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.

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

Molecular Function:

AMP deaminase activity

Directly Involved In:

AMP catabolic process

Cellular Locations:

cytosol

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.

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:25910212

Widespread macromolecular interaction perturbations in human genetic disorders.

PMID:9291127

Regulation of rat AMP deaminase 3 (isoform C) by development and skeletal muscle fibre type.

Reactome:R-HSA-6798748

Exocytosis of secretory granule lumen proteins

Reactome:R-HSA-6800434

Exocytosis of ficolin-rich granule lumen proteins

Reactome:R-HSA-76590

AMP + H2O => IMP + NH4+ (AMPD)

file:human/AMPD3/AMPD3-uniprot.txt

UniProtKB Q01432 (AMPD3_HUMAN) record

📚 Additional Documentation

Notes

(AMPD3-notes.md)

AMPD3 (human) review notes

UniProtKB: Q01432 | HGNC:470 | Gene: AMPD3 | AMP deaminase 3 (erythrocyte isoform, "isoform E")

Core biology

AMPD3 is the erythrocyte isoform of AMP deaminase (EC 3.5.4.6). It catalyses the
hydrolytic deamination of AMP:

AMP + H2O + H+ = IMP + NH4+ (Rhea:RHEA:14777)
[AMPD3-uniprot.txt CATALYTIC ACTIVITY; ECO:0000269|PubMed:9291127]

It is a zinc metalloenzyme (binds 1 Zn2+ per subunit, catalytic) and functions as a
homotetramer [AMPD3-uniprot.txt COFACTOR + SUBUNIT]. It belongs to the
metallo-dependent hydrolases superfamily, adenosine and AMP deaminases family
[AMPD3-uniprot.txt SIMILARITY].

Three human AMPD isoforms exist: E (AMPD3, erythrocyte / broadly expressed), L (AMPD2)
and M (AMPD1, muscle). All are cytosolic tetramers with qualitatively the same catalytic
activity [reactome R-HSA-76590 summary "Cytosolic AMP deaminase (AMPD) catalyzes the
hydrolysis of AMP to yield IMP and ammonia. Three isoforms of AMPD, E, L, and M ... All
occur as tetramers and all have qualitatively the same catalytic activity"].

Physiological role

In red blood cells AMP deaminase regulates the adenylate energy charge and the
adenine-nucleotide pool by draining AMP to IMP (+ NH3), pulling the myokinase/adenylate
kinase equilibrium (2 ADP <=> ATP + AMP) and thus keeping ATP/ADP high while lowering the
total adenine-nucleotide pool. UniProt FUNCTION: "AMP deaminase plays a critical role in
energy metabolism" [ECO:0000305|PubMed:9291127].

Disease: AMPDDE (erythrocyte AMP deaminase deficiency), MIM:612874

Benign / clinically asymptomatic. UniProt DISEASE: "A metabolic disorder due to lack of
activity of the erythrocyte isoform of AMP deaminase. It is a clinically asymptomatic
condition characterized by a 50% increase in steady-state levels of ATP in affected
cells. Individuals with complete deficiency of erythrocyte AMP deaminase are healthy and
have no hematologic disorders." Multiple loss-of-function missense variants documented
(e.g. R573C, enzyme inactive) [PubMed:8004104, 7881427, 9598089, 11139257].

Pathway placement

UniProt PATHWAY: "Purine metabolism; IMP biosynthesis via salvage pathway; IMP from AMP:
step 1/1." UniPathway UPA00591 / UER00663. So the AMP->IMP deamination is the single step
of the salvage arm that regenerates IMP from AMP. Reactome places AMPD3 in "Purine
salvage" (R-HSA-74217) and in the R-HSA-76590 reaction.

