PNP

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004731 purine-nucleoside phosphorylase activity	IBA GO_REF:0000033	ACCEPT	Summary: Core molecular function of PNP: phosphorolytic cleavage of purine (deoxy)ribonucleosides. Phylogenetic (IBA) annotation consistent with abundant human experimental evidence. Reason: This is the well-established core catalytic activity of PNP (EC 2.4.2.1), directly demonstrated for the human enzyme by multiple experimental studies. Supporting Evidence: PMID:6771276 the phosphorolysis of inosine, deoxyinosine, guanosine, and deoxyguanosine with PMID:23438750 catalyzes the reversible phosphorolysis of purine (deoxy)-ribonucleosides to the corresponding purine base
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: PNP is a soluble cytosolic enzyme; phylogenetic assignment of cytosolic localization is correct and matches direct evidence in human cells. Reason: UniProt records the subcellular location as Cytoplasm, cytosol, and human immunofluorescence (HPA) and direct assays place PNP in the cytosol; this is the site of its catalytic function.
GO:0006148 inosine catabolic process	IBA GO_REF:0000033	ACCEPT	Summary: PNP phosphorolyses inosine to hypoxanthine, a committed step of inosine catabolism/salvage. Core biological process. Reason: Directly demonstrated: purified human PNP catalyzes phosphorolysis of inosine, supporting its role in inosine catabolism. Supporting Evidence: PMID:6771276 the phosphorolysis of inosine, deoxyinosine, guanosine, and deoxyguanosine with
GO:0006149 deoxyinosine catabolic process	IBA GO_REF:0000033	ACCEPT	Summary: PNP phosphorolyses 2'-deoxyinosine to hypoxanthine; part of its core (deoxy)nucleoside catabolic activity. Reason: Purified human PNP catalyzes deoxyinosine phosphorolysis, and the enzyme acts equally on ribo- and deoxyribonucleosides of 6-oxopurines. Supporting Evidence: PMID:6771276 the phosphorolysis of inosine, deoxyinosine, guanosine, and deoxyguanosine with
GO:0006161 deoxyguanosine catabolic process	IBA GO_REF:0000033	ACCEPT	Summary: PNP phosphorolyses 2'-deoxyguanosine to guanine; a core catabolic step and the one most relevant to PNP-deficiency pathology (dGTP accumulation). Reason: Purified human PNP catalyzes deoxyguanosine phosphorolysis; failure of this step underlies the T-cell-toxic (deoxy)guanosine/dGTP buildup in PNP deficiency. Supporting Evidence: PMID:6771276 the phosphorolysis of inosine, deoxyinosine, guanosine, and deoxyguanosine with
GO:0034355 NAD+ biosynthetic process via the salvage pathway	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: PNP phosphorolyses nicotinamide riboside (NR) to nicotinamide, providing a kinase-independent entry into NAD+ salvage. Real but not the core catabolic function of PNP. Reason: Mammalian PNP is the enzyme responsible for Nrk1-independent NR utilization, cleaving NR (and nicotinic acid riboside) to feed NAD+ salvage; this is a secondary/alternative-substrate role downstream of nucleoside phosphorolysis rather than PNP's principal purine-catabolic function. Supporting Evidence: PMID:19001417 that mammalian purine nucleoside phosphorylase but not methylthioadenosine
GO:0046115 guanosine catabolic process	IBA GO_REF:0000033	ACCEPT	Summary: PNP phosphorolyses guanosine to guanine; a core catabolic/salvage step. Reason: Purified human PNP catalyzes guanosine phosphorolysis with high affinity (KM ~6 uM), a core substrate of the enzyme. Supporting Evidence: PMID:6771276 the phosphorolysis of inosine, deoxyinosine, guanosine, and deoxyguanosine with
GO:0003824 catalytic activity	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: Root-level catalytic activity term from InterPro mapping; uninformative given the specific EC 2.4.2.1 activity is annotated. Reason: GO:0003824 is the most general molecular-function term and conveys nothing beyond the specific purine-nucleoside phosphorylase activity already annotated.
