AMPD3

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0003876 AMP deaminase activity	IBA GO_REF:0000033	ACCEPT	Summary: Core molecular function. AMPD3 is the erythrocyte isoform of AMP deaminase (EC 3.5.4.6), catalysing AMP + H2O + H+ = IMP + NH4+. The IBA propagation across the AMP deaminase family (AMPD1/AMPD2/AMPD3 orthologs) is correct and is the well-supported molecular function of this protein. Reason: AMP deaminase activity is the defining, experimentally supported molecular function of AMPD3, corroborated by UniProt catalytic-activity annotation and by biochemical characterisation of the AMPD3 gene product. Supporting Evidence: file:human/AMPD3/AMPD3-uniprot.txt Reaction=AMP + H2O + H(+) = IMP + NH4(+); Xref=Rhea:RHEA:14777, PMID:9291127 and human isoform E are homologous cross-species AMPD3 proteins.
GO:0006188 IMP biosynthetic process	IBA GO_REF:0000033	MODIFY	Summary: AMPD3 does not perform de novo IMP biosynthesis. It regenerates IMP by hydrolytic deamination of AMP, which is a catabolic step acting on AMP, so the biological process is more accurately captured as AMP catabolism. UniProt places the reaction in the salvage arm of IMP metabolism, distinct from the de novo IMP biosynthesis branch this term sits under. Reason: The essence (AMPD3 contributes to IMP-yielding metabolism) is sound, but "IMP biosynthetic process" mis-frames a deamination/catabolic step as de novo biosynthesis; AMP catabolic process better describes the actual chemistry. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Proposed replacements: AMP catabolic process Supporting Evidence: file:human/AMPD3/AMPD3-uniprot.txt Purine metabolism; IMP biosynthesis via salvage pathway; IMP
GO:0046033 AMP metabolic process	IBA GO_REF:0000033	ACCEPT	Summary: AMPD3 acts directly on AMP (deaminating it to IMP), so participation in AMP metabolic process is correct. This is a broad but accurate parent process for the enzyme's activity. Reason: AMP is the direct substrate of AMPD3; AMP metabolic process is an accurate, appropriately general biological-process term for this enzyme. Supporting Evidence: file:human/AMPD3/AMPD3-uniprot.txt Reaction=AMP + H2O + H(+) = IMP + NH4(+); Xref=Rhea:RHEA:14777,
GO:0003876 AMP deaminase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assertion of the core molecular function (AMP deaminase), consistent with the RHEA/EC mapping (RHEA:14777, EC:3.5.4.6) and the IBA and literature-based annotations of the same term. Reason: Duplicate of the core AMP deaminase activity; the automated mapping is correct. Supporting Evidence: file:human/AMPD3/AMPD3-uniprot.txt Reaction=AMP + H2O + H(+) = IMP + NH4(+); Xref=Rhea:RHEA:14777,
GO:0006753 nucleoside phosphate metabolic process	IEA GO_REF:0000117	ACCEPT	Summary: Very broad but accurate. AMP (adenosine 5'-monophosphate) is a nucleoside phosphate, and its deamination to IMP is a nucleoside-phosphate metabolic step. This is a high-level parent of the more specific AMP metabolic/catabolic terms. Reason: Correct broad grouping term; consistent with AMPD3 acting on the nucleoside monophosphate AMP. Supporting Evidence: file:human/AMPD3/AMPD3-uniprot.txt Reaction=AMP + H2O + H(+) = IMP + NH4(+); Xref=Rhea:RHEA:14777,
GO:0009168 purine ribonucleoside monophosphate biosynthetic process	IEA GO_REF:0000002	MODIFY	Summary: This InterPro2GO mapping frames AMPD3 as biosynthetic (producing the purine ribonucleoside monophosphate IMP), but AMPD3 makes IMP by deaminating AMP, i.e. a catabolic step acting on AMP rather than de novo biosynthesis. The "biosynthetic process" framing is the same over-reach as the IMP biosynthetic process term. Reason: AMPD3 does not synthesise purine nucleotides de novo; it catabolises AMP to IMP. AMP catabolic process better represents the enzyme's role. Proposed replacements: AMP catabolic process Supporting Evidence: file:human/AMPD3/AMPD3-uniprot.txt Reaction=AMP + H2O + H(+) = IMP + NH4(+); Xref=Rhea:RHEA:14777,
