GCSH

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005515 protein binding	IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in...	REMOVE	Summary: Generic protein binding from a binary interactome screen is uninformative for this mitochondrial matrix lipoyl carrier. Reason: The UniProtKB:Q13287 pair comes from a proteome-scale yeast two-hybrid screen (PMID:16189514) and is not removed as false. GO:0005515 carries no functional information, and no informative binding activity follows: the partner-class refinements considered earlier (transcription coactivator/coregulator binding for NMI, MED11 and MAGEA11) would assert a function for a nuclear or cytosolic partner class that the matrix-resident GCSH has no demonstrated physiological access to. The protein-binding policy therefore calls for REMOVE rather than a partner-class MODIFY. Supporting Evidence: file:human/GCSH/GCSH-source-guide.md These records are not claims of independent physiological validation. file:human/GCSH/GCSH-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269\|PubMed:36190515}.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: Generic protein binding from a binary interactome screen is uninformative for this mitochondrial matrix lipoyl carrier. Reason: The UniProtKB:P43360 pair comes from a proteome-scale yeast two-hybrid screen (PMID:32296183) and is not removed as false. GO:0005515 carries no functional information, and no informative binding activity follows: the partner-class refinements considered earlier (transcription coactivator/coregulator binding for NMI, MED11 and MAGEA11) would assert a function for a nuclear or cytosolic partner class that the matrix-resident GCSH has no demonstrated physiological access to. The protein-binding policy therefore calls for REMOVE rather than a partner-class MODIFY. Supporting Evidence: file:human/GCSH/GCSH-source-guide.md These records are not claims of independent physiological validation. file:human/GCSH/GCSH-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269\|PubMed:36190515}.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: Generic protein binding from a binary interactome screen is uninformative for this mitochondrial matrix lipoyl carrier. Reason: The UniProtKB:P43364 pair comes from a proteome-scale yeast two-hybrid screen (PMID:32296183) and is not removed as false. GO:0005515 carries no functional information, and no informative binding activity follows: the partner-class refinements considered earlier (transcription coactivator/coregulator binding for NMI, MED11 and MAGEA11) would assert a function for a nuclear or cytosolic partner class that the matrix-resident GCSH has no demonstrated physiological access to. The protein-binding policy therefore calls for REMOVE rather than a partner-class MODIFY. Supporting Evidence: file:human/GCSH/GCSH-source-guide.md These records are not claims of independent physiological validation. file:human/GCSH/GCSH-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269\|PubMed:36190515}.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: Generic protein binding from a binary interactome screen is uninformative for this mitochondrial matrix lipoyl carrier. Reason: The UniProtKB:Q13287 pair comes from a proteome-scale yeast two-hybrid screen (PMID:32296183) and is not removed as false. GO:0005515 carries no functional information, and no informative binding activity follows: the partner-class refinements considered earlier (transcription coactivator/coregulator binding for NMI, MED11 and MAGEA11) would assert a function for a nuclear or cytosolic partner class that the matrix-resident GCSH has no demonstrated physiological access to. The protein-binding policy therefore calls for REMOVE rather than a partner-class MODIFY. Supporting Evidence: file:human/GCSH/GCSH-source-guide.md These records are not claims of independent physiological validation. file:human/GCSH/GCSH-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269\|PubMed:36190515}.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: Generic protein binding from a binary interactome screen is uninformative for this mitochondrial matrix lipoyl carrier. Reason: The UniProtKB:Q6NTF9-3 pair comes from a proteome-scale yeast two-hybrid screen (PMID:32296183) and is not removed as false. GO:0005515 carries no functional information, and no informative binding activity follows: the partner-class refinements considered earlier (transcription coactivator/coregulator binding for NMI, MED11 and MAGEA11) would assert a function for a nuclear or cytosolic partner class that the matrix-resident GCSH has no demonstrated physiological access to. The protein-binding policy therefore calls for REMOVE rather than a partner-class MODIFY. Supporting Evidence: file:human/GCSH/GCSH-source-guide.md These records are not claims of independent physiological validation. file:human/GCSH/GCSH-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269\|PubMed:36190515}.