GO:0004731 purine-nucleoside phosphorylase activity	IEA GO_REF:0000120	ACCEPT	Summary: Same core molecular function via automated EC/RHEA/ARBA mapping; correct. Reason: Automated mapping (EC 2.4.2.1 / RHEA:27646) to purine-nucleoside phosphorylase activity is accurate and matches experimental evidence.
GO:0005829 cytosol	IEA GO_REF:0000044	ACCEPT	Summary: Cytosol from UniProt subcellular-location keyword mapping; correct. Reason: Consistent with the curated Cytoplasm/cytosol location and direct human evidence.
GO:0009116 nucleoside metabolic process	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: Broad but correct parent process (nucleoside metabolism) from InterPro mapping. Reason: Accurate as a general process term but less informative than the specific purine (deoxy)nucleoside catabolic/salvage terms already present.
GO:0016763 pentosyltransferase activity	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: Correct parent MF (PNP is a glycosyltransferase/pentosyltransferase, EC 2.4.2) but broader than the specific activity. Reason: GO:0016763 is the accurate broad classification of the reaction chemistry; retained as a non-core parent of purine-nucleoside phosphorylase activity.
GO:0047975 guanosine phosphorylase activity	IEA GO_REF:0000116	ACCEPT	Summary: Substrate-specific child activity (guanosine + phosphate = guanine + ribose-1-phosphate); correct via RHEA mapping. Reason: PNP has robust guanosine phosphorylase activity (KM ~6 uM), a specific facet of its EC 2.4.2.1 activity; automated RHEA:13233 mapping is correct.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	MARK AS OVER ANNOTATED	Summary: Uninformative "protein binding" from a large-scale neurodegenerative-disease Y2H interactome screen; multiple heterogeneous partners with no defined functional consequence for PNP. Reason: This and the other GO:0005515 IPI lines derive from high-throughput binary interactome mapping (yeast two-hybrid); the term is non-specific and does not inform PNP's molecular function. Retained (not removed) per curation policy on experimental IPI, but flagged as over-annotation. Supporting Evidence: PMID:32814053 generated by systematic yeast two-hybrid
GO:0042802 identical protein binding	IPI PMID:20212140 Four generations of transition-state analogues for human pur...	ACCEPT	Summary: Self-association reflecting PNP's obligate homotrimeric quaternary structure; biologically meaningful. Reason: Human PNP is a homotrimer with catalytic sites at subunit interfaces, so identical-protein (self) binding is a genuine structural property of the enzyme. Supporting Evidence: PMID:20212140 Four generations of transition-state analogues for human purine nucleoside
GO:0042802 identical protein binding	IPI PMID:25502805 A massively parallel pipeline to clone DNA variants and exam...	ACCEPT	Summary: Self-association consistent with the homotrimeric architecture of PNP. Reason: Homotrimer formation is a well-established structural feature; identical protein binding is appropriate. Supporting Evidence: PMID:23438750 Human PNP is a homotrimer
GO:0042802 identical protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	ACCEPT	Summary: Self-association consistent with the homotrimeric architecture of PNP. Reason: Homotrimer formation is a well-established structural feature; identical protein binding is appropriate. Supporting Evidence: PMID:23438750 Human PNP is a homotrimer
GO:0042802 identical protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	ACCEPT	Summary: Self-association consistent with the homotrimeric architecture of PNP. Reason: Homotrimer formation is a well-established structural feature; identical protein binding is appropriate. Supporting Evidence: PMID:23438750 Human PNP is a homotrimer
GO:0005829 cytosol	IDA GO_REF:0000052	ACCEPT	Summary: Direct immunofluorescence (HPA) localization to cytosol; correct core location. Reason: Direct human-cell evidence for cytosolic localization, the functional site of the enzyme.
