id: Q01433
gene_symbol: AMPD2
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  AMPD2 is the liver-type ("L") isoform of AMP deaminase, one of three mammalian
  AMP deaminase paralogs (with muscle-type AMPD1 and erythrocyte-type AMPD3).
  It is broadly expressed, including in brain and neurons, and is highly expressed
  in cerebellum. AMPD2 is a cytosolic, zinc-dependent metalloenzyme (binds one Zn2+
  per subunit; assembles as a homotetramer) that catalyzes the hydrolytic deamination
  of AMP to IMP plus ammonia (AMP + H2O + H+ = IMP + NH4+; EC 3.5.4.6). This reaction
  is the committed entry step of the purine nucleotide cycle and a key point of AMP
  catabolism, so AMPD2 helps set the cellular adenylate energy charge (AMP/ADP/ATP
  ratio) and shapes adenine and guanine nucleotide pools. By lowering AMP/adenosine-
  derived nucleotides, AMPD2 relieves feedback inhibition of de novo purine synthesis
  and thereby sustains the guanine nucleotide (GTP) pool; this is especially important
  in neurons and neural progenitors, where GTP is required for translation initiation.
  Loss-of-function mutations cause severe recessive neurodevelopmental/neurodegenerative
  disease, including pontocerebellar hypoplasia type 9 (PCH9) and a form of hereditary
  spastic paraplegia (SPG63); the cellular defect can be partially rescued by purine
  precursor supplementation.
alternative_products:
- name: Ex1B-2-3
  id: Q01433-1
- name: Ex1A-2-3
  id: Q01433-2
  sequence_note: VSP_001271, VSP_001272
- name: Ex1B-3
  id: Q01433-4
  sequence_note: VSP_001273
- name: '5'
  id: Q01433-5
  sequence_note: VSP_045975
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 of AMPD2: hydrolytic deamination of AMP to IMP + ammonia.
      This phylogenetically-inferred MF is the well-established, experimentally supported
      activity of the enzyme and represents the core function of the gene.
    action: ACCEPT
    reason: >-
      AMP deaminase activity is the defining function of AMPD2, confirmed biochemically
      (patient-cell AMP deaminase assays) and by yeast complementation, and captured by
      UniProt catalytic activity (EC 3.5.4.6). The IBA is at the correct level of specificity.
    supported_by:
    - reference_id: file:human/AMPD2/AMPD2-uniprot.txt
      supporting_text: "Catalyzes the deamination of AMP to IMP and plays an important role in"
    - reference_id: PMID:23911318
      supporting_text: which converts AMP to IMP
- term:
    id: GO:0006188
    label: IMP biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      IMP is the direct product of the AMP deaminase reaction; UniProt frames this as
      "IMP biosynthesis via salvage pathway; IMP from AMP: step 1/1". The phylogenetic
      inference is appropriate and reflects the immediate metabolic role of the enzyme.
    action: ACCEPT
    reason: >-
      Producing IMP from AMP is exactly what AMPD2 does, so this process annotation is
      well supported and consistent with the pathway assignment in UniProt.
    supported_by:
    - reference_id: file:human/AMPD2/AMPD2-uniprot.txt
      supporting_text: "Purine metabolism; IMP biosynthesis via salvage pathway; IMP"
- term:
    id: GO:0046033
    label: AMP metabolic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      AMPD2 consumes AMP (deaminating it to IMP), placing it squarely in AMP metabolism.
      This higher-level process term is the natural container for the reaction and is a
      core process for the gene.
    action: ACCEPT
    reason: >-
      Directly supported by the catalyzed reaction (AMP is the substrate). Correct and
      not over-annotated.
    supported_by:
    - reference_id: PMID:23911318
      supporting_text: AMPD2 executes AMP deamination
- term:
    id: GO:0003876
    label: AMP deaminase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Electronic assertion (ARBA/RHEA/EC 3.5.4.6/InterPro AMPD family) of the same core
      AMP deaminase activity. Redundant with the IBA/IGI/NAS annotations but correct.
    action: ACCEPT
    reason: >-
      The InterPro/EC/RHEA mapping to AMP deaminase activity is accurate for AMPD2.
    supported_by:
    - reference_id: file:human/AMPD2/AMPD2-uniprot.txt
      supporting_text: "Reaction=AMP + H2O + H(+) = IMP + NH4(+)"
- term:
    id: GO:0006188
    label: IMP biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: >-
      ARBA electronic annotation of IMP biosynthetic process, consistent with production
      of IMP from AMP. Redundant with the IBA/IGI evidence but correct.
    action: ACCEPT
    reason: >-
      IMP is the reaction product; the process assignment is appropriate.
