HPRT1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004422 hypoxanthine phosphoribosyltransferase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred core catalytic activity, converting hypoxanthine plus PRPP to IMP. This is a defining, experimentally established function of HPRT1. Reason: This is one of the two core molecular functions of HPRT1, supported by direct experimental catalytic-activity data and structural studies, and consistent across IBA, IEA and IDA evidence. EC 2.4.2.8. Supporting Evidence: PMID:9521733 Hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) catalyzes the reversible formation of IMP and GMP from their respective bases hypoxanthine (Hx) and guanine (Gua) and the phosphoribosyl donor 5-phosphoribosyl-1-pyrophosphate (PRPP).
GO:0046100 hypoxanthine metabolic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred involvement in hypoxanthine metabolism, reflecting the enzyme's use of hypoxanthine as a substrate to form IMP. Reason: HPRT1 directly consumes hypoxanthine in the salvage reaction, so involvement in hypoxanthine metabolic process is correct, though the more specific salvage terms (hypoxanthine salvage, IMP salvage) better capture the physiological role. Supporting Evidence: PMID:9521733 catalyzes the reversible formation of IMP and GMP from their respective bases hypoxanthine (Hx) and guanine (Gua)
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred cytosolic localization, consistent with the soluble cytoplasmic nature of the salvage enzyme. Reason: HPRT1 is a soluble cytosolic enzyme (UniProt subcellular location cytoplasm), confirmed by IDA (HPA) and multiple orthogonal lines of evidence. Supporting Evidence: file:human/HPRT1/HPRT1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm.
GO:0032263 GMP salvage	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred role in GMP salvage, matching the guanine to GMP reaction catalyzed by HPRT1. Reason: The guanine phosphoribosyltransferase reaction produces GMP directly from the salvaged base guanine, so involvement in GMP salvage is a core pathway role. Supporting Evidence: file:human/HPRT1/HPRT1-uniprot.txt Reaction=GMP + diphosphate = guanine + 5-phospho-alpha-D-ribose 1-
GO:0006178 guanine salvage	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred role in guanine salvage, reflecting HPRT1 recycling free guanine into GMP. Reason: HPRT1 salvages guanine by phosphoribosylation to GMP; this is a core pathway role also supported by direct experimental evidence. Supporting Evidence: PMID:9521733 catalyzes the reversible formation of IMP and GMP from their respective bases hypoxanthine (Hx) and guanine (Gua)
GO:0032264 IMP salvage	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred role in IMP salvage, matching the hypoxanthine to IMP reaction. Reason: The hypoxanthine phosphoribosyltransferase reaction produces IMP from the salvaged base hypoxanthine; UniProt records IMP biosynthesis via the salvage pathway as step 1/1 for this enzyme. Supporting Evidence: file:human/HPRT1/HPRT1-uniprot.txt Purine metabolism; IMP biosynthesis via salvage pathway
GO:0000287 magnesium ion binding	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred magnesium binding, consistent with the Mg2+ requirement of the phosphoribosyltransfer reaction. Reason: HPRT1 binds two Mg2+ ions per subunit which are essential for catalysis; this is directly supported by structural studies (transition-state analog complex with Mg2+-pyrophosphate) and UniProt cofactor annotation. Supporting Evidence: file:human/HPRT1/HPRT1-uniprot.txt Note=Binds 2 magnesium ions per subunit. PMID:10360366 Two Mg2+ ions sandwich the pyrophosphate and contact both hydroxyls of the ribosyl analog.
GO:0004422 hypoxanthine phosphoribosyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assertion of hypoxanthine phosphoribosyltransferase activity from combined automated methods, redundant with the experimental IDA/IBA annotations. Reason: Correct core catalytic activity; the IEA mapping (ARBA/InterPro/RHEA:17973) agrees with experimental evidence. Supporting Evidence: file:human/HPRT1/HPRT1-uniprot.txt EC=2.4.2.8 {ECO:0000269\|PubMed:10338013, ECO:0000269\|PubMed:19527031};
GO:0005737 cytoplasm	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assertion of cytoplasmic localization, consistent with the cytosolic nature of the enzyme. Reason: Correct localization; cytoplasm is the UniProt SubCell term for this soluble enzyme, redundant with the more specific cytosol annotations. Supporting Evidence: file:human/HPRT1/HPRT1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm.
GO:0006166 purine ribonucleoside salvage	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO electronic assertion of purine ribonucleoside salvage, capturing the general salvage-pathway role of HPRT1. Reason: HPRT1 is the central 6-oxopurine salvage enzyme; the InterPro HGPRT signature (IPR005904) correctly maps to purine salvage. This is a good general parent for the more specific salvage terms. Supporting Evidence: file:human/HPRT1/HPRT1-uniprot.txt Plays a central role in the generation of purine nucleotides through the purine salvage pathway.
GO:0046100 hypoxanthine metabolic process	IEA GO_REF:0000117	ACCEPT	Summary: ARBA electronic assertion of hypoxanthine metabolic process, redundant with the IBA and IMP annotations to the same term. Reason: Correct; hypoxanthine is a direct substrate. The more specific hypoxanthine salvage term better captures the role. Supporting Evidence: PMID:9521733 catalyzes the reversible formation of IMP and GMP from their respective bases hypoxanthine (Hx) and guanine (Gua)
GO:0005515 protein binding	IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in...	MARK AS OVER ANNOTATED	Summary: High-throughput yeast two-hybrid interaction (with NTAQ1/Q96HA8) from a proteome-scale interactome map; the bare protein binding term is uninformative about HPRT1 function. Reason: Per curation guidelines the bare protein binding term should be avoided as it conveys no specific molecular function; this experimental IPI is retained (not removed) but flagged as over-annotated. No evidence that this HT interaction is functionally meaningful for HPRT1's salvage role. Supporting Evidence: PMID:16189514 Here we describe an initial version of a proteome-scale map of human binary protein-protein interactions.
GO:0005515 protein binding	IPI PMID:19060904 An empirical framework for binary interactome mapping.	MARK AS OVER ANNOTATED	Summary: High-throughput binary interactome mapping; bare protein binding term is uninformative. Reason: Uninformative protein binding term from a systematic HT-Y2H interactome study; retained as experimental IPI but marked over-annotated. Supporting Evidence: PMID:19060904 high-throughput yeast two-hybrid (HT-Y2H) interactions for human proteins are more precise than literature-curated interactions supported by a single publication
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	MARK AS OVER ANNOTATED	Summary: High-throughput interactome map (with NTAQ1/Q96HA8); bare protein binding term is uninformative. Reason: Uninformative protein binding term from a proteome-scale interactome study; retained as experimental IPI but marked over-annotated. 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: High-throughput interactome perturbation study (with PRTFDC1/Q9NRG1); bare protein binding term is uninformative. Reason: Uninformative protein binding term from a systematic interactome study; retained as experimental IPI but marked over-annotated. Supporting Evidence: PMID:25910212 Widespread macromolecular interaction perturbations in human genetic disorders.
GO:0005515 protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	MARK AS OVER ANNOTATED	Summary: High-throughput variant-interaction profiling; bare protein binding term is uninformative. Reason: Uninformative protein binding term from a systematic interactome/variant study; retained as experimental IPI but marked over-annotated. 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: High-throughput binary interactome reference map; bare protein binding term is uninformative. Reason: Uninformative protein binding term from a proteome-scale binary interactome study; retained as experimental IPI but marked over-annotated. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	MARK AS OVER ANNOTATED	Summary: High-throughput interactome map of neurodegenerative disease proteins (with HTT/P42858 and SPRED1); bare protein binding term is uninformative. Reason: Uninformative protein binding term from a systematic interactome study; retained as experimental IPI but marked over-annotated. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: High-throughput affinity-purification interactome (BioPlex; with PRTFDC1/Q9NRG1); bare protein binding term is uninformative. Reason: Uninformative protein binding term from a proteome-scale AP-MS interactome study; retained as experimental IPI but marked over-annotated. Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
