cysD encodes a cytoplasmic, PLP-dependent homocysteine synthase/O-acetylhomoserine sulfhydrylase in Aspergillus nidulans. The enzyme catalyzes direct sulfhydrylation of O-acetyl-L-homoserine to L-homocysteine and can also use methanethiol to form L-methionine, linking sulfur assimilation with methionine synthesis and probable methylthioadenosine sulfur recycling. CysD has O-acetylserine sulfhydrylase/cysteine synthase activity in vitro, but genetic analysis identifies CysB rather than CysD as the cysteine synthase of physiological importance in this fungus.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003961 O-acetylhomoserine aminocarboxypropyltransferase activity | EXP PMID:6381643 Mutations affecting the sulphur assimilation pathway in Aspe... | ACCEPT | Summary: Curated UniProt experimental annotation for the methanethiol-dependent O-acetylhomoserine aminocarboxypropyltransferase reaction. Reason: cysD encodes the A. nidulans homocysteine/O-acetylhomoserine sulfhydrylase; although the cached PMID:6381643 record is abstract-only, the enzyme is experimentally characterized as a broad O-acetylhomoserine sulfhydrylase and UniProt curates the methanethiol/OAH reaction to this PMID and Ref.5. Supporting Evidence: PMID:8249501 O-acetylhomoserine sulfhydrylase (OAH SHLase) from Aspergillus nidulans is an oligomeric protein with a broad substrate specificity with regard to sulfhydryl compounds. file:EMENI/cysD/cysD-uniprot.txt Reaction=O-acetyl-L-homoserine + methanethiol = L-methionine + acetate |
| GO:0003961 O-acetylhomoserine aminocarboxypropyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: ARBA/RHEA/EC electronic call to the same methanethiol-dependent activity curated on the UniProt record. Reason: EC 2.5.1.49/RHEA:10048 matches the curated O-acetylhomoserine plus methanethiol reaction of cysD and is consistent with the experimentally characterized OAH SHLase. Supporting Evidence: PMID:8249501 Its major physiological role in Aspergillus nidulans seems to be recycling of the thiomethyl group of methylthio-adenosine but it is also a constituent of the alternative pathway of cysteine synthesis. file:EMENI/cysD/cysD-uniprot.txt Reaction=O-acetyl-L-homoserine + methanethiol = L-methionine + acetate |
| GO:0004124 cysteine synthase activity | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: cysD has O-acetylserine sulfhydrylase activity in vitro, but this cysteine-synthase IBA overstates a side activity that is not physiologically important for cysteine biosynthesis. Reason: A. nidulans cysD can catalyze cysteine-synthase chemistry in vitro, but UniProt restricts its physiological role to the alternative pathway of methionine biosynthesis and the 2007 mutant study found cysB to be the only cysteine synthase of physiological importance. The current PTHR43797 PAINT cache also asserts GO:0051009 and GO:0071269, not GO:0004124, on PTN002887184. Propagation Review Root cause: SOURCE STALE OR MISSING Sources checked: PANTHER:PTN002887184 SOURCE STALE OR MISSING The current PTHR43797 PAINT cache no longer places GO:0004124 on PTN002887184; the node now carries GO:0051009 and GO:0071269 for this catalytic branch. Supporting Evidence: PMID:17482430 This activity is shared by cysteine synthase (CS) encoded by the cysB gene, homocysteine synthase encoded by cysD and by at least one more enzyme. PMID:17482430 Using mutants impaired during various steps of cysteine synthesis we prove that the cysB-encoded enzyme is the only CS of physiological importance in the studied fungus. file:EMENI/cysD/cysD-uniprot.txt CC Ref.5). Also has cysteine synthase (O-acetylserine sulfhydrylase) CC activity in vitro, but seems only be involved in the alternative CC pathway of methionine biosynthesis in E.nidulans (PubMed:17482430, file:EMENI/cysD/cysD-uniprot.txt CC -!- MISCELLANEOUS: E.nidulans has another enzyme having cysteine synthase CC (O-acetylserine sulfhydrylase) activity (cysB) that has been shown to CC be the enzyme of physiological importance in cysteine biosynthesis. file:interpro/panther/PTHR43797/PTHR43797-paint.tsv PTHR43797 PTN002887184 GO:0051009 F IBD false |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT infers cytoplasmic activity at PTN002887184. Reason: PTN002887184 currently asserts cytoplasm for this homocysteine/cysteine synthase branch, and this agrees with UniProt's cytoplasmic placement for cysD by similarity to S. cerevisiae MET17. