: The annotation is supported by strong homology to S. cerevisiae LPL1, which has demonstrated roles in lipid metabolism. Phospholipase B enzymes by definition participate in lipid metabolic processes through hydrolysis of glycerophospholipids. The term accurately captures the core metabolic function without being overly specific.
Supporting Evidence:
file:CANAL/LPL1/LPL1-deep-research.md
The S. cerevisiae LPL1 (YOR059c) gene encodes a phospholipase B... Shows phospholipase activity with broad substrate specificity, acting on all glycerophospholipids primarily at sn-2 position, then at sn-1 position
|
|
GO:0004622
phosphatidylcholine lysophospholipase A1 activity
|
IBA
GO_REF:0000033 |
MODIFY |
Summary: This molecular function represents one of the three activities of phospholipase B enzymes - the lysophospholipase activity. However, this annotation is too narrow as it only captures one aspect of phospholipase B function and is specific to phosphatidylcholine substrates, while the enzyme likely has broader substrate specificity.
Reason: Phospholipase B enzymes have three distinct activities: sn-1/sn-2 fatty acid ester hydrolase, lysophospholipase, and transacylase activity. The current term only captures the lysophospholipase activity on phosphatidylcholine. The more comprehensive term GO:0102545 (phospholipase B activity) would better represent the full enzymatic capability of this protein, as it encompasses all three activities and broader substrate specificity.
Proposed replacements:
phospholipase B activity
Supporting Evidence:
file:CANAL/LPL1/LPL1-deep-research.md
Fungal phospholipase B (PLB) enzymes harbor three distinct activities: 1. sn-1 and sn-2 fatty acid ester hydrolase activity, 2. Lysophospholipase activity, 3. Transacylase activity
|
|
GO:0005811
lipid droplet
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: This cellular component annotation is strongly supported by characterization of the S. cerevisiae homolog LPL1, which shows exclusive localization to lipid droplets during stationary phase. This localization is consistent with the enzyme role in lipid metabolism and storage regulation.
Reason: The S. cerevisiae LPL1 has been experimentally demonstrated to localize exclusively to lipid droplets at stationary phase. This localization makes functional sense for a phospholipase B enzyme involved in lipid metabolism and droplet dynamics. The IBA annotation based on phylogenetic inference from the well-characterized S. cerevisiae ortholog is reliable.
Supporting Evidence:
file:CANAL/LPL1/LPL1-deep-research.md
The S. cerevisiae LPL1 (YOR059c) gene encodes a phospholipase B localized to lipid droplets during stationary phase... Exclusively localized to lipid droplets at stationary phase
|
|
GO:0047372
monoacylglycerol lipase activity
|
IBA
GO_REF:0000033 |
KEEP AS NON CORE |
Summary: This annotation suggests additional lipase activity beyond phospholipase function. While some lipases can have promiscuous substrate specificity, there is no direct evidence that LPL1 homologs have monoacylglycerol lipase activity as a primary function. This appears to be a secondary or promiscuous activity.
Reason: The primary characterized function of LPL1 homologs is phospholipase B activity on glycerophospholipids, not monoacylglycerol hydrolysis. While the enzyme may have some activity on monoacylglycerols due to the general lipase domain, this is likely not the core function. The annotation may reflect substrate promiscuity rather than the primary enzymatic role. Keeping as non-core acknowledges potential activity without overstating its importance.
Supporting Evidence:
file:CANAL/LPL1/LPL1-deep-research.md
Shows phospholipase activity with broad substrate specificity, acting on all glycerophospholipids primarily at sn-2 position, then at sn-1 position [Note: no mention of monoacylglycerol substrates in primary literature]
|
|
GO:0016020
membrane
|
IEA
GO_REF:0000043 |
REMOVE |
Summary: This generic membrane annotation is based on automated prediction from a transmembrane domain (residues 286-306 per UniProt). However, this is inconsistent with the well-characterized lipid droplet localization of the S. cerevisiae homolog. The predicted transmembrane domain may represent a hydrophobic region for lipid droplet association rather than true membrane insertion.
Reason: The annotation conflicts with experimental evidence showing exclusive lipid droplet localization for the S. cerevisiae homolog. While the protein has a predicted hydrophobic region (286-306), this likely mediates lipid droplet association rather than membrane integration. Lipid droplets have a unique phospholipid monolayer structure distinct from bilayer membranes. The generic "membrane" term is misleading and the more specific "lipid droplet" annotation (GO:0005811) is already present and correct.