GO:0042802 identical protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	ACCEPT	Summary: Self-interaction (P00492 with P00492), consistent with the biologically relevant homotetrameric assembly of the active enzyme. Reason: Unlike the bare protein binding term, identical protein binding is informative here because the functional HPRT1 enzyme is a homotetramer, established by multiple crystal structures. Supporting Evidence: file:human/HPRT1/HPRT1-uniprot.txt SUBUNIT: Homotetramer.
GO:0042802 identical protein binding	IPI PMID:25502805 A massively parallel pipeline to clone DNA variants and exam...	ACCEPT	Summary: Self-interaction detected by a massively parallel variant/interaction pipeline, consistent with the homotetrameric assembly. Reason: Informative self-association annotation consistent with the established homotetramer; retained as a valid experimental annotation. Supporting Evidence: file:human/HPRT1/HPRT1-uniprot.txt SUBUNIT: Homotetramer.
GO:0042802 identical protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	ACCEPT	Summary: Self-interaction detected in a systematic variant-interaction study, consistent with homotetramerization. Reason: Informative self-association annotation consistent with the established homotetramer. Supporting Evidence: file:human/HPRT1/HPRT1-uniprot.txt SUBUNIT: Homotetramer.
GO:0042802 identical protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	ACCEPT	Summary: Self-interaction from the human binary interactome reference map, consistent with the homotetrameric enzyme. Reason: Informative self-association annotation consistent with the established homotetramer. Supporting Evidence: file:human/HPRT1/HPRT1-uniprot.txt SUBUNIT: Homotetramer.
GO:0005829 cytosol	IEA GO_REF:0000107	ACCEPT	Summary: Electronic assertion of cytosolic activity transferred from the mouse ortholog, consistent with the soluble cytosolic enzyme. Reason: Correct cytosolic localization, redundant with the IBA and IDA cytosol annotations. Supporting Evidence: file:human/HPRT1/HPRT1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm.
GO:0032264 IMP salvage	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assertion of IMP salvage from combined automated methods (UniPathway UPA00591), redundant with the IBA IMP salvage annotation. Reason: Correct; HPRT1 produces IMP from hypoxanthine in the salvage pathway. Supporting Evidence: file:human/HPRT1/HPRT1-uniprot.txt Purine metabolism; IMP biosynthesis via salvage pathway
GO:0042802 identical protein binding	IEA GO_REF:0000107	ACCEPT	Summary: Electronic assertion of self-interaction transferred from the mouse ortholog, consistent with the homotetrameric assembly. Reason: Informative self-association annotation consistent with the established homotetramer. Supporting Evidence: file:human/HPRT1/HPRT1-uniprot.txt SUBUNIT: Homotetramer.
GO:0044209 AMP salvage	IEA GO_REF:0000107	REMOVE	Summary: Electronic assertion of AMP salvage transferred from the mouse ortholog. HPRT does not act on adenine/AMP; adenine salvage is performed by APRT, not HPRT1. Reason: This is an incorrect over-propagated electronic inference. HPRT1 salvages the 6-oxopurines hypoxanthine and guanine (forming IMP and GMP); it has no activity on adenine and does not directly participate in AMP salvage, which is catalyzed by adenine phosphoribosyltransferase (APRT). The UniProt catalytic activities and substrate specificity (Lys165 confers specificity for guanine and hypoxanthine over adenine) contradict an AMP salvage role. Supporting Evidence: PMID:8044844 Lys-165, which forms a hydrogen bond to O6 of GMP, appears to be critical for determining the specificity for guanine and hypoxanthine over adenine. PMID:9521733 catalyzes the reversible formation of IMP and GMP from their respective bases hypoxanthine (Hx) and guanine (Gua)
GO:0052657 guanine phosphoribosyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assertion of guanine phosphoribosyltransferase activity (RHEA:25424) from combined automated methods, redundant with the experimental IDA/IBA annotations. Reason: Correct core catalytic activity; the IEA mapping agrees with experimental evidence (guanine + PRPP produces GMP). Supporting Evidence: file:human/HPRT1/HPRT1-uniprot.txt Reaction=GMP + diphosphate = guanine + 5-phospho-alpha-D-ribose 1-
GO:0005829 cytosol	IDA GO_REF:0000052	ACCEPT	Summary: Direct immunofluorescence localization (Human Protein Atlas) to the cytosol, confirming the soluble cytoplasmic localization. Reason: Direct experimental (HPA immunofluorescence) support for the core cytosolic localization of this soluble enzyme. Supporting Evidence: file:human/HPRT1/HPRT1-uniprot.txt GO:0005829; C:cytosol; IDA:HPA.
GO:0032263 GMP salvage	IDA PMID:4208686 Human hypoxanthine-guanine phosphoribosyltransferase (HGPRT)...	ACCEPT	Summary: Direct assay of purified human HGPRT (Arnold, Lamb & Kelley 1973) supporting involvement in GMP salvage via the guanine to GMP reaction. Reason: Purified human HGPRT was characterized biochemically; the enzyme's guanine phosphoribosyltransferase activity produces GMP directly, placing it in GMP salvage. The acts_upstream_of_or_within qualifier is acceptable, though involved_in is more precise for a direct pathway enzyme. Supporting Evidence: PMID:4208686 Human hypoxanthine-guanine phosphoribosyltransferase (HGPRT): purification and properties.
GO:0052657 guanine phosphoribosyltransferase activity	IDA PMID:4208686 Human hypoxanthine-guanine phosphoribosyltransferase (HGPRT)...	ACCEPT	Summary: Direct biochemical characterization of purified human HGPRT supporting the guanine phosphoribosyltransferase activity. Reason: Core catalytic activity established by direct assay of the purified human enzyme. Supporting Evidence: PMID:4208686 Human hypoxanthine-guanine phosphoribosyltransferase (HGPRT): purification and properties.
GO:0005829 cytosol	TAS Reactome:R-HSA-9734274	ACCEPT	Summary: Reactome traceable assertion (defective-HPRT1 reaction context) placing the enzyme in the cytosol. Reason: Correct cytosolic localization from Reactome curation, consistent with all other localization evidence. Supporting Evidence: file:human/HPRT1/HPRT1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm.
GO:0032263 GMP salvage	IDA PMID:4208686 Human hypoxanthine-guanine phosphoribosyltransferase (HGPRT)...	ACCEPT	Summary: Direct evidence (purified human HGPRT) for involvement in GMP salvage; duplicate of the acts_upstream_of_or_within annotation with a more precise qualifier. Reason: Core pathway role; the guanine to GMP reaction constitutes GMP salvage. Supporting Evidence: PMID:4208686 Human hypoxanthine-guanine phosphoribosyltransferase (HGPRT): purification and properties.
GO:0042802 identical protein binding	IPI PMID:8044844 The crystal structure of human hypoxanthine-guanine phosphor...	ACCEPT	Summary: Crystal structure of human HGPRT with bound GMP; the enzyme self-associates into the biologically active homotetramer. Reason: Informative self-association annotation directly supported by the crystal structure and by the UniProt homotetramer annotation. Supporting Evidence: file:human/HPRT1/HPRT1-uniprot.txt SUBUNIT: Homotetramer.
GO:0070062 extracellular exosome	HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote...	KEEP AS NON CORE	Summary: High-throughput mass-spectrometry detection of HPRT1 in B-cell-derived exosomes. This is a proteomic sighting rather than the site of catalytic function. Reason: HPRT1 is a soluble cytosolic salvage enzyme; its presence in the exosome proteome is a common finding for abundant cytosolic proteins and does not represent its functional localization. Retained as a non-core localization. Supporting Evidence: PMID:20458337 we first analyzed the total proteome of highly purified B cell-derived exosomes using sensitive and accurate mass spectrometry (MS), and identified 539 proteins
GO:0005829 cytosol	TAS Reactome:R-HSA-74215	ACCEPT	Summary: Reactome traceable assertion placing the HPRT1 catalytic reaction in the cytosol. Reason: Correct cytosolic localization from Reactome curation of the salvage reaction. Supporting Evidence: file:human/HPRT1/HPRT1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm.
GO:0005829 cytosol	TAS Reactome:R-HSA-9748951	ACCEPT	Summary: Reactome traceable assertion (6-mercaptopurine/6TIMP reaction context) placing the HPRT1 tetramer in the cytosol. Reason: Correct cytosolic localization from Reactome curation. Supporting Evidence: file:human/HPRT1/HPRT1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm.
GO:0004422 hypoxanthine phosphoribosyltransferase activity	IDA PMID:19527031 Inhibition of hypoxanthine-guanine phosphoribosyltransferase...	ACCEPT	Summary: Direct catalytic-activity and structural characterization of the human enzyme (Ki determinations and structures of human HGPRT with inhibitors); supports the hypoxanthine phosphoribosyltransferase activity. Reason: Although the abstract foregrounds the Plasmodium falciparum enzyme (antimalarial inhibitor design), the study explicitly assayed the corresponding human enzyme and determined structures of human HGPRT; this is a UniProt EC evidence source for HPRT1 catalytic activity. Core molecular function. Supporting Evidence: PMID:19527031 Structures of human HGPRT in complex with three ANPs are reported. PMID:19527031 K(i) values for 19 ANPs were determined for Pf HGXPRT and the corresponding human enzyme, HGPRT.
