GLDC

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005739 mitochondrion	IBA GO_REF:0000033	ACCEPT	Summary: GLDC is established as a mitochondrial matrix protein. The IBA annotation is consistent with direct experimental evidence from chicken showing mitochondrial localization (PMID:7440562) and conserved across the GcvP family. Reason: Mitochondrial localization is a core characteristic of GLDC. Hiraga & Kikuchi (1980) purified P-protein from chicken liver mitochondria. The deep research confirms "GCS is a mitochondrial (matrix/inner-membrane-associated) multienzyme complex" (file:CHICK/GLDC/GLDC-deep-research-falcon.md). The IBA is phylogenetically sound and experimentally validated. Supporting Evidence: PMID:7440562 Glycine decarboxylase, tentatively called P-protein and considered a constituent of the glycine cleavage system, was purified to apparent homogeneity from chicken liver mitochondria.
GO:0030170 pyridoxal phosphate binding	IBA GO_REF:0000033	ACCEPT	Summary: GLDC is a PLP-dependent enzyme with pyridoxal 5'-phosphate covalently bound to Lys-738 (Lys-35 in the phosphopyridoxyl peptide). This IBA annotation is well-supported by experimental evidence. Reason: PLP binding is a core mechanistic feature of GLDC required for glycine decarboxylation. Fujiwara et al. (1987) determined the amino acid sequence of the phosphopyridoxyl peptide and identified Lys as the PLP attachment site. Hiraga & Kikuchi (1980) showed the enzyme contains equimolar pyridoxal 5'-phosphate. The UniProt annotation confirms EC=1.4.4.2 as PLP-dependent. Supporting Evidence: PMID:7440562 Each subunit appears to contain an equimolar pyridoxal 5'-phosphate which is bound to the protein, possibly through a protonated aldimine linkage. PMID:3426593 The pyridoxal 5'-phosphate-binding site has the His-Lys(PLP)-X structure characteristic of known pyridoxal 5'-phosphate-dependent amino acid decarboxylases, tryptophan synthase, and serine hydroxymethyltransferase.
GO:0004375 glycine dehydrogenase (decarboxylating) activity	IBA GO_REF:0000033	ACCEPT	Summary: This is the correct molecular function term for GLDC (EC 1.4.4.2). The enzyme decarboxylates glycine and transfers the aminomethyl moiety to lipoylated H-protein, releasing CO2. Reason: This is the definitive molecular function of GLDC. The reaction catalyzed is: lipoyl-H-protein + glycine + H+ = aminomethyl-lipoyl-H-protein + CO2 (EC 1.4.4.2). Hiraga & Kikuchi (1980) demonstrated that P-protein could catalyze glycine decarboxylation with the product being methylamine. The IBA annotation correctly captures the ancestral function. Supporting Evidence: PMID:7440562 P-protein could bind glycine, showing a Kd of 33 mM for it, and could catalyze glycine decarboxylation even though the rate of decarboxylation catalyzed by P-protein alone was extremely low. The product of glycine decarboxylation was methylamine
GO:0005960 glycine cleavage complex	IBA GO_REF:0000033	ACCEPT	Summary: GLDC (P-protein) is a core component of the glycine cleavage complex/system, which also includes H (GCSH), T (AMT), and L (DLD) proteins. Reason: The GCS complex membership is a defining characteristic of GLDC. Hiraga & Kikuchi (1980) describe GLDC as a constituent of the glycine cleavage system. UniProt states the glycine cleavage system is composed of four proteins: P (GLDC), T (GCST), L (DLD) and H (GCSH). The IBA correctly identifies this complex membership. Supporting Evidence: PMID:7440562 Glycine decarboxylase, tentatively called P-protein and considered a constituent of the glycine cleavage system PMID:7440563 Functional association of glycine decarboxylase and aminomethyl carrier protein
GO:0016594 glycine binding	IBA GO_REF:0000033	ACCEPT	Summary: GLDC binds glycine as its substrate with a measured Kd of 33 mM. This is essential for its decarboxylating activity. Reason: Glycine binding is intrinsic to GLDC function as a glycine decarboxylase. Hiraga & Kikuchi (1980) directly measured glycine binding with a Kd of 33 mM. The Km for glycine was 40 mM (alone) or 20 mM (with GCSH). The IBA is well-supported. Supporting Evidence: PMID:7440562 P-protein could bind glycine, showing a Kd of 33 mM for it
GO:0019464 glycine decarboxylation via glycine cleavage system	IBA GO_REF:0000033	ACCEPT	Summary: This biological process term accurately captures the core metabolic function of GLDC within the glycine cleavage system pathway. Reason: This is the most specific and accurate BP term for GLDC function. The term describes exactly what GLDC does: glycine decarboxylation within the context of the GCS. The deep research confirms GLDC decarboxylates glycine to release CO2 and transfers the aminomethyl group onto the lipoylated H-protein (file:CHICK/GLDC/GLDC-deep-research-falcon.md). Supporting Evidence: PMID:7440562 P-protein could bind glycine, showing a Kd of 33 mM for it, and could catalyze glycine decarboxylation file:CHICK/GLDC/GLDC-deep-research-falcon.md GLDC encodes the P-protein of the mitochondrial glycine cleavage system (GCS), a PLP-dependent enzyme (EC 1.4.4.2) localized to the mitochondrial matrix