Reference notes

PMID:9291127 (Mahnke-Zizelman et al. 1997, Biochem J): abstract-only in cache
(full_text_available: false). Titled for rat AMPD3 isoform C, but the abstract
explicitly establishes cross-species homology: "baculoviral expression of rat and human
AMPD3 proteins produces enzymes that are chromatographically and kinetically similar
... rat isoform C and human isoform E are homologous cross-species AMPD3 proteins." This
is the UniProt FUNCTION / CATALYTIC ACTIVITY / PATHWAY reference for human AMPD3
(ECO:0000269 / ECO:0000305|PubMed:9291127). It is the source for the two TAS annotations
(GO:0003876, GO:0006196). Treat as supporting human AMPD3 MF + AMP catabolism.
PMID:25910212 (Sahni et al. 2015, Cell): systematic "edgotyping" interactome study. It
is the IntAct source (WITH UniProtKB:P08238 = HSP90AB1) for the IPI "protein binding"
annotation. UniProt INTERACTION lists Q01432-P08238 (HSP90AB1) NbExp=2. This is a
chaperone/QC interaction from a high-throughput screen, not an informative molecular
function -> MARK_AS_OVER_ANNOTATED (bare protein binding; do not REMOVE per policy).

Localization

Cytosol (GO:0005829) is correct and is the IBA/Reactome-supported location for AMPD3
[uniprot GO line "C:cytosol; IBA:GO_Central"; reactome R-HSA-76590 "Cytosolic AMP
deaminase"].

The extracellular-region / secretory-granule-lumen / ficolin-1-rich-granule-lumen
annotations (GO:0005576, GO:0034774, GO:1904813) all derive from Reactome neutrophil
degranulation proteomics (R-HSA-6798748 "Exocytosis of secretory granule lumen proteins",
R-HSA-6800434 "Exocytosis of ficolin-rich granule lumen proteins"). These are bulk
granule-proteome catalog memberships, not evidence of a bona fide secreted / granule
function for a cytosolic purine-metabolism enzyme -> MARK_AS_OVER_ANNOTATED.

Annotation-by-annotation plan (GOA)

GO:0003876 AMP deaminase activity, IBA -> ACCEPT (core MF)
GO:0006188 IMP biosynthetic process, IBA -> MODIFY (AMPD makes IMP by deamination/catabolism
of AMP, not de novo IMP biosynthesis; better = GO:0006196 AMP catabolic process). Keep essence.
GO:0046033 AMP metabolic process, IBA -> ACCEPT (broad but correct)
GO:0003876 AMP deaminase activity, IEA (GO_REF:0000120) -> ACCEPT (dup of core MF)
GO:0006753 nucleoside phosphate metabolic process, IEA (ARBA) -> ACCEPT (broad, correct)
GO:0009168 purine ribonucleoside monophosphate biosynthetic process, IEA InterPro -> MODIFY
(same "biosynthetic" mis-framing; better GO:0006196 AMP catabolic process)
GO:0019239 deaminase activity, IEA InterPro -> ACCEPT (broad parent of core MF)
GO:0032264 IMP salvage, IEA (UniPathway) -> ACCEPT (matches UniProt PATHWAY: IMP biosynthesis
via salvage; AMP->IMP is the salvage step regenerating IMP)
GO:0005515 protein binding, IPI (PMID:25910212, HSP90AB1) -> MARK_AS_OVER_ANNOTATED (bare)
GO:0006196 AMP catabolic process, IEA (Ensembl) -> ACCEPT (core BP)
GO:0034101 erythrocyte homeostasis, IEA (Ensembl ortholog) -> KEEP_AS_NON_CORE (RBC context,
but not the molecular core function; AMPD3 deficiency is benign so it is not required for
erythrocyte homeostasis)
GO:0046031 ADP metabolic process, IEA (Ensembl) -> MARK_AS_OVER_ANNOTATED (AMPD3 acts on AMP,
not ADP; ortholog electronic over-propagation of a broad energy-metabolism grouping)
GO:0046032 ADP catabolic process, IEA (Ensembl) -> MARK_AS_OVER_ANNOTATED (not an ADP enzyme)
GO:0046033 AMP metabolic process, IEA (Ensembl) -> ACCEPT (dup, correct)
GO:0046034 ATP metabolic process, IEA (Ensembl) -> MARK_AS_OVER_ANNOTATED (indirect at best)
GO:0046039 GTP metabolic process, IEA (Ensembl) -> REMOVE (AMPD3 has no GTP activity; wrong
electronic inference)
GO:0003876 AMP deaminase activity, ISS (O08739 mouse) -> ACCEPT (dup core MF)
GO:0005576 extracellular region, TAS Reactome -> MARK_AS_OVER_ANNOTATED (granule proteome)
GO:0005576 extracellular region, TAS Reactome -> MARK_AS_OVER_ANNOTATED (dup)
GO:0034774 secretory granule lumen, TAS Reactome -> MARK_AS_OVER_ANNOTATED
GO:1904813 ficolin-1-rich granule lumen, TAS Reactome -> MARK_AS_OVER_ANNOTATED
GO:0005829 cytosol, TAS Reactome -> ACCEPT (correct core location)
GO:0003876 AMP deaminase activity, TAS (PMID:9291127) -> ACCEPT (core MF, literature)
GO:0006196 AMP catabolic process, TAS (PMID:9291127) -> ACCEPT (core BP, literature)

