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).
| 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) |
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