TPI1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004807 triose-phosphate isomerase activity	IBA GO_REF:0000033	ACCEPT	Summary: Triose-phosphate isomerase activity (EC 5.3.1.1) is the defining, core molecular function of TPI1, phylogenetically conserved across the entire family and directly demonstrated for the human enzyme. Reason: This is the core evolved function of the gene product. The IBA is well supported by the family-wide phylogenetic inference and confirmed for human TPI1 by direct biochemistry and structure. Supporting Evidence: file:human/TPI1/TPI1-uniprot.txt catalyzes the interconversion between dihydroxyacetone ... phosphate (DHAP) and D-glyceraldehyde-3-phosphate (G3P) in glycolysis ... and gluconeogenesis
GO:0006096 glycolytic process	IBA GO_REF:0000033	ACCEPT	Summary: TPI1 acts in glycolysis, isomerizing DHAP (from the aldolase step) to G3P so that both triose units feed into the payoff phase of the pathway. This is a core biological process for the gene. Reason: Glycolysis is one of the two central pathways the isomerase serves; strongly supported by phylogeny and by UniProt/Reactome pathway annotation. Supporting Evidence: file:human/TPI1/TPI1-uniprot.txt Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-
GO:0006094 gluconeogenesis	IBA GO_REF:0000033	ACCEPT	Summary: TPI1 also functions in gluconeogenesis, catalyzing the reverse (G3P to DHAP) reaction that supplies DHAP for fructose-1,6-bisphosphate synthesis. Core process. Reason: Gluconeogenesis is the second central pathway served by the reversible isomerase; supported by phylogeny and UniProt pathway annotation. Supporting Evidence: file:human/TPI1/TPI1-uniprot.txt Carbohydrate biosynthesis; gluconeogenesis
GO:0046166 glyceraldehyde-3-phosphate biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: The TPI1 reaction produces D-glyceraldehyde-3-phosphate from DHAP; the UniProt/UniPathway description of the glycolytic step is the formation of G3P from glycerone phosphate. Reason: A correct, more granular restatement of the isomerase's productive role in glycolysis (formation of G3P). Consistent with the core function; retained but subsidiary to the glycolytic-process/MF annotations. Supporting Evidence: file:human/TPI1/TPI1-uniprot.txt glycolysis; D-glyceraldehyde 3-
GO:0004807 triose-phosphate isomerase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assertion of the core triose-phosphate isomerase activity (EC 5.3.1.1, RHEA:18585) via InterPro/ARBA. Redundant with the experimental and phylogenetic evidence but correct. Reason: Correctly maps the TIM InterPro signatures and EC 5.3.1.1 to the core molecular function. Supporting Evidence: file:human/TPI1/TPI1-uniprot.txt EC=5.3.1.1
GO:0005737 cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: TPI1 is a cytoplasmic/cytosolic enzyme; UniProt Subcellular Location is Cytoplasm. Reason: Correct localization derived from the UniProt Subcellular Location mapping; the more specific cytosol term is also annotated and is preferred for core function. Supporting Evidence: file:human/TPI1/TPI1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm
GO:0006096 glycolytic process	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assertion of the core glycolytic-process role via InterPro and UniPathway (UPA00109). Redundant with the IBA but correct. Reason: Correctly captures TPI1's central role in glycolysis; consistent with the IBA and pathway annotations. Supporting Evidence: file:human/TPI1/TPI1-uniprot.txt Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-
GO:0008929 methylglyoxal synthase activity	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: TPI1 has a documented minor methylglyoxal-synthase-like side activity (EC 4.2.3.3), generating the cytotoxic side-product methylglyoxal from DHAP. This is a genuine but non-core promiscuous activity, not the enzyme's evolved physiological function. Reason: UniProt records the methylglyoxal-synthase activity (EC 4.2.3.3, RHEA:17937) as a secondary function responsible for "non-negligible" methylglyoxal production. It is real, so it is retained, but it is a promiscuous side reaction rather than the core triose-phosphate isomerase function and should not be treated as a core MF. Supporting Evidence: file:human/TPI1/TPI1-uniprot.txt It is also responsible for the non-negligible production of ... methylglyoxal a reactive cytotoxic side-product
