PRPS1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004749 ribose phosphate diphosphokinase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) annotation to the defining catalytic activity of PRPS1, the transfer of a diphosphoryl group from ATP to ribose-5-phosphate to make PRPP. This is the core molecular function and is corroborated by direct experimental evidence for the human enzyme. Reason: Correct and appropriately specific molecular function term for the PRPS family; supported experimentally in human (PMID:16939420, PMID:7593598). Supporting Evidence: file:human/PRPS1/PRPS1-uniprot.txt Catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP) PMID:16939420 catalyses synthesis of PRPP from
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic annotation placing PRPS1 activity in the cytoplasm, consistent with the enzyme being a soluble cytosolic housekeeping metabolic enzyme. Reason: Correct localization; the more specific cytosol annotation is captured separately (GO:0005829). Retained as accurate but general. Supporting Evidence: file:human/PRPS1/PRPS1-uniprot.txt Belongs to the ribose-phosphate pyrophosphokinase family.
GO:0006164 purine nucleotide biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic annotation to purine nucleotide biosynthesis. PRPP produced by PRPS1 is the activated ribose donor for both de novo purine synthesis and purine salvage (HGPRT/APRT), so the process is directly downstream of PRPS1 catalysis. Reason: Well supported; loss-of-function PRPS1 variants impair purine biosynthesis in patients (PMID:17701896). Supporting Evidence: PMID:17701896 likely result in impaired purine biosynthesis
GO:0006015 5-phosphoribose 1-diphosphate biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic annotation to PRPP biosynthesis, the specific pathway step catalyzed by PRPS1 (route I, step 1/1). This is the most precise biological-process term for the enzyme's direct action. Reason: Precisely matches the reaction catalyzed; strongly supported experimentally and by pathway assignment. Supporting Evidence: file:human/PRPS1/PRPS1-uniprot.txt PATHWAY: Metabolic intermediate biosynthesis; 5-phospho-alpha-D-ribose
GO:0002189 ribose phosphate diphosphokinase complex	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic annotation placing PRPS1 in the PRPP synthetase complex. PRPS1 functions as a homodimer that oligomerizes (probably a hexamer of three dimers) and also associates with regulatory subunits (PRPSAP1/PRPSAP2), consistent with this complex assignment. Reason: Supported by the demonstrated oligomeric assembly of the human enzyme. Supporting Evidence: file:human/PRPS1/PRPS1-uniprot.txt SUBUNIT: Homodimer. The active form is probably a hexamer composed of 3
GO:0000287 magnesium ion binding	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based electronic annotation to magnesium ion binding. PRPS1 requires Mg2+ as cofactor; the crystal structure resolves metal ion coordination at the active site and UniProt annotates Mg2+-binding residues. Reason: Correct; Mg2+ is a required cofactor and binding residues are annotated (BINDING 130/139/143). Supporting Evidence: file:human/PRPS1/PRPS1-uniprot.txt Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
GO:0004749 ribose phosphate diphosphokinase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation of the core catalytic activity via InterPro/EC 2.7.6.1/RHEA:15609 mapping. Redundant with the experimentally supported MF annotation. Reason: Correct EC/RHEA-based mapping to the enzyme's defining activity. Supporting Evidence: file:human/PRPS1/PRPS1-uniprot.txt D-ribose 5-phosphate + ATP = 5-phospho-alpha-D-ribose 1-
GO:0009156 ribonucleoside monophosphate biosynthetic process	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based annotation to ribonucleoside monophosphate biosynthesis. PRPP supplied by PRPS1 is the ribose-phosphate donor for the pathways generating purine and pyrimidine (ribo)nucleoside monophosphates. Reason: Consistent with the enzyme's role upstream of NMP synthesis; a broader but correct grouping alongside GO:0006164/GO:0006221. Supporting Evidence: PMID:16939420 important metabolite essential for