    supported_by:
    - reference_id: file:human/AMPD2/AMPD2-uniprot.txt
      supporting_text: "Purine metabolism; IMP biosynthesis via salvage pathway; IMP"
- term:
    id: GO:0009168
    label: purine ribonucleoside monophosphate biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: >-
      InterPro2GO mapping to a parent process term (IMP is a purine ribonucleoside
      monophosphate). Broader than the specific IMP biosynthetic process term but not
      wrong for this enzyme.
    action: KEEP_AS_NON_CORE
    reason: >-
      IMP, the product of AMPD2, is a purine ribonucleoside monophosphate, so this
      higher-level biosynthetic term is consistent. It is more general than GO:0006188
      and is retained as non-core context rather than the primary process term.
    supported_by:
    - reference_id: file:human/AMPD2/AMPD2-uniprot.txt
      supporting_text: "Purine metabolism; IMP biosynthesis via salvage pathway; IMP"
- term:
    id: GO:0019239
    label: deaminase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      InterPro2GO mapping to the generic parent "deaminase activity". The specific and
      informative child term GO:0003876 (AMP deaminase activity) is already annotated,
      making this general term uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Too general; the precise activity (AMP deaminase activity, GO:0003876) is already
      captured by multiple annotations. Retaining the generic parent adds no information.
    proposed_replacement_terms:
    - id: GO:0003876
      label: AMP deaminase activity
    supported_by:
    - reference_id: file:human/AMPD2/AMPD2-uniprot.txt
      supporting_text: "Catalyzes the deamination of AMP to IMP and plays an important role in"
- term:
    id: GO:0032264
    label: IMP salvage
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: >-
      UniPathway-derived electronic annotation. UniProt assigns AMP->IMP deamination to
      the "IMP biosynthesis via salvage pathway" (UPA00591), so IMP salvage is a
      reasonable process context for AMPD2.
    action: KEEP_AS_NON_CORE
    reason: >-
      Consistent with the UniProt/UniPathway framing of the AMP->IMP step as part of IMP
      salvage. Retained as non-core process context alongside the more direct AMP/IMP
      metabolic terms.
    supported_by:
    - reference_id: file:human/AMPD2/AMPD2-uniprot.txt
      supporting_text: "Purine metabolism; IMP biosynthesis via salvage pathway; IMP"
- term:
    id: GO:0097009
    label: energy homeostasis
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: >-
      AMP deaminase sets the cellular adenylate energy charge by regulating AMP levels,
      linking it to energy homeostasis. Supported by the primary literature framing of
      purine metabolism as essential for energy homeostasis.
    action: KEEP_AS_NON_CORE
    reason: >-
      A valid higher-level physiological role that is downstream of the catalytic function
      rather than the core molecular activity itself; retained as non-core.
    supported_by:
    - reference_id: PMID:23911318
      supporting_text: essential for cellular energy homeostasis and nucleic acid synthesis
- term:
    id: GO:0106380
    label: purine ribonucleotide salvage
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: >-
      ARBA electronic annotation placing AMPD2 in purine ribonucleotide salvage, consistent
      with the UniProt/UniPathway assignment of the AMP->IMP step to IMP salvage.
    action: KEEP_AS_NON_CORE
    reason: >-
      Compatible with the salvage-pathway framing of the AMP->IMP reaction. Broad process
      context; retained as non-core.
    supported_by:
    - reference_id: file:human/AMPD2/AMPD2-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:21044950
  qualifier: enables
  review:
    summary: >-
      IntAct IPI capturing a binary interaction with TERF1 (P54274) detected in a
      genome-wide fluorescence-complementation telomere-signaling screen. "protein binding"
      is uninformative and no functional module for AMPD2 is established by this.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Per curation guidance, bare protein binding (GO:0005515) is uninformative; this is a
      high-throughput interaction from a telomere-signaling screen with no evidence that it
      reflects a physiological AMPD2 function. Not removed (experimental IPI), but marked as
      over-annotated.
    supported_by:
    - reference_id: file:human/AMPD2/AMPD2-uniprot.txt
      supporting_text: "Q01433; P54274: TERF1"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: >-
      IntAct IPI capturing a binary interaction with CCNDBP1 (O95273) from a proteome-scale
      human interactome map (yeast two-hybrid). Uninformative bare protein binding.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput interactome interaction; "protein binding" gives no functional insight
      and no AMPD2-specific module is established. Retained (experimental IPI) but marked
      over-annotated.