Supporting Evidence:
file:CANAL/LPL1/LPL1-deep-research.md
Exclusively localized to lipid droplets at stationary phase
file:CANAL/LPL1/LPL1-uniprot.txt
FT TRANSMEM 286..306 [Note: This hydrophobic region likely mediates lipid droplet binding rather than membrane insertion]
|
|
GO:0016042
lipid catabolic process
|
IEA
GO_REF:0000043 |
ACCEPT |
Summary: This biological process annotation accurately describes the catabolic aspect of phospholipase B activity - the hydrolysis of phospholipids into fatty acids and lysophospholipids. This is a appropriate child term of the broader lipid metabolic process already annotated.
Reason: Phospholipase B enzymes catalyze the hydrolytic breakdown of glycerophospholipids, which is definitionally a lipid catabolic process. The annotation correctly captures this catabolic function. While based on automated keyword mapping (IEA), it aligns with the known enzymatic activity of phospholipase B family members.
Supporting Evidence:
file:CANAL/LPL1/LPL1-deep-research.md
Phospholipase B enzymes harbor... sn-1 and sn-2 fatty acid ester hydrolase activity [hydrolysis represents catabolism of lipids]
|
|
GO:0016787
hydrolase activity
|
IEA
GO_REF:0000043 |
REMOVE |
Summary: This is an overly broad molecular function term that provides minimal information about the specific enzymatic activity. While technically correct (phospholipases are hydrolases), this annotation adds no value beyond what is already captured by more specific terms.
Reason: The term "hydrolase activity" is too generic and uninformative. The protein already has more specific molecular function annotations (phospholipase/lysophospholipase activities) that are children of hydrolase activity in the GO hierarchy. This broad parent term adds no additional information and represents the type of vague annotation that should be avoided according to curation guidelines. The specific phospholipase B activity (GO:0102545) provides much more informative functional annotation.
Supporting Evidence:
file:CANAL/LPL1/LPL1-deep-research.md
Contains the canonical lipase motif GXSXG essential for catalytic activity [specific lipase, not generic hydrolase]
|
The S. cerevisiae LPL1 (YOR059c) gene encodes a phospholipase B localized to lipid droplets during stationary phase [https://www.sciencedirect.com/science/article/abs/pii/S1388198114001243]. Key features include:
- Contains the canonical lipase motif GXSXG essential for catalytic activity
- Shows phospholipase activity with broad substrate specificity, acting on all glycerophospholipids primarily at sn-2 position, then at sn-1 position
- Deletion of LPL1 results in altered lipid droplet morphology
- Exclusively localized to lipid droplets at stationary phase
Fungal phospholipase B (PLB) enzymes harbor three distinct activities [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2077850/]:
1. sn-1 and sn-2 fatty acid ester hydrolase activity
2. Lysophospholipase activity
3. Transacylase activity
The GXSXG consensus sequence contains critical catalytic residues [https://pmc.ncbi.nlm.nih.gov/articles/PMC7072546/]:
- Serine residue acts as nucleophile to form enzyme-acyl intermediate
- Aspartate residue acts as general base to activate catalytic serine
- Forms a Ser/Asp catalytic dyad mechanism
Many fungal species possess multiple PLB genes [https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2010.00125/full]:
- S. cerevisiae: 3 PLB genes
- C. albicans: 5-member PLB family (PLB1, PLB2, PLB3, PLB4, PLB5)
- The expansion of PLB genes in pathogenic fungi suggests roles in virulence
Key genes in C. albicans phospholipid metabolism include [https://journals.asm.org/doi/10.1128/ec.00054-15]:
- CHO1: Phosphatidylserine synthase
- PSD1/PSD2: Phosphatidylserine decarboxylases
These genes affect extracellular vesicle morphology, cargo, and immunostimulatory properties
Lipid metabolism in C. albicans is crucial for [https://pubmed.ncbi.nlm.nih.gov/23974286/]:
- Biofilm formation - biofilms contain higher phospholipid and sphingolipid levels than planktonic cells [https://pmc.ncbi.nlm.nih.gov/articles/PMC3352276/]
- Hypoxic adaptation - dynamic lipidome reprogramming under oxygen limitation [https://journals.asm.org/doi/10.1128/msphere.00913-19]
- Multidrug resistance acquisition through lipid-mediated cellular circuit crosstalk
De novo sphingolipid biosynthesis is hypha-associated and essential for filamentation [https://journals.asm.org/doi/10.1128/msystems.00539-22]. Major sphingolipids include:
- IPC (inositolphosphorylceramide)