📄 View Raw YAML

id: Q01432
gene_symbol: AMPD3
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: AMPD3 is the erythrocyte isoform (isoform E) of AMP deaminase (EC 3.5.4.6),
  a cytosolic zinc metalloenzyme that assembles into a homotetramer and catalyses the
  hydrolytic deamination of AMP to IMP plus ammonia (AMP + H2O + H+ = IMP + NH4+). It
  belongs to the metallo-dependent hydrolases superfamily, adenosine and AMP deaminases
  family, and is one of three vertebrate AMP deaminase isoforms (E/AMPD3, L/AMPD2,
  M/AMPD1) that share qualitatively the same catalytic activity but differ in tissue
  expression. By draining AMP to IMP, AMPD3 helps regulate the adenylate energy charge
  and the adenine-nucleotide pool; in red blood cells this maintains high ATP/ADP ratios
  while lowering the total adenine-nucleotide pool. Loss-of-function variants cause
  erythrocyte AMP deaminase deficiency (AMPDDE, MIM:612874), a clinically benign
  condition marked by an approximately 50% increase in steady-state erythrocyte ATP with
  no hemolysis or hematologic disease.
alternative_products:
- name: 1B
  id: Q01432-1
- name: 1A
  id: Q01432-2
  sequence_note: VSP_001275, VSP_001277
- name: 1C
  id: Q01432-3
  sequence_note: VSP_001276, VSP_001278
- name: '2'
  id: Q01432-4
  sequence_note: VSP_001275
- name: '3'
  id: Q01432-5
  sequence_note: VSP_001276
- name: '4'
  id: Q01432-6
  sequence_note: VSP_044230
existing_annotations:
- term:
    id: GO:0003876
    label: AMP deaminase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: file:human/AMPD3/AMPD3-uniprot.txt
      supporting_text: Reaction=AMP + H2O + H(+) = IMP + NH4(+); Xref=Rhea:RHEA:14777,
    - reference_id: PMID:9291127
      supporting_text: and human isoform E are homologous cross-species AMPD3 proteins.
- term:
    id: GO:0006188
    label: IMP biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    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.
    action: MODIFY
    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.
    proposed_replacement_terms:
    - id: GO:0006196
      label: AMP catabolic process
    supported_by:
    - reference_id: file:human/AMPD3/AMPD3-uniprot.txt
      supporting_text: 'Purine metabolism; IMP biosynthesis via salvage pathway; IMP'
    propagation_review:
      root_cause: TERM_SCOPING_PROBLEM
      failure_modes:
      - GRANULARITY_MISMATCH
- term:
    id: GO:0046033
    label: AMP metabolic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    reason: AMP is the direct substrate of AMPD3; AMP metabolic process is an accurate,
      appropriately general biological-process term for this enzyme.
    supported_by:
    - reference_id: file:human/AMPD3/AMPD3-uniprot.txt
      supporting_text: Reaction=AMP + H2O + H(+) = IMP + NH4(+); Xref=Rhea:RHEA:14777,
- term:
    id: GO:0003876
    label: AMP deaminase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: Duplicate of the core AMP deaminase activity; the automated mapping is
      correct.
    supported_by:
    - reference_id: file:human/AMPD3/AMPD3-uniprot.txt
      supporting_text: Reaction=AMP + H2O + H(+) = IMP + NH4(+); Xref=Rhea:RHEA:14777,
- term:
    id: GO:0006753
    label: nucleoside phosphate metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    reason: Correct broad grouping term; consistent with AMPD3 acting on the nucleoside
      monophosphate AMP.
    supported_by:
    - reference_id: file:human/AMPD3/AMPD3-uniprot.txt
      supporting_text: Reaction=AMP + H2O + H(+) = IMP + NH4(+); Xref=Rhea:RHEA:14777,
- term:
    id: GO:0009168
    label: purine ribonucleoside monophosphate biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    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.
    action: MODIFY
    reason: AMPD3 does not synthesise purine nucleotides de novo; it catabolises AMP to
      IMP. AMP catabolic process better represents the enzyme's role.
    proposed_replacement_terms:
    - id: GO:0006196
      label: AMP catabolic process
    supported_by:
    - reference_id: file:human/AMPD3/AMPD3-uniprot.txt
      supporting_text: Reaction=AMP + H2O + H(+) = IMP + NH4(+); Xref=Rhea:RHEA:14777,
- term:
    id: GO:0019239
    label: deaminase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: file:human/AMPD3/AMPD3-uniprot.txt