GO:0006178 guanine salvage	IDA PMID:19527031 Inhibition of hypoxanthine-guanine phosphoribosyltransferase...	ACCEPT	Summary: Direct characterization of the human enzyme's activity supporting its role in guanine salvage (guanine to GMP). Reason: HPRT1 salvages guanine to GMP; the human enzyme was directly assayed in this study. Supporting Evidence: PMID:19527031 K(i) values for 19 ANPs were determined for Pf HGXPRT and the corresponding human enzyme, HGPRT.
GO:0043103 hypoxanthine salvage	IDA PMID:19527031 Inhibition of hypoxanthine-guanine phosphoribosyltransferase...	ACCEPT	Summary: Direct characterization of the human enzyme supporting its role in hypoxanthine salvage (hypoxanthine to IMP). Reason: HPRT1 salvages hypoxanthine to IMP; the human enzyme was directly assayed in this study. This is the most specific salvage term for the hypoxanthine reaction. Supporting Evidence: PMID:19527031 The purine salvage enzyme hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT) is essential for purine nucleotide and hence nucleic acid synthesis
GO:0046038 GMP catabolic process	IDA PMID:19527031 Inhibition of hypoxanthine-guanine phosphoribosyltransferase...	KEEP AS NON CORE	Summary: The HPRT1 reaction is reversible; in the pyrophosphorolysis direction the enzyme can consume GMP (GMP + diphosphate produces guanine + PRPP), supporting a GMP catabolic-process role. Reason: The physiological direction of HPRT1 is anabolic salvage (base + PRPP produces NMP), but the reaction is reversible and the reverse (pyrophosphorolysis) reaction was assayed. GMP catabolic process reflects this reverse activity but is not the core physiological role; retained as non-core. Supporting Evidence: file:human/HPRT1/HPRT1-uniprot.txt Reaction=GMP + diphosphate = guanine + 5-phospho-alpha-D-ribose 1-
GO:0046040 IMP metabolic process	IDA PMID:19527031 Inhibition of hypoxanthine-guanine phosphoribosyltransferase...	ACCEPT	Summary: Direct characterization of the human enzyme supporting involvement in IMP metabolism (hypoxanthine to IMP and the reverse reaction). Reason: HPRT1 directly produces and (reversibly) consumes IMP; involvement in IMP metabolic process is correct, though IMP salvage is the more specific term. Supporting Evidence: file:human/HPRT1/HPRT1-uniprot.txt Reaction=IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-
GO:0051289 protein homotetramerization	IPI PMID:15990111 The crystal structure of free human hypoxanthine-guanine pho...	ACCEPT	Summary: The free-enzyme crystal structure describes movement of subunits within the tetramer, consistent with the biologically active homotetrameric assembly. Reason: HPRT1 assembles into a homotetramer, established by multiple crystal structures including the apoenzyme structure cited here; this is a meaningful, informative annotation. Supporting Evidence: PMID:15990111 relative movement of subunits within the tetramer file:human/HPRT1/HPRT1-uniprot.txt SUBUNIT: Homotetramer.
GO:0052657 guanine phosphoribosyltransferase activity	IDA PMID:19527031 Inhibition of hypoxanthine-guanine phosphoribosyltransferase...	ACCEPT	Summary: Direct characterization of the human enzyme supporting the guanine phosphoribosyltransferase activity. Reason: Core catalytic activity; the human enzyme was directly assayed in this study. Supporting Evidence: PMID:19527031 K(i) values for 19 ANPs were determined for Pf HGXPRT and the corresponding human enzyme, HGPRT.
GO:0006166 purine ribonucleoside salvage	IMP PMID:9824441 Purine metabolism in female heterozygotes for hypoxanthine-g...	ACCEPT	Summary: Study of purine metabolism in female heterozygotes for HPRT deficiency; reduced HPRT activity leads to purine overproduction, evidencing HPRT1's role in purine salvage. Reason: Loss/reduction of HPRT activity in carriers causes enhanced purine nucleotide degradation and overproduction, demonstrating the enzyme's normal role in purine salvage (recycling bases and sparing de novo synthesis). Supporting Evidence: PMID:9824441 Female heterozygotes for HPRT deficiency show an enhanced purine nucleotide degradation and purine overproduction.
GO:0045964 positive regulation of dopamine metabolic process	IMP PMID:8643611 Dopamine transporters are markedly reduced in Lesch-Nyhan di...	MARK AS OVER ANNOTATED	Summary: The cited study reports markedly reduced striatal dopamine transporters in Lesch-Nyhan disease patients. This reflects a downstream neurochemical consequence of complete HPRT deficiency, not a direct molecular role of HPRT1 in regulating dopamine metabolism. Reason: HPRT1 is a purine salvage enzyme with no known direct activity on dopamine metabolism. The dopaminergic deficit observed in LND is a distal, poorly understood consequence of the metabolic/developmental derangement caused by HPRT loss; inferring positive regulation of dopamine metabolic process as an HPRT1 function over-interprets a disease-phenotype association. Retained (experimental IMP) but flagged as over-annotated rather than a core function. Supporting Evidence: PMID:8643611 a 50-63% reduction of the binding to DA transporters in the caudate, and a 64-75% reduction in the putamen of the LND patients was observed compared to the normal control group
GO:0046100 hypoxanthine metabolic process	IMP PMID:9824441 Purine metabolism in female heterozygotes for hypoxanthine-g...	ACCEPT	Summary: HPRT-deficiency carrier study showing elevated hypoxanthine (and xanthine) excretion, evidencing HPRT1's normal role in metabolizing/salvaging hypoxanthine. Reason: Reduced HPRT activity elevates hypoxanthine excretion, demonstrating the enzyme normally consumes hypoxanthine; involvement in hypoxanthine metabolic process is correct (hypoxanthine salvage is the more specific term). Supporting Evidence: PMID:9824441 An elevated hypoxanthine and/or xanthine excretion rate differentiated most heterozygotes for HPRT deficiency from non-carrier women
GO:0005737 cytoplasm	IDA PMID:6300847 Isolation and characterization of a full-length expressible ...	ACCEPT	Summary: Expression of the cloned human HPRT cDNA yields active enzyme in cells, consistent with cytoplasmic localization of the salvage enzyme. Reason: Correct cytoplasmic localization of this soluble enzyme, consistent with all other localization evidence. Supporting Evidence: file:human/HPRT1/HPRT1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm.
GO:0006164 purine nucleotide biosynthetic process	IMP PMID:9824441 Purine metabolism in female heterozygotes for hypoxanthine-g...	KEEP AS NON CORE	Summary: HPRT-deficiency carrier study; the salvage pathway produces the purine nucleotides IMP and GMP, contributing to purine nucleotide biosynthesis. Reason: HPRT1 does biosynthesize purine nucleotides (IMP, GMP) via salvage, so this broad parent term is correct, but the specific salvage terms (IMP salvage, GMP salvage, purine ribonucleoside salvage) capture the function more precisely. Retained as non-core general parent. Supporting Evidence: file:human/HPRT1/HPRT1-uniprot.txt Plays a central role in the generation of purine nucleotides through the purine salvage pathway.
GO:0000287 magnesium ion binding	IDA PMID:10360366 The 2.0 A structure of human hypoxanthine-guanine phosphorib...	ACCEPT	Summary: Transition-state analog crystal structure showing two Mg2+ ions bound at the active site sandwiching the pyrophosphate, directly supporting magnesium ion binding. Reason: Directly demonstrated by the structure of human HGPRT with the transition-state analog and Mg2+-pyrophosphate; the enzyme binds two Mg2+ ions per subunit essential for catalysis. Supporting Evidence: PMID:10360366 Two Mg2+ ions sandwich the pyrophosphate and contact both hydroxyls of the ribosyl analog.
GO:0004422 hypoxanthine phosphoribosyltransferase activity	IDA PMID:6300847 Isolation and characterization of a full-length expressible ...	ACCEPT	Summary: The cloned full-length human HPRT cDNA expresses functional HPRT enzyme activity, directly supporting the hypoxanthine phosphoribosyltransferase activity. Reason: Expression of the human cDNA restored HPRT enzyme activity in HPRT-deficient cells (HAT selection), confirming the core catalytic function. Supporting Evidence: PMID:6300847 leads to the expression of human HPRT enzyme activity in cells stably transfected and selected for enzyme activity in hypoxanthine/aminopterin/thymidine medium
GO:0004422 hypoxanthine phosphoribosyltransferase activity	IDA PMID:9521733 Catalysis in human hypoxanthine-guanine phosphoribosyltransf...	ACCEPT	Summary: Catalytic mechanism study of human HGPRTase (Asp137 general acid/base; characterization of the hypoxanthine to IMP reaction), directly supporting the hypoxanthine phosphoribosyltransferase activity. Reason: Detailed kinetic and mechanistic characterization of the purified/mutant human enzyme; core catalytic function. Supporting Evidence: PMID:9521733 catalyzes the reversible formation of IMP and GMP from their respective bases hypoxanthine (Hx) and guanine (Gua)