GO:0004375 glycine dehydrogenase (decarboxylating) activity	IEA GO_REF:0000120	ACCEPT	Summary: Correct IEA annotation for the molecular function of GLDC. Consistent with IBA and experimental evidence. Reason: This IEA correctly identifies the molecular function (EC 1.4.4.2). It is redundant with the IBA but correctly assigned. The automated annotation pipelines appropriately identified this function.
GO:0005739 mitochondrion	IEA GO_REF:0000044	ACCEPT	Summary: Correct IEA annotation based on UniProt subcellular location. Consistent with IBA and IDA evidence. Reason: Mitochondrial localization is well-established for GLDC. This IEA is consistent with experimental evidence and correctly mapped from UniProt subcellular location annotation.
GO:0006520 amino acid metabolic process	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: This is a broad parent term of glycine metabolic/catabolic processes. While technically correct, it is less informative than more specific terms. Reason: This term is too general for GLDC. The more specific terms GO:0006544 (glycine metabolic process) and GO:0006546 (glycine catabolic process) are already annotated and more informative. The IEA from InterPro is not wrong but provides minimal information beyond what more specific terms convey.
GO:0006544 glycine metabolic process	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: Parent term of glycine catabolic process. While correct, the more specific catabolic term is more informative. Reason: GLDC specifically catabolizes glycine; it does not synthesize it. The term GO:0006546 (glycine catabolic process) is more specific and accurately describes GLDC function. This parent term adds little beyond what the catabolic child term provides. Better represented by GO:0019464.
GO:0006546 glycine catabolic process	IEA GO_REF:0000002	ACCEPT	Summary: GLDC participates in glycine catabolism via the glycine cleavage system. This IEA is correct but less specific than GO:0019464. Reason: GLDC is indeed involved in glycine catabolic process. The IEA correctly identifies this role. While GO:0019464 (glycine decarboxylation via glycine cleavage system) is more specific, this term accurately describes GLDC's role in glycine breakdown.
GO:0016491 oxidoreductase activity	IEA GO_REF:0000043	MARK AS OVER ANNOTATED	Summary: Very broad parent term for molecular function. GLDC has a specific oxidoreductase activity (EC 1.4.4.2) that is better captured by GO:0004375. Reason: This is an extremely broad parent term that provides minimal informative value. GO:0004375 (glycine dehydrogenase (decarboxylating) activity) already correctly and specifically captures the oxidoreductase activity of GLDC. This IEA from keyword mapping is technically not wrong but uninformative.
GO:0016829 lyase activity	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: Broad parent term. GLDC does have lyase-like activity (decarboxylation) but this is better captured by the specific GO:0004375 term. Reason: While GLDC does catalyze a decarboxylation (lyase-type) reaction, the specific term GO:0004375 already captures this. The InterPro-based IEA correctly identifies the broad enzymatic class but provides minimal informative value beyond what more specific terms convey.
GO:0005739 mitochondrion	IDA PMID:7440562 The mitochondrial glycine cleavage system. Purification and ...	ACCEPT	Summary: Direct experimental evidence for mitochondrial localization from the seminal purification study by Hiraga & Kikuchi (1980). Reason: This is strong experimental evidence. Hiraga & Kikuchi purified P-protein from chicken liver mitochondria to apparent homogeneity. This IDA appropriately captures the direct demonstration of mitochondrial localization. Supporting Evidence: PMID:7440562 Glycine decarboxylase, tentatively called P-protein and considered a constituent of the glycine cleavage system, was purified to apparent homogeneity from chicken liver mitochondria.
