RPE is human ribulose-5-phosphate 3-epimerase (EC 5.1.3.1), an enzyme of the non-oxidative branch of the pentose phosphate pathway. It catalyses the reversible epimerisation of D-ribulose 5-phosphate to D-xylulose 5-phosphate. Acting alongside ribose-5-phosphate isomerase (RPIA), it converts the ribulose-5-phosphate generated by the oxidative branch into the xylulose-5-phosphate and ribose-5-phosphate substrates used by transketolase and transaldolase, thereby linking the pentose phosphate pathway back to glycolysis and supplying pentoses for nucleotide biosynthesis. The enzyme is a cytosolic, metal-dependent (divalent cation, physiologically Fe2+) TIM-barrel epimerase that functions as a homodimer, with two aspartate residues carrying out the acid-base proton transfers of the epimerisation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004750 D-ribulose-phosphate 3-epimerase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Core molecular function of RPE: reversible epimerisation of D-ribulose 5-phosphate to D-xylulose 5-phosphate (EC 5.1.3.1). The phylogenetic (IBA) call is fully consistent with direct human biochemical/structural data. Reason: This is the defining activity of RPE, directly demonstrated for the human enzyme and conserved across the family. The same term is independently supported by IDA (PMID:20923965) and IEA (EC/RHEA mapping). Supporting Evidence: PMID:20923965 RPE functions in the PPP, catalyzing file:human/RPE/RPE-uniprot.txt Catalyzes the reversible epimerization of D-ribulose 5- |
| GO:0009052 pentose-phosphate shunt, non-oxidative branch | IBA GO_REF:0000033 | ACCEPT | Summary: RPE acts in the non-oxidative branch of the pentose phosphate pathway, the most specific and accurate biological-process term for this enzyme. Reason: RPE converts ribulose-5-phosphate (from the oxidative branch) to xylulose-5-phosphate, one of the substrates for transketolase in the non-oxidative branch. This IBA term is the precise, correct process term. Supporting Evidence: PMID:20923965 RPE functions in the PPP, catalyzing |
| GO:0005975 carbohydrate metabolic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Broad grouping term for carbohydrate metabolism. Correct but far less specific than the pentose-phosphate-shunt terms also annotated to RPE. Reason: A high-level ancestor of the pentose phosphate pathway terms. Not wrong, but non-informative relative to GO:0009052; retained as non-core context. Supporting Evidence: PMID:20923965 RPE functions in the PPP, catalyzing |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: RPE is a soluble cytosolic enzyme; the pentose phosphate pathway operates in the cytosol. Correct subcellular localisation. Reason: Consistent across IBA and TAS (Reactome) evidence and with the enzyme's role in cytosolic carbohydrate metabolism. Supporting Evidence: Reactome:R-HSA-71303 Cytosolic ribulose-5-phosphate-3-epimerase (RPE) |
| GO:0046872 metal ion binding | IBA GO_REF:0000033 | ACCEPT | Summary: RPE binds one divalent metal cation per subunit (physiologically Fe2+), required for catalysis. Metal-ion binding is an intrinsic part of the active site. Reason: Supported by human structural/biochemical data showing an octahedrally coordinated Fe2+ in the active site and by the UniProt cofactor annotation (Fe2+, Mn2+, Zn2+, Co2+). Independently annotated by IDA. Supporting Evidence: PMID:20923965 octahedrally coordinated Fe(2+) ion file:human/RPE/RPE-uniprot.txt Binds 1 divalent metal cation per subunit. Active with Fe(2+), and |
| GO:0004750 D-ribulose-phosphate 3-epimerase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic assignment of the core epimerase activity via EC 5.1.3.1 / RHEA:13677 / InterPro. Agrees with experimental and phylogenetic evidence. Reason: The EC 5.1.3.1 and RHEA:13677 mappings correctly capture the demonstrated human enzymatic activity. Duplicate of the IDA/IBA GO:0004750 annotations. Supporting Evidence: file:human/RPE/RPE-uniprot.txt Reaction=D-ribulose 5-phosphate = D-xylulose 5-phosphate; |
| GO:0005975 carbohydrate metabolic process | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro2GO electronic assignment of the broad carbohydrate-metabolism term. Correct but non-specific. Reason: A high-level ancestor of the pentose-phosphate-shunt terms; retained as non-core context, superseded in specificity by GO:0009052 / GO:0006098. Supporting Evidence: file:human/RPE/RPE-uniprot.txt Belongs to the ribulose-phosphate 3-epimerase family. |
