AMPD1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0003876 AMP deaminase activity	IBA GO_REF:0000033	ACCEPT	Summary: Core molecular function. AMPD1 hydrolytically deaminates AMP to IMP plus ammonia (EC 3.5.4.6), the defining and experimentally established activity of this enzyme. The phylogenetic (IBA) call is well supported and consistent with direct human evidence. Reason: AMP deaminase activity is the primary, catalytically demonstrated function of AMPD1. UniProt records the reaction and EC number with experimental evidence, and disease-causing mutations abolish this activity. Supporting Evidence: file:human/AMPD1/AMPD1-uniprot.txt Reaction=AMP + H2O + H(+) = IMP + NH4(+) PMID:11102975 undetectable AMPD activity in the
GO:0006188 IMP biosynthetic process	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: IMP is the direct product of AMPD1-catalysed AMP deamination, so participation in IMP biosynthesis is correct. UniProt frames the pathway as "IMP biosynthesis via salvage pathway; IMP from AMP: step 1/1", which is captured more precisely by GO:0032264 IMP salvage. Reason: Accurate but less precise than the salvage-specific term; retained as a correct broader process annotation rather than the core process framing. Supporting Evidence: file:human/AMPD1/AMPD1-uniprot.txt Purine metabolism; IMP biosynthesis via salvage pathway
GO:0046033 AMP metabolic process	IBA GO_REF:0000033	ACCEPT	Summary: AMPD1 acts directly on AMP (its substrate), so participation in AMP metabolic process is accurate and reflects the enzyme's role in the purine nucleotide cycle and adenylate energy-charge regulation. Reason: Directly describes the metabolism of the enzyme's substrate; well supported by the catalytic activity and by the phylogenetic inference. Supporting Evidence: file:human/AMPD1/AMPD1-uniprot.txt Reaction=AMP + H2O + H(+) = IMP + NH4(+)
GO:0003876 AMP deaminase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assertion of the core AMP deaminase activity (via mouse ortholog, InterPro AMPD signature, RHEA:14777 and EC 3.5.4.6). Consistent with the experimental human evidence. Reason: Correct molecular function; redundant with the experimental and IBA calls but appropriately mapped. Supporting Evidence: file:human/AMPD1/AMPD1-uniprot.txt Reaction=AMP + H2O + H(+) = IMP + NH4(+)
GO:0006753 nucleoside phosphate metabolic process	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Very general parent process (AMP and IMP are nucleoside phosphates), so the annotation is correct but uninformative relative to the specific AMP/IMP terms already present. Reason: Correct but high-level ARBA electronic annotation; superseded in specificity by GO:0046033 (AMP metabolic process) and GO:0032264 (IMP salvage). Supporting Evidence: file:human/AMPD1/AMPD1-uniprot.txt Reaction=AMP + H2O + H(+) = IMP + NH4(+)
GO:0009168 purine ribonucleoside monophosphate biosynthetic process	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: InterPro2GO electronic mapping. AMPD1 produces the purine ribonucleoside monophosphate IMP from AMP, so the biosynthetic framing is broadly correct, but AMP salvage/catabolism to IMP (GO:0032264) captures the enzyme's role more precisely. Reason: Broadly correct generic IEA; the enzyme's actual step is better described by IMP salvage / AMP metabolism, which are already annotated. Supporting Evidence: file:human/AMPD1/AMPD1-uniprot.txt Purine metabolism; IMP biosynthesis via salvage pathway
GO:0019239 deaminase activity	IEA GO_REF:0000002	MODIFY	Summary: InterPro2GO mapping to the generic parent term. The specific and correct molecular function is AMP deaminase activity (GO:0003876), already annotated with experimental support. Reason: Too general; AMPD1 specifically deaminates AMP. Replace with the child term AMP deaminase activity. Proposed replacements: AMP deaminase activity Supporting Evidence: file:human/AMPD1/AMPD1-uniprot.txt Reaction=AMP + H2O + H(+) = IMP + NH4(+)
GO:0032264 IMP salvage	IEA GO_REF:0000120	ACCEPT	Summary: AMPD1 forms IMP directly from AMP; UniProt/UniPathway annotate this as "IMP biosynthesis via salvage pathway; IMP from AMP: step 1/1" (UPA00591). This is the precise process for the enzyme's product-forming reaction. Reason: Directly matches the enzyme's committed step (AMP -> IMP), the most informative process term for AMPD1. Supporting Evidence: file:human/AMPD1/AMPD1-uniprot.txt Purine metabolism; IMP biosynthesis via salvage pathway
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" from the human binary interactome (HuRI, IntAct). The captured interactions are AMPD1 with the paralogs AMPD2 (Q01433-2) and AMPD3 (Q01432-4). The term itself is uninformative about molecular function. Reason: Experimental IPI, retained per curation policy (not removed), but the generic "protein binding" term conveys no specific function. The biologically meaningful oligomerisation is captured by GO:0042802 (identical protein binding), matching the documented homotetramer. Supporting Evidence: file:human/AMPD1/AMPD1-uniprot.txt AMPD3; NbExp=3
GO:0042802 identical protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	ACCEPT	Summary: AMPD1 self-interaction detected in the human binary interactome, matching the well-established homotetrameric quaternary structure of AMP deaminase. Reason: Consistent with the documented homotetramer; a biologically meaningful self-association annotation. Supporting Evidence: file:human/AMPD1/AMPD1-uniprot.txt Homotetramer.