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002887184 SUPPORTS TRANSFER The current PTHR43797 PAINT cache places GO:0005737 on PTN002887184. Supporting Evidence: file:EMENI/cysD/cysD-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P06106}. file:interpro/panther/PTHR43797/PTHR43797-paint.tsv PTHR43797 PTN002887184 GO:0005737 C IBD false |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping of the cytoplasm placement. Reason: The UniProt SubCell mapping is exactly the curated cysD cytoplasmic location; there is no contrary localization evidence in the local cysD records. Supporting Evidence: file:EMENI/cysD/cysD-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P06106}. |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | ACCEPT | Summary: UniProt curator transfer of cytoplasmic localization from S. cerevisiae MET17. Reason: The cytoplasmic ISS transfer from MET17 is consistent with the PAINT cytoplasm call at PTN002887184 and with cysD encoding a soluble OAH sulfhydrylase. Supporting Evidence: file:EMENI/cysD/cysD-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P06106}. |
| GO:0006520 amino acid metabolic process | IEA GO_REF:0000002 | TOO GENERAL | Summary: Broad InterPro process parent for sulfur amino acid metabolism. Reason: cysD is an amino acid metabolic enzyme, but the accepted homocysteine- and methionine-biosynthesis rows capture the biological process much more specifically. Supporting Evidence: PMID:9506902 The A. nidulans cysD gene encoding homocysteine synthase (O-acetyl-L-homoserine sulphydrylase) has been isolated by functional complementation of a cysD11 mutation. file:interpro/panther/PTHR43797/PTHR43797-paint.tsv PTHR43797 PTN002887184 GO:0071269 P IBD false |
| GO:0016765 transferase activity, transferring alkyl or aryl (other than methyl) groups | IEA GO_REF:0000002 | TOO GENERAL | Summary: Broad InterPro molecular-function parent for the specific O-acetylhomoserine sulfhydrylase activities. Reason: The PLP-dependent transferase assignment is true of cysD but uninformative because the review already accepts the specific O-acetylhomoserine aminocarboxypropyltransferase and O-acetylhomoserine sulfhydrylase activities. Supporting Evidence: file:EMENI/cysD/cysD-uniprot.txt Reaction=O-acetyl-L-homoserine + hydrogen sulfide = L-homocysteine + |
| GO:0019344 L-cysteine biosynthetic process | IEA GO_REF:0000108 | MARK AS OVER ANNOTATED | Summary: Inter-ontology inference from the in-vitro cysteine-synthase activity. Reason: The O-acetylserine reaction is detectable in vitro, but the process annotation overstates that side activity; A. nidulans cysB, not cysD, is the cysteine synthase with physiological importance. Supporting Evidence: PMID:17482430 Using mutants impaired during various steps of cysteine synthesis we prove that the cysB-encoded enzyme is the only CS of physiological importance in the studied fungus. file:EMENI/cysD/cysD-uniprot.txt CC Ref.5). Also has cysteine synthase (O-acetylserine sulfhydrylase) CC activity in vitro, but seems only be involved in the alternative CC pathway of methionine biosynthesis in E.nidulans (PubMed:17482430, file:EMENI/cysD/cysD-uniprot.txt CC -!- MISCELLANEOUS: E.nidulans has another enzyme having cysteine synthase CC (O-acetylserine sulfhydrylase) activity (cysB) that has been shown to CC be the enzyme of physiological importance in cysteine biosynthesis. |
| GO:0019346 obsolete transsulfuration | IEA GO_REF:0000002 | REMOVE | Summary: Over-broad InterPro transsulfuration mapping for a direct sulfhydrylase. Reason: cysD catalyzes direct sulfhydrylation of O-acetylhomoserine rather than a cystathionine-mediated transsulfuration step; the accepted homocysteine-biosynthesis term is the supported process. Supporting Evidence: PMID:6381643 the enzyme which constitutes an alternative pathway for homocysteine synthesis PMID:9506902 The A. nidulans cysD gene encoding homocysteine synthase (O-acetyl-L-homoserine sulphydrylase) has been isolated by functional complementation of a cysD11 mutation. |