GO:0009165 nucleotide biosynthetic process	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based annotation to the general nucleotide biosynthetic process. Correct but general; PRPP is the shared precursor for purine, pyrimidine, and pyridine nucleotide synthesis. Reason: Accurate high-level grouping term; more specific children (GO:0006015, GO:0006164) are also present. Supporting Evidence: PMID:16939420 important metabolite essential for
GO:0005515 protein binding	IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in...	MARK AS OVER ANNOTATED	Summary: Generic protein-binding annotation from a proteome-scale two-hybrid interactome screen. The specific, biologically meaningful self-association is captured by GO:0042802/GO:0042803. Reason: Bare "protein binding" is uninformative about molecular function and derives from high-throughput interactome mapping; per curation guidance a more specific MF term should be used instead.
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	MARK AS OVER ANNOTATED	Summary: Generic protein-binding annotation from a proteome-scale interactome map. Reason: Uninformative bare "protein binding" from high-throughput mapping; more specific self-association terms already capture the meaningful function.
GO:0005515 protein binding	IPI PMID:25910212 Widespread macromolecular interaction perturbations in human...	MARK AS OVER ANNOTATED	Summary: Generic protein-binding annotation from a large-scale interactome perturbation study. Reason: Uninformative bare "protein binding" from high-throughput mapping.
GO:0005515 protein binding	IPI PMID:26496610 A human interactome in three quantitative dimensions organiz...	MARK AS OVER ANNOTATED	Summary: Generic protein-binding annotation from a quantitative interactome study. Reason: Uninformative bare "protein binding" from high-throughput mapping.
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	MARK AS OVER ANNOTATED	Summary: Generic protein-binding annotation from an interactome-architecture study. Reason: Uninformative bare "protein binding" from high-throughput mapping.
GO:0005515 protein binding	IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m...	MARK AS OVER ANNOTATED	Summary: Generic protein-binding annotation from an interactome-perturbation framework. Reason: Uninformative bare "protein binding" from high-throughput mapping.
GO:0005515 protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	MARK AS OVER ANNOTATED	Summary: Generic protein-binding annotation from a population-scale variant interactome study. Reason: Uninformative bare "protein binding" from high-throughput mapping.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Generic protein-binding annotation from a reference binary interactome map. Reason: Uninformative bare "protein binding" from high-throughput mapping; the meaningful PRPS1 self-association is captured by GO:0042802.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	MARK AS OVER ANNOTATED	Summary: Generic protein-binding annotation from a neurodegenerative-disease interactome screen reporting dozens of candidate partners for PRPS1. These are unvalidated high-throughput hits and do not define a specific molecular function. Reason: Uninformative bare "protein binding" from a large high-throughput screen; no specific functional partnership is established.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: Generic protein-binding annotation from a proteome-scale cell-specific interactome study. Reason: Uninformative bare "protein binding" from high-throughput mapping.
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	MARK AS OVER ANNOTATED	Summary: Generic protein-binding annotation from a multimodal cell-map interactome study. Reason: Uninformative bare "protein binding" from high-throughput mapping.
GO:0042802 identical protein binding	IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in...	ACCEPT	Summary: Self-association (PRPS1-PRPS1) detected by interactome mapping. This is biologically meaningful because PRPS1 functions as a homodimer that further oligomerizes. Reason: Consistent with the well-established homo-oligomeric assembly of the enzyme (crystal structure PMID:16939420). Supporting Evidence: file:human/PRPS1/PRPS1-uniprot.txt SUBUNIT: Homodimer. The active form is probably a hexamer composed of 3
GO:0042802 identical protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	ACCEPT	Summary: PRPS1 self-association detected in a proteome-scale interactome map, consistent with the enzyme's homo-oligomeric quaternary structure. Reason: Meaningful self-interaction supporting the homodimer/hexamer assembly. Supporting Evidence: file:human/PRPS1/PRPS1-uniprot.txt SUBUNIT: Homodimer. The active form is probably a hexamer composed of 3