GO:0019239 deaminase activity	IEA GO_REF:0000002	ACCEPT	Summary: Broad parent of the specific AMP deaminase activity. AMPD3 is a deaminase (it hydrolytically removes an amino group from AMP, releasing ammonia), so this general molecular-function term is correct, if less informative than GO:0003876. Reason: Accurate but general; it is the direct parent of the specific AMP deaminase activity already annotated. No harm in retaining the broad InterPro grouping. Supporting Evidence: file:human/AMPD3/AMPD3-uniprot.txt Reaction=AMP + H2O + H(+) = IMP + NH4(+); Xref=Rhea:RHEA:14777,
GO:0032264 IMP salvage	IEA GO_REF:0000120	ACCEPT	Summary: Matches the UniProt pathway assignment, which places AMPD3 in IMP biosynthesis via the salvage pathway (IMP from AMP, the single step of that arm). Deaminating AMP to IMP salvages the purine ring back into the IMP pool, so IMP salvage is an appropriate biological-process term. Reason: Consistent with the curated UniProt PATHWAY line placing AMPD3 in the salvage route that regenerates IMP from AMP. Supporting Evidence: file:human/AMPD3/AMPD3-uniprot.txt Purine metabolism; IMP biosynthesis via salvage pathway; IMP
GO:0005515 protein binding	IPI PMID:25910212 Widespread macromolecular interaction perturbations in human...	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" from a high-throughput edgotyping/interactome study. The WITH field cites UniProtKB:P08238 (HSP90AB1), matching the UniProt INTERACTION record (Q01432 with HSP90AB1, NbExp=2), i.e. a chaperone/quality-control interaction detected in a genome-scale mutation-perturbation screen. This term conveys no specific molecular function for AMPD3. Reason: GO:0005515 protein binding is uninformative and here derives from a large-scale interactome screen (HSP90AB1 chaperone interaction) rather than a functional partnership that defines AMPD3's activity. Per curation policy, an IPI protein-binding annotation is marked as over-annotated rather than removed. Supporting Evidence: PMID:25910212 Approximately 60% of disease-associated missense mutations perturb PPIs
GO:0006196 AMP catabolic process	IEA GO_REF:0000107	ACCEPT	Summary: Core biological process. Deamination of AMP to IMP consumes AMP, so AMPD3 participates directly in AMP catabolism. This electronically-transferred term (from the mouse ortholog Ampd3, O08739) accurately reflects the enzyme's role and is corroborated by the literature-based TAS annotation of the same term. Reason: AMP catabolic process is the accurate, appropriately specific biological process for the AMP-to-IMP deamination catalysed by AMPD3. Supporting Evidence: file:human/AMPD3/AMPD3-uniprot.txt Reaction=AMP + H2O + H(+) = IMP + NH4(+); Xref=Rhea:RHEA:14777,
GO:0034101 erythrocyte homeostasis	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Reflects the erythrocyte context of the "erythrocyte" AMP deaminase isoform and its role in setting the red-cell adenine-nucleotide pool. However, complete loss of erythrocyte AMP deaminase (AMPDDE) is clinically asymptomatic with no hematologic disorder, so AMPD3 is not required for erythrocyte homeostasis per se. This is a contextual, non-core process rather than the molecular core function. Reason: The RBC/erythrocyte context is real (AMPD3 is the erythrocyte isoform and shapes the RBC nucleotide pool), but the benign deficiency phenotype shows AMPD3 is dispensable for erythrocyte homeostasis; retain as non-core context. Supporting Evidence: file:human/AMPD3/AMPD3-uniprot.txt of erythrocyte AMP deaminase are healthy and have no hematologic
GO:0046031 ADP metabolic process	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: AMPD3's substrate is AMP, not ADP; the enzyme deaminates AMP to IMP. ADP is not a substrate or product of AMPD3. This appears to be an over-propagated electronic transfer of a broad adenine-nucleotide energy-metabolism grouping from the mouse ortholog rather than a distinct AMPD3 activity on ADP. Reason: AMPD3 does not act on ADP; while ADP levels are indirectly coupled to AMP metabolism via adenylate kinase, this term over-states a direct role in ADP metabolism. Supporting Evidence: file:human/AMPD3/AMPD3-uniprot.txt Reaction=AMP + H2O + H(+) = IMP + NH4(+); Xref=Rhea:RHEA:14777,