GO:0006546 glycine catabolic process	IDA PMID:1993704 The glycine cleavage system. Molecular cloning of the chicke...	ACCEPT	Summary: The cDNA cloning paper by Kume et al. (1991) characterized the enzyme and its role in glycine catabolism. Reason: Kume et al. (1991) cloned GLDC cDNA and characterized the protein involved in glycine catabolism. The IDA is appropriate for demonstrating involvement in glycine catabolic process through molecular and functional characterization. Supporting Evidence: PMID:1993704 A cDNA encoding chicken glycine decarboxylase (pCP15b) was isolated using an antibody specific to this protein
GO:0006546 glycine catabolic process	IDA PMID:7440562 The mitochondrial glycine cleavage system. Purification and ...	ACCEPT	Summary: Direct experimental evidence that GLDC catalyzes glycine degradation (catabolism) from the purification and characterization study. Reason: Hiraga & Kikuchi demonstrated that P-protein catalyzes glycine decarboxylation, which is a key step in glycine catabolism. The IDA is well-supported by the biochemical evidence presented. Supporting Evidence: PMID:7440562 P-protein could bind glycine, showing a Kd of 33 mM for it, and could catalyze glycine decarboxylation
GO:0036255 response to methylamine	IDA PMID:7440562 The mitochondrial glycine cleavage system. Purification and ...	UNDECIDED	Summary: GLDC activity is inhibited by methylamine, which can bind to P-protein (Kd = 63 mM). This is an in vitro kinetic observation, not a cellular response. Reason: The available evidence reflects in vitro inhibition of enzyme activity, not a demonstrated cellular/organismal response. Without access to all relevant publications, this must remain UNDECIDED. Supporting Evidence: PMID:7440562 Methylamine could bind to P-protein, giving a Kd value of 63 mM, and it inhibited the glycine decarboxylation.
GO:0036255 response to methylamine	IDA PMID:7440563 The mitochondrial glycine cleavage system. Functional associ...	UNDECIDED	Summary: Duplicate annotation for response to methylamine from the companion paper. The publication text is not available in the local cache. Reason: Unable to access the publication text to confirm the evidence. Per guidelines, this must remain UNDECIDED until the source can be reviewed. Supporting Evidence: PMID:7440563 The mitochondrial glycine cleavage system. Functional association of glycine decarboxylase and aminomethyl carrier protein.
GO:0042803 protein homodimerization activity	IDA PMID:3426593 Amino acid sequence of the phosphopyridoxyl peptide from P-p...	UNDECIDED	Summary: GLDC forms homodimers. This is a structural characteristic demonstrated by protein characterization studies. Reason: Unable to access all relevant publications to confirm the evidence supporting this annotation. Supporting Evidence: PMID:7440562 P-protein is a homodimer having a Mr = approximately 200,000 and consisting of identical subunits with Mr = approximately 100,000.
GO:0042803 protein homodimerization activity	IDA PMID:7440562 The mitochondrial glycine cleavage system. Purification and ...	UNDECIDED	Summary: Direct demonstration that GLDC is a homodimer from the purification study. Reason: Unable to access all relevant publications to confirm the evidence supporting this annotation. Supporting Evidence: PMID:7440562 P-protein is a homodimer having a Mr = approximately 200,000 and consisting of identical subunits with Mr = approximately 100,000.
GO:0042803 protein homodimerization activity	IDA PMID:7440563 The mitochondrial glycine cleavage system. Functional associ...	UNDECIDED	Summary: Duplicate homodimerization annotation from companion paper. Reason: Unable to access the publication text to confirm the evidence. Per guidelines, this must remain UNDECIDED until the source can be reviewed. Supporting Evidence: PMID:7440563 The mitochondrial glycine cleavage system. Functional association of glycine decarboxylase and aminomethyl carrier protein.
GO:0047960 glycine dehydrogenase (NAD+) activity	IDA PMID:1993704 The glycine cleavage system. Molecular cloning of the chicke...	MODIFY	Summary: CRITICAL ERROR: This annotation uses the WRONG GO term. GO:0047960 describes the reaction "glycine + H2O + NAD+ = glyoxylate + NH3 + NADH" which is NOT what GLDC catalyzes. GLDC catalyzes EC 1.4.4.2 (GO:0004375): glycine decarboxylation with aminomethyl transfer to lipoyl-H-protein. Reason: GO:0047960 catalyzes a completely different reaction (glycine oxidation to glyoxylate) than what GLDC does. GLDC (EC 1.4.4.2) decarboxylates glycine and transfers the aminomethyl group to lipoylated H-protein, releasing CO2 (not glyoxylate). The correct term is GO:0004375 (glycine dehydrogenase (decarboxylating) activity). This is a significant mis-annotation that must be corrected. Proposed replacements: glycine dehydrogenase (decarboxylating) activity Supporting Evidence: PMID:1993704 A cDNA encoding chicken glycine decarboxylase (pCP15b) was isolated using an antibody specific to this protein