GO:0005515 protein binding	IPI PMID:20849852 Proliferating cell nuclear antigen in the cytoplasm interact...	MARK AS OVER ANNOTATED	Summary: TPI1 was identified among six glycolytic enzymes co-purifying with cytoplasmic PCNA (P12004) in a Far-Western/mass-spectrometry screen. The bare "protein binding" term is uninformative and this interaction is peripheral to the enzyme's function. Reason: GO:0005515 "protein binding" conveys no specific molecular function. The supporting paper is a proteomic interaction screen (PCNA-associated glycolytic enzymes) that does not establish a defined functional interaction for TPI1. Per curation policy the experimental IPI is retained (not removed) but flagged as an uninformative over-annotation. Supporting Evidence: PMID:20849852 PCNA is also associated with six glycolytic enzymes that are involved in the regulation of steps 4-9 in the glycolysis pathway
GO:0005515 protein binding	IPI PMID:21044950 Genome-wide YFP fluorescence complementation screen identifi...	MARK AS OVER ANNOTATED	Summary: TPI1 (with TERF1/P54274) was flagged as a candidate telomere-protein interactor in a genome-wide split-YFP (BiFC) complementation screen. Bare "protein binding"; a high-throughput, transient-interaction screen not indicative of TPI1's core function. Reason: GO:0005515 is uninformative, and the source is a large-scale complementation screen for telomere-interactome candidates in which many identified proteins were acknowledged as possible false positives. The experimental IPI is kept per policy but marked as an over-annotation. Supporting Evidence: PMID:21044950 we identified over 300 proteins that associated with the six core telomeric proteins
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	MARK AS OVER ANNOTATED	Summary: TPI1 (with huntingtin, HTT/P42858) appears as an edge in a large yeast two-hybrid neurodegenerative-disease interactome map. Bare "protein binding" from a systematic interactome screen; not a defined functional interaction. Reason: GO:0005515 is uninformative and the evidence is a systematic Y2H/literature interactome connecting ~5,000 proteins via ~30,000 candidate interactions. The experimental IPI is retained per policy but flagged as an over-annotation. Supporting Evidence: PMID:32814053 connects ∼5,000 human proteins via ∼30,000 candidate interactions
GO:0005829 cytosol	IEA GO_REF:0000107	ACCEPT	Summary: Cytosol is the compartment where TPI1 carries out its glycolytic/gluconeogenic function. The is_active_in qualifier is appropriate for the site of the core activity. Reason: Correct and specific location for the enzyme's core activity; transferred from the mouse ortholog and consistent with UniProt Cytoplasm localization. Supporting Evidence: file:human/TPI1/TPI1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm
GO:0006094 gluconeogenesis	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assertion (UniPathway UPA00138, ortholog transfer) of the core gluconeogenic role. Redundant with the IBA/Reactome annotations but correct. Reason: Correctly captures TPI1's role in gluconeogenesis; consistent with the IBA and UniProt pathway annotation. Supporting Evidence: file:human/TPI1/TPI1-uniprot.txt Carbohydrate biosynthesis; gluconeogenesis
GO:0016853 isomerase activity	IEA GO_REF:0000107	MODIFY	Summary: The generic parent term isomerase activity is far too general for a well-characterized enzyme whose specific reaction (EC 5.3.1.1) is known. Reason: The enzyme's specific molecular function (EC 5.3.1.1) is known and directly annotated as GO:0004807. The generic parent term should be replaced by the specific child term. Proposed replacements: triose-phosphate isomerase activity Supporting Evidence: file:human/TPI1/TPI1-uniprot.txt EC=5.3.1.1
GO:0019682 glyceraldehyde-3-phosphate metabolic process	IEA GO_REF:0000107	ACCEPT	Summary: TPI1 metabolizes G3P (interconverting it with DHAP); this term correctly but broadly describes that involvement. Reason: A correct, if general, restatement of the isomerase's role in triose-phosphate metabolism; subsidiary to the glycolytic-process and MF annotations. Supporting Evidence: file:human/TPI1/TPI1-uniprot.txt catalyzes the interconversion between dihydroxyacetone ... phosphate (DHAP) and D-glyceraldehyde-3-phosphate (G3P) in glycolysis
GO:0061621 canonical glycolysis	IEA GO_REF:0000107	ACCEPT	Summary: Canonical glycolysis (the classical Embden-Meyerhof-Parnas pathway) is the specific glycolytic process TPI1 participates in. A precise child of glycolytic process. Reason: Accurately places TPI1 in the canonical glycolytic pathway; more specific than, and consistent with, the glycolytic-process annotation. Supporting Evidence: file:human/TPI1/TPI1-uniprot.txt Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-
GO:0006094 gluconeogenesis	TAS Reactome:R-HSA-70263	ACCEPT	Summary: Reactome traceable assertion placing TPI1 in the gluconeogenesis pathway. Consistent with the core gluconeogenic role. Reason: Authoritative pathway-database assertion of a core process for the gene.