GO:0047975 guanosine phosphorylase activity	EXP PMID:9305964 Purine nucleoside phosphorylase. 3. Reversal of purine base ...	ACCEPT	Summary: Experimentally measured guanosine phosphorylase activity (a specific facet of EC 2.4.2.1) for human PNP. Reason: Kinetic characterization of human PNP includes guanosine as a high-affinity substrate, supporting guanosine phosphorylase activity. Supporting Evidence: PMID:9305964 highly specific for 6-oxopurine
GO:0004731 purine-nucleoside phosphorylase activity	IDA PMID:6771276 Characterization of purine nucleoside phosphorylase from hum...	ACCEPT	Summary: Direct assay of purified human (granulocyte) PNP demonstrating phosphorolysis of 6-oxopurine (deoxy)nucleosides. Core function. Reason: Purified human enzyme catalyzes phosphorolysis of inosine, deoxyinosine, guanosine and deoxyguanosine, directly establishing the activity. Supporting Evidence: PMID:6771276 the phosphorolysis of inosine, deoxyinosine, guanosine, and deoxyguanosine with
GO:0006149 deoxyinosine catabolic process	IDA PMID:6771276 Characterization of purine nucleoside phosphorylase from hum...	ACCEPT	Summary: PNP phosphorolyses 2'-deoxyinosine (to hypoxanthine); part of deoxyinosine catabolism. Reason: Directly demonstrated deoxyinosine phosphorolysis by the purified human enzyme. Supporting Evidence: PMID:6771276 the phosphorolysis of inosine, deoxyinosine, guanosine, and deoxyguanosine with
GO:0006157 deoxyadenosine catabolic process	IDA PMID:6771276 Characterization of purine nucleoside phosphorylase from hum...	KEEP AS NON CORE	Summary: Pathway-level (acts_upstream_of_or_within) annotation for deoxyadenosine catabolism. PNP does not act directly on deoxyadenosine (an adenine nucleoside), but participates downstream in the pathway after deamination. Reason: The cited paper explicitly states that adenine (deoxy)ribonucleosides are NOT substrates of PNP, so this is not a direct enzymatic activity; however the curator's acts_upstream_of_or_within annotation reflects PNP's downstream role in the broader deoxyadenosine catabolic pathway (relevant to the dATP/dGTP accumulation of PNP deficiency). Retained as non-core rather than removed. Supporting Evidence: PMID:6771276 ribonucleosides and deoxyribonucleosides of adenine and the pyrimidines are not
GO:0006204 IMP catabolic process	IDA PMID:6771276 Characterization of purine nucleoside phosphorylase from hum...	KEEP AS NON CORE	Summary: Pathway-level annotation for IMP catabolism. PNP acts on inosine (the dephosphorylated nucleoside), not on IMP directly, but functions downstream in the IMP-degradation pathway. Reason: PNP's substrate is inosine (from IMP after 5'-nucleotidase), not IMP itself; the acts_upstream_of_or_within qualifier captures its downstream role in the IMP catabolic pathway. Retained as non-core.
GO:0046059 dAMP catabolic process	IDA PMID:6771276 Characterization of purine nucleoside phosphorylase from hum...	KEEP AS NON CORE	Summary: Pathway-level annotation for dAMP catabolism. PNP does not act on dAMP or on adenine deoxynucleosides directly; downstream/pathway-context annotation. Reason: PNP does not phosphorolyse adenine nucleosides (the paper states adenine deoxyribonucleosides are not substrates) and acts on nucleosides not nucleotides; the annotation reflects downstream pathway participation. Retained as non-core rather than removed for an experimental IDA. Supporting Evidence: PMID:6771276 ribonucleosides and deoxyribonucleosides of adenine and the pyrimidines are not
GO:0005829 cytosol	TAS Reactome:R-HSA-9735775	ACCEPT	Summary: Cytosol localization from Reactome (defective-PNP inosine reaction); correct core location. Reason: Consistent with the established cytosolic site of PNP function.