📄 View Raw YAML

id: P00492
gene_symbol: HPRT1
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: Cytosolic hypoxanthine-guanine phosphoribosyltransferase (HGPRT; EC 2.4.2.8),
  the central enzyme of the purine salvage pathway. It transfers the 5-phosphoribosyl
  group from 5-phospho-alpha-D-ribose 1-diphosphate (PRPP) onto a 6-oxopurine base,
  converting hypoxanthine to inosine monophosphate (IMP) and guanine to guanosine
  monophosphate (GMP), thereby recycling free purine bases into nucleotides and sparing
  the energetically costly de novo purine biosynthesis pathway. The catalytic reaction
  requires magnesium (two Mg2+ ions per subunit, bound largely via the substrate) and the
  active enzyme is a homotetramer. HPRT1 is expressed broadly with highest relative
  activity in the basal ganglia. Complete loss of HPRT activity causes Lesch-Nyhan
  syndrome (hyperuricemia with severe neurological dysfunction including dystonia,
  choreoathetosis, intellectual disability and compulsive self-injurious behavior);
  partial deficiency causes HPRT-related hyperuricemia/gout (Kelley-Seegmiller syndrome).
existing_annotations:
- term:
    id: GO:0004422
    label: hypoxanthine phosphoribosyltransferase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Phylogenetically inferred core catalytic activity, converting hypoxanthine
      plus PRPP to IMP. This is a defining, experimentally established function of HPRT1.
    action: ACCEPT
    reason: This is one of the two core molecular functions of HPRT1, supported by direct
      experimental catalytic-activity data and structural studies, and consistent across
      IBA, IEA and IDA evidence. EC 2.4.2.8.
    supported_by:
    - reference_id: PMID:9521733
      supporting_text: Hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) catalyzes
        the reversible formation of IMP and GMP from their respective bases hypoxanthine
        (Hx) and guanine (Gua) and the phosphoribosyl donor 5-phosphoribosyl-1-pyrophosphate
        (PRPP).
- term:
    id: GO:0046100
    label: hypoxanthine metabolic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetically inferred involvement in hypoxanthine metabolism, reflecting
      the enzyme's use of hypoxanthine as a substrate to form IMP.
    action: ACCEPT
    reason: HPRT1 directly consumes hypoxanthine in the salvage reaction, so involvement
      in hypoxanthine metabolic process is correct, though the more specific salvage terms
      (hypoxanthine salvage, IMP salvage) better capture the physiological role.
    supported_by:
    - reference_id: PMID:9521733
      supporting_text: catalyzes the reversible formation of IMP and GMP from their respective
        bases hypoxanthine (Hx) and guanine (Gua)
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetically inferred cytosolic localization, consistent with the
      soluble cytoplasmic nature of the salvage enzyme.
    action: ACCEPT
    reason: HPRT1 is a soluble cytosolic enzyme (UniProt subcellular location cytoplasm),
      confirmed by IDA (HPA) and multiple orthogonal lines of evidence.
    supported_by:
    - reference_id: file:human/HPRT1/HPRT1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm.'
- term:
    id: GO:0032263
    label: GMP salvage
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetically inferred role in GMP salvage, matching the guanine to GMP
      reaction catalyzed by HPRT1.
    action: ACCEPT
    reason: The guanine phosphoribosyltransferase reaction produces GMP directly from the
      salvaged base guanine, so involvement in GMP salvage is a core pathway role.
    supported_by:
    - reference_id: file:human/HPRT1/HPRT1-uniprot.txt
      supporting_text: Reaction=GMP + diphosphate = guanine + 5-phospho-alpha-D-ribose 1-
- term:
    id: GO:0006178
    label: guanine salvage
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetically inferred role in guanine salvage, reflecting HPRT1 recycling
      free guanine into GMP.
    action: ACCEPT
    reason: HPRT1 salvages guanine by phosphoribosylation to GMP; this is a core pathway
      role also supported by direct experimental evidence.
    supported_by:
    - reference_id: PMID:9521733
      supporting_text: catalyzes the reversible formation of IMP and GMP from their respective
        bases hypoxanthine (Hx) and guanine (Gua)
- term:
    id: GO:0032264
    label: IMP salvage
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetically inferred role in IMP salvage, matching the hypoxanthine to
      IMP reaction.
    action: ACCEPT
    reason: The hypoxanthine phosphoribosyltransferase reaction produces IMP from the
      salvaged base hypoxanthine; UniProt records IMP biosynthesis via the salvage pathway
      as step 1/1 for this enzyme.
    supported_by:
    - reference_id: file:human/HPRT1/HPRT1-uniprot.txt
      supporting_text: Purine metabolism; IMP biosynthesis via salvage pathway
- term:
    id: GO:0000287
    label: magnesium ion binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Phylogenetically inferred magnesium binding, consistent with the Mg2+
      requirement of the phosphoribosyltransfer reaction.
    action: ACCEPT
    reason: HPRT1 binds two Mg2+ ions per subunit which are essential for catalysis; this
      is directly supported by structural studies (transition-state analog complex with
      Mg2+-pyrophosphate) and UniProt cofactor annotation.
    supported_by:
    - reference_id: file:human/HPRT1/HPRT1-uniprot.txt
      supporting_text: Note=Binds 2 magnesium ions per subunit.
    - reference_id: PMID:10360366
      supporting_text: Two Mg2+ ions sandwich the pyrophosphate and contact both hydroxyls
        of the ribosyl analog.
- term:
    id: GO:0004422
    label: hypoxanthine phosphoribosyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Electronic assertion of hypoxanthine phosphoribosyltransferase activity from
      combined automated methods, redundant with the experimental IDA/IBA annotations.
    action: ACCEPT
    reason: Correct core catalytic activity; the IEA mapping (ARBA/InterPro/RHEA:17973)
      agrees with experimental evidence.
    supported_by:
    - reference_id: file:human/HPRT1/HPRT1-uniprot.txt
      supporting_text: EC=2.4.2.8 {ECO:0000269|PubMed:10338013, ECO:0000269|PubMed:19527031};
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: Electronic assertion of cytoplasmic localization, consistent with the
      cytosolic nature of the enzyme.
    action: ACCEPT
    reason: Correct localization; cytoplasm is the UniProt SubCell term for this soluble
      enzyme, redundant with the more specific cytosol annotations.
    supported_by:
    - reference_id: file:human/HPRT1/HPRT1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm.'
- term:
    id: GO:0006166
    label: purine ribonucleoside salvage
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: InterPro2GO electronic assertion of purine ribonucleoside salvage, capturing
      the general salvage-pathway role of HPRT1.
    action: ACCEPT
    reason: HPRT1 is the central 6-oxopurine salvage enzyme; the InterPro HGPRT signature
      (IPR005904) correctly maps to purine salvage. This is a good general parent for the
      more specific salvage terms.
    supported_by:
    - reference_id: file:human/HPRT1/HPRT1-uniprot.txt
      supporting_text: Plays a central role in the generation of purine nucleotides through
        the purine salvage pathway.
- term:
    id: GO:0046100
    label: hypoxanthine metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: ARBA electronic assertion of hypoxanthine metabolic process, redundant with
      the IBA and IMP annotations to the same term.
    action: ACCEPT
    reason: Correct; hypoxanthine is a direct substrate. The more specific hypoxanthine
      salvage term better captures the role.
    supported_by:
    - reference_id: PMID:9521733
      supporting_text: catalyzes the reversible formation of IMP and GMP from their respective
        bases hypoxanthine (Hx) and guanine (Gua)
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16189514
  qualifier: enables
  review:
    summary: High-throughput yeast two-hybrid interaction (with NTAQ1/Q96HA8) from a
      proteome-scale interactome map; the bare protein binding term is uninformative about
      HPRT1 function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Per curation guidelines the bare protein binding term should be avoided as it
      conveys no specific molecular function; this experimental IPI is retained (not
      removed) but flagged as over-annotated. No evidence that this HT interaction is