GO:0061621 canonical glycolysis	TAS Reactome:R-HSA-70171	ACCEPT	Summary: Reactome traceable assertion placing TPI1 in the (canonical) glycolysis pathway. Consistent with the core glycolytic role. Reason: Authoritative pathway-database assertion of a core process for the gene.
GO:0004807 triose-phosphate isomerase activity	EXP PMID:6434534 Primary structure of human triosephosphate isomerase.	ACCEPT	Summary: Direct experimental study of purified human (placental) triosephosphate isomerase establishing the enzyme, its high specific activity, and its dimeric structure. Supports the core triose-phosphate isomerase activity. Reason: Experimental characterization of the purified human enzyme (highest specific activity reported at the time), confirming the core molecular function. Supporting Evidence: PMID:6434534 Human placental triosephosphate isomerase was isolated by an improved procedure and recovered with the highest specific activity ever reported
GO:0008929 methylglyoxal synthase activity	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Sequence-similarity transfer (from P00939) of the minor methylglyoxal-synthase-like side activity. Genuine but non-core promiscuous activity, duplicate of the IEA methylglyoxal synthase annotation. Reason: Same minor side reaction (EC 4.2.3.3) as the IEA annotation; it is real but is a promiscuous side activity, not the enzyme's core function. Supporting Evidence: file:human/TPI1/TPI1-uniprot.txt It is also responsible for the non-negligible production of ... methylglyoxal a reactive cytotoxic side-product
GO:0005829 cytosol	TAS Reactome:R-HSA-70454	ACCEPT	Summary: Reactome localizes the TPI1-catalyzed reaction (DHAP to GA3P) to the cytosol. Correct core location. Reason: Authoritative pathway-database assertion of the cytosolic site of the core isomerase reaction.
GO:0005829 cytosol	TAS Reactome:R-HSA-70481	ACCEPT	Summary: Reactome localizes the reverse TPI1 reaction (GA3P to DHAP) to the cytosol. Correct core location; duplicate of the preceding cytosol annotation. Reason: Authoritative pathway-database assertion of the cytosolic site of the core isomerase reaction.