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: Generic protein binding from a binary interactome screen is uninformative for this mitochondrial matrix lipoyl carrier. Reason: The UniProtKB:Q9NYP9 pair comes from a proteome-scale yeast two-hybrid screen (PMID:32296183) and is not removed as false. GO:0005515 carries no functional information, and no informative binding activity follows: the partner-class refinements considered earlier (transcription coactivator/coregulator binding for NMI, MED11 and MAGEA11) would assert a function for a nuclear or cytosolic partner class that the matrix-resident GCSH has no demonstrated physiological access to. The protein-binding policy therefore calls for REMOVE rather than a partner-class MODIFY. Supporting Evidence: file:human/GCSH/GCSH-source-guide.md These records are not claims of independent physiological validation. file:human/GCSH/GCSH-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269\|PubMed:36190515}.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: Generic protein binding from a binary interactome screen is uninformative for this mitochondrial matrix lipoyl carrier. Reason: The UniProtKB:Q9P086 pair comes from a proteome-scale yeast two-hybrid screen (PMID:32296183) and is not removed as false. GO:0005515 carries no functional information, and no informative binding activity follows: the partner-class refinements considered earlier (transcription coactivator/coregulator binding for NMI, MED11 and MAGEA11) would assert a function for a nuclear or cytosolic partner class that the matrix-resident GCSH has no demonstrated physiological access to. The protein-binding policy therefore calls for REMOVE rather than a partner-class MODIFY. Supporting Evidence: file:human/GCSH/GCSH-source-guide.md These records are not claims of independent physiological validation. file:human/GCSH/GCSH-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269\|PubMed:36190515}.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: Generic protein binding from a binary interactome screen is uninformative for this mitochondrial matrix lipoyl carrier. Reason: The UniProtKB:Q9UHD4 pair comes from a proteome-scale yeast two-hybrid screen (PMID:32296183) and is not removed as false. GO:0005515 carries no functional information, and no informative binding activity follows: the partner-class refinements considered earlier (transcription coactivator/coregulator binding for NMI, MED11 and MAGEA11) would assert a function for a nuclear or cytosolic partner class that the matrix-resident GCSH has no demonstrated physiological access to. The protein-binding policy therefore calls for REMOVE rather than a partner-class MODIFY. Supporting Evidence: file:human/GCSH/GCSH-source-guide.md These records are not claims of independent physiological validation. file:human/GCSH/GCSH-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269\|PubMed:36190515}.
GO:0005739 mitochondrion	EXP PMID:36190515 Pathogenic variants in GCSH encoding the moonlighting H-prot...	ACCEPT	Summary: Human GCSH constructs localize to mitochondria in the experimental cell model. Reason: PMID:36190515 expresses full-length human GCSH constructs in COS7 cells after endogenous H-protein knockdown and examines localization by confocal microscopy with a cytochrome-c marker. Wild-type and individual variant observations must remain distinct. This supports the mitochondrial pool, without claiming native human tissue imaging or a complete submitochondrial topology determination. Supporting Evidence: PMID:36190515 PMID:36190515 Representative merged images (40X objective lens) showing colocalization of mitochondrial marker cytochrome C (red) and GCS H-protein (green) in knockdown COS7 cells co-transfected with pCMV-GCSH WT or variants. file:human/GCSH/GCSH-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269\|PubMed:36190515}.
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	ACCEPT	Summary: The actual MitoCoP target row supports human mitochondrial localization. Reason: Original Table S1A row 403 identifies P23434-containing protein group 4249 as subtractive Class 1, spatial Cluster 1 and importomics Class 1. The experiments combine HEK293T fractionation with HeLa TOMM40 depletion. The group contains additional accessions, so this is not isoform-specific or mature-peptide mapping. Its membrane-association category is Ambiguous; the matrix annotation column is prior GO information rather than a new direct matrix assay. Supporting Evidence: PMID:34800366 PMID:34800366 We classified >8,000 proteins in mitochondrial preparations of human cells and defined a mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP).