      functionally meaningful for HPRT1's salvage role.
    supported_by:
    - reference_id: PMID:16189514
      supporting_text: Here we describe an initial version of a proteome-scale map of human
        binary protein-protein interactions.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19060904
  qualifier: enables
  review:
    summary: High-throughput binary interactome mapping; bare protein binding term is
      uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative protein binding term from a systematic HT-Y2H interactome study;
      retained as experimental IPI but marked over-annotated.
    supported_by:
    - reference_id: PMID:19060904
      supporting_text: high-throughput yeast two-hybrid (HT-Y2H) interactions for human
        proteins are more precise than literature-curated interactions supported by a single
        publication
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: High-throughput interactome map (with NTAQ1/Q96HA8); bare protein binding
      term is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative protein binding term from a proteome-scale interactome study;
      retained as experimental IPI but marked over-annotated.
    supported_by:
    - reference_id: PMID:25416956
      supporting_text: A proteome-scale map of the human interactome network.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25910212
  qualifier: enables
  review:
    summary: High-throughput interactome perturbation study (with PRTFDC1/Q9NRG1); bare
      protein binding term is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative protein binding term from a systematic interactome study;
      retained as experimental IPI but marked over-annotated.
    supported_by:
    - reference_id: PMID:25910212
      supporting_text: Widespread macromolecular interaction perturbations in human genetic
        disorders.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31515488
  qualifier: enables
  review:
    summary: High-throughput variant-interaction profiling; bare protein binding term is
      uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative protein binding term from a systematic interactome/variant study;
      retained as experimental IPI but marked over-annotated.
    supported_by:
    - reference_id: PMID:31515488
      supporting_text: Extensive disruption of protein interactions by genetic variants
        across the allele frequency spectrum in human populations.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: High-throughput binary interactome reference map; bare protein binding term
      is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative protein binding term from a proteome-scale binary interactome
      study; retained as experimental IPI but marked over-annotated.
    supported_by:
    - reference_id: PMID:32296183
      supporting_text: A reference map of the human binary protein interactome.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  qualifier: enables
  review:
    summary: High-throughput interactome map of neurodegenerative disease proteins (with
      HTT/P42858 and SPRED1); bare protein binding term is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative protein binding term from a systematic interactome study;
      retained as experimental IPI but marked over-annotated.
    supported_by:
    - reference_id: PMID:32814053
      supporting_text: Interactome Mapping Provides a Network of Neurodegenerative Disease
        Proteins
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: High-throughput affinity-purification interactome (BioPlex; with PRTFDC1/Q9NRG1);
      bare protein binding term is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative protein binding term from a proteome-scale AP-MS interactome
      study; retained as experimental IPI but marked over-annotated.
    supported_by:
    - reference_id: PMID:33961781
      supporting_text: Dual proteome-scale networks reveal cell-specific remodeling of the
        human interactome.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: Self-interaction (P00492 with P00492), consistent with the biologically
      relevant homotetrameric assembly of the active enzyme.
    action: ACCEPT
    reason: Unlike the bare protein binding term, identical protein binding is
      informative here because the functional HPRT1 enzyme is a homotetramer, established
      by multiple crystal structures.
    supported_by:
    - reference_id: file:human/HPRT1/HPRT1-uniprot.txt
      supporting_text: 'SUBUNIT: Homotetramer.'
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:25502805
  qualifier: enables
  review:
    summary: Self-interaction detected by a massively parallel variant/interaction pipeline,
      consistent with the homotetrameric assembly.
    action: ACCEPT
    reason: Informative self-association annotation consistent with the established
      homotetramer; retained as a valid experimental annotation.
    supported_by:
    - reference_id: file:human/HPRT1/HPRT1-uniprot.txt
      supporting_text: 'SUBUNIT: Homotetramer.'
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:31515488
  qualifier: enables
  review:
    summary: Self-interaction detected in a systematic variant-interaction study,
      consistent with homotetramerization.
    action: ACCEPT
    reason: Informative self-association annotation consistent with the established
      homotetramer.
    supported_by:
    - reference_id: file:human/HPRT1/HPRT1-uniprot.txt
      supporting_text: 'SUBUNIT: Homotetramer.'
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: Self-interaction from the human binary interactome reference map, consistent
      with the homotetrameric enzyme.
    action: ACCEPT
    reason: Informative self-association annotation consistent with the established
      homotetramer.
    supported_by:
    - reference_id: file:human/HPRT1/HPRT1-uniprot.txt
      supporting_text: 'SUBUNIT: Homotetramer.'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: is_active_in
  review:
    summary: Electronic assertion of cytosolic activity transferred from the mouse
      ortholog, consistent with the soluble cytosolic enzyme.
    action: ACCEPT
    reason: Correct cytosolic localization, redundant with the IBA and IDA cytosol
      annotations.
    supported_by:
    - reference_id: file:human/HPRT1/HPRT1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm.'
- term:
    id: GO:0032264
    label: IMP salvage
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: Electronic assertion of IMP salvage from combined automated methods
      (UniPathway UPA00591), redundant with the IBA IMP salvage annotation.
    action: ACCEPT
    reason: Correct; HPRT1 produces IMP from hypoxanthine in the salvage pathway.
    supported_by:
    - reference_id: file:human/HPRT1/HPRT1-uniprot.txt
      supporting_text: Purine metabolism; IMP biosynthesis via salvage pathway
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: Electronic assertion of self-interaction transferred from the mouse ortholog,
      consistent with the homotetrameric assembly.
    action: ACCEPT
    reason: Informative self-association annotation consistent with the established
      homotetramer.
    supported_by:
    - reference_id: file:human/HPRT1/HPRT1-uniprot.txt
      supporting_text: 'SUBUNIT: Homotetramer.'
- term:
    id: GO:0044209
    label: AMP salvage
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Electronic assertion of AMP salvage transferred from the mouse ortholog. HPRT
      does not act on adenine/AMP; adenine salvage is performed by APRT, not HPRT1.
    action: REMOVE
    reason: This is an incorrect over-propagated electronic inference. HPRT1 salvages the
      6-oxopurines hypoxanthine and guanine (forming IMP and GMP); it has no activity on
      adenine and does not directly participate in AMP salvage, which is catalyzed by
      adenine phosphoribosyltransferase (APRT). The UniProt catalytic activities and
      substrate specificity (Lys165 confers specificity for guanine and hypoxanthine over
      adenine) contradict an AMP salvage role.
    supported_by:
    - reference_id: PMID:8044844
      supporting_text: Lys-165, which forms a hydrogen bond to O6 of GMP, appears to be
        critical for determining the specificity for guanine and hypoxanthine over adenine.
    - reference_id: PMID:9521733
      supporting_text: catalyzes the reversible formation of IMP and GMP from their respective
        bases hypoxanthine (Hx) and guanine (Gua)
- term:
    id: GO:0052657
