MET15

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0003961 O-acetylhomoserine aminocarboxypropyltransferase activity	IEA GO_REF:0000120	MODIFY	Summary: CaMet15p directly catalyzes O-acetyl-L-homoserine sulfhydrolysis, but the evidence supports the sulfide-specific child term. Reason: GO:0003961 is the broader EC 2.5.1.49 activity that includes transfer to methanethiol and other thiols. The purified C. albicans enzyme was tested directly with O-acetyl-L-homoserine and sulfide and produced L-homocysteine, so the more precise supported term is GO:0051009 O-acetylhomoserine sulfhydrylase activity. Proposed replacements: O-acetylhomoserine sulfhydrylase activity Supporting Evidence: PMID:39548263 catalyzing formation of L-homocysteine (HCT) from O-acetyl-L-homoserine (OAH), with Na2S as a source of sulfide ion and a PLP as a cofactor
GO:0004124 cysteine synthase activity	IBA GO_REF:0000033	REMOVE	Summary: Remove the PAINT-propagated cysteine synthase activity because CaMet15p lacks detectable O-acetyl-L-serine sulfhydrylase activity. Reason: The PTN002887184 direct-sulfhydrylation ancestor is the correct PAINT source to inspect here. Its current cached PTHR43797 assertions support cytoplasm, O-acetylhomoserine sulfhydrylase activity, and L-homocysteine biosynthesis, but not GO:0004124 cysteine synthase activity; that older activity also conflicts with the direct C. albicans assay in which O-acetyl-L-serine did not yield detectable L-cysteine. Propagation Review Root cause: SOURCE STALE OR MISSING Failure modes: FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN002887184 SOURCE STALE OR MISSING Current cached PTHR43797 PAINT assertions for PTN002887184 no longer include GO:0004124 for cysteine synthase activity. Supporting Evidence: PMID:39548263 no L-Cys production was detected when O-acetyl-L-serine was present in the reaction mixture instead of OAH
GO:0004124 cysteine synthase activity	IEA GO_REF:0000120	REMOVE	Summary: Remove the transferred cysteine synthase activity because purified CaMet15p did not detectably use O-acetyl-L-serine. Reason: This EC 2.5.1.47 transfer infers the O-acetyl-L-serine sulfhydrylase reaction from a fission-yeast family member. The C. albicans enzyme kept the homocysteine-synthase reaction, but direct testing found no L-cysteine production when O-acetyl-L-serine replaced O-acetyl-L-homoserine, indicating target-specific divergence of this side activity. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE Sources checked: PomBase:SPBC428.11.1:pep SUPPORTS SOURCE BUT NOT TARGET The fission-yeast source does not override direct loss of detectable O-acetyl-L-serine sulfhydrylase activity in C. albicans Met15p. UniProtKB:O13326 SUPPORTS SOURCE BUT NOT TARGET The orthologous source can support its own EC 2.5.1.47 annotation without supporting transfer of that activity to C. albicans MET15. Supporting Evidence: PMID:39548263 no L-Cys production was detected when O-acetyl-L-serine was present in the reaction mixture instead of OAH
GO:0005576 extracellular region	IDA PMID:34201883 Mass Spectrometry-Based Proteomic and Immunoproteomic Analys...	KEEP AS NON CORE	Summary: Keep the extracellular-region proteomics hit as a peripheral localization. Reason: Vaz et al. identified proteins present reproducibly in the C. albicans hyphal secretome by LC-MS/MS. The localization is compatible with a proteomic extracellular-region call but is secondary to MET15's cytosolic biosynthetic role, so it is retained as non-core rather than folded into the core function. Supporting Evidence: PMID:34201883 Hyphal secreted proteins in Lee medium from S1 and S2 were in-gel digested and further analyzed by LC-MS/MS. A total of 301 proteins were identified in both replicate batches with at least 2 peptides (Table S3).
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: Accept the PAINT-inferred cytoplasmic activity site for this soluble PLP-dependent biosynthetic enzyme. Reason: The PTN002887184 PAINT node places cytoplasm on the fungal homocysteine/cysteine synthase clade, and a cytoplasmic site is biologically coherent for a soluble PLP enzyme that catalyzes the L-homocysteine-forming step in de novo methionine biosynthesis.
GO:0005737 cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: Accept the cytoplasmic localization as the expected core location of Met15p activity. Reason: MET15 encodes a soluble enzyme of amino-acid biosynthesis and its accepted PAINT active-site annotation also places the activity in the cytoplasm. The additional hyphal secretome hits describe peripheral extracellular detection and do not contradict cytosolic catalytic function.
