GAPDH

Existing Annotations Review

Gene Description

Existing Annotations Review

Core Functions

Primary glycolytic function - catalyzes oxidative phosphorylation of G3P to 1,3-BPG

Moonlighting nuclear function - S-nitrosylates target proteins to regulate apoptosis

Moonlighting GAIT complex function - regulates inflammatory mRNA translation

Moonlighting antimicrobial function - secreted GAPDH has antifungal activity

References

Tags

Deep Research

Falcon

Perplexity

📚 Additional Documentation

Notes

Bioreason Rl Predictions

Bioreason Rl Review

Falcon Research

📄 View Raw YAML

GO Term	Evidence	Action	Reason
GO:0006096 glycolytic process	IBA GO_REF:0000033	ACCEPT	Summary: Core metabolic function of GAPDH, well-established Supporting Evidence: file:human/GAPDH/GAPDH-falcon-research.md See deep research file for comprehensive analysis
GO:0004365 glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity	IBA GO_REF:0000033	ACCEPT	Summary: Primary enzymatic activity, catalyzing G3P to 1,3-BPG conversion Supporting Evidence: PMID:38611852 The enzymatic function of GAPDH is mainly observed in glycolysis, where it catalyzes the conversion of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate.
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: Primary localization for glycolytic function
GO:0002376 immune system process	IEA GO_REF:0000043	MODIFY	Summary: Too general; GAPDH has specific roles in innate immunity via TRAF2/3 Proposed replacements: innate immune response
GO:0004365 glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity	IEA GO_REF:0000120	ACCEPT	Summary: glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity annotation for GAPDH. Reason: Glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity is the primary catalytic function of GAPDH. Multiple evidence codes support this annotation.
GO:0005634 nucleus	IEA GO_REF:0000044	ACCEPT	Summary: GAPDH translocates to the nucleus under stress conditions where it functions as a S-nitrosylase to regulate apoptosis by modifying nuclear proteins through S-nitrosylation. Reason: Nuclear localization is essential for GAPDH's moonlighting function as a peptidyl-cysteine S-nitrosylase that regulates apoptotic processes by S-nitrosylating nuclear target proteins. Supporting Evidence: PMID:38615102 At the molecular levels such stressors lead to S-nitrosylation (or possibly oxidation) at Cys-150, which allows post-translationally modified GAPDH to interact with a chaperon protein Siah1 creating a protein complex of GAPDH-Siah1. Through this process, GAPDH loses its glycolytic activity and is translocated to the nucleus as a GAPDH-Siah1 complex PMID:38615102 Our group also reported that the replacement of lysine 225 for alanine (K225A) on GAPDH abolished GAPDH-Siah1 binding PMID:38611852 In the context of DNA repair, it is found that the activation of the tyrosine kinase Src occurs under DNA damage stress, leading to the phosphorylation of GAPDH at Tyr41. This phosphorylation event is crucial for the nuclear translocation of GAPDH.
GO:0005829 cytosol	IEA GO_REF:0000044	ACCEPT	Summary: cytosol annotation for GAPDH. Reason: Cytosol is the primary localization for GAPDH's glycolytic function. Multiple evidence codes support this annotation.
GO:0005856 cytoskeleton	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Interacts with microtubules via CHP1, moonlighting function
GO:0006006 glucose metabolic process	IEA GO_REF:0000002	ACCEPT	Summary: Core metabolic function, part of glycolysis
GO:0006096 glycolytic process	IEA GO_REF:0000120	ACCEPT	Summary: glycolytic process annotation for GAPDH. Reason: Glycolytic process is the core metabolic pathway for GAPDH. Multiple evidence codes support this annotation. Supporting Evidence: PMID:38611852 In the cytosol, it primarily performs as a pivotal enzyme in the metabolic process of glycolysis, catalyzing the conversion of glyceraldehyde 3-phosphate into 1,3-bisphosphoglycerate.
GO:0006417 regulation of translation	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: Component of GAIT complex, regulates translation of inflammatory mRNAs
GO:0006915 apoptotic process	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: Nuclear translocation under stress activates p53-dependent apoptosis Supporting Evidence: PMID:38611852 For example, apoptotic stimuli can activate NO formation and lead to the S-nitrosylation of GAPDH. This modification inhibits GAPDH's catalytic activity and enables it to bind to Siah, an E3-ubiquitin-ligase, which transports GAPDH to the nucleus. Inside the nucleus, GAPDH stabilizes Siah, allowing it to degrade specific target proteins and influence apoptosis.