GO:0005739 mitochondrion	IBA GO_REF:0000033	ACCEPT	Summary: Mitochondrial localization is consistent with the actual PAINT lineage and human evidence. Reason: The mitochondrial IBD at AN2/PTN001711613 is inherited by the sequence-verified human target AN32 in the actual family tree. Human target proteomics, localization of human constructs, and the processed mitochondrial chain independently agree. This organelle-level claim is retained alongside the more specific matrix evidence. Supporting Evidence: GO_REF:0000033 PMID:34800366 PMID:36190515 file:interpro/panther/PTHR11715/PTHR11715-paint.tsv PTHR11715 PTN001711613 GO:0005739 C IBD false file:human/GCSH/GCSH-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269\|PubMed:36190515}.
GO:0005739 mitochondrion	IEA GO_REF:0000044	ACCEPT	Summary: The reviewed mitochondrial localization mapping is supported. Reason: The UniProt subcellular-location mapping is consistent with the N-terminal targeting sequence, mature chain, residues 49–173 and human mitochondrial evidence. It assigns the organelle rather than a membrane topology. More specific matrix localization is established separately by the curated target entities. Supporting Evidence: GO_REF:0000044 UniProtKB:P23434 PMID:34800366 file:human/GCSH/GCSH-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269\|PubMed:36190515}.
GO:0005739 mitochondrion	TAS PMID:3348809 Cloning of cDNA encoding human H-protein, a constituent of t...	ACCEPT	Summary: The early human H-protein characterization supports the mitochondrial organelle assignment. Reason: The authentic PMID:3348809 abstract reports a human-liver cDNA identified using H-protein immunoreactivity and agreement with the purified human protein N-terminus. The full original localization methods were not inspected. The incoming TAS mitochondrial claim agrees with independently established human mitochondrial residence and the mature H-protein identity; no specific fractionation experiment is invented from the abstract. Supporting Evidence: PMID:3348809 PMID:34800366 UniProtKB:P23434 PMID:3348809 A cDNA that encodes human H-protein, a constituent protein of the glycine cleavage system, was cloned with anti-rat H-protein antibody as a probe from a human liver cDNA library constructed with an expression vector, lambda gt11. file:human/GCSH/GCSH-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269\|PubMed:36190515}.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-5693967	ACCEPT	Summary: The GLDC reaction explicitly contains matrix-localized human lipoyl-GCSH. Reason: The actual Reactome event connects input Lipo-K107-GCSH 6793611 to human P23434, mature residues 49–173, in GO:0005759. Its aminomethylated output reaches the same target through complex 5693969 and modified entity9930732. GCSH carries the reaction intermediate; GLDC is the decarboxylating catalyst. Supporting Evidence: Reactome:R-HSA-5693967 UniProtKB:P23434 Reactome:R-HSA-5693967 Mitochondrial glycine cleavage system H protein (GCSH) is used as a co-substrate in this reaction.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-5693977	ACCEPT	Summary: The AMT reaction represents the human GCSH carrier in the matrix. Reason: Actual input complex 5693969 contains modified GCSH 9930732, and output complex 5693982 contains GCSH 5693951. Both target chains resolve to P23434 residues 49–173 in mitochondrial matrix. This supports the compartment annotation without assigning AMT catalysis or a fixed noncovalent ligand-binding stoichiometry to GCSH. Supporting Evidence: Reactome:R-HSA-5693977 UniProtKB:P23434 Reactome:R-HSA-5693977 the decarboxylated moiety from glycine decarboxylation attached to H protein (GCSH:SAMDLL) is further degraded by mitochondrial aminomethyltransferase (AMT, GCST, T protein) to ammonia (NH3) and GCSH with reduced lipoate.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-5694018	ACCEPT	Summary: The DLD regeneration reaction retains the matrix GCSH carrier. Reason: Actual input GCSH:DHLL complex 5693982 resolves through GCSH 5693951 to P23434; output lipoyl-GCSH 6793611 has the same human sequence and matrix compartment. DLD performs oxidation of the reduced lipoyl arm. This is target-specific localization evidence, not GCSH dehydrogenase activity. Supporting Evidence: Reactome:R-HSA-5694018 UniProtKB:P23434 Reactome:R-HSA-5694018 The last step in the glycine cleavage system is the reoxidation of the reduced lipoate (dihydrolipoyl group) attached to the H protein (GCSH:DHLL) catalysed by the L protein (mitochondrial dihydrolipoyl dehydrogenase, DLD) (Harris et al. 1997, Ciszak et al. 2006).