    label: guanine phosphoribosyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Electronic assertion of guanine phosphoribosyltransferase activity
      (RHEA:25424) from combined automated methods, redundant with the experimental
      IDA/IBA annotations.
    action: ACCEPT
    reason: Correct core catalytic activity; the IEA mapping agrees with experimental
      evidence (guanine + PRPP produces GMP).
    supported_by:
    - reference_id: file:human/HPRT1/HPRT1-uniprot.txt
      supporting_text: Reaction=GMP + diphosphate = guanine + 5-phospho-alpha-D-ribose 1-
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Direct immunofluorescence localization (Human Protein Atlas) to the cytosol,
      confirming the soluble cytoplasmic localization.
    action: ACCEPT
    reason: Direct experimental (HPA immunofluorescence) support for the core cytosolic
      localization of this soluble enzyme.
    supported_by:
    - reference_id: file:human/HPRT1/HPRT1-uniprot.txt
      supporting_text: 'GO:0005829; C:cytosol; IDA:HPA.'
- term:
    id: GO:0032263
    label: GMP salvage
  evidence_type: IDA
  original_reference_id: PMID:4208686
  qualifier: acts_upstream_of_or_within
  review:
    summary: Direct assay of purified human HGPRT (Arnold, Lamb & Kelley 1973) supporting
      involvement in GMP salvage via the guanine to GMP reaction.
    action: ACCEPT
    reason: Purified human HGPRT was characterized biochemically; the enzyme's guanine
      phosphoribosyltransferase activity produces GMP directly, placing it in GMP salvage.
      The acts_upstream_of_or_within qualifier is acceptable, though involved_in is more
      precise for a direct pathway enzyme.
    supported_by:
    - reference_id: PMID:4208686
      supporting_text: 'Human hypoxanthine-guanine phosphoribosyltransferase (HGPRT): purification
        and properties.'
- term:
    id: GO:0052657
    label: guanine phosphoribosyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:4208686
  qualifier: enables
  review:
    summary: Direct biochemical characterization of purified human HGPRT supporting the
      guanine phosphoribosyltransferase activity.
    action: ACCEPT
    reason: Core catalytic activity established by direct assay of the purified human
      enzyme.
    supported_by:
    - reference_id: PMID:4208686
      supporting_text: 'Human hypoxanthine-guanine phosphoribosyltransferase (HGPRT): purification
        and properties.'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9734274
  qualifier: located_in
  review:
    summary: Reactome traceable assertion (defective-HPRT1 reaction context) placing the
      enzyme in the cytosol.
    action: ACCEPT
    reason: Correct cytosolic localization from Reactome curation, consistent with all
      other localization evidence.
    supported_by:
    - reference_id: file:human/HPRT1/HPRT1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm.'
- term:
    id: GO:0032263
    label: GMP salvage
  evidence_type: IDA
  original_reference_id: PMID:4208686
  qualifier: involved_in
  review:
    summary: Direct evidence (purified human HGPRT) for involvement in GMP salvage;
      duplicate of the acts_upstream_of_or_within annotation with a more precise qualifier.
    action: ACCEPT
    reason: Core pathway role; the guanine to GMP reaction constitutes GMP salvage.
    supported_by:
    - reference_id: PMID:4208686
      supporting_text: 'Human hypoxanthine-guanine phosphoribosyltransferase (HGPRT): purification
        and properties.'
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:8044844
  qualifier: enables
  review:
    summary: Crystal structure of human HGPRT with bound GMP; the enzyme self-associates
      into the biologically active homotetramer.
    action: ACCEPT
    reason: Informative self-association annotation directly supported by the crystal
      structure and by the UniProt homotetramer annotation.
    supported_by:
    - reference_id: file:human/HPRT1/HPRT1-uniprot.txt
      supporting_text: 'SUBUNIT: Homotetramer.'
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:20458337
  qualifier: located_in
  review:
    summary: High-throughput mass-spectrometry detection of HPRT1 in B-cell-derived
      exosomes. This is a proteomic sighting rather than the site of catalytic function.
    action: KEEP_AS_NON_CORE
    reason: HPRT1 is a soluble cytosolic salvage enzyme; its presence in the exosome
      proteome is a common finding for abundant cytosolic proteins and does not represent
      its functional localization. Retained as a non-core localization.
    supported_by:
    - reference_id: PMID:20458337
      supporting_text: we first analyzed the total proteome of highly purified B cell-derived
        exosomes using sensitive and accurate mass spectrometry (MS), and identified 539
        proteins
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-74215
  qualifier: located_in
  review:
    summary: Reactome traceable assertion placing the HPRT1 catalytic reaction in the
      cytosol.
    action: ACCEPT
    reason: Correct cytosolic localization from Reactome curation of the salvage reaction.
    supported_by:
    - reference_id: file:human/HPRT1/HPRT1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm.'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9748951
  qualifier: located_in
  review:
    summary: Reactome traceable assertion (6-mercaptopurine/6TIMP reaction context)
      placing the HPRT1 tetramer in the cytosol.
    action: ACCEPT
    reason: Correct cytosolic localization from Reactome curation.
    supported_by:
    - reference_id: file:human/HPRT1/HPRT1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm.'
- term:
    id: GO:0004422
    label: hypoxanthine phosphoribosyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:19527031
  qualifier: enables
  review:
    summary: Direct catalytic-activity and structural characterization of the human enzyme
      (Ki determinations and structures of human HGPRT with inhibitors); supports the
      hypoxanthine phosphoribosyltransferase activity.
    action: ACCEPT
    reason: Although the abstract foregrounds the Plasmodium falciparum enzyme (antimalarial
      inhibitor design), the study explicitly assayed the corresponding human enzyme and
      determined structures of human HGPRT; this is a UniProt EC evidence source for HPRT1
      catalytic activity. Core molecular function.
    supported_by:
    - reference_id: PMID:19527031
      supporting_text: Structures of human HGPRT in complex with three ANPs are reported.
    - reference_id: PMID:19527031
      supporting_text: K(i) values for 19 ANPs were determined for Pf HGXPRT and the corresponding
        human enzyme, HGPRT.
- term:
    id: GO:0006178
    label: guanine salvage
  evidence_type: IDA
  original_reference_id: PMID:19527031
  qualifier: involved_in
  review:
    summary: Direct characterization of the human enzyme's activity supporting its role in
      guanine salvage (guanine to GMP).
    action: ACCEPT
    reason: HPRT1 salvages guanine to GMP; the human enzyme was directly assayed in this
      study.
    supported_by:
    - reference_id: PMID:19527031
      supporting_text: K(i) values for 19 ANPs were determined for Pf HGXPRT and the corresponding
        human enzyme, HGPRT.
- term:
    id: GO:0043103
    label: hypoxanthine salvage
  evidence_type: IDA
  original_reference_id: PMID:19527031
  qualifier: involved_in
  review:
    summary: Direct characterization of the human enzyme supporting its role in
      hypoxanthine salvage (hypoxanthine to IMP).
    action: ACCEPT
    reason: HPRT1 salvages hypoxanthine to IMP; the human enzyme was directly assayed in
      this study. This is the most specific salvage term for the hypoxanthine reaction.
    supported_by:
    - reference_id: PMID:19527031
      supporting_text: The purine salvage enzyme hypoxanthine-guanine-xanthine phosphoribosyltransferase
        (HGXPRT) is essential for purine nucleotide and hence nucleic acid synthesis
- term:
    id: GO:0046038
    label: GMP catabolic process
  evidence_type: IDA
  original_reference_id: PMID:19527031
  qualifier: involved_in
  review:
    summary: The HPRT1 reaction is reversible; in the pyrophosphorolysis direction the
      enzyme can consume GMP (GMP + diphosphate produces guanine + PRPP), supporting a GMP
      catabolic-process role.
    action: KEEP_AS_NON_CORE
    reason: The physiological direction of HPRT1 is anabolic salvage (base + PRPP produces
      NMP), but the reaction is reversible and the reverse (pyrophosphorolysis) reaction was
