LDHA encodes the L-lactate dehydrogenase A chain (LDH-A / LDH-M, the "muscle" subunit; EC 1.1.1.27), a cytosolic NAD+-dependent oxidoreductase that catalyses the reversible interconversion of pyruvate + NADH and L-lactate + NAD+. The A/M subunit kinetically favours the reduction of pyruvate to lactate, thereby regenerating cytosolic NAD+ so that glycolysis can continue under anaerobic or high-flux conditions; this is the terminal step of lactate fermentation and a hallmark of the Warburg effect in tumours. The catalytically active enzyme is a tetramer assembled from LDHA (A/M) and LDHB (B/H) subunits, giving five isoenzymes (A4 through B4); the LDHA homotetramer (M4, LDH-5) predominates in skeletal muscle and liver. Loss-of-function of LDHA causes glycogen storage disease type XI (LDH-M deficiency), characterized by exertional myopathy, myoglobinuria and cramps.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0019244 pyruvate fermentation to lactate | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) annotation to the specific process that LDHA terminates - reduction of pyruvate to lactate as the final step of lactate fermentation, regenerating NAD+ for glycolysis. This is a core biological process for the A/M subunit. Reason: LDHA catalyses exactly this reaction, and the A/M subunit kinetically favours the pyruvate-to-lactate direction, which is the defining role of this isoform. UniProt assigns the pathway "pyruvate fermentation to lactate" to LDHA. Well-supported core BP. Supporting Evidence: PMID:24816116 predominantly found in skeletal muscle and catalyses the reversible conversion file:human/LDHA/LDHA-uniprot.txt pyruvate fermentation to lactate |
| GO:0004459 L-lactate dehydrogenase (NAD+) activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) annotation to the precise EC 1.1.1.27 molecular function of LDHA. This is the core molecular function of the gene product. Reason: Directly supported by structural/enzymatic work on human LDH-A and by the UniProt catalytic-activity statement (RHEA:23444, EC 1.1.1.27). The IBA is at exactly the right level of specificity. Supporting Evidence: PMID:11276087 interconverts pyruvate and lactate with concomitant file:human/LDHA/LDHA-uniprot.txt Interconverts simultaneously and stereospecifically pyruvate |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Phylogenetic (IBA) annotation placing LDHA activity in the mitochondrion. LDHA is canonically a cytosolic enzyme; a mitochondrial LDH pool ("mLDH") has been proposed but remains contested and is not the core localization of the human A/M subunit. Reason: UniProt records LDHA subcellular location as Cytoplasm, and the experimental/HPA/Reactome annotations consistently place it in the cytosol. Although some literature invokes a mitochondrial lactate-oxidation pool, this is disputed and not established for human LDHA; the IBA projection should not be treated as a core location. Retained as a possible non-core pool rather than removed, since it is a reviewed phylogenetic call. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Supporting Evidence: PMID:33406399 competing with mitochondrial lactate dehydrogenase (mLDH) for nicotinamide file:human/LDHA/LDHA-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0003824 catalytic activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO electronic annotation to the root catalytic-activity term. Correct but far too general given that LDHA has a precisely defined EC-level function. Reason: LDHA is a well-characterized oxidoreductase with a specific NAD+-dependent lactate dehydrogenase activity; the generic "catalytic activity" term is uninformative and should be replaced by the specific function. Proposed replacements: L-lactate dehydrogenase (NAD+) activity Supporting Evidence: file:human/LDHA/LDHA-uniprot.txt Interconverts simultaneously and stereospecifically pyruvate |