| GO:0030170 pyridoxal phosphate binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro PLP-binding call for the transsulfuration-family enzyme. Reason: PLP binding is a correct cofactor feature of the cysD enzyme, but it is subsidiary to the O-acetylhomoserine sulfhydrylase reaction rather than a standalone core function. Supporting Evidence: file:EMENI/cysD/cysD-uniprot.txt Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326; |
| GO:0051009 O-acetylhomoserine sulfhydrylase activity | IEA GO_REF:0000116 | ACCEPT | Summary: RHEA mapping to the homocysteine-forming O-acetylhomoserine sulfhydrylase reaction. Reason: cysD is the A. nidulans homocysteine synthase, and RHEA:27822 is the hydrogen-sulfide/O-acetylhomoserine reaction that produces L-homocysteine. Supporting Evidence: PMID:6381643 the enzyme which constitutes an alternative pathway for homocysteine synthesis file:EMENI/cysD/cysD-uniprot.txt Reaction=O-acetyl-L-homoserine + hydrogen sulfide = L-homocysteine + |
| GO:0051009 O-acetylhomoserine sulfhydrylase activity | ISS GO_REF:0000024 | ACCEPT | Summary: UniProt curator transfer of O-acetylhomoserine sulfhydrylase activity from S. cerevisiae MET17. Reason: The transferred MET17 activity matches the experimentally supported A. nidulans homocysteine synthase reaction. Supporting Evidence: PMID:9506902 The cysD cDNA is able to complement a S. cerevisiae mutation impairing homocysteine synthase. file:EMENI/cysD/cysD-uniprot.txt Reaction=O-acetyl-L-homoserine + hydrogen sulfide = L-homocysteine + |
| GO:0071266 'de novo' L-methionine biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: UniProt automatic process inference from cysD OAH sulfhydrylase activities. Reason: cysD makes homocysteine from O-acetylhomoserine, which UniProt assigns to the L-homocysteine-from-O-acetylhomoserine step of de novo L-methionine biosynthesis. The PMID:8249501 OAH-SHLase-negative mutants were prototrophic, so this cysD branch is not essential under the assayed conditions, but the hydrogen-sulfide/OAH reaction still contributes a direct homocysteine-forming step. Supporting Evidence: PMID:6381643 the enzyme which constitutes an alternative pathway for homocysteine synthesis PMID:8249501 In contrast to Saccharomyces cerevisiae the enzyme is not essential for Aspergillus nidulans as indicated by the completely prototrophic phenotype of OAH SHLase-negative mutants file:EMENI/cysD/cysD-uniprot.txt CC -!- PATHWAY: Amino-acid biosynthesis; L-methionine biosynthesis via de novo CC pathway; L-homocysteine from O-acetyl-L-homoserine. |
| GO:0071267 L-methionine salvage | IC PMID:8249501 Comparative studies on O-acetylhomoserine sulfhydrylase: phy... | NEW | Summary: Proposed salvage process for cysD methanethiol-dependent L-methionine formation. Reason: The purified A. nidulans OAH SHLase can use methanethiol to form L-methionine from O-acetyl-L-homoserine, and PMID:8249501 concluded that its major physiological role appears to be recycling methylthioadenosine-derived sulfur. The exact fungal salvage pathway term remains open, so the generic L-methionine salvage term is the conservative process-level addition. Supporting Evidence: PMID:8249501 Its major physiological role in Aspergillus nidulans seems to be recycling of the thiomethyl group of methylthio-adenosine file:EMENI/cysD/cysD-uniprot.txt Reaction=O-acetyl-L-homoserine + methanethiol = L-methionine + acetate |
| GO:0071269 L-homocysteine biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT homocysteine-biosynthesis inference at PTN002887184. Reason: The current PTHR43797 PAINT cache places L-homocysteine biosynthesis on PTN002887184, and cysD's own literature identifies its product as a homocysteine synthase/O-acetylhomoserine sulfhydrylase. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002887184 SUPPORTS TRANSFER The current PTHR43797 PAINT cache places GO:0071269 on PTN002887184. Supporting Evidence: PMID:6381643 the enzyme which constitutes an alternative pathway for homocysteine synthesis PMID:9506902 The A. nidulans cysD gene encoding homocysteine synthase (O-acetyl-L-homoserine sulphydrylase) has been isolated by functional complementation of a cysD11 mutation. |
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