RPIA

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004751 ribose-5-phosphate isomerase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically-inferred core molecular function; RPIA is the human member of the ribose-5-phosphate isomerase (RpiA) family and catalyses the R5P <-> Ru5P isomerisation. This is the correct, most specific MF term and is corroborated by direct experimental and NAS evidence. Reason: IBA at the correct level of specificity, concordant with the experimentally-verified catalytic activity of the enzyme. Supporting Evidence: file:human/RPIA/RPIA-uniprot.txt Catalyzes the reversible conversion of ribose-5-phosphate to PMID:14988808 the reversible phase of the PPP
GO:0009052 pentose-phosphate shunt, non-oxidative branch	IBA GO_REF:0000033	ACCEPT	Summary: Core biological process. RPIA acts in the first step of the non-oxidative branch of the pentose phosphate pathway, isomerising ribulose-5-phosphate and ribose-5-phosphate. Reason: Correct and specific BP term, consistent with the UniProt PATHWAY annotation (non-oxidative stage, step 1/1) and the enzyme's characterised reaction. Supporting Evidence: file:human/RPIA/RPIA-uniprot.txt pentose phosphate pathway; D-ribose
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: RPIA is a soluble cytoplasmic/cytosolic enzyme with no signal or transit peptide. Cytoplasm is correct, though the more specific cytosol term (GO:0005829) is also annotated and preferred for core representation. Reason: Consistent with the cytosolic Reactome/UniProt localisation of this housekeeping metabolic enzyme. Supporting Evidence: file:human/RPIA/RPIA-uniprot.txt Belongs to the ribose 5-phosphate isomerase family
GO:0006014 D-ribose metabolic process	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: RPIA interconverts D-ribose-5-phosphate and D-ribulose-5-phosphate, so it participates in ribose-phosphate (D-ribose) metabolism. This is a correct but broader process term relative to the pentose-phosphate-shunt terms. Reason: True but less specific than the pentose-phosphate-shunt, non-oxidative branch term; retained as supporting rather than core process. Supporting Evidence: file:human/RPIA/RPIA-uniprot.txt Catalyzes the reversible conversion of ribose-5-phosphate to
GO:0004751 ribose-5-phosphate isomerase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assignment of the core isomerase activity, backed by RHEA:14657 (aldehydo-D-ribose 5-phosphate = D-ribulose 5-phosphate), EC 5.3.1.6 and the RpiA InterPro signatures. Fully consistent with experimental evidence. Reason: Correct EC/RHEA/InterPro-to-GO mapping for the family; matches the experimentally-verified catalytic activity. Supporting Evidence: file:human/RPIA/RPIA-uniprot.txt Reaction=aldehydo-D-ribose 5-phosphate = D-ribulose 5-phosphate
GO:0009052 pentose-phosphate shunt, non-oxidative branch	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assignment of the correct, specific non-oxidative PPP branch process, concordant with the IBA annotation. Reason: Correct and specific BP term for a ribose-5-phosphate isomerase. Supporting Evidence: file:human/RPIA/RPIA-uniprot.txt pentose phosphate pathway; D-ribose
GO:0005515 protein binding	IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in...	MARK AS OVER ANNOTATED	Summary: Bare protein binding from a high-throughput proteome-scale yeast two-hybrid interactome map (CCSB-HI1). Uninformative for RPIA's molecular function. Reason: Generic protein binding derived from a large-scale binary interactome screen; per curation guidance this uninformative term should not be treated as representing RPIA function. Retained (not removed) as an experimental IPI. Supporting Evidence: PMID:16189514 an initial version of a proteome-scale map
GO:0005515 protein binding	IPI PMID:21516116 Next-generation sequencing to generate interactome datasets.	MARK AS OVER ANNOTATED	Summary: Bare protein binding from a high-throughput interactome-mapping pipeline (Stitch-seq). Uninformative for RPIA's molecular function. Reason: Generic protein binding from a large-scale interactome dataset; not informative of molecular function. Retained as an experimental IPI. Supporting Evidence: PMID:21516116 Next-generation sequencing to generate interactome datasets.