- MIPC (mannosyl-inositolphosphorylceramide)
- M(IP)2C (mannosyl diinositolphosphoryl ceramide)
Given the homology to S. cerevisiae LPL1, the C. albicans LPL1 likely functions as:
- Phospholipase B with activity on glycerophospholipids
- Lipid droplet-associated enzyme active during stationary phase/nutrient limitation
- Regulator of lipid droplet morphology and dynamics
Phospholipase B enzymes in pathogenic fungi contribute to [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3109512/]:
- Host membrane disruption through phospholipid hydrolysis
- Cell signaling modulation affecting virulence trait expression
- Production of immunomodulatory lipid effectors
- Evasion of host immune defense mechanisms
The enzyme likely participates in:
- Membrane lipid remodeling during morphological transitions (yeast-to-hyphae)
- Lipid droplet metabolism during nutrient scavenging
- Generation of signaling lipids affecting stress responses
Recent genome-wide screens identified essential genes in C. albicans [https://www.cell.com/cell-reports/fulltext/S2211-1247(24)00940-9]:
- ~70% of C. albicans genes remain uncharacterized (as of 2019)
- Machine learning models predict gene essentiality for antifungal target identification [https://pubmed.ncbi.nlm.nih.gov/34764269/]
- Functional genomic screening identifies genes important for fitness in host-relevant environments
Despite extensive research on C. albicans lipid metabolism:
- Specific functional characterization of CAL0000180378/LPL1 remains limited
- Direct experimental evidence for phospholipase B activity needs confirmation
- Role in virulence and host-pathogen interactions requires investigation
- Potential as antifungal target unexplored
Based on fungal phospholipase B family features:
- Expected to contain GXSXG lipase motif
- Likely possesses α/β hydrolase fold characteristic of this enzyme family
- May contain lipid droplet targeting sequences
Predicted to utilize:
- Serine-aspartate catalytic dyad
- Two-step reaction: acylation followed by deacylation
- Broad substrate specificity for glycerophospholipids
C. albicans causes severe infections with limited treatment options [https://pmc.ncbi.nlm.nih.gov/articles/PMC11416860/]:
- Fourth leading cause of hospital-acquired bloodstream infections
- High mortality rates (30-60%) for invasive candidiasis
- Increasing antifungal resistance
Phospholipase B enzymes represent attractive antifungal targets because:
- Essential for virulence in multiple pathogenic fungi
- Absent or significantly different in mammalian hosts
- Druggable enzyme active site with defined catalytic mechanism
The Candida albicans LPL1 gene (CAL0000180378/Q5AMS2) encodes a putative phospholipase B homologous to S. cerevisiae LPL1. Based on family characteristics, it likely contains the GXSXG lipase motif and functions in phospholipid metabolism, potentially contributing to virulence through membrane disruption and lipid signaling. Despite its potential importance, direct experimental characterization remains limited, representing a significant knowledge gap in understanding C. albicans pathogenesis and identifying novel antifungal targets. The expansion of phospholipase B genes in C. albicans compared to non-pathogenic yeasts suggests specialized roles in host adaptation and virulence that warrant further investigation.
id: Q5AMS2
gene_symbol: LPL1
taxon:
id: NCBITaxon:237561
label: Candida albicans SC5314
description: Putative phospholipase B homolog of S. cerevisiae LPL1, likely encoding a lipid droplet-associated enzyme with phospholipase activity on glycerophospholipids. Based on homology, predicted to contain GXSXG lipase motif and function in phospholipid metabolism during stationary phase.
existing_annotations:
- term:
id: GO:0006629
label: lipid metabolic process
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: This broad biological process term is appropriate for a phospholipase B enzyme. The S. cerevisiae homolog LPL1 is well-characterized as functioning in lipid metabolism, specifically in phospholipid hydrolysis and lipid droplet dynamics. The IBA annotation is based on phylogenetic inference from characterized orthologs.
action: ACCEPT
reason: The annotation is supported by strong homology to S. cerevisiae LPL1, which has demonstrated roles in lipid metabolism. Phospholipase B enzymes by definition participate in lipid metabolic processes through hydrolysis of glycerophospholipids. The term accurately captures the core metabolic function without being overly specific.