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-6792572	ACCEPT	Summary: Human GCSH is explicitly matrix-localized in the LIPT1 donor reaction. Reason: The actual LIPT1 transfer event has lipoyl-GCSH 6793611 as input and GCSH 5693951 as output, both human P23434 residues 49–173 in GO:0005759. The DBT/DLST set describes recipient alternatives. Matrix localization is supported independently of whether GCSH should receive a protein-maturation process annotation; LIPT1 performs the transfer. Supporting Evidence: Reactome:R-HSA-6792572 UniProtKB:P23434 Reactome:R-HSA-6792572 Mitochondrial lipoyltransferase 1 (LIPT1) catalyses the transfer of a lipoyl group from lipoyl-K107-GCSH to lysine residue(s) of lipoate-dependent enzymes (Fujiwara et al. 1999; Cao et al., 2018).
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-6793590	ACCEPT	Summary: The LIPT2 model assigns GCSH specifically to the mitochondrial matrix. Reason: Actual GCSH 5693951 and octanoyl-GCSH 6793586 resolve to human P23434 residues 49–173 in matrix. The same event contains NDUFAB1 at the inner membrane, but that other participant does not relocate GCSH. LIPT2 catalysis and GCSH as the accepting carrier remain distinct. Supporting Evidence: Reactome:R-HSA-6793590 UniProtKB:P23434 Reactome:R-HSA-6793590 Mitochondrial lipoyltransferase 2 (LIPT2) transfers an octanoyl group bound to the acyl-carrier protein NDUFAB1 (ACP) to mitochondrial glycine cleavage system H protein (GCSH) at lysine 107 (Schonauer et al. 2009; Cao et al., 2018).
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-6793591	ACCEPT	Summary: The LIAS reaction explicitly locates its human GCSH carrier substrate in the matrix. Reason: The actual octanoyl-GCSH 6793586 input and lipoyl-GCSH 6793611 output share the P23434 reference, mature coordinates 49–173 and GO:0005759 compartment. This supports matrix residence through a target-specific chain, without attributing sulfur insertion or iron-sulfur catalysis to GCSH. Supporting Evidence: Reactome:R-HSA-6793591 UniProtKB:P23434 Reactome:R-HSA-6793591 Mitochondrial lipoyl synthase (LIAS) mediates the radical-mediated insertion of two sulfur atoms into the C-6 and C-8 positions of the octanoyl moiety bound to glycine cleavage system H protein (GCSH), transforming the octanoyl moiety to a lipoyl moiety.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9858752	ACCEPT	Summary: The DLAT lipoylation model places the human GCSH donor in the matrix. Reason: Actual event 9858752 connects lipoyl-GCSH 6793611 to unmodified GCSH 5693951 in the matrix, both P23434 mature residues 49–173. Repeated numeric input/output references are preserved as model multiplicity, not alternative products. LIPT1 transfers the lipoyl group to DLAT; the localization claim does not confer that catalytic activity on GCSH. Supporting Evidence: Reactome:R-HSA-9858752 UniProtKB:P23434 Reactome:R-HSA-9858752 Mitochondrial lipoyltransferase 1 (LIPT1) catalyses the transfer of a lipoyl group from lipoyl-K107-GCSH to two lysine residues of the PDH complex subunit E2 (DLAT) (Fujiwara et al. 1999; Cao et al., 2018).
GO:0005960 glycine cleavage complex	IBA GO_REF:0000033	ACCEPT	Summary: Actual PAINT placement supports membership in the glycine-cleavage complex. Reason: The complex-membership IBD is placed at AN2/PTN001711613 above the exact human target AN32/PTN002482330 in the genuine PTHR11715 tree. All literal donor joins agree and no target-path negative record is retained. This is inherited component membership, consistent with the established H-protein carrier role, rather than a transfer of another subunit’s catalytic function. Supporting Evidence: GO_REF:0000033 UniProtKB:P23434 PMID:36190515 file:interpro/panther/PTHR11715/PTHR11715-paint.tsv PTHR11715 PTN001711613 GO:0005960 C IBD false file:human/GCSH/GCSH-uniprot.txt The glycine cleavage system is composed of four proteins: P (GLDC), T (GCST), L (DLD) and H (GCSH).