GO:0005515 protein binding	IPI PMID:24722188 Protein interaction network of alternatively spliced isoform...	MARK AS OVER ANNOTATED	Summary: Bare protein binding from a brain alternatively-spliced-isoform interactome screen. Uninformative for RPIA's molecular function. Reason: Generic protein binding from a large-scale interactome dataset; not informative of molecular function. Retained as an experimental IPI. Supporting Evidence: PMID:24722188 Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism.
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	MARK AS OVER ANNOTATED	Summary: Bare protein binding from a proteome-scale human interactome map (HI-II-14). Uninformative for RPIA's molecular function. Reason: Generic protein binding from a large-scale binary interactome screen; not informative of molecular function. Retained as an experimental IPI. Supporting Evidence: PMID:25416956 A proteome-scale map of the human interactome network
GO:0005515 protein binding	IPI PMID:25910212 Widespread macromolecular interaction perturbations in human...	MARK AS OVER ANNOTATED	Summary: Bare protein binding from an interactome-perturbation study of human genetic disorders. Uninformative for RPIA's molecular function. Reason: Generic protein binding from a large-scale interactome dataset; not informative of molecular function. Retained as an experimental IPI. Supporting Evidence: PMID:25910212 Widespread macromolecular interaction perturbations in human genetic disorders.
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	MARK AS OVER ANNOTATED	Summary: Bare protein binding from a large-scale affinity-purification/interactome community-network study. Uninformative for RPIA's molecular function. Reason: Generic protein binding from a large-scale interactome dataset; not informative of molecular function. Retained as an experimental IPI. Supporting Evidence: PMID:28514442 Architecture of the human interactome defines protein communities and disease networks.
GO:0005515 protein binding	IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m...	MARK AS OVER ANNOTATED	Summary: Bare protein binding from an interactome-perturbation framework for developmental-disorder missense variants. Uninformative for RPIA function. Reason: Generic protein binding from a large-scale interactome dataset; not informative of molecular function. Retained as an experimental IPI. Supporting Evidence: PMID:29892012 An interactome perturbation framework prioritizes damaging missense mutations for developmental disorders.
GO:0005515 protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	MARK AS OVER ANNOTATED	Summary: Bare protein binding from a large-scale study of interaction disruption by human genetic variants. Uninformative for RPIA's molecular function. Reason: Generic protein binding from a large-scale interactome dataset; not informative of molecular function. Retained as an experimental IPI. Supporting Evidence: PMID:31515488 Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Bare protein binding from the HuRI reference binary interactome map. Uninformative for RPIA's molecular function. Reason: Generic protein binding from a large-scale binary interactome screen; not informative of molecular function. Retained as an experimental IPI. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: Bare protein binding from a dual proteome-scale (BioPlex) affinity-capture interactome study. Uninformative for RPIA's molecular function. Reason: Generic protein binding from a large-scale interactome dataset; not informative of molecular function. Retained as an experimental IPI. Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
GO:0042802 identical protein binding	IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in...	KEEP AS NON CORE	Summary: Self-interaction (P49247 with P49247) detected in a high-throughput binary interactome map. Ribose-5-phosphate isomerase A enzymes are characteristically homodimeric, so self-association is biologically plausible, but this remains a screen-derived binding term rather than a core catalytic function. Reason: Homodimerisation is consistent with RpiA family architecture; kept as a non-core structural property rather than a core molecular function. Supporting Evidence: PMID:16189514 an initial version of a proteome-scale map