GO:0042802 identical protein binding	IPI PMID:25502805 A massively parallel pipeline to clone DNA variants and exam...	ACCEPT	Summary: PRPS1 self-association reported in a parallel clone/variant molecular-phenotyping study, consistent with the enzyme's homo-oligomeric assembly. Reason: Consistent with the demonstrated homodimer/hexamer quaternary structure. Supporting Evidence: file:human/PRPS1/PRPS1-uniprot.txt SUBUNIT: Homodimer. The active form is probably a hexamer composed of 3
GO:0042802 identical protein binding	IPI PMID:25910212 Widespread macromolecular interaction perturbations in human...	ACCEPT	Summary: PRPS1 self-association reported in an interactome-perturbation study, consistent with homo-oligomerization. Reason: Consistent with the demonstrated homodimer/hexamer quaternary structure. Supporting Evidence: file:human/PRPS1/PRPS1-uniprot.txt SUBUNIT: Homodimer. The active form is probably a hexamer composed of 3
GO:0042802 identical protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	ACCEPT	Summary: PRPS1 self-association reported in a population-scale variant interactome study, consistent with homo-oligomerization. Reason: Consistent with the demonstrated homodimer/hexamer quaternary structure. Supporting Evidence: file:human/PRPS1/PRPS1-uniprot.txt SUBUNIT: Homodimer. The active form is probably a hexamer composed of 3
GO:0042802 identical protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	ACCEPT	Summary: PRPS1 self-association reported in a reference binary interactome map, consistent with homo-oligomerization. Reason: Consistent with the demonstrated homodimer/hexamer quaternary structure. Supporting Evidence: file:human/PRPS1/PRPS1-uniprot.txt SUBUNIT: Homodimer. The active form is probably a hexamer composed of 3
GO:0008584 male gonad development	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic annotation transferred from a rat ortholog via Ensembl Compara. There is no human evidence that PRPS1 has a specific role in testis development; PRPS1 is a ubiquitously expressed housekeeping metabolic enzyme. Reason: Single-organism electronic transfer of a tissue-specific developmental process to a ubiquitous housekeeping enzyme; not a demonstrated PRPS1 function in human and likely reflects the enzyme's general requirement in proliferating tissue rather than a specific developmental role.
GO:0006164 purine nucleotide biosynthetic process	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity annotation (from PRPS2) to purine nucleotide biosynthesis, duplicating the IBA and IMP annotations to the same process. Reason: Correct; PRPP is the ribose-phosphate donor for de novo and salvage purine nucleotide synthesis. Supporting Evidence: PMID:17701896 likely result in impaired purine biosynthesis
GO:0034214 protein hexamerization	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity annotation (from PRPS2) to protein hexamerization. The active human enzyme is proposed to be a hexamer assembled from three homodimers, consistent with this annotation. Reason: Consistent with the demonstrated oligomeric assembly of PRPS1. Supporting Evidence: file:human/PRPS1/PRPS1-uniprot.txt SUBUNIT: Homodimer. The active form is probably a hexamer composed of 3
GO:0006015 5-phosphoribose 1-diphosphate biosynthetic process	IEA GO_REF:0000041	ACCEPT	Summary: UniPathway-based electronic annotation to PRPP biosynthesis, the direct pathway step catalyzed by PRPS1. Redundant with the IBA annotation to the same term. Reason: Precisely matches the enzyme's pathway role (UPA00087, route I step 1/1). Supporting Evidence: file:human/PRPS1/PRPS1-uniprot.txt PATHWAY: Metabolic intermediate biosynthesis; 5-phospho-alpha-D-ribose
GO:0004749 ribose phosphate diphosphokinase activity	EXP PMID:7593598 The genetic and functional basis of purine nucleotide feedba...	ACCEPT	Summary: Experimental (kinetic) characterization of recombinant human PRS1, including wild-type and superactivity variants, confirming PRPP synthetase activity and its allosteric regulation by inorganic phosphate and purine nucleotides. Reason: Direct experimental support for the core catalytic activity in human, with measured kinetic parameters (KM 23 uM ATP, 54 uM R5P). Supporting Evidence: PMID:7593598 Kinetic analysis of recombinant mutant PRS1s file:human/PRPS1/PRPS1-uniprot.txt KM=23 uM for ATP