GO:0047960 glycine dehydrogenase (NAD+) activity	IDA PMID:7440562 The mitochondrial glycine cleavage system. Purification and ...	MODIFY	Summary: CRITICAL ERROR: Same incorrect GO term assignment as above. GO:0047960 is the WRONG term for GLDC. The paper clearly describes glycine DECARBOXYLATION, not oxidation to glyoxylate. Reason: This annotation must be corrected. Hiraga & Kikuchi (1980) clearly state that P-protein could catalyze glycine decarboxylation and the product was methylamine. This is EC 1.4.4.2 (GO:0004375), NOT the glyoxylate-producing reaction of GO:0047960. The reaction is fundamentally different: GLDC releases CO2 and produces aminomethyl-lipoyl-H, not glyoxylate. Proposed replacements: glycine dehydrogenase (decarboxylating) activity Supporting Evidence: PMID:7440562 P-protein could bind glycine, showing a Kd of 33 mM for it, and could catalyze glycine decarboxylation even though the rate of decarboxylation catalyzed by P-protein alone was extremely low. The product of glycine decarboxylation was methylamine
GO:0070280 pyridoxal binding	IDA PMID:7440562 The mitochondrial glycine cleavage system. Purification and ...	MODIFY	Summary: GLDC binds pyridoxal 5'-phosphate (PLP) covalently. Note that GO:0030170 (pyridoxal phosphate binding) may be more precise since GLDC binds PLP, not free pyridoxal. Reason: While GLDC does bind pyridoxal (as part of PLP), the more accurate term is GO:0030170 (pyridoxal phosphate binding) since the actual cofactor is pyridoxal 5'-phosphate. Hiraga & Kikuchi state the enzyme contains equimolar pyridoxal 5'-phosphate bound to the protein. The phosphate moiety is functionally important. GO:0030170 is already annotated via IBA and is more accurate. Proposed replacements: pyridoxal phosphate binding Supporting Evidence: PMID:7440562 Each subunit appears to contain an equimolar pyridoxal 5'-phosphate which is bound to the protein, possibly through a protonated aldimine linkage.
GO:1903442 response to lipoic acid	IDA PMID:7440562 The mitochondrial glycine cleavage system. Purification and ...	UNDECIDED	Summary: GLDC activity is stimulated by lipoic acid. This reflects the functional requirement for lipoylated H-protein in the GCS. Reason: The available evidence reflects in vitro stimulation of enzyme activity, not a demonstrated cellular/organismal response. Without access to all relevant publications, this must remain UNDECIDED. Supporting Evidence: PMID:7440562 Both glycine decarboxylation and the glycine-CO2 exchange catalyzed by P-protein were stimulated 100-fold or more by the addition of lipoic acid, which is a functional group of H-protein.
GO:1903442 response to lipoic acid	IDA PMID:7440563 The mitochondrial glycine cleavage system. Functional associ...	UNDECIDED	Summary: Duplicate annotation for response to lipoic acid from companion paper. Reason: Unable to access the publication text to confirm the evidence. Per guidelines, this must remain UNDECIDED until the source can be reviewed. Supporting Evidence: PMID:7440563 The mitochondrial glycine cleavage system. Functional association of glycine decarboxylase and aminomethyl carrier protein.
GO:0004375 glycine dehydrogenase (decarboxylating) activity	ISS GO_REF:0000024	ACCEPT	Summary: ISS annotation correctly identifies the molecular function of GLDC. Consistent with IBA and experimental evidence. Reason: This ISS correctly identifies GO:0004375 as the molecular function based on sequence similarity to characterized orthologs. The annotation is consistent with IBA, IEA, and the UniProt-curated EC number (1.4.4.2).
GO:0005739 mitochondrion	ISS GO_REF:0000024	ACCEPT	Summary: ISS annotation for mitochondrial localization. Consistent with IDA and IBA evidence. Reason: Mitochondrial localization is well-established for GLDC across species. This ISS is consistent with the IDA from PMID:7440562 and IBA annotations.
GO:0006546 glycine catabolic process	ISS GO_REF:0000024	ACCEPT	Summary: ISS annotation for involvement in glycine catabolic process. Consistent with IDA annotations. Reason: GLDC involvement in glycine catabolism is well-established. This ISS is consistent with the IDA annotations from the chicken literature.

Gene Description

Existing Annotations Review

Core Functions

GLDC is the P-protein of the glycine cleavage system, catalyzing the PLP-dependent decarboxylation of glycine and transfer of the aminomethyl moiety to lipoylated H-protein (GCSH), releasing CO2. This provides one-carbon units to folate metabolism.

References

Suggested Questions for Experts

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Deep Research

Falcon

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