GO:0042802 identical protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	KEEP AS NON CORE	Summary: Self-interaction (P49247 with P49247) detected in the HuRI reference binary interactome map, consistent with the homodimeric architecture of RpiA-family isomerases. Reason: Homodimerisation is consistent with RpiA family architecture; kept as a non-core structural property rather than a core molecular function. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome
GO:0005829 cytosol	IEA GO_REF:0000120	ACCEPT	Summary: Cytosol is the correct subcellular location for this soluble PPP enzyme, consistent with the Reactome TAS cytosol annotations and the absence of any signal/transit peptide. Reason: Correct, specific cellular-component term for the active enzyme. Supporting Evidence: file:human/RPIA/RPIA-uniprot.txt Belongs to the ribose 5-phosphate isomerase family
GO:0006098 pentose-phosphate shunt	IEA GO_REF:0000120	ACCEPT	Summary: RPIA participates in the pentose phosphate pathway; this is the correct but broader parent of the non-oxidative-branch term. Reason: Correct process term; a more specific non-oxidative-branch annotation (GO:0009052) is also present and preferred for the core representation. Supporting Evidence: file:human/RPIA/RPIA-uniprot.txt pentose phosphate pathway; D-ribose
GO:0030246 carbohydrate binding	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic transfer (Ensembl Compara, from the rat ortholog) of a generic carbohydrate-binding term. RPIA binds its phosphorylated pentose substrate at the active site as part of catalysis; a standalone lectin-like carbohydrate-binding function is not supported and this term is uninformative/over-general. Reason: Over-general electronic mapping; substrate binding is already captured by the isomerase activity term and there is no evidence of a distinct carbohydrate-binding role. Supporting Evidence: file:human/RPIA/RPIA-uniprot.txt Reaction=aldehydo-D-ribose 5-phosphate = D-ribulose 5-phosphate
GO:0048029 monosaccharide binding	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic transfer (Ensembl Compara, from the rat ortholog) of a generic monosaccharide-binding term. As with carbohydrate binding, RPIA's binding of its phosphorylated pentose substrate is part of catalysis, not a distinct sugar-binding function. Reason: Over-general electronic mapping subsumed by the isomerase activity term; no evidence of a distinct monosaccharide-binding role. Supporting Evidence: file:human/RPIA/RPIA-uniprot.txt Reaction=aldehydo-D-ribose 5-phosphate = D-ribulose 5-phosphate
GO:0006098 pentose-phosphate shunt	TAS Reactome:R-HSA-71336	ACCEPT	Summary: Reactome traceable-author annotation placing RPIA in the pentose phosphate pathway. Correct; the broader parent of the non-oxidative-branch term. Reason: Correct process term supported by curated Reactome pathway knowledge. Supporting Evidence: file:human/RPIA/RPIA-uniprot.txt pentose phosphate pathway; D-ribose
GO:0004751 ribose-5-phosphate isomerase activity	EXP PMID:14988808 Ribose-5-phosphate isomerase deficiency: new inborn error in...	ACCEPT	Summary: Direct experimental evidence: RPI enzyme activity (EC 5.3.1.6) was measured and found deficient in patient fibroblasts, establishing the human protein as a functional ribose-5-phosphate isomerase. This is the definitive core molecular function. Reason: Experimentally verified catalytic activity of the human enzyme; assay of RPI activity in patient fibroblasts and disease-causing loss of function. Supporting Evidence: PMID:14988808 pentose-phosphate-pathway (PPP) enzymes, was demonstrated in fibroblasts
GO:0004751 ribose-5-phosphate isomerase activity	TAS Reactome:R-HSA-5660013	ACCEPT	Summary: Reactome traceable-author annotation of the core isomerase activity (in the context of a reaction whose defective form underlies RPIA deficiency). Correct core molecular function. Reason: Correct MF term from curated Reactome knowledge, concordant with experimental evidence. Supporting Evidence: file:human/RPIA/RPIA-uniprot.txt Reaction=aldehydo-D-ribose 5-phosphate = D-ribulose 5-phosphate