      assayed. GMP catabolic process reflects this reverse activity but is not the core
      physiological role; retained as non-core.
    supported_by:
    - reference_id: file:human/HPRT1/HPRT1-uniprot.txt
      supporting_text: Reaction=GMP + diphosphate = guanine + 5-phospho-alpha-D-ribose 1-
- term:
    id: GO:0046040
    label: IMP metabolic process
  evidence_type: IDA
  original_reference_id: PMID:19527031
  qualifier: involved_in
  review:
    summary: Direct characterization of the human enzyme supporting involvement in IMP
      metabolism (hypoxanthine to IMP and the reverse reaction).
    action: ACCEPT
    reason: HPRT1 directly produces and (reversibly) consumes IMP; involvement in IMP
      metabolic process is correct, though IMP salvage is the more specific term.
    supported_by:
    - reference_id: file:human/HPRT1/HPRT1-uniprot.txt
      supporting_text: Reaction=IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-
- term:
    id: GO:0051289
    label: protein homotetramerization
  evidence_type: IPI
  original_reference_id: PMID:15990111
  qualifier: involved_in
  review:
    summary: The free-enzyme crystal structure describes movement of subunits within the
      tetramer, consistent with the biologically active homotetrameric assembly.
    action: ACCEPT
    reason: HPRT1 assembles into a homotetramer, established by multiple crystal structures
      including the apoenzyme structure cited here; this is a meaningful, informative
      annotation.
    supported_by:
    - reference_id: PMID:15990111
      supporting_text: relative movement of subunits within the tetramer
    - reference_id: file:human/HPRT1/HPRT1-uniprot.txt
      supporting_text: 'SUBUNIT: Homotetramer.'
- term:
    id: GO:0052657
    label: guanine phosphoribosyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:19527031
  qualifier: enables
  review:
    summary: Direct characterization of the human enzyme supporting the guanine
      phosphoribosyltransferase activity.
    action: ACCEPT
    reason: Core catalytic activity; the human enzyme was directly assayed in this study.
    supported_by:
    - reference_id: PMID:19527031
      supporting_text: K(i) values for 19 ANPs were determined for Pf HGXPRT and the corresponding
        human enzyme, HGPRT.
- term:
    id: GO:0006166
    label: purine ribonucleoside salvage
  evidence_type: IMP
  original_reference_id: PMID:9824441
  qualifier: involved_in
  review:
    summary: Study of purine metabolism in female heterozygotes for HPRT deficiency;
      reduced HPRT activity leads to purine overproduction, evidencing HPRT1's role in
      purine salvage.
    action: ACCEPT
    reason: Loss/reduction of HPRT activity in carriers causes enhanced purine nucleotide
      degradation and overproduction, demonstrating the enzyme's normal role in purine
      salvage (recycling bases and sparing de novo synthesis).
    supported_by:
    - reference_id: PMID:9824441
      supporting_text: Female heterozygotes for HPRT deficiency show an enhanced purine
        nucleotide degradation and purine overproduction.
- term:
    id: GO:0045964
    label: positive regulation of dopamine metabolic process
  evidence_type: IMP
  original_reference_id: PMID:8643611
  qualifier: involved_in
  review:
    summary: The cited study reports markedly reduced striatal dopamine transporters in
      Lesch-Nyhan disease patients. This reflects a downstream neurochemical consequence
      of complete HPRT deficiency, not a direct molecular role of HPRT1 in regulating
      dopamine metabolism.
    action: MARK_AS_OVER_ANNOTATED
    reason: HPRT1 is a purine salvage enzyme with no known direct activity on dopamine
      metabolism. The dopaminergic deficit observed in LND is a distal, poorly understood
      consequence of the metabolic/developmental derangement caused by HPRT loss; inferring
      positive regulation of dopamine metabolic process as an HPRT1 function over-interprets
      a disease-phenotype association. Retained (experimental IMP) but flagged as
      over-annotated rather than a core function.
    supported_by:
    - reference_id: PMID:8643611
      supporting_text: a 50-63% reduction of the binding to DA transporters in the caudate,
        and a 64-75% reduction in the putamen of the LND patients was observed compared to
        the normal control group
- term:
    id: GO:0046100
    label: hypoxanthine metabolic process
  evidence_type: IMP
  original_reference_id: PMID:9824441
  qualifier: involved_in
  review:
    summary: HPRT-deficiency carrier study showing elevated hypoxanthine (and xanthine)
      excretion, evidencing HPRT1's normal role in metabolizing/salvaging hypoxanthine.
    action: ACCEPT
    reason: Reduced HPRT activity elevates hypoxanthine excretion, demonstrating the
      enzyme normally consumes hypoxanthine; involvement in hypoxanthine metabolic process
      is correct (hypoxanthine salvage is the more specific term).
    supported_by:
    - reference_id: PMID:9824441
      supporting_text: An elevated hypoxanthine and/or xanthine excretion rate differentiated
        most heterozygotes for HPRT deficiency from non-carrier women
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:6300847
  qualifier: located_in
  review:
    summary: Expression of the cloned human HPRT cDNA yields active enzyme in cells,
      consistent with cytoplasmic localization of the salvage enzyme.
    action: ACCEPT
    reason: Correct cytoplasmic localization of this soluble enzyme, consistent with all
      other localization evidence.
    supported_by:
    - reference_id: file:human/HPRT1/HPRT1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm.'
- term:
    id: GO:0006164
    label: purine nucleotide biosynthetic process
  evidence_type: IMP
  original_reference_id: PMID:9824441
  qualifier: involved_in
  review:
    summary: HPRT-deficiency carrier study; the salvage pathway produces the purine
      nucleotides IMP and GMP, contributing to purine nucleotide biosynthesis.
    action: KEEP_AS_NON_CORE
    reason: HPRT1 does biosynthesize purine nucleotides (IMP, GMP) via salvage, so this
      broad parent term is correct, but the specific salvage terms (IMP salvage, GMP
      salvage, purine ribonucleoside salvage) capture the function more precisely. Retained
      as non-core general parent.
    supported_by:
    - reference_id: file:human/HPRT1/HPRT1-uniprot.txt
      supporting_text: Plays a central role in the generation of purine nucleotides through
        the purine salvage pathway.
- term:
    id: GO:0000287
    label: magnesium ion binding
  evidence_type: IDA
  original_reference_id: PMID:10360366
  qualifier: enables
  review:
    summary: Transition-state analog crystal structure showing two Mg2+ ions bound at the
      active site sandwiching the pyrophosphate, directly supporting magnesium ion binding.
    action: ACCEPT
    reason: Directly demonstrated by the structure of human HGPRT with the transition-state
      analog and Mg2+-pyrophosphate; the enzyme binds two Mg2+ ions per subunit essential
      for catalysis.
    supported_by:
    - reference_id: PMID:10360366
      supporting_text: Two Mg2+ ions sandwich the pyrophosphate and contact both hydroxyls
        of the ribosyl analog.
- term:
    id: GO:0004422
    label: hypoxanthine phosphoribosyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:6300847
  qualifier: enables
  review:
    summary: The cloned full-length human HPRT cDNA expresses functional HPRT enzyme
      activity, directly supporting the hypoxanthine phosphoribosyltransferase activity.
    action: ACCEPT
    reason: Expression of the human cDNA restored HPRT enzyme activity in HPRT-deficient
      cells (HAT selection), confirming the core catalytic function.
    supported_by:
    - reference_id: PMID:6300847
      supporting_text: leads to the expression of human HPRT enzyme activity in cells stably
        transfected and selected for enzyme activity in hypoxanthine/aminopterin/thymidine
        medium
- term:
    id: GO:0004422
    label: hypoxanthine phosphoribosyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:9521733
  qualifier: enables
  review:
    summary: Catalytic mechanism study of human HGPRTase (Asp137 general acid/base;
      characterization of the hypoxanthine to IMP reaction), directly supporting the
      hypoxanthine phosphoribosyltransferase activity.
    action: ACCEPT
    reason: Detailed kinetic and mechanistic characterization of the purified/mutant human
      enzyme; core catalytic function.