supported_by:
- reference_id: file:CANAL/LPL1/LPL1-deep-research.md
supporting_text: The S. cerevisiae LPL1 (YOR059c) gene encodes a phospholipase B... Shows phospholipase activity with broad substrate specificity, acting on all glycerophospholipids primarily at sn-2 position, then at sn-1 position
- term:
id: GO:0004622
label: phosphatidylcholine lysophospholipase A1 activity
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: This molecular function represents one of the three activities of phospholipase B enzymes - the lysophospholipase activity. However, this annotation is too narrow as it only captures one aspect of phospholipase B function and is specific to phosphatidylcholine substrates, while the enzyme likely has broader substrate specificity.
action: MODIFY
reason: 'Phospholipase B enzymes have three distinct activities: sn-1/sn-2 fatty acid ester hydrolase, lysophospholipase, and transacylase activity. The current term only captures the lysophospholipase activity on phosphatidylcholine. The more comprehensive term GO:0102545 (phospholipase B activity) would better represent the full enzymatic capability of this protein, as it encompasses all three activities and broader substrate specificity.'
proposed_replacement_terms:
- id: GO:0102545
label: phospholipase B activity
supported_by:
- reference_id: file:CANAL/LPL1/LPL1-deep-research.md
supporting_text: 'Fungal phospholipase B (PLB) enzymes harbor three distinct activities: 1. sn-1 and sn-2 fatty acid ester hydrolase activity, 2. Lysophospholipase activity, 3. Transacylase activity'
- term:
id: GO:0005811
label: lipid droplet
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: This cellular component annotation is strongly supported by characterization of the S. cerevisiae homolog LPL1, which shows exclusive localization to lipid droplets during stationary phase. This localization is consistent with the enzyme role in lipid metabolism and storage regulation.
action: ACCEPT
reason: The S. cerevisiae LPL1 has been experimentally demonstrated to localize exclusively to lipid droplets at stationary phase. This localization makes functional sense for a phospholipase B enzyme involved in lipid metabolism and droplet dynamics. The IBA annotation based on phylogenetic inference from the well-characterized S. cerevisiae ortholog is reliable.
supported_by:
- reference_id: file:CANAL/LPL1/LPL1-deep-research.md
supporting_text: The S. cerevisiae LPL1 (YOR059c) gene encodes a phospholipase B localized to lipid droplets during stationary phase... Exclusively localized to lipid droplets at stationary phase
- term:
id: GO:0047372
label: monoacylglycerol lipase activity
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: This annotation suggests additional lipase activity beyond phospholipase function. While some lipases can have promiscuous substrate specificity, there is no direct evidence that LPL1 homologs have monoacylglycerol lipase activity as a primary function. This appears to be a secondary or promiscuous activity.
action: KEEP_AS_NON_CORE
reason: The primary characterized function of LPL1 homologs is phospholipase B activity on glycerophospholipids, not monoacylglycerol hydrolysis. While the enzyme may have some activity on monoacylglycerols due to the general lipase domain, this is likely not the core function. The annotation may reflect substrate promiscuity rather than the primary enzymatic role. Keeping as non-core acknowledges potential activity without overstating its importance.
supported_by:
- reference_id: file:CANAL/LPL1/LPL1-deep-research.md
supporting_text: 'Shows phospholipase activity with broad substrate specificity, acting on all glycerophospholipids primarily at sn-2 position, then at sn-1 position [Note: no mention of monoacylglycerol substrates in primary literature]'
- term:
id: GO:0016020
label: membrane
evidence_type: IEA
original_reference_id: GO_REF:0000043
review:
summary: This generic membrane annotation is based on automated prediction from a transmembrane domain (residues 286-306 per UniProt). However, this is inconsistent with the well-characterized lipid droplet localization of the S. cerevisiae homolog. The predicted transmembrane domain may represent a hydrophobic region for lipid droplet association rather than true membrane insertion.
action: REMOVE
reason: The annotation conflicts with experimental evidence showing exclusive lipid droplet localization for the S. cerevisiae homolog. While the protein has a predicted hydrophobic region (286-306), this likely mediates lipid droplet association rather than membrane integration. Lipid droplets have a unique phospholipid monolayer structure distinct from bilayer membranes. The generic "membrane" term is misleading and the more specific "lipid droplet" annotation (GO:0005811) is already present and correct.
