Glycine cleavage system H-protein of Saccharomyces cerevisiae, a small mitochondrial lipoyl-carrier protein. Its lipoylated Lys-102 swinging arm accepts the aminomethyl group from glycine decarboxylation by the P-protein (Gcv2), presents it to the T-protein (Gcv1) for transfer to tetrahydrofolate, and is reoxidised by dihydrolipoyl dehydrogenase (Lpd1). GCV3 is required for growth on glycine as sole nitrogen source and is induced by glycine. Independently of glycine cleavage, lipoylated Gcv3 is required for lipoylation of the E2 subunits of pyruvate dehydrogenase (Lat1) and 2-oxoglutarate dehydrogenase (Kgd2), acting as the first lipoylated acceptor from which lipoate is relayed in the yeast Lip2/Lip5/Lip3 pathway.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005739 mitochondrion | HDA PMID:14576278 The proteome of Saccharomyces cerevisiae mitochondria. | ACCEPT | Summary: Gcv3 found in the purified mitochondrial proteome. Supporting Evidence: PMID:14576278 The proteins of highly pure yeast mitochondria were separated by several independent methods and analyzed by tandem MS |
| GO:0005739 mitochondrion | HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | ACCEPT | Summary: Gcv3 found in the PROMITO mitochondrial proteome. Supporting Evidence: PMID:16823961 A total of 851 different proteins (PROMITO dataset) were identified by use of multidimensional LC-MS/MS, 1D-SDS-PAGE combined with nano-LC-MS/MS and 2D-PAGE with subsequent MALDI-mass fingerprinting. |
| GO:0005739 mitochondrion | HDA PMID:24769239 Quantitative variations of the mitochondrial proteome and ph... | ACCEPT | Summary: Gcv3 quantified in the mitochondrial proteome across growth conditions. Supporting Evidence: PMID:24769239 The yeast Saccharomyces cerevisiae is a facultative aerobe able to adapt its metabolism according to the carbon substrate |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA (PTN001711613) for mitochondrial GcvH; Gcv3 is an experimental leaf. Supporting Evidence: PMID:19570983 All three lipoic acid-modified proteins, Lat1, Kgd2, and Gcv3, were detected at wild-type levels in the mitochondrial fractions of the wild-type and Lip3-GFP strains |
| GO:0005739 mitochondrion | IDA PMID:19570983 Lipoic acid synthesis and attachment in yeast mitochondria. | ACCEPT | Summary: Schonauer et al. detected lipoylated Gcv3 (and Gcv3-GFP) in mitochondrial fractions. Supporting Evidence: PMID:19570983 All three lipoic acid-modified proteins, Lat1, Kgd2, and Gcv3, were detected at wild-type levels in the mitochondrial fractions of the wild-type and Lip3-GFP strains |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt SubCell mapping (mitochondrion); Gcv3 has a 47-residue presequence. Supporting Evidence: PMID:9020168 GCV3 encodes a 177-residue protein with a putative mitochondrial targeting signal at its amino terminus |
| GO:0005739 mitochondrion | NAS PMID:8830251 Specific induction by glycine of the gene for the P-subunit ... | ACCEPT | Summary: Author statement from the GCV2 paper on mitochondrial GDC; correct. Supporting Evidence: PMID:8830251 The glycine decarboxylase complex (GDC) is composed of four subunits referred to as H-, L-, P-, and T-proteins PMID:19570983 All three lipoic acid-modified proteins, Lat1, Kgd2, and Gcv3, were detected at wild-type levels in the mitochondrial fractions of the wild-type and Lip3-GFP strains |
| GO:0005960 glycine cleavage complex | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for glycine cleavage complex membership of GcvH proteins; correct. Supporting Evidence: PMID:9020168 is shown to code for the H-protein subunit of the multienzyme glycine cleavage system |
| GO:0005960 glycine cleavage complex | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO (GcvH domain IPR002930/IPR017453) to glycine cleavage complex; correct. Supporting Evidence: PMID:9020168 is shown to code for the H-protein subunit of the multienzyme glycine cleavage system |
| GO:0005960 glycine cleavage complex | IMP PMID:9020168 Molecular characterization of GCV3, the Saccharomyces cerevi... | ACCEPT | Summary: Nagarajan & Storms identified YAL044C as the H-protein subunit; gcv3 null cannot use glycine as N source. Supporting Evidence: PMID:9020168 is shown to code for the H-protein subunit of the multienzyme glycine cleavage system PMID:9020168 it is essential when glycine serves as the sole nitrogen source |
| GO:0005960 glycine cleavage complex | NAS PMID:7498764 Genetics of the synthesis of serine from glycine and the uti... | ACCEPT | Summary: NAS from Sinclair & Dawes on the yeast GDC; H-protein is a component. Supporting Evidence: PMID:8830251 The glycine decarboxylase complex (GDC) is composed of four subunits referred to as H-, L-, P-, and T-proteins |
| GO:0006546 glycine catabolic process | IMP PMID:9020168 Molecular characterization of GCV3, the Saccharomyces cerevi... | MODIFY | Summary: True but broad parent of the glycine cleavage process. Reason: Correct but general: glycine catabolic process is an ancestor of GO:0019464 glycine decarboxylation via glycine cleavage system, which this gene already carries and which is the process the gene product directly performs a step of. MODIFY to that descendant; applied the same way to every P-, H-, T- and L-protein review in the glycine cleavage system module. Proposed replacements: glycine decarboxylation via glycine cleavage system Supporting Evidence: PMID:9020168 is shown to code for the H-protein subunit of the multienzyme glycine cleavage system |