GO:0046032 ADP catabolic process	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: As with ADP metabolic process, AMPD3 does not catabolise ADP; its reaction is AMP to IMP plus ammonia. This is an over-propagated electronic energy-metabolism grouping from the mouse ortholog, not a direct AMPD3 function on ADP. Reason: AMPD3 has no ADP-directed catalytic activity; the term over-states its role. Supporting Evidence: file:human/AMPD3/AMPD3-uniprot.txt Reaction=AMP + H2O + H(+) = IMP + NH4(+); Xref=Rhea:RHEA:14777,
GO:0046033 AMP metabolic process	IEA GO_REF:0000107	ACCEPT	Summary: Electronic (Ensembl ortholog) duplicate of the IBA AMP metabolic process annotation. AMP is the direct substrate of AMPD3, so this is correct. Reason: AMP metabolic process accurately captures AMPD3 acting on its direct substrate AMP; duplicate of an already-accepted term. Supporting Evidence: file:human/AMPD3/AMPD3-uniprot.txt Reaction=AMP + H2O + H(+) = IMP + NH4(+); Xref=Rhea:RHEA:14777,
GO:0046034 ATP metabolic process	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: AMPD3 does not act on ATP. Its only direct effect on ATP is indirect, via pulling the adenylate kinase equilibrium (removing AMP raises the ATP/ADP ratio), which is why AMPD3 deficiency raises steady-state erythrocyte ATP by roughly 50%. A direct "ATP metabolic process" annotation over-states this indirect coupling and is an over-propagated ortholog energy-metabolism grouping. Reason: The effect on ATP is indirect (through the adenylate kinase equilibrium), not a direct AMPD3-catalysed ATP-metabolic step; annotate as over-annotation. Supporting Evidence: file:human/AMPD3/AMPD3-uniprot.txt asymptomatic condition characterized by a 50% increase in steady-state
GO:0046039 GTP metabolic process	IEA GO_REF:0000107	REMOVE	Summary: AMPD3 has no role in GTP metabolism. Its substrate is AMP and its product IMP; it neither binds nor produces GTP. This electronic transfer is a demonstrably wrong over-propagation of a broad purine-nucleotide grouping from the ortholog. Reason: There is no biochemical basis for a GTP metabolic role; AMPD3 acts solely on AMP. This is an incorrect electronic (Ensembl ortholog) inference that should be removed. Supporting Evidence: file:human/AMPD3/AMPD3-uniprot.txt Reaction=AMP + H2O + H(+) = IMP + NH4(+); Xref=Rhea:RHEA:14777,
GO:0003876 AMP deaminase activity	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity transfer of the core AMP deaminase activity from the mouse ortholog Ampd3 (O08739). Consistent with the experimentally supported, IBA and literature-based annotations of this same molecular function. Reason: Duplicate of the well-supported core molecular function; the ortholog-based ISS transfer is sound. Supporting Evidence: file:human/AMPD3/AMPD3-uniprot.txt Reaction=AMP + H2O + H(+) = IMP + NH4(+); Xref=Rhea:RHEA:14777,
GO:0005576 extracellular region	TAS Reactome:R-HSA-6798748	MARK AS OVER ANNOTATED	Summary: This localization derives from the Reactome "Exocytosis of secretory granule lumen proteins" neutrophil-degranulation pathway, which catalogs proteins found in neutrophil granule proteomes. AMPD3 is a cytosolic purine-metabolism enzyme; catalog membership in a granule/exocytosis proteome does not establish a bona fide extracellular localization or function for it. Reason: Extracellular localization for a cytosolic AMP deaminase arises from bulk neutrophil-granule proteomics rather than a genuine secreted role; treat as over-annotation, not core localization. Supporting Evidence: Reactome:R-HSA-6798748 Secretory vesicles provide a reservoir of secreted proteins and membrane-associated receptors that are required at the earliest stages of the neutrophil-mediated inflammatory response.
GO:0005576 extracellular region	TAS Reactome:R-HSA-6800434	MARK AS OVER ANNOTATED	Summary: Same situation as the other extracellular-region annotation, but sourced from the Reactome "Exocytosis of ficolin-rich granule lumen proteins" neutrophil-degranulation pathway. AMPD3's presence in this granule-exocytosis proteome does not establish a genuine extracellular localization for a cytosolic AMP deaminase. Reason: Duplicate extracellular-region assertion from bulk ficolin-rich-granule proteomics; over-annotation rather than a real secreted localization. Supporting Evidence: Reactome:R-HSA-6800434 Ficoli-1 rich granules are a relatively new fourth neutrophil granule population that is enriched in the microbial lectin ficolin-1.