GO:0004751 ribose-5-phosphate isomerase activity	TAS Reactome:R-HSA-5660015	ACCEPT	Summary: Reactome traceable-author annotation of the core isomerase activity. Correct core molecular function. Reason: Correct MF term from curated Reactome knowledge, concordant with experimental evidence. Supporting Evidence: file:human/RPIA/RPIA-uniprot.txt Reaction=aldehydo-D-ribose 5-phosphate = D-ribulose 5-phosphate
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	MARK AS OVER ANNOTATED	Summary: RPIA appears in a large-scale high-throughput mitochondrial proteome (MitoCoP) dataset. RPIA is a soluble cytosolic housekeeping enzyme with no mitochondrial transit peptide, and its established site of action is the cytosol; the mitochondrial signal most likely reflects co-purification in the proteomic preparation rather than a genuine mitochondrial pool. Reason: Isolated HTP proteomics hit that conflicts with the well-established cytosolic localisation and the lack of any targeting sequence; treated as an over-annotation rather than removed, as it is an experimental (high-throughput) dataset whose full detail is not verifiable here. Supporting Evidence: PMID:34800366 Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context. file:human/RPIA/RPIA-uniprot.txt Belongs to the ribose 5-phosphate isomerase family
GO:0005829 cytosol	TAS Reactome:R-HSA-177784	ACCEPT	Summary: Reactome traceable-author localisation of RPIA to the cytosol, consistent with its role as a soluble PPP enzyme. Core location. Reason: Correct, specific cytosolic localisation from curated Reactome knowledge. Supporting Evidence: file:human/RPIA/RPIA-uniprot.txt Belongs to the ribose 5-phosphate isomerase family
GO:0005829 cytosol	TAS Reactome:R-HSA-71306	ACCEPT	Summary: Reactome traceable-author localisation of RPIA to the cytosol. Core location, concordant with the other cytosol annotations. Reason: Correct, specific cytosolic localisation from curated Reactome knowledge. Supporting Evidence: file:human/RPIA/RPIA-uniprot.txt Belongs to the ribose 5-phosphate isomerase family
GO:0005829 cytosol	TAS Reactome:R-HSA-5660013	ACCEPT	Summary: Reactome traceable-author localisation of RPIA to the cytosol. Core location. Reason: Correct, specific cytosolic localisation from curated Reactome knowledge. Supporting Evidence: file:human/RPIA/RPIA-uniprot.txt Belongs to the ribose 5-phosphate isomerase family
GO:0005829 cytosol	TAS Reactome:R-HSA-5660015	ACCEPT	Summary: Reactome traceable-author localisation of RPIA to the cytosol. Core location. Reason: Correct, specific cytosolic localisation from curated Reactome knowledge. Supporting Evidence: file:human/RPIA/RPIA-uniprot.txt Belongs to the ribose 5-phosphate isomerase family
GO:0004751 ribose-5-phosphate isomerase activity	NAS PMID:7758956 The ribose 5-phosphate isomerase-encoding gene is located im...	ACCEPT	Summary: Non-traceable author statement assigning ribose-5-phosphate isomerase activity, based on cloning of the mouse/human RPI gene and demonstration that a recombinant GST-RPI fusion has enzymatic activity. Supports the core molecular function. Reason: Correct core MF term; the underlying study cloned the RPI gene and showed a recombinant fusion protein is enzymatically active, corroborating the human enzyme's identity. Supporting Evidence: PMID:7758956 protein has enzymatic activity and that an anti-mRPI antibody detects a protein PMID:7758956 the RPI gene is evolutionarily conserved

Gene Description

Existing Annotations Review

Core Functions

Ribose-5-phosphate isomerase catalysing the reversible aldose-ketose interconversion of D-ribose-5-phosphate and D-ribulose-5-phosphate in the non-oxidative branch of the pentose phosphate pathway, in the cytosol.

References

Suggested Questions for Experts

Suggested Experiments

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Notes

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