| GO:0006546 glycine catabolic process | NAS PMID:7498764 Genetics of the synthesis of serine from glycine and the uti... | MODIFY | Summary: True but broad parent of the glycine cleavage process. Reason: Correct but general: glycine catabolic process is an ancestor of GO:0019464 glycine decarboxylation via glycine cleavage system, which this gene already carries and which is the process the gene product directly performs a step of. MODIFY to that descendant; applied the same way to every P-, H-, T- and L-protein review in the glycine cleavage system module. Proposed replacements: glycine decarboxylation via glycine cleavage system Supporting Evidence: PMID:9020168 is shown to code for the H-protein subunit of the multienzyme glycine cleavage system |
| GO:0006730 one-carbon metabolic process | IGI PMID:10871621 Regulation of the balance of one-carbon metabolism in Saccha... | ACCEPT | Summary: Piper et al.: GCS (including GCV3) supplies mitochondrial one-carbon units; IGI with SHM2. Gcv3 carries the aminomethyl intermediate that becomes the methylene unit of 5,10-CH2-THF. Supporting Evidence: PMID:10871621 particularly those encoding the unique components of the glycine decarboxylase complex (GCV1, GCV2, and GCV3) PMID:10871621 one-carbon units generated from glycine in mitochondria are more directed to purine biosynthesis |
| GO:0009249 protein lipoylation | IMP PMID:19570983 Lipoic acid synthesis and attachment in yeast mitochondria. | ACCEPT | Summary: Schonauer et al. show that lipoylated Gcv3 (Lys-102) is absolutely required for lipoylation of Lat1 and Kgd2, independently of glycine cleavage activity. Gcv3 is the first lipoylated acceptor (via Lip2/Lip5) from which the lipoyl moiety is relayed to the E2 subunits, so it does part of the work of protein lipoylation, not merely being a substrate. Supporting Evidence: PMID:19570983 GCV3, encoding the H protein target of lipoylation, is itself absolutely required for lipoylation of Lat1 and Kgd2 PMID:19570983 suggesting that the lipoylated form of Gcv3 is required for lipoylation of the E2 subunits, Lat1 and Kgd2 |
| GO:0019464 glycine decarboxylation via glycine cleavage system | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for glycine decarboxylation via glycine cleavage system; correct for the H-protein. Supporting Evidence: PMID:9020168 is shown to code for the H-protein subunit of the multienzyme glycine cleavage system |
| GO:0019464 glycine decarboxylation via glycine cleavage system | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO for GcvH; correct. Supporting Evidence: PMID:9020168 is shown to code for the H-protein subunit of the multienzyme glycine cleavage system |
| GO:0031405 lipoic acid binding | IDA PMID:32974306 Mechanism-Driven Metabolic Engineering for Bio-Based Product... | KEEP AS NON CORE | Summary: Chen et al. confirmed protein-bound lipoate in yeast by LC-MS/MS; Gcv3 is the lipoyl-bearing GCS subunit. Reason: The experiment shows that Gcv3 carries bound lipoate, which is true and is the basis of its carrier role. The lipoyl group is a covalently attached prosthetic group (Lys-102), so this cofactor attribute is kept as non-core, and the core activity is recorded as GO:0140104 molecular carrier activity, consistently with the other H-protein reviews and the glycine_cleavage_system module. Supporting Evidence: PMID:32974306 Lipoyl-Gcv3p is the lipoic acid bound subunit of glycine cleavage system (GCV). PMID:32974306 confirmed the availability of protein-bound lipoate in yeast cells through LC-MS/MS |
| GO:0140104 molecular carrier activity | IC PMID:9020168 Molecular characterization of GCV3, the Saccharomyces cerevi... | NEW | Summary: Gcv3 is the lipoyl-arm carrier of the glycine cleavage system and the lipoyl relay intermediate for E2 lipoylation. Reason: GO:0140104 is defined as 'Directly binding to a specific ion or molecule and delivering it either to an acceptor molecule or to a specific location'. The H protein carries the glycine-derived aminomethyl intermediate on its covalently attached lipoyl arm from the P protein to the T protein and presents the reduced arm to the L protein, which is carrier activity. Lipoic acid binding (GO:0031405) is not used for this role because GO binding is defined as non-covalent and the lipoyl group is covalently attached; GO:0140104 matches the glycine_cleavage_system module and the PomBase GO-CAM for the S. pombe H protein. Supporting Evidence: PMID:9020168 is shown to code for the H-protein subunit of the multienzyme glycine cleavage system PMID:32974306 Lipoyl-Gcv3p is the lipoic acid bound subunit of glycine cleavage system (GCV). |
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Download this section (compressed HTML)Q: Is Gcv3 a direct lipoyl donor for Lip3-catalysed transfer to Lat1/Kgd2 (as for GcvH/LipL in Bacillus), or does it act as a structural or regulatory component of a lipoylation complex?
Q: Should GO:0140104 molecular carrier activity get a glycine-cleavage-system H-protein child for the lipoyl/aminomethyl swinging-arm carrier role?
Experiment: Reconstitute in vitro lipoyl transfer from purified octanoyl/lipoyl-Gcv3 to apo-Lat1 or apo-Kgd2 with purified Lip3 to test whether Gcv3 is a direct lipoyl donor.
H subunit of the mitochondrial glycine decarboxylase complex; glycine decarboxylase is required for the catabolism of glycine to 5,10-methylene-THF; also required for all protein lipoylation; expression is regulated by levels of 5,10-methylene-THF
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