GO:0006520 amino acid metabolic process	IEA GO_REF:0000002	TOO GENERAL	Summary: The amino-acid metabolism parent is true but uninformative beside the accepted methionine-biosynthesis terms. Reason: MET15 functions in de novo L-methionine biosynthesis through the L-homocysteine intermediate. GO:0006520 is entailed by those more informative process annotations and does not add useful coverage. Supporting Evidence: PMID:39548263 One of the enzymes that participate in L-Met biosynthesis is the O-acetyl-L-homoserine sulfhydrylase (Met15p), which catalyzes conversion of O-acetyl-L-homoserine (OAH) into L-homocysteine (HCT) with a sulfide ion as a sulfur donor
GO:0016765 transferase activity, transferring alkyl or aryl (other than methyl) groups	IEA GO_REF:0000002	TOO GENERAL	Summary: The transferase parent is correct but too broad relative to the directly assayed O-acetylhomoserine sulfhydrylase activity. Reason: The Cys/Met PLP-dependent enzyme family signature reaches only a broad transferase class. Direct C. albicans biochemistry establishes the specific GO:0051009 O-acetylhomoserine sulfhydrylase activity, which makes GO:0016765 redundant in this review. Supporting Evidence: PMID:39548263 The purified CaMet15NHp, as well as CaMet15CHp, displayed an activity of O-acetyl-L-homoserine sulfhydrylase
GO:0019344 L-cysteine biosynthetic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Keep the cysteine-biosynthesis process transfer as a non-core upstream sulfur-amino-acid role. Reason: MET15 executes the L-homocysteine-forming step of direct sulfhydrylation, not a detectable O-acetyl-L-serine-to-L-cysteine step, so L-cysteine biosynthesis is not its core direct reaction. The process term is nevertheless defensible as non-core because Met15p makes L-homocysteine and C. albicans retains the CYS4/CYS3 transsulfuration route for cysteine and homocysteine interconversion. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PomBase:SPBC428.11.1:pep SUPPORTS TRANSFER The transferred process is supportable through the L-homocysteine intermediate rather than through direct O-acetyl-L-serine sulfhydrylation by C. albicans Met15p. Supporting Evidence: PMID:39548263 catalyzing formation of L-homocysteine (HCT) from O-acetyl-L-homoserine (OAH), with Na2S as a source of sulfide ion and a PLP as a cofactor PMID:42003610 CYS4, CYS3), which allows the interconversion between cysteine and homocysteine
GO:0019346 obsolete transsulfuration	IEA GO_REF:0000002	REMOVE	Summary: Remove the generic transsulfuration-domain process call because Met15p catalyzes direct sulfhydrylation of O-acetylhomoserine. Reason: IPR000277 marks a broad Cys/Met PLP-dependent enzyme family spanning several sulfur-amino-acid reactions. CaMet15p's demonstrated role is the direct sulfhydrylation of O-acetyl-L-homoserine to L-homocysteine in methionine biosynthesis, not a cystathionine-mediated transsulfuration reaction. Supporting Evidence: PMID:39548263 One of the enzymes that participate in L-Met biosynthesis is the O-acetyl-L-homoserine sulfhydrylase (Met15p), which catalyzes conversion of O-acetyl-L-homoserine (OAH) into L-homocysteine (HCT) with a sulfide ion as a sulfur donor
GO:0030170 pyridoxal phosphate binding	IEA GO_REF:0000002	ACCEPT	Summary: Accept PLP binding as the cofactor requirement of CaMet15p. Reason: CaMet15p is a PLP-dependent enzyme and the purified C. albicans protein was assayed with PLP; the same biochemical work reported that activity was lower without added PLP, consistent with PLP as a bound cofactor. Supporting Evidence: PMID:39548263 its activity in the reaction mixture lacking PLP was ∼50% lower than that in the presence of 0.2 mM PLP
GO:0030446 hyphal cell wall	IDA PMID:1383159 Characterization of cell wall proteins from yeast and myceli...	UNDECIDED	Summary: Leave the 1992 hyphal-cell-wall localization undecided because the cached abstract does not identify MET15. Reason: The abstract-only cached paper describes biotin labeling and extraction of C. albicans mycelial and yeast cell-wall proteins, but it does not name MET15 or provide a gene-specific band assignment. That is insufficient to reject an experimental CGD annotation whose curator may have used the full text, but it is also insufficient to verify the specific hyphal-cell-wall claim here. Supporting Evidence: PMID:1383159 Labelling with biotin allowed identification of a complex array of cell wall protein and glycoprotein components within a very wide molecular mass range
GO:0051009 O-acetylhomoserine sulfhydrylase activity	IDA PMID:39548263 Targeting Candida albicans O-acetyl-L-homoserine sulfhydryla...	ACCEPT	Summary: Accept the direct biochemical O-acetylhomoserine sulfhydrylase annotation. Reason: Kuplinska et al. cloned C. albicans MET15, purified N- and C-terminally His-tagged CaMet15p variants, and showed that both catalyze the PLP-dependent conversion of O-acetyl-L-homoserine and sulfide to L-homocysteine. Supporting Evidence: PMID:39548263 The purified CaMet15NHp, as well as CaMet15CHp, displayed an activity of O-acetyl-L-homoserine sulfhydrylase