GO:0005829 cytosol	TAS Reactome:R-HSA-9735789	ACCEPT	Summary: Cytosol localization from Reactome (defective-PNP guanosine reaction); correct. Reason: Consistent with the established cytosolic site of PNP function.
GO:0006149 deoxyinosine catabolic process	IDA PMID:6771276 Characterization of purine nucleoside phosphorylase from hum...	ACCEPT	Summary: Duplicate (involved_in) annotation of deoxyinosine catabolism; directly supported. Reason: Direct assay of deoxyinosine phosphorolysis by purified human PNP. Supporting Evidence: PMID:6771276 the phosphorolysis of inosine, deoxyinosine, guanosine, and deoxyguanosine with
GO:0006157 deoxyadenosine catabolic process	IDA PMID:6771276 Characterization of purine nucleoside phosphorylase from hum...	KEEP AS NON CORE	Summary: involved_in duplicate of the deoxyadenosine-catabolism pathway annotation. PNP does not act on deoxyadenosine directly. Reason: As above: adenine deoxyribonucleosides are not PNP substrates, so this reflects a downstream/pathway role rather than a direct activity; retained as non-core. Supporting Evidence: PMID:6771276 ribonucleosides and deoxyribonucleosides of adenine and the pyrimidines are not
GO:0006204 IMP catabolic process	IDA PMID:6771276 Characterization of purine nucleoside phosphorylase from hum...	KEEP AS NON CORE	Summary: involved_in duplicate of the IMP-catabolism pathway annotation; PNP acts on inosine downstream of IMP. Reason: PNP's direct substrate is inosine, not IMP; retained as a downstream pathway-level annotation.
GO:0000255 allantoin metabolic process	IDA PMID:6771276 Characterization of purine nucleoside phosphorylase from hum...	MARK AS OVER ANNOTATED	Summary: Allantoin metabolism is several steps downstream of PNP (via urate) and does not occur in humans, who lack urate oxidase; this appears to be an over-propagated/incorrect pathway annotation for the human gene. Reason: The cited human granulocyte study characterizes PNP nucleoside phosphorolysis and does not address allantoin; humans do not synthesize allantoin (uricase is a pseudogene), so an allantoin metabolic process annotation is not appropriate for human PNP. Flagged as over-annotation rather than removed, since it is an experimental IDA whose full text was not reviewed here.
GO:0046059 dAMP catabolic process	IDA PMID:6771276 Characterization of purine nucleoside phosphorylase from hum...	KEEP AS NON CORE	Summary: involved_in duplicate of the dAMP-catabolism pathway annotation; PNP acts on nucleosides, not dAMP, and not on adenine nucleosides. Reason: Retained as a downstream pathway-level annotation; PNP does not directly act on dAMP or adenine (deoxy)nucleosides. Supporting Evidence: PMID:6771276 ribonucleosides and deoxyribonucleosides of adenine and the pyrimidines are not
GO:0004731 purine-nucleoside phosphorylase activity	IDA PMID:5056638 Purine nucleoside phosphorylase activity of human erythrocyt...	ACCEPT	Summary: PNP enzymatic activity measured in human erythrocytes; supports the core molecular function. Reason: Human erythrocyte PNP activity assay supports the enzyme's phosphorylase activity (abstract-only cache; defer to the experimental curator).