GO:0034774 secretory granule lumen	TAS Reactome:R-HSA-6798748	MARK AS OVER ANNOTATED	Summary: Secretory-granule-lumen localization is asserted from the Reactome neutrophil secretory-granule exocytosis pathway proteome. AMPD3 is a cytosolic homotetrameric AMP deaminase; its appearance in the granule proteome catalog does not establish a genuine luminal granule localization or secretory function. Reason: Granule-lumen localization for a cytosolic enzyme comes from bulk neutrophil granule proteomics; over-annotation rather than a verified compartment for AMPD3. Supporting Evidence: Reactome:R-HSA-6798748 Secretory vesicles provide a reservoir of secreted proteins and membrane-associated receptors that are required at the earliest stages of the neutrophil-mediated inflammatory response.
GO:1904813 ficolin-1-rich granule lumen	TAS Reactome:R-HSA-6800434	MARK AS OVER ANNOTATED	Summary: Ficolin-1-rich-granule-lumen localization is asserted from the Reactome ficolin-rich granule exocytosis pathway proteome. As with the other granule localizations, this is bulk neutrophil-granule proteome membership for a cytosolic AMP deaminase, not evidence of a bona fide luminal localization or function. Reason: Ficolin-1-rich-granule-lumen localization for a cytosolic enzyme derives from neutrophil granule proteomics; over-annotation, not a verified compartment. Supporting Evidence: Reactome:R-HSA-6800434 Ficoli-1 rich granules are a relatively new fourth neutrophil granule population that is enriched in the microbial lectin ficolin-1.
GO:0005829 cytosol	TAS Reactome:R-HSA-76590	ACCEPT	Summary: Correct core subcellular localization. AMPD3 is a cytosolic AMP deaminase; the Reactome AMP deaminase reaction module describes cytosolic AMPD activity, and this is consistent with the IBA cytosol annotation from GO_Central. Reason: Cytosol is the verified compartment for AMPD3 catalysis and is corroborated by both Reactome and the IBA annotation. Supporting Evidence: Reactome:R-HSA-76590 Cytosolic AMP deaminase (AMPD) catalyzes the hydrolysis of AMP to yield IMP and ammonia.
GO:0003876 AMP deaminase activity	TAS PMID:9291127 Regulation of rat AMP deaminase 3 (isoform C) by development...	ACCEPT	Summary: Literature-based (TAS) assertion of the core molecular function. Mahnke- Zizelman et al. (1997) cloned, expressed and kinetically characterised the AMPD3 gene product, showing that recombinant rat AMPD3 (isoform C) and human AMPD3 (isoform E) are chromatographically and kinetically similar homologous proteins. This is the UniProt CATALYTIC ACTIVITY / FUNCTION reference for human AMPD3. Reason: AMP deaminase activity is directly supported by biochemical characterisation of the AMPD3 gene product; this is the defining core molecular function. Supporting Evidence: PMID:9291127 and human isoform E are homologous cross-species AMPD3 proteins. file:human/AMPD3/AMPD3-uniprot.txt AMP deaminase plays a critical role in energy metabolism.
GO:0006196 AMP catabolic process	TAS PMID:9291127 Regulation of rat AMP deaminase 3 (isoform C) by development...	ACCEPT	Summary: Literature-based (TAS) assertion of the core biological process. By deaminating AMP to IMP plus ammonia, AMPD3 catabolises AMP. Consistent with the UniProt FUNCTION statement that AMP deaminase plays a critical role in energy metabolism, and with the Ensembl-transferred AMP catabolic process annotation. Reason: AMP catabolic process is the accurate core biological process for AMPD3, supported by the biochemically characterised AMP-to-IMP deamination activity. Supporting Evidence: file:human/AMPD3/AMPD3-uniprot.txt AMP deaminase plays a critical role in energy metabolism.

Gene Description

Existing Annotations Review

Core Functions

Cytosolic AMP deaminase catalysing the hydrolytic deamination of AMP to IMP plus ammonia, regulating the adenylate energy charge and the adenine-nucleotide pool

References

📚 Additional Documentation

Notes

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