GO:0051009 O-acetylhomoserine sulfhydrylase activity	IEA GO_REF:0000107	ACCEPT	Summary: Accept the orthology-transferred O-acetylhomoserine sulfhydrylase call because it is now directly verified in C. albicans. Reason: The same O-acetylhomoserine sulfhydrylase activity transferred from the fungal orthologous source was demonstrated directly for purified CaMet15p, so this inference agrees with target-specific biochemistry. Supporting Evidence: PMID:39548263 The purified CaMet15NHp, as well as CaMet15CHp, displayed an activity of O-acetyl-L-homoserine sulfhydrylase
GO:0071265 L-methionine biosynthetic process	IDA PMID:39548263 Targeting Candida albicans O-acetyl-L-homoserine sulfhydryla...	ACCEPT	Summary: Accept the direct methionine-biosynthesis annotation. Reason: CaMet15p catalyzes the second direct-sulfhydrylation step of fungal methionine biosynthesis, forming the L-homocysteine intermediate from O-acetyl-L-homoserine and sulfide. Supporting Evidence: PMID:39548263 Met15p is involved in the direct sulfhydrylation pathway
GO:0071265 L-methionine biosynthetic process	IMP PMID:10992284 MET15 as a visual selection marker for Candida albicans.	ACCEPT	Summary: Accept the mutant-phenotype support for MET15 in methionine biosynthesis. Reason: Viaene et al. generated a C. albicans met15-deficient strain that grew only slowly without methionine, and growth was restored by either integrative or replicative plasmids carrying MET15. That phenotype fits the direct biochemical role in L-homocysteine and methionine synthesis. Supporting Evidence: PMID:10992284 methionine-depleted medium. However, this growth was severely delayed.
GO:0071265 L-methionine biosynthetic process	IMP PMID:16043373 Gene disruption in Candida albicans using a synthetic, codon...	ACCEPT	Summary: Accept the Cre-loxP MET15-disruption phenotype annotation in the context of the established MET15 methionine role. Reason: The cached 2005 abstract verifies construction of a C. albicans met15 null mutant using the synthetic Cre-loxP system. Although the abstract focuses on the genetic-tool method, the CGD IMP should be retained because independent mutant complementation and direct enzyme assays establish the same L-methionine biosynthetic function for MET15. Supporting Evidence: PMID:16043373 disrupting two C. albicans loci: ADE2 and MET15. Ade2 and met15 null mutants were made using loxP-flanked ARG4- and HIS1-based disruption cassettes.
GO:0071266 'de novo' L-methionine biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: Accept de novo L-methionine biosynthesis because CaMet15p catalyzes the O-acetylhomoserine branch. Reason: CaMet15p forms L-homocysteine from the de novo pathway intermediate O-acetyl-L-homoserine, and MET15 inhibitors perturb methionine biosynthesis in C. albicans, placing the enzyme in the de novo L-methionine biosynthetic route. Supporting Evidence: PMID:39548263 One of the enzymes that participate in L-Met biosynthesis is the O-acetyl-L-homoserine sulfhydrylase (Met15p), which catalyzes conversion of O-acetyl-L-homoserine (OAH) into L-homocysteine (HCT) with a sulfide ion as a sulfur donor
GO:0071269 L-homocysteine biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: Accept the PAINT-inferred L-homocysteine biosynthetic process. Reason: PTN002887184 is the PAINT source for the L-homocysteine biosynthetic process in PTHR43797, and this propagation is supported in C. albicans by direct detection of L-homocysteine produced from O-acetyl-L-homoserine by purified CaMet15p. Supporting Evidence: PMID:39548263 catalyzing formation of L-homocysteine (HCT) from O-acetyl-L-homoserine (OAH), with Na2S as a source of sulfide ion and a PLP as a cofactor
GO:0071269 L-homocysteine biosynthetic process	IEA GO_REF:0000107	ACCEPT	Summary: Accept the orthology-transferred L-homocysteine biosynthetic process. Reason: The EnsemblFungi transfer of L-homocysteine biosynthesis is consistent with both the current PAINT node and direct target evidence that CaMet15p produces L-homocysteine from O-acetyl-L-homoserine. Supporting Evidence: PMID:39548263 catalyzing formation of L-homocysteine (HCT) from O-acetyl-L-homoserine (OAH), with Na2S as a source of sulfide ion and a PLP as a cofactor

Gene Description

Existing Annotations Review

Core Functions

O-acetylhomoserine sulfhydrylase that produces L-homocysteine from O-acetyl-L-homoserine and sulfide in the direct sulfhydrylation branch of de novo L-methionine biosynthesis.

References

📚 Additional Documentation

Notes

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