GO:0005829 cytosol	TAS Reactome:R-HSA-76590	ACCEPT	Summary: AMP deaminase is a cytosolic enzyme. Reactome curates the AMPD reaction (AMP + H2O => IMP + NH4+) in the cytosol; in skeletal muscle AMPD1 is classically associated with the myofibrillar/contractile apparatus. Reason: Correct subcellular localisation, consistent with Reactome and the enzyme's role in cytosolic purine nucleotide metabolism. 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	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity transfer of AMP deaminase activity from the rat ortholog (P10759). Correct and concordant with the experimental human evidence. Reason: Correct core molecular function; ISS transfer is appropriate for this well-conserved enzyme. Supporting Evidence: file:human/AMPD1/AMPD1-uniprot.txt Reaction=AMP + H2O + H(+) = IMP + NH4(+)
GO:0003876 AMP deaminase activity	IMP PMID:11102975 First missense mutations (R388W and R425H) of AMPD1 accompan...	ACCEPT	Summary: Direct human functional evidence. The MMDD missense variants R388W and R425H, expressed recombinantly, produced comparable amounts of AMPD1 protein but had undetectable AMP deaminase activity, confirming that AMPD1 enables AMP deaminase activity and that its loss causes myopathy. Reason: Loss-of-function mutations abolishing AMPD activity provide strong experimental support for this being the enzyme's core molecular function. Supporting Evidence: PMID:11102975 undetectable AMPD activity in the PMID:11102975 AMPD1 indeed has a key role in muscle metabolism
GO:0032263 GMP salvage	IDA PMID:29079593 Hypoxia modulates the purine salvage pathway and decreases r...	MARK AS OVER ANNOTATED	Summary: This annotation derives from a red-blood-cell storage metabolomics study of the purine salvage/deamination pathway. AMP deaminase acts on AMP to make IMP + ammonia and does not act on guanine nucleotides, so "GMP salvage" is a pathway-level co-annotation rather than a direct function of AMPD1. Reason: Experimental IDA, retained per curation policy (not removed), but GMP salvage is not the direct biochemistry of AMP deaminase; the enzyme's role is in the AMP -> IMP branch, better captured by GO:0032264 IMP salvage and GO:0046033 AMP metabolic process. Supporting Evidence: PMID:29079593 purine salvage pathway
GO:0032263 GMP salvage	IDA PMID:29079593 Hypoxia modulates the purine salvage pathway and decreases r...	MARK AS OVER ANNOTATED	Summary: Duplicate GMP salvage annotation (involved_in qualifier) from the same RBC storage metabolomics study. As above, AMP deaminase does not act on guanine nucleotides; this is a pathway-level co-annotation, not AMPD1's direct function. Reason: Experimental IDA retained per policy, but not the enzyme's direct process; the AMP -> IMP step is captured by IMP salvage and AMP metabolic process. Supporting Evidence: PMID:29079593 purine salvage pathway
GO:0003876 AMP deaminase activity	TAS PMID:644316 Myoadenylate deaminase deficiency: a new disease of muscle.	ACCEPT	Summary: Author statement supporting AMP deaminase (adenylate deaminase) activity as the muscle enzyme whose deficiency defines myoadenylate deaminase deficiency. Fishbein et al. showed patient muscle biopsies lacked adenylate deaminase by stain and solution assay. Reason: Consistent with the core molecular function; the foundational clinical description linking loss of muscle AMP deaminase activity to disease. Supporting Evidence: PMID:644316 lacked adenylate deaminase by