GO:0004731 purine-nucleoside phosphorylase activity	IDA PMID:23438750 Catalytic site conformations in human PNP by 19F-NMR and cry...	ACCEPT	Summary: Kinetic/structural characterization of human PNP demonstrating phosphorolysis of purine (deoxy)ribonucleosides. Core function. Reason: Directly establishes reversible phosphorolysis of purine (deoxy)ribonucleosides by the human enzyme, including steady-state kinetics for inosine. Supporting Evidence: PMID:23438750 catalyzes the reversible phosphorolysis of purine (deoxy)-ribonucleosides to the corresponding purine base
GO:0006148 inosine catabolic process	IDA PMID:23438750 Catalytic site conformations in human PNP by 19F-NMR and cry...	ACCEPT	Summary: PNP phosphorolyses inosine (to hypoxanthine); core catabolic step, kinetically characterized. Reason: Inosine phosphorolysis is directly characterized (steady-state kinetics) for the human enzyme. Supporting Evidence: PMID:23438750 catalyzes the reversible phosphorolysis of purine (deoxy)-ribonucleosides to the corresponding purine base
GO:0043101 purine-containing compound salvage	IDA PMID:18938130 Effect of the phosphate substrate on drug-inhibitor binding ...	ACCEPT	Summary: PNP participates in purine salvage by generating free bases (hypoxanthine, guanine) for re-use; core biological role. Reason: PNP's phosphorolysis of purine nucleosides yields free bases that are salvaged (e.g. by HPRT1); the reaction equilibrium in vivo also supports nucleoside (re)synthesis, consistent with a salvage role. UniProt assigns the pathway "purine nucleoside salvage".
GO:0009165 nucleotide biosynthetic process	IGI PMID:19001417 Nicotinamide riboside and nicotinic acid riboside salvage in...	MARK AS OVER ANNOTATED	Summary: Broad "nucleotide biosynthetic process" from a genetic-interaction study of NR salvage; PNP itself catabolizes nucleosides, so nucleotide biosynthesis is an over-broad downstream framing. Reason: PNP produces free bases/ribose-1-phosphate that can be recycled into nucleotides via salvage, but PNP is a phosphorylase (nucleoside catabolism), and GO:0009165 is a broad biosynthetic term better assigned to the downstream salvage kinases. The specific NR-catabolism and salvage terms already capture the relevant biology.
GO:0005576 extracellular region	TAS Reactome:R-HSA-6798748	KEEP AS NON CORE	Summary: Extracellular localization via Reactome neutrophil-degranulation (secretory-granule exocytosis) pathway; PNP is detected extracellularly but this is not its functional compartment. Reason: PNP is a cytosolic enzyme released during neutrophil degranulation/secretion and detected in the extracellular space; not the site of its catalytic function.
GO:0005576 extracellular region	TAS Reactome:R-HSA-6800434	KEEP AS NON CORE	Summary: Extracellular localization via Reactome ficolin-rich-granule exocytosis; detected extracellularly, non-functional compartment. Reason: Same as the secretory-granule route: released cytosolic protein, not the functional location.
GO:0034774 secretory granule lumen	TAS Reactome:R-HSA-6798748	KEEP AS NON CORE	Summary: Secretory-granule-lumen localization from neutrophil-degranulation Reactome pathway; reflects presence in granules, not functional site. Reason: PNP is packaged in neutrophil granules and released on degranulation; a non-core localization for a cytosolic enzyme.
GO:1904813 ficolin-1-rich granule lumen	TAS Reactome:R-HSA-6800434	KEEP AS NON CORE	Summary: Ficolin-1-rich granule lumen from neutrophil-degranulation Reactome; non-core localization. Reason: Reflects granule content in neutrophils, not the cytosolic functional site.
GO:0070062 extracellular exosome	HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres...	KEEP AS NON CORE	Summary: Detected in extracellular exosomes by high-throughput proteomics; PNP is an abundant cytosolic protein commonly captured in exosome preparations. Reason: Exosome proteomics frequently recovers abundant cytosolic enzymes; this does not indicate a functional exosomal role for PNP.
GO:0070062 extracellular exosome	HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos...	KEEP AS NON CORE	Summary: Detected in urinary exosomes by proteomics; non-functional localization. Reason: High-throughput exosome/proteomics detection of an abundant cytosolic enzyme; not its functional compartment.
GO:0070062 extracellular exosome	HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote...	KEEP AS NON CORE	Summary: Detected in B-cell exosomes by proteomics; non-functional localization. Reason: As above; proteomic detection in exosomes does not establish a functional role.