| GO:0004459 L-lactate dehydrogenase (NAD+) activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic (UniProt IEA, GO_REF:0000120) annotation to the precise EC 1.1.1.27 function, mapped via RHEA:23444/EC:1.1.1.27. Core molecular function; consistent with the experimental annotations. Reason: Correct, specific MF supported by UniProt catalytic-activity data and experimental enzymology. Supporting Evidence: file:human/LDHA/LDHA-uniprot.txt EC=1.1.1.27 |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | MODIFY | Summary: Electronic (UniProt IEA) annotation to cytoplasm, matching the UniProt subcellular-location statement. Correct but less precise than the cytosol annotations. Reason: LDHA is a soluble cytosolic enzyme; the more specific term GO:0005829 cytosol (supported experimentally by HPA and Reactome) is preferable to the broad "cytoplasm". Proposed replacements: cytosol Supporting Evidence: file:human/LDHA/LDHA-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0016491 oxidoreductase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO annotation to the broad oxidoreductase parent. Correct in class but too general. Reason: LDHA's oxidoreductase activity is specifically NAD+-dependent L-lactate dehydrogenase; replace the generic parent with the specific function. Proposed replacements: L-lactate dehydrogenase (NAD+) activity Supporting Evidence: file:human/LDHA/LDHA-uniprot.txt EC=1.1.1.27 |
| GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO annotation to the CH-OH/NAD(P) oxidoreductase parent. This is the correct branch (LDHA acts on the CH-OH group of lactate using NAD+), but a level too general. Reason: The specific child term GO:0004459 L-lactate dehydrogenase (NAD+) activity is the appropriate function and is already supported experimentally. Proposed replacements: L-lactate dehydrogenase (NAD+) activity Supporting Evidence: file:human/LDHA/LDHA-uniprot.txt EC=1.1.1.27 |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | MARK AS OVER ANNOTATED | Summary: IntAct-curated binary interaction (LDHA-LDHB, P07195) from a large-scale liver interactome study, annotated to the uninformative "protein binding" term. Reason: Per curation guidelines, bare "protein binding" is uninformative and is not retained as a core function. The interaction itself (LDHA-LDHB) is real and biologically meaningful (A/B heterotetramer isoenzymes), but the generic MF term adds nothing beyond what identical/heterosubunit association already captures. Retained (not removed) as an experimental IPI. Supporting Evidence: PMID:21988832 Toward an understanding of the protein interaction network of the human liver |
| GO:0005515 protein binding | IPI PMID:23523103 Lysine-5 acetylation negatively regulates lactate dehydrogen... | MARK AS OVER ANNOTATED | Summary: IntAct interaction with HSPA8/HSC70 (P11142). HSC70 recognizes K5-acetylated LDHA and delivers it to lysosomes for chaperone-mediated degradation, a regulatory (turnover) interaction. Reason: Bare "protein binding" is uninformative and non-core; retained as an experimental IPI. The underlying biology (acetylation-triggered HSC70-mediated degradation) is a regulatory mechanism, not the enzyme's molecular function. Supporting Evidence: PMID:23523103 LDH-A is recognized by the HSC70 chaperone and delivered to lysosomes for |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: IntAct interaction (LDHA-LDHB, P07195) from a large-scale human interactome mapping study, annotated to the generic "protein binding" term. Reason: Uninformative bare "protein binding"; non-core. Retained as an experimental IPI (LDHA-LDHB subunit association). Supporting Evidence: PMID:28514442 Architecture of the human interactome defines protein communities and disease |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: IntAct interaction with LDHC (P07864) from the same human interactome study, annotated to the generic "protein binding" term. Reason: Uninformative bare "protein binding"; non-core. Retained as an experimental IPI (LDHA-LDHC subunit association). Supporting Evidence: PMID:28514442 Architecture of the human interactome defines protein communities and disease |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | MARK AS OVER ANNOTATED | Summary: IntAct interaction (LDHA-LDHB, P07195) from a variant-effect interactome study, annotated to the generic "protein binding" term. Reason: Uninformative bare "protein binding"; non-core. Retained as an experimental IPI. Supporting Evidence: PMID:31515488 Extensive disruption of protein interactions by genetic variants |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: IntAct interaction (LDHA-LDHB, P07195) from a proteome-scale interactome network study, annotated to the generic "protein binding" term. Reason: Uninformative bare "protein binding"; non-core. Retained as an experimental IPI. Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling of the human |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: IntAct interaction with LDHC (P07864) from the same proteome-scale study, annotated to the generic "protein binding" term. Reason: Uninformative bare "protein binding"; non-core. Retained as an experimental IPI. Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling of the human |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MARK AS OVER ANNOTATED | Summary: IntAct interaction (LDHA-LDHB, P07195) from the OpenCell endogenous tagging study, annotated to the generic "protein binding" term. Reason: Uninformative bare "protein binding"; non-core. Retained as an experimental IPI. Supporting Evidence: PMID:35271311 OpenCell: Endogenous tagging for the cartography of human cellular organization |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MARK AS OVER ANNOTATED | Summary: IntAct interaction with LDHC (P07864) from the OpenCell study, annotated to the generic "protein binding" term. Reason: Uninformative bare "protein binding"; non-core. Retained as an experimental IPI. Supporting Evidence: PMID:35271311 OpenCell: Endogenous tagging for the cartography of human cellular organization |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MARK AS OVER ANNOTATED | Summary: IntAct interaction with LDHC (P07864) from a multimodal cell-map study, annotated to the generic "protein binding" term. Reason: Uninformative bare "protein binding"; non-core. Retained as an experimental IPI. Supporting Evidence: PMID:40205054 Multimodal cell maps as a foundation for structural and functional genomics |
| GO:0042802 identical protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | ACCEPT | Summary: IntAct self-interaction (LDHA-LDHA, P00338). Reflects the homotypic subunit association that builds the active LDHA homotetramer (M4/LDH-5). Reason: Informative and biologically core - LDHA self-associates into a homotetramer, which is required for catalytic activity. Directly corroborated by crystallography showing homotetramerization. Supporting Evidence: PMID:11276087 the M form, predominantly found in file:human/LDHA/LDHA-uniprot.txt Homotetramer |
| GO:0042802 identical protein binding | IPI PMID:25502805 A massively parallel pipeline to clone DNA variants and exam... | ACCEPT | Summary: IntAct self-interaction (LDHA-LDHA) from a massively parallel variant-phenotyping pipeline, supporting homotetramer self-association. Reason: Informative, core - consistent with the LDHA homotetramer required for function. Supporting Evidence: PMID:25502805 A massively parallel pipeline to clone DNA variants |
| GO:0042802 identical protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | ACCEPT | Summary: IntAct self-interaction (LDHA-LDHA), supporting homotetramer self-association. Reason: Informative, core - consistent with the LDHA homotetramer required for catalytic activity. Supporting Evidence: PMID:31515488 Extensive disruption of protein interactions by genetic variants |
| GO:0004457 lactate dehydrogenase activity | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl-Compara orthology (IEA) transfer of lactate dehydrogenase activity from the mouse ortholog. Correct; a slightly broader parent of the NAD+-specific term. Reason: Accurately captures LDHA's function; retained even though it is one level broader than GO:0004459, as it is not incorrect and is well-supported. Supporting Evidence: file:human/LDHA/LDHA-uniprot.txt EC=1.1.1.27 |
| GO:0005829 cytosol | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl-Compara orthology (IEA) transfer of cytosolic localization. Matches the experimental cytosol annotations. Reason: LDHA is a soluble cytosolic glycolytic enzyme; localization is correct and core. Supporting Evidence: file:human/LDHA/LDHA-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0035686 sperm fibrous sheath | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl-Compara orthology (IEA) transfer of a sperm fibrous sheath localization from the mouse ortholog. This is a specialized germ-cell localization more characteristic of the testis-specific paralog LDHC, not a core localization of somatic LDHA. Reason: LDHA is predominantly a cytosolic enzyme of muscle and liver; a sperm fibrous sheath localization is peripheral/germ-cell-specific and is not part of the core function. Retained as a possible non-core localization from orthology transfer rather than removed. Supporting Evidence: file:human/LDHA/LDHA-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0042867 pyruvate catabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl-Compara orthology (IEA) transfer of pyruvate catabolic process. LDHA consumes pyruvate (reducing it to lactate), so this is a correct process annotation. Reason: LDHA catalyses pyruvate reduction to lactate, a catabolic