GO:0005829 cytosol	TAS Reactome:R-HSA-111215	ACCEPT	Summary: Reactome traceable-author annotation placing PRPS1 catalysis in the cytosol, the compartment where PRPP synthesis occurs. Reason: Correct and specific subcellular localization for this soluble cytosolic enzyme. Supporting Evidence: file:human/PRPS1/PRPS1-uniprot.txt Belongs to the ribose-phosphate pyrophosphokinase family.
GO:0005829 cytosol	TAS Reactome:R-HSA-73580	ACCEPT	Summary: Reactome traceable-author annotation placing the PRPS dimer-catalyzed reaction in the cytosol. Reason: Correct and specific cytosolic localization; duplicate of the other Reactome cytosol annotation. Supporting Evidence: file:human/PRPS1/PRPS1-uniprot.txt Belongs to the ribose-phosphate pyrophosphokinase family.
GO:0004749 ribose phosphate diphosphokinase activity	IMP PMID:12847698 Phosphoribosylpyrophosphate synthetase overactivity as a cau...	ACCEPT	Summary: A PRPS1 mutation causing enzyme overactivity underlies uric acid overproduction in a patient, providing mutant-phenotype support for PRPS1 possessing PRPP synthetase activity. Reason: Mutant-phenotype evidence linking the PRPS1 gene product to the catalytic activity via disordered allosteric regulation. Supporting Evidence: PMID:12847698 defective allosteric regulation of PRS activity
GO:0004749 ribose phosphate diphosphokinase activity	IMP PMID:17701896 Arts syndrome is caused by loss-of-function mutations in PRP...	ACCEPT	Summary: Loss-of-function PRPS1 missense mutations (L152P, Q133P) reduce PRPP synthetase activity in patient erythrocytes and fibroblasts, demonstrating the gene product carries this catalytic activity. Reason: Mutant-phenotype evidence in human patient cells directly supports the core catalytic activity. Supporting Evidence: PMID:17701896 result in a loss of phosphoribosyl pyrophosphate synthetase 1 activity
GO:0006144 purine nucleobase metabolic process	IMP PMID:8253776 Human X-linked phosphoribosylpyrophosphate synthetase supera...	ACCEPT	Summary: PRPS1 superactivity variants perturb purine metabolism, causing uric acid overproduction. PRPP supply by PRPS1 governs flux through purine nucleobase salvage and de novo synthesis. Reason: Correct, if broad; PRPS1 is central to purine nucleobase/nucleotide metabolism and gain-of-function variants dysregulate it. Supporting Evidence: PMID:8253776 X chromosome-linked disorder of purine metabolism
GO:0006164 purine nucleotide biosynthetic process	IMP PMID:12847698 Phosphoribosylpyrophosphate synthetase overactivity as a cau...	ACCEPT	Summary: A gain-of-function PRPS1 variant accelerates purine nucleotide production, providing mutant-phenotype evidence that PRPS1 participates in purine nucleotide biosynthesis. Reason: Directly supported; disease variant increases purine nucleotide and uric acid production. Supporting Evidence: PMID:12847698 accelerated purine nucleotide and uric acid production
GO:0006221 pyrimidine nucleotide biosynthetic process	NAS PMID:17701896 Arts syndrome is caused by loss-of-function mutations in PRP...	ACCEPT	Summary: Author statement that PRPS1 is critical for nucleotide biosynthesis. PRPP is the obligatory ribose-phosphate substrate used by orotate phosphoribosyltransferase in de novo pyrimidine synthesis, so PRPS1 supplies pyrimidine as well as purine pathways. Reason: Biologically correct; PRPP feeds de novo pyrimidine nucleotide synthesis, making PRPS1 an upstream contributor to this process. Supporting Evidence: PMID:16939420 important metabolite essential for
GO:0007399 nervous system development	IMP PMID:17701900 Mutations in PRPS1, which encodes the phosphoribosyl pyropho...	KEEP AS NON CORE	Summary: Loss-of-function PRPS1 mutations cause CMTX5, a hereditary peripheral neuropathy with hearing loss and optic neuropathy. This reflects a pleiotropic disease consequence of reduced nucleotide supply in the nervous system rather than a neuron-specific developmental function of the housekeeping enzyme. Reason: The neuropathy phenotype is a downstream, tissue-vulnerability consequence of impaired PRPP/nucleotide metabolism, not the enzyme's core molecular role; retain as a non-core, disease-associated process. Supporting Evidence: PMID:17701900 The enzyme mediates the biochemical step critical