GO:0005829 cytosol	TAS Reactome:R-HSA-112033	ACCEPT	Summary: Cytosol localization from Reactome (PNP inosine synthesis reaction); correct core location. Reason: Consistent with the established cytosolic site of PNP function.
GO:0005829 cytosol	TAS Reactome:R-HSA-112034	ACCEPT	Summary: Cytosol localization from Reactome (PNP guanosine synthesis reaction); correct. Reason: Consistent with the established cytosolic site of PNP function.
GO:0005829 cytosol	TAS Reactome:R-HSA-74242	ACCEPT	Summary: Cytosol localization from Reactome (PNP inosine phosphorolysis); correct. Reason: Consistent with the established cytosolic site of PNP function.
GO:0005829 cytosol	TAS Reactome:R-HSA-74249	ACCEPT	Summary: Cytosol localization from Reactome (PNP guanosine phosphorolysis); correct. Reason: Consistent with the established cytosolic site of PNP function.
GO:0005829 cytosol	TAS Reactome:R-HSA-9755044	ACCEPT	Summary: Cytosol localization from Reactome (PNP-mediated ribavirin transformation); correct core location. Reason: Consistent with the established cytosolic site of PNP function.
GO:0032743 positive regulation of interleukin-2 production	IMP PMID:16930574 Intracellular delivery of purine nucleoside phosphorylase (P...	KEEP AS NON CORE	Summary: Restoring PNP in PNP-deficient T lymphocytes corrects IL-2 secretion; an indirect, downstream immunological consequence of the metabolic enzyme. Reason: PNP does not directly regulate IL-2 transcription; loss of PNP causes dGTP-mediated T-cell dysfunction, and enzyme replacement rescues IL-2 secretion. This is a physiological consequence, not a core molecular role. Supporting Evidence: PMID:16930574 functions of PNP-deficient T lymphocytes including their response to stimulation
GO:0001882 nucleoside binding	IDA PMID:9305962 Purine nucleoside phosphorylase. 1. Structure-function studi...	ACCEPT	Summary: PNP binds its purine-nucleoside substrate in the active site; supporting molecular function underlying catalysis. Reason: Structure-function studies define the purine-binding/active site of human PNP that engages the nucleoside substrate. Supporting Evidence: PMID:9305962 Purine nucleoside phosphorylase. 1. Structure-function studies.
GO:0002060 purine nucleobase binding	IDA PMID:9305962 Purine nucleoside phosphorylase. 1. Structure-function studi...	ACCEPT	Summary: PNP binds the purine base (product/substrate) in its active site; supporting MF consistent with structural studies. Reason: The purine base binding site (Asn243/Glu201) is defined by structure-function mutagenesis; base binding is integral to the phosphorolysis reaction. Supporting Evidence: PMID:9305962 Purine nucleoside phosphorylase. 1. Structure-function studies.
GO:0004731 purine-nucleoside phosphorylase activity	IDA PMID:16930574 Intracellular delivery of purine nucleoside phosphorylase (P...	ACCEPT	Summary: PNP enzymatic activity assayed in the enzyme-replacement study; supports the core molecular function. Reason: Intracellular PNP activity is measured/restored in PNP-deficient lymphocytes, confirming the enzyme's phosphorylase activity. Supporting Evidence: PMID:16930574 Purine nucleoside phosphorylase (PNP) is an intracellular enzyme crucial for
GO:0004731 purine-nucleoside phosphorylase activity	IDA PMID:18938130 Effect of the phosphate substrate on drug-inhibitor binding ...	ACCEPT	Summary: PNP enzymatic activity measured by ITC-based assay; supports the core MF. Reason: The study assays human PNP enzymatic activity (7-methylguanosine + phosphate), confirming phosphorylase activity.