GO:0016020 membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: GAPDH associates with the plasma and nuclear membranes, so the generic membrane term is true, but it is not the protein's core location. Reason: True but not GAPDH's core location: nuclear membrane and plasma membrane, kept in this review, entail this term. KEEP_AS_NON_CORE, matching the HDA row for this term, rather than REMOVE.
GO:0016491 oxidoreductase activity	IEA GO_REF:0000043	TOO GENERAL	Summary: Too general; specific activity is glyceraldehyde-3-phosphate dehydrogenase Reason: TOO_GENERAL rather than REMOVE: glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity, kept in this review, entails this term, so the claim is true but less informative.
GO:0016620 oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor	IEA GO_REF:0000002	TOO GENERAL	Summary: Parent term of GO:0004365, acceptable but redundant Reason: TOO_GENERAL rather than REMOVE: glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity, kept in this review, entails this term, so the claim is true but less informative.
GO:0016740 transferase activity	IEA GO_REF:0000043	TOO GENERAL	Summary: Too general and imprecise for GAPDH function Reason: TOO_GENERAL rather than REMOVE: peptidyl-cysteine S-nitrosylase activity, kept in this review, entails this term, so the claim is true but less informative.
GO:0035605 peptidyl-cysteine S-nitrosylase activity	IEA GO_REF:0000116	KEEP AS NON CORE	Summary: Important moonlighting function, S-nitrosylates nuclear targets like SIRT1 Supporting Evidence: PMID:38615102 Beyond its classic role in glycolysis [46,47], during stress, a pool of this multi-functional protein [45,48] is post-translationally modified at specific residues, such as cysteine 150 (Cys-150) and lysine 160 (Lys-160), which converts this glycolytic enzyme into a signaling molecule
GO:0045087 innate immune response	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: Promotes NF-kB activation and type I interferon via TRAF2/3 interactions
GO:0048471 perinuclear region of cytoplasm	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Can localize here during nuclear translocation
GO:0050661 NADP binding	IEA GO_REF:0000002	REMOVE	Summary: InterPro-derived NADP binding. Human GAPDH is the NAD-dependent enzyme; the family signature also covers NADP-dependent dehydrogenases of other lineages. Reason: The term comes from an InterPro signature for the glyceraldehyde-3-phosphate/erythrose-4-phosphate dehydrogenase family, which also covers NADP-dependent enzymes of plants and bacteria, and the mapping assigns both NAD binding and NADP binding to every member. Human GAPDH is the NAD-dependent phosphorylating enzyme of glycolysis and uses NAD+ as its coenzyme; no evidence indicates that it binds NADP. The NAD binding annotation from the same signature is accepted, and the NADP half of the mapping is an over-propagation to an NAD-specific member, so it is removed.
GO:0051287 NAD binding	IEA GO_REF:0000002	ACCEPT	Summary: Essential for catalytic activity, NAD+ is the cofactor
GO:0005515 protein binding	IPI PMID:16169070 A human protein-protein interaction network: a resource for ...	REMOVE	Summary: Non-specific annotation - need more specific binding terms Supporting Evidence: PMID:16169070 A human protein-protein interaction network: a resource for annotating the proteome.
GO:0005515 protein binding	IPI PMID:16799092 Dynamic profiling of the post-translational modifications an...	REMOVE	Summary: Non-specific annotation - need more specific binding terms Supporting Evidence: PMID:16799092 Epub 2006 Jun 23. Dynamic profiling of the post-translational modifications and interaction partners of epidermal growth factor receptor signaling after stimulation by epidermal growth factor using Extended Range Proteomic Analysis (ERPA).
GO:0005515 protein binding	IPI PMID:17353931 Large-scale mapping of human protein-protein interactions by...	REMOVE	Summary: Non-specific annotation - need more specific binding terms Supporting Evidence: PMID:17353931 Large-scale mapping of human protein-protein interactions by mass spectrometry.
GO:0005515 protein binding	IPI PMID:17500595 Huntingtin interacting proteins are genetic modifiers of neu...	REMOVE	Summary: Non-specific annotation - need more specific binding terms Supporting Evidence: PMID:17500595 Huntingtin interacting proteins are genetic modifiers of neurodegeneration.