    supported_by:
    - reference_id: PMID:9521733
      supporting_text: catalyzes the reversible formation of IMP and GMP from their respective
        bases hypoxanthine (Hx) and guanine (Gua)
core_functions:
- description: Hypoxanthine phosphoribosyltransferase activity; transfers the
    5-phosphoribosyl group from PRPP onto hypoxanthine to form IMP, salvaging hypoxanthine
    into the purine nucleotide pool.
  molecular_function:
    id: GO:0004422
    label: hypoxanthine phosphoribosyltransferase activity
  directly_involved_in:
  - id: GO:0006166
    label: purine ribonucleoside salvage
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: file:human/HPRT1/HPRT1-uniprot.txt
    supporting_text: Reaction=IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-
  - reference_id: PMID:9521733
    supporting_text: catalyzes the reversible formation of IMP and GMP from their respective
      bases hypoxanthine (Hx) and guanine (Gua)
- description: Guanine phosphoribosyltransferase activity; transfers the 5-phosphoribosyl
    group from PRPP onto guanine to form GMP, salvaging guanine into the purine nucleotide
    pool. Requires magnesium as cofactor; the active enzyme is a cytosolic homotetramer.
  molecular_function:
    id: GO:0052657
    label: guanine phosphoribosyltransferase activity
  directly_involved_in:
  - id: GO:0006166
    label: purine ribonucleoside salvage
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: file:human/HPRT1/HPRT1-uniprot.txt
    supporting_text: Reaction=GMP + diphosphate = guanine + 5-phospho-alpha-D-ribose 1-
  - reference_id: PMID:4208686
    supporting_text: 'Human hypoxanthine-guanine phosphoribosyltransferase (HGPRT): purification
      and properties.'
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10360366
  title: The 2.0 A structure of human hypoxanthine-guanine phosphoribosyltransferase
    in complex with a transition-state analog inhibitor.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Structure of human HGPRT with transition-state analog and Mg2+-PPi;
      directly supports magnesium ion binding and catalytic mechanism.
- id: PMID:15990111
  title: The crystal structure of free human hypoxanthine-guanine phosphoribosyltransferase
    reveals extensive conformational plasticity throughout the catalytic cycle.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Apoenzyme structure; describes movement of subunits within the tetramer,
      supporting the homotetramer annotation.
- id: PMID:16189514
  title: Towards a proteome-scale map of the human protein-protein interaction network.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput Y2H interactome; supports only a bare protein binding
      annotation, uninformative for HPRT1 function.
- id: PMID:19060904
  title: An empirical framework for binary interactome mapping.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Systematic HT-Y2H framework paper; underlies a bare protein binding
      annotation.
- id: PMID:19527031
  title: 'Inhibition of hypoxanthine-guanine phosphoribosyltransferase by acyclic
    nucleoside phosphonates: a new class of antimalarial therapeutics.'
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Abstract foregrounds the P. falciparum enzyme but explicitly assays the
      corresponding human HGPRT (Ki values) and reports structures of human HGPRT; a
      UniProt EC 2.4.2.8 evidence source for HPRT1 catalytic activity.
- id: PMID:20458337
  title: MHC class II-associated proteins in B-cell exosomes and potential functional
    implications for exosome biogenesis.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: HT mass-spec detection of HPRT1 in B-cell exosome proteome; a sighting,
      not functional localization.
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: HT interactome map; supports bare protein binding and self-interaction
      (identical protein binding) annotations.
- id: PMID:25502805
  title: A massively parallel pipeline to clone DNA variants and examine molecular
    phenotypes of human disease mutations.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: HT variant/interaction pipeline; supports a self-interaction (identical
      protein binding) annotation consistent with the homotetramer.
- id: PMID:25910212
  title: Widespread macromolecular interaction perturbations in human genetic disorders.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: HT interactome perturbation study; supports a bare protein binding
      annotation.
- id: PMID:31515488
  title: Extensive disruption of protein interactions by genetic variants across the
    allele frequency spectrum in human populations.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: HT variant-interaction study; supports bare protein binding and
      self-interaction annotations.
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: HT binary interactome reference map (HuRI); supports bare protein binding
      and self-interaction annotations.
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins
    and Uncovers Widespread Protein Aggregation in Affected Brains.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: HT interactome of neurodegenerative disease proteins; supports a bare
      protein binding annotation (incl. HTT).
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: BioPlex AP-MS interactome; supports a bare protein binding annotation.
- id: PMID:4208686
  title: 'Human hypoxanthine-guanine phosphoribosyltransferase (HGPRT): purification
    and properties.'
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Classic purification/biochemical characterization of the human enzyme;
      supports guanine PRT activity and GMP salvage (abstract-only in cache; curator read
      full text).
- id: PMID:6300847
  title: Isolation and characterization of a full-length expressible cDNA for human
    hypoxanthine phosphoribosyl transferase.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cloned human HPRT cDNA expresses functional enzyme activity (HAT
      selection); supports hypoxanthine PRT activity and cytoplasmic localization.
- id: PMID:8044844
  title: The crystal structure of human hypoxanthine-guanine phosphoribosyltransferase
    with bound GMP.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Structure with bound GMP; Lys165 confers specificity for guanine and
      hypoxanthine over adenine (argues against AMP salvage).
- id: PMID:8643611
  title: Dopamine transporters are markedly reduced in Lesch-Nyhan disease in vivo.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: MISCITED
    review_notes: Documents reduced striatal DA transporters in LND patients (a downstream
      disease phenotype); does not establish an HPRT1 molecular function of regulating
      dopamine metabolism. Underlies an over-annotated GO:0045964 annotation.
- id: PMID:9521733
  title: 'Catalysis in human hypoxanthine-guanine phosphoribosyltransferase: Asp 137
    acts as a general acid/base.'
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Mechanistic study of human HGPRTase; states the enzyme catalyzes
      reversible IMP/GMP formation from hypoxanthine/guanine and PRPP.
- id: PMID:9824441
  title: Purine metabolism in female heterozygotes for hypoxanthine-guanine phosphoribosyltransferase
    deficiency.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Carrier study; reduced HPRT activity causes purine overproduction and
      elevated hypoxanthine/xanthine excretion, evidencing the salvage role.
- id: Reactome:R-HSA-74215
  title: HPRT1 catalyzes the conversion of guanine or hypoxanthine to GMP or IMP
  findings: []
- id: Reactome:R-HSA-9734274
  title: Defective HPRT1 does not convert guanine or hypoxanthine to GMP or IMP
  findings: []
- id: Reactome:R-HSA-9748951
  title: HPRT1 tetramer transfers phosphoribosyl group to 6MP to form 6TIMP
  findings: []

Gene Description

Existing Annotations Review

Core Functions

Hypoxanthine phosphoribosyltransferase activity; transfers the 5-phosphoribosyl group from PRPP onto hypoxanthine to form IMP, salvaging hypoxanthine into the purine nucleotide pool.

Guanine phosphoribosyltransferase activity; transfers the 5-phosphoribosyl group from PRPP onto guanine to form GMP, salvaging guanine into the purine nucleotide pool. Requires magnesium as cofactor; the active enzyme is a cytosolic homotetramer.

References

📚 Additional Documentation

Notes

HPRT1 (Hypoxanthine-guanine phosphoribosyltransferase, HGPRT) — review notes

Core function (well established)

Structure

Disease

Annotation review reasoning

📄 View Raw YAML