GO:0004731 purine-nucleoside phosphorylase activity	IDA PMID:3029074 A human purine nucleoside phosphorylase deficiency caused by...	ACCEPT	Summary: PNP catalytic activity (and its loss in the E89K deficiency variant) directly demonstrated; supports the core MF. Reason: Reversion of the single-base E89K mutation restores PNP catalytic activity, directly linking the gene product to phosphorylase activity. Supporting Evidence: PMID:3029074 This single base mutation alters the codon at position 89 from Glu to Lys, a
GO:0004731 purine-nucleoside phosphorylase activity	IDA PMID:9305962 Purine nucleoside phosphorylase. 1. Structure-function studi...	ACCEPT	Summary: Steady-state kinetics of human PNP and active-site mutants; core MF. Reason: Structure-function/mutagenesis study directly characterizes the phosphorylase activity of human PNP. Supporting Evidence: PMID:9305962 Purine nucleoside phosphorylase. 1. Structure-function studies.
GO:0005737 cytoplasm	IDA PMID:16930574 Intracellular delivery of purine nucleoside phosphorylase (P...	ACCEPT	Summary: Direct evidence that PNP is predominantly cytoplasmic; consistent with the cytosol annotations. Reason: Endogenous and delivered PNP are predominantly distributed in the cytoplasm, supporting the cytoplasm/cytosol localization. Supporting Evidence: PMID:16930574 distributed in the cytoplasm
GO:0005737 cytoplasm	IDA PMID:3029074 A human purine nucleoside phosphorylase deficiency caused by...	ACCEPT	Summary: Cytoplasmic localization of PNP; consistent with cytosolic function. Reason: Consistent with the curated cytoplasm/cytosol location of the enzyme.
GO:0006139 nucleobase-containing compound metabolic process	IDA PMID:3029074 A human purine nucleoside phosphorylase deficiency caused by...	MARK AS OVER ANNOTATED	Summary: Very broad "nucleobase-containing compound metabolic process"; correct but far less informative than the specific purine catabolic/salvage terms. Reason: This high-level parent term is subsumed by the specific inosine/guanosine (deoxy)nucleoside catabolic and purine salvage terms already annotated.
GO:0006738 nicotinamide riboside catabolic process	IDA PMID:19001417 Nicotinamide riboside and nicotinic acid riboside salvage in...	ACCEPT	Summary: PNP phosphorolyses nicotinamide riboside to nicotinamide, a genuine alternative-substrate activity feeding NAD+ salvage. Reason: Mammalian PNP (not MTAP) is responsible for kinase-independent NR utilization, cleaving NR to nicotinamide; directly demonstrated in mammalian extracts and by Immucillin-H (PNP-specific inhibitor) sensitivity. Supporting Evidence: PMID:19001417 that mammalian purine nucleoside phosphorylase but not methylthioadenosine
GO:0006955 immune response	IMP PMID:16930574 Intracellular delivery of purine nucleoside phosphorylase (P...	KEEP AS NON CORE	Summary: PNP is required for normal T-cell immune function; its deficiency causes T-cell immunodeficiency. Indirect, downstream physiological role. Reason: "Immune response" is a broad downstream consequence of PNP's metabolic role (dGTP toxicity to T lymphocytes on loss of function); enzyme replacement in PNP-deficient T cells corrects their function. Not a core molecular function. Supporting Evidence: PMID:16930574 functions of PNP-deficient T lymphocytes including their response to stimulation
GO:0009410 response to xenobiotic stimulus	IMP PMID:15047506 Role of purine nucleoside phosphorylase in interactions betw...	KEEP AS NON CORE	Summary: PNP phosphorolyses the antiviral prodrug 2',3'-dideoxyinosine (ddI), a drug/xenobiotic-metabolism role. Reason: PNP-dependent breakdown of the xenobiotic ddI is a pharmacologically relevant but peripheral activity reflecting its broad nucleoside-phosphorolysis chemistry, not a core physiological process. Supporting Evidence: PMID:15047506 A metabolic route for ddI clearance is its breakdown by purine nucleoside
GO:0042301 phosphate ion binding	IDA PMID:18938130 Effect of the phosphate substrate on drug-inhibitor binding ...	ACCEPT	Summary: PNP binds inorganic phosphate, the co-substrate/nucleophile of phosphorolysis, in a dedicated phosphate-binding site; supporting MF. Reason: Phosphate is the second substrate of the phosphorolysis reaction and binds a defined active-site pocket; phosphate binding is integral to catalysis and modulates inhibitor binding. Supporting Evidence: PMID:18938130 Effect of the phosphate substrate on drug-inhibitor binding to human purine
GO:0034418 urate biosynthetic process	IDA PMID:16964310 TAT-mediated intracellular delivery of purine nucleoside pho...	KEEP AS NON CORE	Summary: PNP acts upstream in urate production (PNP -> hypoxanthine -> xanthine oxidase -> urate); an indirect downstream pathway role. Reason: PNP generates hypoxanthine, the substrate for downstream oxidation to urate by xanthine oxidoreductase; PNP does not itself synthesize urate, so this is a pathway-level (acts_upstream_of_or_within) annotation.