| GO:0006098 pentose-phosphate shunt | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic assignment placing RPE in the pentose phosphate pathway. Correct; slightly less specific than the non-oxidative-branch term. Reason: RPE is a bona fide PPP enzyme. This parent-level pathway term is accurate and independently supported by IDA (PMID:20923965). Supporting Evidence: PMID:20923965 RPE functions in the PPP, catalyzing |
| GO:0016857 racemase and epimerase activity, acting on carbohydrates and derivatives | IEA GO_REF:0000002 | MODIFY | Summary: Grouping term for carbohydrate-acting racemases/epimerases. RPE is a carbohydrate epimerase, but the specific child term GO:0004750 is available and experimentally supported. Reason: GO:0016857 is a direct ancestor of the specific, demonstrated activity GO:0004750 (D-ribulose-phosphate 3-epimerase activity). The more specific term should be used for this well-characterised enzyme. Proposed replacements: D-ribulose-phosphate 3-epimerase activity Supporting Evidence: file:human/RPE/RPE-uniprot.txt Reaction=D-ribulose 5-phosphate = D-xylulose 5-phosphate; |
| 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 a high-throughput binary interactome screen (HuRI), reporting a heterotypic interaction with PLEKHF2 (Q9H8W4). The interaction is corroborated by UniProt (NbExp=3) but the term is uninformative about molecular function. Reason: Per curation guidelines, bare GO:0005515 conveys no functional information. The underlying PPI (RPE-PLEKHF2) is real but its biological significance for RPE is unknown; the annotation should not be treated as a molecular function of RPE. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions file:human/RPE/RPE-uniprot.txt Q96AT9; Q9H8W4: PLEKHF2; |
| 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-self interaction (Q96AT9-Q96AT9) detected in a large-scale yeast-two-hybrid interactome screen, reflecting the RPE homodimer. Reason: Captures the biologically real homodimer, but the informative term for the quaternary structure is GO:0042803 (protein homodimerization activity), which is separately annotated. This identical-protein-binding IPI is a lower-value duplicate; retained as non-core. Supporting Evidence: file:human/RPE/RPE-uniprot.txt SUBUNIT: Homodimer. |
| GO:0042802 identical protein binding | IPI PMID:20923965 Conversion of D-ribulose 5-phosphate to D-xylulose 5-phospha... | KEEP AS NON CORE | Summary: Self-interaction supported by the human structural study, which crystallised RPE as a dimer. Reflects the physiological homodimer. Reason: Real homodimer self-interaction, better represented by GO:0042803 (protein homodimerization activity, also annotated from this same paper). Retained as non-core. Supporting Evidence: file:human/RPE/RPE-uniprot.txt SUBUNIT: Homodimer. |
| GO:0042802 identical protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Self-self interaction detected in a proteome-scale binary interactome map, consistent with the RPE homodimer. Reason: Duplicate homodimer self-interaction; the informative term is GO:0042803. Retained as non-core. Supporting Evidence: PMID:25416956 a systematic map of ?14,000 high-quality human file:human/RPE/RPE-uniprot.txt SUBUNIT: Homodimer. |
| GO:0042802 identical protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Self-self interaction detected in the HuRI binary interactome, consistent with the RPE homodimer. Reason: Duplicate homodimer self-interaction; the informative term for the quaternary structure is GO:0042803. Retained as non-core. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions file:human/RPE/RPE-uniprot.txt SUBUNIT: Homodimer. |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | MARK AS OVER ANNOTATED | Summary: RPE was detected in a shotgun proteomic survey of exosomes from expressed prostatic secretions (~900 proteins identified). This is a bulk proteomic detection, not evidence of a functional extracellular localisation for this cytosolic enzyme. Reason: Cytosolic metabolic enzymes are frequently reported in exosome/proteomic datasets as passengers. RPE's established localisation and function are cytosolic; the exosome detection does not indicate a biological role for RPE in the extracellular space. Supporting Evidence: PMID:23533145 exosome samples, ~900 proteins were detected |