GO:0005960 glycine cleavage complex	IEA GO_REF:0000002	ACCEPT	Summary: The H-protein family mapping supports glycine-cleavage complex membership. Reason: The InterPro H-protein/lipoyl-domain assignment agrees with the conserved GCSH carrier role in the four-component glycine-cleavage system. Human H/P-protein functional assays and the reviewed subunit account corroborate that role. Complex membership does not mean the H-protein independently catalyzes the overall reaction. Supporting Evidence: GO_REF:0000002 UniProtKB:P23434 PMID:36190515 file:human/GCSH/GCSH-uniprot.txt The glycine cleavage system is composed of four proteins: P (GLDC), T (GCST), L (DLD) and H (GCSH). file:human/GCSH/GCSH-uniprot.txt DR NCBIfam; TIGR00527; gcvH; 1.
GO:0005960 glycine cleavage complex	TAS PMID:3348809 Cloning of cDNA encoding human H-protein, a constituent of t...	ACCEPT	Summary: The cloned human H-protein is an established component of the glycine-cleavage system. Reason: The authentic PMID:3348809 abstract identifies human H-protein cDNA using immunological and N-terminal sequence evidence. Its traceable component assignment is consistent with the reviewed four-protein system and later human H/P-protein assays. The abstract is not represented as a full purified-complex assembly experiment. Supporting Evidence: PMID:3348809 partial primary structure of H-protein in an open reading frame. UniProtKB:P23434 PMID:36190515 file:human/GCSH/GCSH-uniprot.txt The glycine cleavage system is composed of four proteins: P (GLDC), T (GCST), L (DLD) and H (GCSH).
GO:0006091 generation of precursor metabolites and energy	TAS PMID:36190515 Pathogenic variants in GCSH encoding the moonlighting H-prot...	KEEP AS NON CORE	Summary: The broad bioenergetic association is supported but is not the defining GCSH activity. Reason: PMID:36190515 connects human GCSH variants to impaired E2 lipoylation and reduced mitochondrial respiratory reserve. Its primary carrier role also supports glycine cleavage and one-carbon production. This broad annotation captures the bioenergetic context; it does not mean GCSH independently catalyzes oxidative phosphorylation or generates ATP. The specific carrier contribution is described separately. Supporting Evidence: PMID:36190515 UniProtKB:P23434 PMID:36190515 Thus, this single protein intersects two essential roles in the mitochondrion: one-carbon metabolism and cellular bioenergetics (10,11). file:human/GCSH/GCSH-uniprot.txt Has a pivotal role in the lipoylation of enzymes involved in cellular energetics such as the mitochondrial dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex (DLAT), and the mitochondrial dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex (DLST) (PubMed:36190515).
GO:0019464 glycine decarboxylation via glycine cleavage system	IBA GO_REF:0000033	ACCEPT	Summary: Actual PAINT ancestry supports the glycine-cleavage carrier role. Reason: The literal PTHR11715 tree places the exact human 173-residue sequence at AN32/PTN002482330 below the asserted AN2/PTN001711613 node. The current IBD and donor identities agree, with no retained negative record on that lineage. Human functional evidence is consistent with the inherited H-protein carrier role; donor count or target self-evidence is not a reason to weaken it. Supporting Evidence: GO_REF:0000033 PMID:36190515 file:interpro/panther/PTHR11715/PTHR11715-paint.tsv PTHR11715 PTN001711613 GO:0019464 P IBD false file:human/GCSH/GCSH-uniprot.txt The H protein (GCSH) shuttles the methylamine group of glycine from the P protein (GLDC) to the T protein (GCST).
GO:0019464 glycine decarboxylation via glycine cleavage system	IEA GO_REF:0000002	ACCEPT	Summary: The conserved H-protein carrier supports glycine cleavage. Reason: The InterPro mapping identifies the GcvH lipoyl domain and H-protein family. This is consistent with human GCSH providing the lipoyl arm that carries the glycine-derived intermediate between catalytic components. Human recombinant H/P-protein glycine-exchange experiments independently support its contribution, without assigning P-protein decarboxylase catalysis to GCSH. Supporting Evidence: GO_REF:0000002 PMID:36190515 file:human/GCSH/GCSH-uniprot.txt The H protein (GCSH) shuttles the methylamine group of glycine from the P protein (GLDC) to the T protein (GCST).