GO:0005515 protein binding	IPI PMID:20029029 Regulation of epidermal growth factor receptor trafficking b...	REMOVE	Summary: Non-specific annotation - need more specific binding terms Supporting Evidence: PMID:20029029 Regulation of epidermal growth factor receptor trafficking by lysine deacetylase HDAC6.
GO:0005515 protein binding	IPI PMID:20392205 Loose interaction between glyceraldehyde-3-phosphate dehydro...	REMOVE	Summary: Non-specific annotation - need more specific binding terms Supporting Evidence: PMID:20392205 Loose interaction between glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate kinase revealed by fluorescence resonance energy transfer-fluorescence lifetime imaging microscopy in living cells.
GO:0005515 protein binding	IPI PMID:20849852 Proliferating cell nuclear antigen in the cytoplasm interact...	REMOVE	Summary: Non-specific annotation - need more specific binding terms Supporting Evidence: PMID:20849852 Epub 2010 Sep 16. Proliferating cell nuclear antigen in the cytoplasm interacts with components of glycolysis and cancer.
GO:0005515 protein binding	IPI PMID:21044950 Genome-wide YFP fluorescence complementation screen identifi...	REMOVE	Summary: Non-specific annotation - need more specific binding terms Supporting Evidence: PMID:21044950 Epub 2010 Nov 2. Genome-wide YFP fluorescence complementation screen identifies new regulators for telomere signaling in human cells.
GO:0005515 protein binding	IPI PMID:23348613 Prolyl oligopeptidase is a glyceraldehyde-3-phosphate dehydr...	REMOVE	Summary: Non-specific annotation - need more specific binding terms Supporting Evidence: PMID:23348613 Prolyl oligopeptidase is a glyceraldehyde-3-phosphate dehydrogenase-binding protein that regulates genotoxic stress-induced cell death.
GO:0005515 protein binding	IPI PMID:24658140 The mammalian-membrane two-hybrid assay (MaMTH) for probing ...	REMOVE	Summary: Non-specific annotation - need more specific binding terms Supporting Evidence: PMID:24658140 The mammalian-membrane two-hybrid assay (MaMTH) for probing membrane-protein interactions in human cells.
GO:0005515 protein binding	IPI PMID:25417112 Target-selective protein S-nitrosylation by sequence motif r...	REMOVE	Summary: Non-specific annotation - need more specific binding terms Supporting Evidence: PMID:25417112 Oct 16. Target-selective protein S-nitrosylation by sequence motif recognition.
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	REMOVE	Summary: Non-specific annotation - need more specific binding terms Supporting Evidence: PMID:28514442 Architecture of the human interactome defines protein communities and disease networks.
GO:0005515 protein binding	IPI PMID:29028794 Condensin II and GAIT complexes cooperate to restrict LINE-1...	REMOVE	Summary: Non-specific annotation - need more specific binding terms Supporting Evidence: PMID:29028794 eCollection 2017 Oct.
GO:0005515 protein binding	IPI PMID:29128334 A Map of Human Mitochondrial Protein Interactions Linked to ...	REMOVE	Summary: Non-specific annotation - need more specific binding terms Supporting Evidence: PMID:29128334 2017 Nov 8. A Map of Human Mitochondrial Protein Interactions Linked to Neurodegeneration Reveals New Mechanisms of Redox Homeostasis and NF-κB Signaling.
GO:0005515 protein binding	IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ...	REMOVE	Summary: Non-specific annotation - need more specific binding terms Supporting Evidence: PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRAS(G13D).
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: Non-specific annotation - need more specific binding terms Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	REMOVE	Summary: Non-specific annotation - need more specific binding terms Supporting Evidence: PMID:33961781 2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
GO:0042802 identical protein binding	IPI PMID:20392205 Loose interaction between glyceraldehyde-3-phosphate dehydro...	ACCEPT	Summary: Forms homotetramers, essential for enzymatic activity Supporting Evidence: PMID:20392205 Loose interaction between glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate kinase revealed by fluorescence resonance energy transfer-fluorescence lifetime imaging microscopy in living cells.
GO:0042802 identical protein binding	IPI PMID:21988832 Toward an understanding of the protein interaction network o...	ACCEPT	Summary: identical protein binding annotation for GAPDH. Reason: GAPDH forms homotetramers (identical protein binding) which is essential for its catalytic activity. Multiple evidence codes support this annotation. Supporting Evidence: PMID:21988832 Toward an understanding of the protein interaction network of the human liver.