fate of pyruvate that regenerates NAD+. Correct, though the more specific fermentation term is the primary process. Supporting Evidence: PMID:24816116 predominantly found in skeletal muscle and catalyses the reversible conversion |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: HPA immunofluorescence (IDA) localization of LDHA to the cytosol. Direct experimental support for the core cytosolic localization. Reason: Direct experimental evidence for cytosolic localization, consistent with LDHA being a soluble glycolytic enzyme. Supporting Evidence: file:human/LDHA/LDHA-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0004459 L-lactate dehydrogenase (NAD+) activity | EXP PMID:11276087 Structural basis for altered activity of M- and H-isozyme fo... | ACCEPT | Summary: Experimental (crystallography + enzymology) demonstration of the NAD+-dependent lactate dehydrogenase activity of human LDH-M (LDHA). Core molecular function. Reason: Definitive experimental support - the study determined the crystal structure of the human M (LDHA) isoform as a ternary complex with NADH and the substrate analog oxamate and characterized its catalytic activity. Supporting Evidence: PMID:11276087 interconverts pyruvate and lactate with concomitant |
| GO:0006089 lactate metabolic process | IDA PMID:24816116 Structural characterization of the apo form and NADH binary ... | ACCEPT | Summary: ComplexPortal IDA linking the LDH complex to lactate metabolism, based on the structural/enzymatic characterization of human LDH-A. Core biological process. Reason: LDHA directly interconverts pyruvate and lactate; participation in lactate metabolic process is well-supported experimentally. Supporting Evidence: PMID:24816116 predominantly found in skeletal muscle and catalyses the reversible conversion |
| GO:1990204 oxidoreductase complex | IPI PMID:24816116 Structural characterization of the apo form and NADH binary ... | ACCEPT | Summary: ComplexPortal annotation that LDHA is part of an oxidoreductase complex (the LDH tetramer). The active enzyme is an oligomeric oxidoreductase. Reason: The functional LDH enzyme is a homo/heterotetramer that is a bona fide oxidoreductase complex; this correctly captures LDHA's participation in an oligomeric enzyme. Supporting Evidence: PMID:24816116 assemble to form hLDH-1 (B4), hLDH-2 (AB3), hLDH-3 (A2B2), hLDH-4 (A3B) and hLDH-5 (A4) |
| GO:0006089 lactate metabolic process | IDA PMID:34381247 The tumor suppressor folliculin inhibits lactate dehydrogena... | ACCEPT | Summary: UniProt IDA linking LDHA to lactate metabolic process, based on the FLCN study demonstrating that LDHA activity (lactate production) is directly regulated. Core process. Reason: This study experimentally established LDHA as the enzyme driving lactate production (Warburg effect), directly supporting its role in lactate metabolism. Supporting Evidence: PMID:34381247 we identify the human tumor suppressor folliculin (FLCN) as a binding partner and uncompetitive inhibitor of LDHA |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9861563 | ACCEPT | Summary: Reactome TAS cytosolic localization (from the CTLH-ligase ubiquitination reaction). Consistent with the core cytosolic location. Reason: Cytosolic localization is well-established for LDHA and supported by multiple independent sources. Supporting Evidence: file:human/LDHA/LDHA-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0004459 L-lactate dehydrogenase (NAD+) activity | IMP PMID:34381247 The tumor suppressor folliculin inhibits lactate dehydrogena... | ACCEPT | Summary: IMP annotation of the L-lactate dehydrogenase activity, from the FLCN study using the LDHA R106 mutant to probe activity regulation. Core molecular function. Reason: The study functionally assayed LDHA enzymatic activity (including a mutagenesis of Arg-106 affecting FLCN binding), directly supporting the MF annotation. Supporting Evidence: PMID:34381247 we identify the human tumor suppressor folliculin (FLCN) as a binding partner and uncompetitive inhibitor of LDHA |
| GO:0005515 protein binding | IPI PMID:34381247 The tumor suppressor folliculin inhibits lactate dehydrogena... | MARK AS OVER ANNOTATED | Summary: UniProt IPI for the direct LDHA-FLCN (folliculin, Q8NFG4) interaction. FLCN is a direct, uncompetitive inhibitor of LDHA - a physiologically important regulatory interaction, but annotated to the uninformative "protein binding" term. Reason: Bare "protein binding" is uninformative per curation policy and is not retained as a core MF. The interaction itself is real, direct and functionally important (activity regulation), and is retained as an experimental IPI rather than removed. Supporting Evidence: PMID:34381247 we identify the human tumor suppressor folliculin (FLCN) as a binding partner and uncompetitive inhibitor of LDHA file:human/LDHA/LDHA-uniprot.txt the interaction is direct and inhibits enzymatic activity |