| GO:0005829 cytosol | TAS Reactome:R-HSA-199803 | ACCEPT | Summary: Reactome (author statement) localises RPE to the cytosol, where it catalyses the RU5P<->XY5P interconversion. Reason: Consistent with the IBA cytosol annotation and with the enzyme's role in the cytosolic pentose phosphate pathway. Supporting Evidence: Reactome:R-HSA-199803 Cytosolic ribulose-5-phosphate-3-epimerase (RPE) |
| GO:0005829 cytosol | TAS Reactome:R-HSA-71303 | ACCEPT | Summary: Reactome (author statement) localises RPE to the cytosol for the RU5P->XY5P reaction, using Fe2+ as cofactor. Reason: Consistent with all other cytosol annotations and with the cytosolic pentose phosphate pathway. Supporting Evidence: Reactome:R-HSA-71303 Cytosolic ribulose-5-phosphate-3-epimerase (RPE) |
| GO:0004750 D-ribulose-phosphate 3-epimerase activity | IDA PMID:20923965 Conversion of D-ribulose 5-phosphate to D-xylulose 5-phospha... | ACCEPT | Summary: Direct experimental demonstration of the epimerase activity on the human enzyme, including structures with substrate/product and mutagenesis of catalytic residues. This is the strongest evidence for the core function. Reason: Liang et al. determined RPE structures bound to D-ribulose 5-phosphate and D-xylulose 5-phosphate and showed by mutagenesis (e.g. S10A) that specific residues are required for activity, directly establishing EC 5.1.3.1. Supporting Evidence: PMID:20923965 Ser-10 to alanine almost abolished the enzymatic activity PMID:20923965 RPE functions in the PPP, catalyzing |
| GO:0005975 carbohydrate metabolic process | IDA PMID:20923965 Conversion of D-ribulose 5-phosphate to D-xylulose 5-phospha... | KEEP AS NON CORE | Summary: Broad carbohydrate-metabolism term supported by the direct enzymatic study. Correct but non-specific relative to the pentose-phosphate terms. Reason: High-level ancestor of the pentose phosphate pathway process terms; retained as non-core context. Supporting Evidence: PMID:20923965 RPE functions in the PPP, catalyzing |
| GO:0006098 pentose-phosphate shunt | IDA PMID:20923965 Conversion of D-ribulose 5-phosphate to D-xylulose 5-phospha... | ACCEPT | Summary: Direct evidence places RPE in the pentose phosphate pathway, catalysing a key non-oxidative-branch step and contributing to the antioxidant response. Reason: Experimentally supported; RPE is an integral PPP enzyme. Complements the more specific non-oxidative-branch IBA term (GO:0009052). Supporting Evidence: PMID:20923965 an important enzyme for cellular response against oxidative stress |
| GO:0042803 protein homodimerization activity | IPI PMID:20923965 Conversion of D-ribulose 5-phosphate to D-xylulose 5-phospha... | ACCEPT | Summary: RPE functions as a homodimer; the human structural study crystallised the enzyme as a dimer and UniProt records the subunit structure as a homodimer. This is the informative molecular-function term for RPE self-association. Reason: The homodimer is the biologically active form of RPE (also stated by Reactome). This is the correct, specific representation of the self-interactions captured more vaguely by the GO:0042802 IPIs. Supporting Evidence: file:human/RPE/RPE-uniprot.txt SUBUNIT: Homodimer. |
| GO:0046872 metal ion binding | IDA PMID:20923965 Conversion of D-ribulose 5-phosphate to D-xylulose 5-phospha... | ACCEPT | Summary: Direct structural demonstration of a catalytic divalent metal ion (Fe2+) in the active site of human RPE. Reason: Liang et al. resolved an octahedrally coordinated Fe2+ buried in the active site and showed the enzyme uses Fe2+ for catalysis; UniProt records binding of one divalent cation per subunit. Supporting Evidence: PMID:20923965 (hRPE) uses Fe(2+) for catalysis PMID:20923965 octahedrally coordinated Fe(2+) ion |
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Download this section (compressed HTML)Q: Does the RPE-PLEKHF2 (Q9H8W4) interaction reported in the binary interactome screens have any physiological relevance, or is it a screening artefact?
Q: Are any of the alternatively spliced isoforms (e.g. those missing the N-terminal region or catalytic residues) catalytically active or regulatory?
Experiment: Metabolic flux analysis (e.g. 13C tracing through the non-oxidative PPP) in RPE-knockdown cells to quantify RPE's contribution to xylulose-5-phosphate and ribose-5-phosphate pools and to NADPH-dependent oxidative-stress resistance.
Experiment: Co-immunoprecipitation and orthogonal validation of the RPE-PLEKHF2 interaction in relevant cell types to test its physiological significance.
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