GO:0019464 glycine decarboxylation via glycine cleavage system	TAS PMID:1671321 The glycine cleavage system: structure of a cDNA encoding hu...	ACCEPT	Summary: The human H-protein is a component of the glycine-cleavage pathway. Reason: The original human cDNA study describes the H-protein carrier within the glycine-cleavage system and establishes the precursor/mature sequence context. This supports the incoming traceable-author-statement claim. Its covalent lipoylation discussion is distinct from a direct lipoic-acid affinity assay, and the source is not relabeled as such. Later human functional experiments corroborate glycine-cleavage contribution. Supporting Evidence: PMID:1671321 precursor form of human H-protein. PMID:36190515 file:human/GCSH/GCSH-uniprot.txt The H protein (GCSH) shuttles the methylamine group of glycine from the P protein (GLDC) to the T protein (GCST).
GO:0051604 protein maturation	TAS PMID:36190515 Pathogenic variants in GCSH encoding the moonlighting H-prot...	MODIFY	Summary: GCSH is the obligatory lipoyl-relay intermediate in mitochondrial protein lipoylation; protein lipoylation is the specific descendant of protein maturation. Reason: GO:0051604 protein maturation is defined as 'Any process leading to the attainment of the full functional capacity of a protein'; GO:0009249 protein lipoylation is its specific descendant for this case. In human mitochondria LIPT2 octanoylates apo-GCSH, LIAS converts the octanoyl to a lipoyl group on GCSH, and LIPT1 transfers the lipoyl group from GCSH to the DLAT and DLST E2 subunits. GCSH therefore does part of the work of the process, as the scaffold that carries the group being built and transferred, not merely as a substrate. This matches the accepted protein-lipoylation IMP on yeast Gcv3 (PMID:19570983) and contrasts with bacteria using the LipB/LipA route, where GcvH is only modified. Proposed replacements: protein lipoylation Supporting Evidence: file:human/GCSH/GCSH-uniprot.txt Has a pivotal role in the lipoylation of enzymes involved in cellular energetics such as the mitochondrial dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex (DLAT), and the mitochondrial dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex (DLST) (PubMed:36190515). PMID:36190515 Lipoate biogenesis is initiated by the transfer of octanoate from intramitochondrial fatty acid synthesis (FASII) on octanoyl-ACP through lipoyltransferase 2 (LIPT2) onto apo-H protein to generate octanoyl-H (4–6). PMID:36190515 Subsequently, lipoyltransferase 1 (LIPT1) transfers the lipoyl moiety from H-protein to form an acyl-enzyme intermediate on recipient 2-ketoacid dehydrogenase enzymes such as dihydrolipoamide-S-acetyltransferase (DLAT), the E2 component of the PDH complex, and dihydrolipoamide-S-transsuccinylase (DLST), the E2 component of the mitochondrial 2-KGDH complex.
GO:0140104 molecular carrier activity	IC PMID:36190515 Pathogenic variants in GCSH encoding the moonlighting H-prot...	NEW	Summary: GCSH carries the glycine-derived aminomethyl intermediate on its lipoyl arm between the P and T proteins. 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'. GCSH delivers the aminomethyl intermediate on its covalently attached lipoyl arm from GLDC to AMT and presents the reduced arm to DLD. GO:0140104 is the existing parent of the proposed lipoyl-dependent carrier activity term (proposed_new_terms) and is used for the H protein in the glycine_cleavage_system module and the PomBase GO-CAM 67b1629100001554. Supporting Evidence: file:human/GCSH/GCSH-uniprot.txt The H protein (GCSH) shuttles the methylamine group of glycine from the P protein (GLDC) to the T protein (GCST). PMID:36190515 the H-protein itself is the lipoate carrier of this enzyme complex.

Gene Description

Proposed New Ontology Terms

lipoyl-dependent carrier activity

Existing Annotations Review

Core Functions

Carries the aminomethyl intermediate on its covalent lipoyl arm within the mitochondrial glycine-cleavage system, coupling the component reactions without independently supplying their decarboxylase, aminomethyltransferase or dehydrogenase catalysis.

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Notes

Source Guide

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