| GO:0042802 identical protein binding | IPI PMID:34381247 The tumor suppressor folliculin inhibits lactate dehydrogena... | ACCEPT | Summary: UniProt IPI self-interaction (LDHA-LDHA) reported in the FLCN study, consistent with the LDHA homotetramer / dimer-tetramer equilibrium described there. Reason: Informative and core - LDHA self-association underlies the active tetramer; the FLCN study explicitly discusses the LDHA dimer/tetramer states. Supporting Evidence: PMID:34381247 FLCN prefers binding to the less active LDHA dimer, compared to the hyperactive LDHA tetramer |
| GO:0005515 protein binding | IPI PMID:33406399 An Upstream Open Reading Frame in Phosphatase and Tensin Hom... | MARK AS OVER ANNOTATED | Summary: UniProt IPI for the LDHA-MP31 (C0HLV8) interaction. MP31, a micropeptide from the PTEN uORF, competes with LDH for NAD+ and limits lactate-pyruvate conversion; annotated to the uninformative "protein binding" term. Reason: Bare "protein binding" is uninformative and non-core. The MP31 interaction is real (mutagenesis of Asp-56 and Arg-99 abolishes it) and regulatory, retained as an experimental IPI rather than removed. Supporting Evidence: PMID:33406399 competing with mitochondrial lactate dehydrogenase (mLDH) for nicotinamide |
| GO:0045296 cadherin binding | HDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by... | MARK AS OVER ANNOTATED | Summary: High-throughput BioID proximity-biotinylation proteomics detected LDHA in the vicinity of the E-cadherin cytoplasmic tail. This is a proximity hit, not a demonstrated direct/functional cadherin interaction. Reason: BioID labels proteins within ~20-30 nm of the bait and captures many abundant cytosolic proteins; the authors note most identified proteins are not junctional. LDHA is an abundant glycolytic enzyme with no established cadherin adhesion role, so this is an over-annotation. Retained (not removed) as an experimental high-throughput observation. Supporting Evidence: PMID:25468996 we employed proximity biotinylation and quantitative proteomics to isolate and identify 612 proteins in the vicinity of E-cadherin |
| GO:0070062 extracellular exosome | HDA PMID:11487543 Intestinal epithelial cells secrete exosome-like vesicles. | MARK AS OVER ANNOTATED | Summary: High-throughput proteomic detection of LDHA in secreted exosome-like vesicles. LDHA is an abundant cytosolic protein commonly detected in exosome preparations. Reason: Detection of a highly abundant cytosolic glycolytic enzyme in exosome proteomes does not establish exosome localization as a core function; likely reflects passive incorporation/contamination. Retained as a high-throughput observation, not core. Supporting Evidence: PMID:11487543 exosome-like vesicles |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | MARK AS OVER ANNOTATED | Summary: High-throughput proteomic detection of LDHA in prostatic-secretion exosomes. Reason: As with other exosome-proteomics hits, this reflects the abundance of the cytosolic enzyme rather than a dedicated exosomal function; non-core, retained as an observation. Supporting Evidence: PMID:23533145 exosomes isolated from expressed prostatic secretions |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MARK AS OVER ANNOTATED | Summary: High-throughput membrane-proteome (NK cell) detection of LDHA. LDHA is a soluble cytosolic enzyme; membrane co-fractionation is likely peripheral association or contamination of the membrane fraction. Reason: No evidence that LDHA is an integral or functionally membrane-associated protein; this large-scale fractionation hit is non-core. Retained as an observation rather than removed. Supporting Evidence: PMID:19946888 membrane proteome of NK cells |