      supporting_text: Reaction=AMP + H2O + H(+) = IMP + NH4(+); Xref=Rhea:RHEA:14777,
- term:
    id: GO:0032264
    label: IMP salvage
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    reason: Consistent with the curated UniProt PATHWAY line placing AMPD3 in the
      salvage route that regenerates IMP from AMP.
    supported_by:
    - reference_id: file:human/AMPD3/AMPD3-uniprot.txt
      supporting_text: 'Purine metabolism; IMP biosynthesis via salvage pathway; IMP'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25910212
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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."
    supported_by:
    - reference_id: PMID:25910212
      supporting_text: Approximately 60% of disease-associated missense mutations perturb
        PPIs
- term:
    id: GO:0006196
    label: AMP catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    reason: AMP catabolic process is the accurate, appropriately specific biological
      process for the AMP-to-IMP deamination catalysed by AMPD3.
    supported_by:
    - reference_id: file:human/AMPD3/AMPD3-uniprot.txt
      supporting_text: Reaction=AMP + H2O + H(+) = IMP + NH4(+); Xref=Rhea:RHEA:14777,
- term:
    id: GO:0034101
    label: erythrocyte homeostasis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:human/AMPD3/AMPD3-uniprot.txt
      supporting_text: of erythrocyte AMP deaminase are healthy and have no hematologic
- term:
    id: GO:0046031
    label: ADP metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:human/AMPD3/AMPD3-uniprot.txt
      supporting_text: Reaction=AMP + H2O + H(+) = IMP + NH4(+); Xref=Rhea:RHEA:14777,
- term:
    id: GO:0046032
    label: ADP catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: AMPD3 has no ADP-directed catalytic activity; the term over-states its role.
    supported_by:
    - reference_id: file:human/AMPD3/AMPD3-uniprot.txt
      supporting_text: Reaction=AMP + H2O + H(+) = IMP + NH4(+); Xref=Rhea:RHEA:14777,
- term:
    id: GO:0046033
    label: AMP metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Electronic (Ensembl ortholog) duplicate of the IBA AMP metabolic process
      annotation. AMP is the direct substrate of AMPD3, so this is correct.
    action: ACCEPT
    reason: AMP metabolic process accurately captures AMPD3 acting on its direct
      substrate AMP; duplicate of an already-accepted term.
    supported_by:
    - reference_id: file:human/AMPD3/AMPD3-uniprot.txt
      supporting_text: Reaction=AMP + H2O + H(+) = IMP + NH4(+); Xref=Rhea:RHEA:14777,
- term:
    id: GO:0046034
    label: ATP metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: The effect on ATP is indirect (through the adenylate kinase equilibrium), not
      a direct AMPD3-catalysed ATP-metabolic step; annotate as over-annotation.
    supported_by:
    - reference_id: file:human/AMPD3/AMPD3-uniprot.txt
      supporting_text: asymptomatic condition characterized by a 50% increase in steady-state
- term:
    id: GO:0046039
    label: GTP metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: REMOVE
    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.
    supported_by:
    - reference_id: file:human/AMPD3/AMPD3-uniprot.txt
      supporting_text: Reaction=AMP + H2O + H(+) = IMP + NH4(+); Xref=Rhea:RHEA:14777,
- term:
    id: GO:0003876
    label: AMP deaminase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: Duplicate of the well-supported core molecular function; the ortholog-based
      ISS transfer is sound.
    supported_by:
    - reference_id: file:human/AMPD3/AMPD3-uniprot.txt
      supporting_text: Reaction=AMP + H2O + H(+) = IMP + NH4(+); Xref=Rhea:RHEA:14777,
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6798748
  qualifier: located_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-6798748
      supporting_text: 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.
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6800434
  qualifier: located_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: Duplicate extracellular-region assertion from bulk ficolin-rich-granule
      proteomics; over-annotation rather than a real secreted localization.