GO:0042102 positive regulation of T cell proliferation	IDA PMID:16964310 TAT-mediated intracellular delivery of purine nucleoside pho...	KEEP AS NON CORE	Summary: Restoring PNP in PNP-deficient mice corrects T-cell immunity; an indirect downstream immunological consequence. Reason: PNP is not a direct regulator of T-cell proliferation; its loss causes dGTP-mediated T-cell toxicity, and enzyme replacement (TAT-PNP) rescues immune function in PNP-deficient mice. Physiological consequence, not core function. Supporting Evidence: PMID:16964310 severe T cell immunodeficiency, neurological
GO:0004731 purine-nucleoside phosphorylase activity	IDA PMID:16964310 TAT-mediated intracellular delivery of purine nucleoside pho...	ACCEPT	Summary: PNP catalytic activity assayed/restored in the mouse enzyme-replacement study; supports the core MF. Reason: TAT-PNP delivery restores PNP enzymatic activity in PNP-deficient tissues, confirming the phosphorylase activity of the enzyme. Supporting Evidence: PMID:16964310 severe T cell immunodeficiency, neurological
GO:0006148 inosine catabolic process	IDA PMID:16964310 TAT-mediated intracellular delivery of purine nucleoside pho...	ACCEPT	Summary: PNP catabolizes inosine; restoring the activity corrects nucleoside homeostasis in PNP-deficient mice. Core catabolic role. Reason: Correction of abnormal nucleoside homeostasis on PNP replacement is consistent with PNP's core inosine-catabolic function. Supporting Evidence: PMID:16964310 abnormal nucleoside homeostasis, severe T cell immunodeficiency, neurological
GO:0046638 positive regulation of alpha-beta T cell differentiation	IDA PMID:16964310 TAT-mediated intracellular delivery of purine nucleoside pho...	KEEP AS NON CORE	Summary: Indirect downstream immunological consequence of PNP activity (T-cell development/function rescued by enzyme replacement). Reason: PNP does not directly regulate alpha-beta T-cell differentiation; the phenotype reflects relief of dGTP toxicity to developing/activated T cells upon restoring enzyme activity. Non-core physiological consequence. Supporting Evidence: PMID:16964310 severe T cell immunodeficiency, neurological

Gene Description

Existing Annotations Review

Core Functions

Phosphorolytic cleavage of the N-glycosidic bond of 6-oxopurine (deoxy)ribonucleosides (inosine, guanosine, 2'-deoxyinosine, 2'-deoxyguanosine), using inorganic phosphate to produce the free purine base (hypoxanthine or guanine) plus (2'-deoxy)-alpha-D-ribose-1-phosphate.

Generation of free purine bases (hypoxanthine, guanine) from purine nucleosides, supplying the purine salvage pathway; the reversible reaction also contributes to nucleoside interconversion in purine-containing compound salvage.

References

📚 Additional Documentation

Notes

📄 View Raw YAML