| GO:0005634 nucleus | HDA PMID:21630459 Proteomic characterization of the human sperm nucleus. | MARK AS OVER ANNOTATED | Summary: High-throughput proteomic detection of LDHA in the human sperm nucleus fraction. A nuclear pool of LDHA has been reported in some contexts, but this HDA hit does not establish a core nuclear function. Reason: LDHA is predominantly cytosolic; nuclear detection in a sperm-nucleus proteome is peripheral/context-specific and non-core. Retained as a high-throughput observation. Supporting Evidence: PMID:21630459 sperm nucleus |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | MARK AS OVER ANNOTATED | Summary: High-throughput proteomic detection of LDHA in urinary exosomes. Reason: Abundant cytosolic enzyme detected in exosome proteomics; non-core. Retained as a high-throughput observation. Supporting Evidence: PMID:19056867 proteomics and phosphoproteomics of urinary exosomes |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | MARK AS OVER ANNOTATED | Summary: High-throughput proteomic detection of LDHA in B-cell exosomes. Reason: As with other exosome-proteomics hits, non-core; reflects abundance rather than dedicated exosomal function. Retained as an observation. Supporting Evidence: PMID:20458337 exosomes and potential functional |
| GO:0005829 cytosol | TAS Reactome:R-HSA-70510 | ACCEPT | Summary: Reactome TAS cytosolic localization (LDH tetramer oxidises lactate to pyruvate reaction). Consistent with core cytosolic location. Reason: Well-established cytosolic localization for the glycolytic LDH enzyme. Supporting Evidence: file:human/LDHA/LDHA-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-71849 | ACCEPT | Summary: Reactome TAS cytosolic localization (LDH tetramer reduces pyruvate to lactate reaction). Consistent with core cytosolic location. Reason: Well-established cytosolic localization for the glycolytic LDH enzyme. Supporting Evidence: file:human/LDHA/LDHA-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0004459 L-lactate dehydrogenase (NAD+) activity | TAS PMID:2334430 Molecular characterization of genetic mutation in human lact... | ACCEPT | Summary: Traceable-author-statement MF annotation from the molecular characterization of human LDH-A(M) deficiency. Core molecular function. Reason: This genetics paper characterizes the LDH-A (Muscle) subunit and its deficiency, treating the L-lactate dehydrogenase activity of LDHA as established. Core MF, consistent with all other evidence. Supporting Evidence: PMID:2334430 deficient in LDH-A (Muscle) subunit |
| GO:0005829 cytosol | TAS PMID:2434947 Centrosomal proteins and lactate dehydrogenase possess a com... | ACCEPT | Summary: Traceable-author-statement cytosolic localization from an older study. Consistent with the core cytosolic location. Reason: Cytosolic localization is robustly established for LDHA across many sources. Supporting Evidence: file:human/LDHA/LDHA-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0004459 L-lactate dehydrogenase (NAD+) activity | NAS PMID:1953713 Analysis of genetic mutations in human lactate dehydrogenase... | ACCEPT | Summary: Non-traceable-author-statement MF annotation from a study of LDH-A(M) deficiency mutations. Core molecular function. Reason: The paper analyzes disease-causing mutations in the human LDH-A gene, treating the lactate dehydrogenase activity of LDHA as established. Core MF, concordant with the experimental annotations. Supporting Evidence: PMID:1953713 Human lactate dehydrogenase (LDH)-A mutant gene was analyzed |
| GO:0006096 glycolytic process | NAS PMID:1953713 Analysis of genetic mutations in human lactate dehydrogenase... | ACCEPT | Summary: Author-stated involvement of LDHA in the glycolytic process. LDHA regenerates cytosolic NAD+ (by reducing pyruvate to lactate) required to sustain glycolytic flux; a core process for the A/M subunit under anaerobic / high-flux conditions. Reason: LDHA is a canonical glycolysis-associated enzyme - its lactate-forming reaction recycles NAD+ that keeps glycolysis (specifically GAPDH) running. Correct core process annotation. Supporting Evidence: PMID:1953713 Human lactate dehydrogenase (LDH)-A mutant gene was analyzed |
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Download this section (compressed HTML)Q: Is there a genuine, functionally significant mitochondrial pool of human LDHA ("mLDH"), or is the mitochondrial IBA annotation an over-projection?
Q: To what extent do the reported nuclear and cadherin-proximal localizations of LDHA reflect moonlighting functions versus abundance-driven proteomics artifacts?
Experiment: Quantitative subcellular fractionation with activity assays to test whether a catalytically active mitochondrial LDHA pool exists in human cells.
Experiment: Structure-guided mutagenesis of the FLCN- and MP31-interaction interfaces to define how these regulators modulate LDHA activity and oligomeric state in vivo.
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