GO:0019242 methylglyoxal biosynthetic process	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: The process counterpart of the minor methylglyoxal-synthase side activity; TPI1 produces methylglyoxal as a cytotoxic side-product from DHAP. Non-core. Reason: Corresponds to the promiscuous methylglyoxal-synthase side reaction, which is a genuine but minor/deleterious byproduct pathway rather than an evolved core biological process of TPI1. Supporting Evidence: file:human/TPI1/TPI1-uniprot.txt It is also responsible for the non-negligible production of ... methylglyoxal a reactive cytotoxic side-product
GO:0046166 glyceraldehyde-3-phosphate biosynthetic process	IDA PMID:18562316 Structural basis of human triosephosphate isomerase deficien...	ACCEPT	Summary: The structural/biochemical study of recombinant human TPI1 (WT and E104D) characterized the isomerase reaction that produces G3P. Supports the productive role in G3P formation. Subsidiary to glycolytic process / MF. Reason: The paper directly assayed catalytic activity of purified recombinant human TPI1, supporting its role in producing D-glyceraldehyde-3-phosphate. Supporting Evidence: PMID:18562316 the purified, recombinant mutant enzyme E104D, while exhibiting normal catalytic activity
GO:0004807 triose-phosphate isomerase activity	IDA PMID:18562316 Structural basis of human triosephosphate isomerase deficien...	ACCEPT	Summary: Direct assay of purified recombinant human TPI1 confirms the core triose-phosphate isomerase activity (with measured KM and Vmax reported in UniProt). Reason: Experimental (IDA) confirmation of the core molecular function for the human enzyme; this is the anchor experimental evidence for EC 5.3.1.1. Supporting Evidence: PMID:18562316 the purified, recombinant mutant enzyme E104D, while exhibiting normal catalytic activity
GO:0042803 protein homodimerization activity	IDA PMID:18562316 Structural basis of human triosephosphate isomerase deficien...	ACCEPT	Summary: TPI1 is an obligate homodimer, and the active dimer is required for full function; this study directly showed the E104D disease mutant is impaired in forming active dimers. Homodimerization is integral to the enzyme's core activity. Reason: Directly demonstrated homodimerization and its functional importance (the most common disease mutation acts by destabilizing the dimer). Retained as a core structural aspect of the isomerase's molecular function. Supporting Evidence: PMID:18562316 shows impairments in the formation of active dimers and low thermostability and monomerizes under conditions in which the wild type retains its dimeric form
GO:0005515 protein binding	IPI PMID:23355646 Identification of sperm head proteins involved in zona pellu...	MARK AS OVER ANNOTATED	Summary: TPI1 was identified among sperm-head proteins in a screen for zona-pellucida binding partners (a putative moonlighting role). Bare "protein binding"; the paper itself frames these glycolytic enzymes as multifaceted/moonlighting rather than as a defined interaction. Reason: GO:0005515 is uninformative, and the supporting evidence is a proteomic sperm-protein screen describing possible moonlighting functions, not a specific characterized molecular interaction of TPI1. The experimental IPI is retained per policy but marked as an over-annotation. Supporting Evidence: PMID:23355646 Their multiple roles ... suggest that these sperm proteins are multifaceted or moonlighting proteins
GO:0031625 ubiquitin protein ligase binding	IPI PMID:19725078 Proteomic analysis of increased Parkin expression and its in...	MARK AS OVER ANNOTATED	Summary: TPI1 co-purified with the E3 ubiquitin-protein ligase Parkin (PARK2/O60260) in a tandem-affinity-purification/MS proteomics screen, alongside many mitochondrial and glycolytic proteins. A peripheral interactome finding, not a core function. Reason: The evidence is a Parkin-interactome proteomics screen in which TPI1 is one of many glycolytic/energy-metabolism proteins recovered; this does not establish a characterized, functionally meaningful ubiquitin-ligase-binding activity for TPI1. Retained per policy but flagged as an over-annotation. Supporting Evidence: PMID:19725078 Nine of these are directly involved in mitochondrial energy metabolism and glycolysis
GO:0070062 extracellular exosome	HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres...	KEEP AS NON CORE	Summary: TPI1 was detected by shotgun proteomics of exosomes from expressed prostatic secretions in urine. A high-throughput MS detection consistent with the common presence of abundant cytosolic glycolytic enzymes in exosomes; not the site of the core function. Reason: Valid high-throughput proteomic detection, but exosomal localization is a secondary/moonlighting or passive-packaging observation rather than where TPI1 performs its core glycolytic function. Supporting Evidence: PMID:23533145 exosome preparations were characterized by a shotgun proteomics procedure