supported_by:
- reference_id: file:CANAL/LPL1/LPL1-deep-research.md
supporting_text: Exclusively localized to lipid droplets at stationary phase
- reference_id: file:CANAL/LPL1/LPL1-uniprot.txt
supporting_text: 'FT TRANSMEM 286..306 [Note: This hydrophobic region likely mediates lipid droplet binding rather than membrane insertion]'
- term:
id: GO:0016042
label: lipid catabolic process
evidence_type: IEA
original_reference_id: GO_REF:0000043
review:
summary: This biological process annotation accurately describes the catabolic aspect of phospholipase B activity - the hydrolysis of phospholipids into fatty acids and lysophospholipids. This is a appropriate child term of the broader lipid metabolic process already annotated.
action: ACCEPT
reason: Phospholipase B enzymes catalyze the hydrolytic breakdown of glycerophospholipids, which is definitionally a lipid catabolic process. The annotation correctly captures this catabolic function. While based on automated keyword mapping (IEA), it aligns with the known enzymatic activity of phospholipase B family members.
supported_by:
- reference_id: file:CANAL/LPL1/LPL1-deep-research.md
supporting_text: Phospholipase B enzymes harbor... sn-1 and sn-2 fatty acid ester hydrolase activity [hydrolysis represents catabolism of lipids]
- term:
id: GO:0016787
label: hydrolase activity
evidence_type: IEA
original_reference_id: GO_REF:0000043
review:
summary: This is an overly broad molecular function term that provides minimal information about the specific enzymatic activity. While technically correct (phospholipases are hydrolases), this annotation adds no value beyond what is already captured by more specific terms.
action: REMOVE
reason: The term "hydrolase activity" is too generic and uninformative. The protein already has more specific molecular function annotations (phospholipase/lysophospholipase activities) that are children of hydrolase activity in the GO hierarchy. This broad parent term adds no additional information and represents the type of vague annotation that should be avoided according to curation guidelines. The specific phospholipase B activity (GO:0102545) provides much more informative functional annotation.
supported_by:
- reference_id: file:CANAL/LPL1/LPL1-deep-research.md
supporting_text: Contains the canonical lipase motif GXSXG essential for catalytic activity [specific lipase, not generic hydrolase]
core_functions:
- description: Phospholipid hydrolysis at lipid droplets
molecular_function:
id: GO:0102545
label: B-type glycerophospholipase activity
supported_by:
- reference_id: file:CANAL/LPL1/LPL1-deep-research.md
supporting_text: 'Fungal phospholipase B (PLB) enzymes harbor three distinct activities: 1. sn-1 and sn-2 fatty acid ester hydrolase activity, 2. Lysophospholipase activity, 3. Transacylase activity'
- reference_id: file:CANAL/LPL1/LPL1-deep-research.md
supporting_text: Shows phospholipase activity with broad substrate specificity, acting on all glycerophospholipids primarily at sn-2 position, then at sn-1 position
directly_involved_in:
- id: GO:0006629
label: lipid metabolic process
- id: GO:0016042
label: lipid catabolic process
locations:
- id: GO:0005811
label: lipid droplet
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: file:CANAL/LPL1/LPL1-deep-research.md
title: Deep research analysis of C. albicans LPL1 gene
findings:
- statement: S. cerevisiae homolog LPL1 encodes phospholipase B with conserved catalytic motif
supporting_text: Contains the canonical lipase motif GXSXG essential for catalytic activity
- statement: Phospholipase B enzymes have three distinct enzymatic activities
supporting_text: 'Fungal phospholipase B (PLB) enzymes harbor three distinct activities: 1. sn-1 and sn-2 fatty acid ester hydrolase activity, 2. Lysophospholipase activity, 3. Transacylase activity'
- statement: Exclusive localization to lipid droplets during stationary phase
supporting_text: The S. cerevisiae LPL1 (YOR059c) gene encodes a phospholipase B localized to lipid droplets during stationary phase... Exclusively localized to lipid droplets at stationary phase
- statement: Broad substrate specificity for glycerophospholipids
supporting_text: Shows phospholipase activity with broad substrate specificity, acting on all glycerophospholipids primarily at sn-2 position, then at sn-1 position
- id: file:CANAL/LPL1/LPL1-uniprot.txt
title: UniProt entry for C. albicans LPL1 (Q5AMS2)
findings:
- statement: Contains DUF676 lipase-like domain
supporting_text: DOMAIN 14..213 /note="DUF676"
- statement: Predicted hydrophobic region for lipid droplet association
supporting_text: TRANSMEM 286..306 /note="Helical"
- statement: Member of putative lipase ROG1 family
supporting_text: 'SIMILARITY: Belongs to the putative lipase ROG1 family'
status: COMPLETE
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