GO:0007399 nervous system development	IMP PMID:8253776 Human X-linked phosphoribosylpyrophosphate synthetase supera...	KEEP AS NON CORE	Summary: PRPS1 superactivity is associated in some families with neurodevelopmental impairment, again reflecting a systemic metabolic effect on the nervous system rather than a dedicated developmental function. Reason: Pleiotropic disease association; retain as non-core rather than a core function of this ubiquitous metabolic enzyme. Supporting Evidence: PMID:8253776 in some families, neurodevelopmental impairment
GO:0034418 urate biosynthetic process	IMP PMID:12847698 Phosphoribosylpyrophosphate synthetase overactivity as a cau...	KEEP AS NON CORE	Summary: Gain-of-function PRPS1 overactivity drives uric acid overproduction. Urate is a distal catabolic product of the purine nucleotides whose synthesis PRPS1 accelerates, so this is a downstream metabolic consequence rather than a direct enzymatic role. Reason: Biologically valid as a disease phenotype but several steps removed from the PRPP synthetase reaction; retain as non-core. Supporting Evidence: PMID:12847698 uric acid overproduction
GO:0046101 hypoxanthine biosynthetic process	IMP PMID:17701896 Arts syndrome is caused by loss-of-function mutations in PRP...	KEEP AS NON CORE	Summary: In PRPS1 loss-of-function (Arts syndrome) hypoxanthine is undetectable in urine, indicating altered purine catabolite levels. This reflects downstream consequences of reduced PRPP/purine metabolism rather than a direct PRPS1 catalytic role in hypoxanthine synthesis. Reason: Downstream metabolic consequence of the enzyme's activity, not its core molecular function; retain as non-core. Supporting Evidence: PMID:17701896 undetectable hypoxanthine in urine
GO:0004749 ribose phosphate diphosphokinase activity	IDA PMID:16939420 Crystal structure of human phosphoribosylpyrophosphate synth...	ACCEPT	Summary: Direct assay of recombinant human PRS1, whose crystal structure was solved in complex with ATP/AMP and metal ion, confirming the PRPP synthetase catalytic activity and defining the active and allosteric sites. Reason: Direct experimental evidence for the core catalytic activity of the human enzyme. Supporting Evidence: PMID:16939420 PRS (PRPP synthetase) catalyses synthesis of PRPP from
GO:0004749 ribose phosphate diphosphokinase activity	IDA PMID:17701900 Mutations in PRPS1, which encodes the phosphoribosyl pyropho...	ACCEPT	Summary: Direct measurement showing decreased PRPP synthetase enzyme activity in cells from CMTX5 patients carrying the M115T variant, confirming that PRPS1 carries this catalytic activity. Reason: Direct experimental support for the core catalytic activity, including reduced activity for a disease variant. Supporting Evidence: PMID:17701900 showed decreased enzyme activity in patients with M115T
GO:0005524 ATP binding	IDA PMID:16939420 Crystal structure of human phosphoribosylpyrophosphate synth...	ACCEPT	Summary: The crystal structure of human PRS1 was solved in complex with the AMP moiety of ATP bound at the ATP-binding site, directly demonstrating ATP binding. Reason: Direct structural evidence for ATP binding, a required substrate-binding activity for the enzyme. Supporting Evidence: PMID:16939420 The AMP moiety of ATP binds at the ATP-binding site
GO:0042803 protein homodimerization activity	IPI PMID:16939420 Crystal structure of human phosphoribosylpyrophosphate synth...	ACCEPT	Summary: The crystal structure demonstrates that human PRS1 forms a homodimer that is the building block of the higher-order oligomer, directly supporting homodimerization activity. Reason: Structurally demonstrated homodimerization; the homodimer is the functional building block of the active hexamer. Supporting Evidence: file:human/PRPS1/PRPS1-uniprot.txt SUBUNIT: Homodimer. The active form is probably a hexamer composed of 3

Gene Description

Existing Annotations Review

Core Functions

Catalyzes the Mg2+-dependent transfer of the beta,gamma-diphosphoryl group of ATP to D-ribose 5-phosphate, producing 5-phospho-alpha-D-ribose 1-diphosphate (PRPP) plus AMP, the committed step that generates the activated ribose-phosphate donor for nucleotide biosynthesis and salvage.

Provides PRPP as the essential ribose-phosphate precursor for de novo and salvage purine nucleotide biosynthesis, bridging the pentose phosphate pathway to purine metabolism.

References

📚 Additional Documentation

Notes

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