    supported_by:
    - reference_id: Reactome:R-HSA-6800434
      supporting_text: Ficoli-1 rich granules are a relatively new fourth neutrophil
        granule population that is enriched in the microbial lectin ficolin-1.
- term:
    id: GO:0034774
    label: secretory granule lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6798748
  qualifier: located_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: Granule-lumen localization for a cytosolic enzyme comes from bulk neutrophil
      granule proteomics; over-annotation rather than a verified compartment for AMPD3.
    supported_by:
    - reference_id: Reactome:R-HSA-6798748
      supporting_text: 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.
- term:
    id: GO:1904813
    label: ficolin-1-rich granule lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6800434
  qualifier: located_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: Ficolin-1-rich-granule-lumen localization for a cytosolic enzyme derives from
      neutrophil granule proteomics; over-annotation, not a verified compartment.
    supported_by:
    - reference_id: Reactome:R-HSA-6800434
      supporting_text: Ficoli-1 rich granules are a relatively new fourth neutrophil
        granule population that is enriched in the microbial lectin ficolin-1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-76590
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    reason: Cytosol is the verified compartment for AMPD3 catalysis and is corroborated
      by both Reactome and the IBA annotation.
    supported_by:
    - reference_id: Reactome:R-HSA-76590
      supporting_text: Cytosolic AMP deaminase (AMPD) catalyzes the hydrolysis of AMP to
        yield IMP and ammonia.
- term:
    id: GO:0003876
    label: AMP deaminase activity
  evidence_type: TAS
  original_reference_id: PMID:9291127
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: AMP deaminase activity is directly supported by biochemical characterisation
      of the AMPD3 gene product; this is the defining core molecular function.
    supported_by:
    - reference_id: PMID:9291127
      supporting_text: and human isoform E are homologous cross-species AMPD3 proteins.
    - reference_id: file:human/AMPD3/AMPD3-uniprot.txt
      supporting_text: AMP deaminase plays a critical role in energy metabolism.
- term:
    id: GO:0006196
    label: AMP catabolic process
  evidence_type: TAS
  original_reference_id: PMID:9291127
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    reason: AMP catabolic process is the accurate core biological process for AMPD3,
      supported by the biochemically characterised AMP-to-IMP deamination activity.
    supported_by:
    - reference_id: file:human/AMPD3/AMPD3-uniprot.txt
      supporting_text: AMP deaminase plays a critical role in energy metabolism.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  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:25910212
  title: Widespread macromolecular interaction perturbations in human genetic disorders.
  findings: []
- id: PMID:9291127
  title: Regulation of rat AMP deaminase 3 (isoform C) by development and skeletal
    muscle fibre type.
  findings: []
- id: Reactome:R-HSA-6798748
  title: Exocytosis of secretory granule lumen proteins
  findings: []
- id: Reactome:R-HSA-6800434
  title: Exocytosis of ficolin-rich granule lumen proteins
  findings: []
- id: Reactome:R-HSA-76590
  title: AMP + H2O => IMP + NH4+ (AMPD)
  findings: []
- id: file:human/AMPD3/AMPD3-uniprot.txt
  title: UniProtKB Q01432 (AMPD3_HUMAN) record
  findings: []
core_functions:
- description: Cytosolic AMP deaminase catalysing the hydrolytic deamination of AMP to
    IMP plus ammonia, regulating the adenylate energy charge and the adenine-nucleotide
    pool
  molecular_function:
    id: GO:0003876
    label: AMP deaminase activity
  directly_involved_in:
  - id: GO:0006196
    label: AMP catabolic process
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: file:human/AMPD3/AMPD3-uniprot.txt
    supporting_text: Reaction=AMP + H2O + H(+) = IMP + NH4(+); Xref=Rhea:RHEA:14777,
  - reference_id: PMID:9291127
    supporting_text: and human isoform E are homologous cross-species AMPD3 proteins.

AMPD3

Gene Description