GO:0005576 extracellular region	HDA PMID:16502470 Human colostrum: identification of minor proteins in the aqu...	KEEP AS NON CORE	Summary: TPI1 was among low-abundance proteins detected in the aqueous phase of human colostrum by proteomics. An extracellular-fluid MS detection, not the core cytosolic site of function. Reason: Valid proteomic detection in a body fluid; extracellular presence is secondary and does not reflect the enzyme's core intracellular glycolytic function. Supporting Evidence: PMID:16502470 investigated the low abundance proteins in the aqueous phase of human colostrum
GO:0005634 nucleus	HDA PMID:21630459 Proteomic characterization of the human sperm nucleus.	KEEP AS NON CORE	Summary: TPI1 was detected in a proteomic catalogue of the human sperm nucleus (403 proteins). A high-throughput detection; likely cytoplasmic carryover or a specialized moonlighting context rather than a general nuclear function of TPI1. Reason: Valid MS detection in isolated sperm nuclei, but nuclear localization is not part of TPI1's core glycolytic function and may reflect a cell-type-specific or contaminating signal. Retained as non-core. Supporting Evidence: PMID:21630459 403 different proteins have been identified from the isolated sperm nuclei
GO:0005576 extracellular region	HDA PMID:22664934 Comparison of tear protein levels in breast cancer patients ...	KEEP AS NON CORE	Summary: TPI (TPI1) was among proteins identified in human tear fluid in a breast-cancer biomarker proteomics study. An extracellular-fluid detection, not the core site of function. Reason: Valid proteomic detection in tears; extracellular presence is secondary and does not reflect the enzyme's core intracellular function. Supporting Evidence: PMID:22664934 different metabolic cascades (ALDH3A or ... TPI)
GO:0005576 extracellular region	HDA PMID:23580065 Shotgun proteomics reveals specific modulated protein patter...	KEEP AS NON CORE	Summary: TPI1 was among proteins detected in a shotgun-proteomics analysis of tears from glaucoma patients. Extracellular-fluid MS detection; not the core site of function. Duplicate extracellular-region evidence. Reason: Valid proteomic detection in a body fluid; extracellular presence is secondary to the core intracellular glycolytic function. Supporting Evidence: PMID:23580065 shotgun proteomics approach to tears of patients with POAG
GO:0070062 extracellular exosome	HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos...	KEEP AS NON CORE	Summary: TPI1 was detected in a large-scale proteomic profile of human urinary exosomes. High-throughput MS detection consistent with exosomal packaging of abundant cytosolic enzymes; not the core site of function. Duplicate exosome evidence. Reason: Valid proteomic detection in exosomes, but this localization is secondary and does not reflect where TPI1 performs its core glycolytic function. Supporting Evidence: PMID:19056867 used LC-MS/MS to profile the proteome of human urinary exosomes
GO:0004807 triose-phosphate isomerase activity	TAS PMID:2579079 Human triosephosphate isomerase cDNA and protein structure. ...	ACCEPT	Summary: Early cloning/protein-structure study of human triosephosphate isomerase (and TPI deficiency), supporting the core isomerase molecular function. Reason: Traceable assertion of the core enzyme identity/function from a foundational human TPI cDNA and protein-structure paper; redundant with the experimental IDA but correct. Supporting Evidence: PMID:2579079 Nine cDNA clones of human adult liver triosephosphate (TP) isomerase have been isolated and characterized
GO:0004807 triose-phosphate isomerase activity	NAS PMID:2876430 Human triose-phosphate isomerase deficiency: a single amino ...	ACCEPT	Summary: Study of the Glu104Asp TPI-deficiency mutation, defining TPI as D-glyceraldehyde-3-phosphate ketol-isomerase (EC 5.3.1.1). Non-traceable author statement of the core molecular function. Reason: Correctly asserts the core triose-phosphate isomerase identity/function of the gene; consistent with all experimental evidence. Redundant with the IDA/EXP annotations but not wrong. Supporting Evidence: PMID:2876430 Triose-phosphate isomerase (TPI; D-glyceraldehyde-3-phosphate ketol-isomerase, EC 5.3.1.1)

Gene Description

Existing Annotations Review

Core Functions

Triose-phosphate isomerase activity — the reversible, near-diffusion-limited interconversion of dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde-3-phosphate (G3P) (EC 5.3.1.1) — carried out by the cytosolic homodimeric enzyme in glycolysis and gluconeogenesis.

References

📚 Additional Documentation

Notes

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