    supported_by:
    - reference_id: file:human/AMPD2/AMPD2-uniprot.txt
      supporting_text: "Q01433; O95273: CCNDBP1"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31515488
  qualifier: enables
  review:
    summary: >-
      IntAct IPI, again reporting an interaction involving CCNDBP1 (O95273), from a study of
      variant-mediated disruption of protein interactions. Uninformative bare protein binding.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput interaction; "protein binding" is uninformative and no functional
      module is established. Retained (experimental IPI) but marked over-annotated.
    supported_by:
    - reference_id: file:human/AMPD2/AMPD2-uniprot.txt
      supporting_text: "Q01433; O95273: CCNDBP1"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: >-
      IntAct IPI reporting an interaction with HIRIP3 (Q9BW71) from a dual proteome-scale
      interactome (BioPlex) study. Uninformative bare protein binding.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput interaction; "protein binding" is uninformative and no functional
      module is established. Retained (experimental IPI) but marked over-annotated.
    supported_by:
    - reference_id: file:human/AMPD2/AMPD2-uniprot.txt
      supporting_text: "Q01433; Q9BW71: HIRIP3"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:34819669
  qualifier: enables
  review:
    summary: >-
      IntAct IPI reporting an interaction with HIRIP3 (Q9BW71) from a multi-scale cell-structure
      map (AP-MS/imaging). Uninformative bare protein binding.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput interaction; "protein binding" is uninformative and no functional
      module is established. Retained (experimental IPI) but marked over-annotated.
    supported_by:
    - reference_id: file:human/AMPD2/AMPD2-uniprot.txt
      supporting_text: "Q01433; Q9BW71: HIRIP3"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: >-
      IntAct IPI reporting an interaction with HIRIP3 (Q9BW71) from a multimodal cell-map
      study. Uninformative bare protein binding.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput interaction; "protein binding" is uninformative and no functional
      module is established. Retained (experimental IPI) but marked over-annotated.
    supported_by:
    - reference_id: file:human/AMPD2/AMPD2-uniprot.txt
      supporting_text: "Q01433; Q9BW71: HIRIP3"
- term:
    id: GO:0046033
    label: AMP metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Ensembl orthology-based electronic transfer (from mouse Ampd2, Q9DBT5) of AMP metabolic
      process. Correct, and redundant with the IBA annotation of the same term.
    action: ACCEPT
    reason: >-
      AMP is the substrate of AMPD2; this is a correct core process annotation.
    supported_by:
    - reference_id: PMID:23911318
      supporting_text: AMPD2 executes AMP deamination
- term:
    id: GO:0046034
    label: ATP metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Ensembl orthology-based electronic annotation (from mouse Q9DBT5). AMPD2 loss elevates
      ATP levels, so its activity indirectly influences ATP/adenylate pools, but ATP is
      neither substrate nor product of the deaminase reaction.
    action: KEEP_AS_NON_CORE
    reason: >-
      Biologically supported as an indirect/regulatory effect (AMPD2-deficient cells accumulate
      ATP), not the direct catalyzed reaction. Retained as non-core.
    supported_by:
    - reference_id: PMID:23911318
      supporting_text: elevated ATP levels, more striking in AMPD2 homozygous mutant cells
- term:
    id: GO:0046039
    label: GTP metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Ensembl orthology-based electronic annotation (from mouse Q9DBT5). AMPD2 activity is
      required to sustain the guanine nucleotide (GTP) pool by relieving feedback inhibition
      of de novo purine synthesis; AMPD2 loss depletes GTP. This is an indirect/regulatory
      role rather than the direct catalyzed reaction.
    action: KEEP_AS_NON_CORE
    reason: >-
      Strongly supported biologically as a downstream consequence of AMPD2 activity (GTP
      halved in patient neural progenitors), but AMPD2 does not directly metabolize GTP.
      Retained as an important non-core process.
    supported_by:
    - reference_id: PMID:23911318
      supporting_text: dramatic reduction in guanine nucleotides, most remarkable for GTP, which was reduced by half
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-76590
  qualifier: located_in
  review:
    summary: >-
      Cytosolic localization of AMP deaminase, asserted by Reactome. Consistent with the
      known subcellular distribution of the enzyme.
    action: ACCEPT
    reason: >-
      AMPD is a cytosolic enzyme; the localization is well established and appropriate as the
      core cellular component.
    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:0032263
    label: GMP salvage
  evidence_type: IDA
  original_reference_id: PMID:29079593
  qualifier: acts_upstream_of_or_within
  review:
    summary: >-
      MGI IDA to GMP salvage citing a red-blood-cell purine-metabolism study. That study
      centers on the erythrocyte AMPD isoform (AMPD3) and the RBC purine salvage/deamination
      network; it does not establish AMPD2 specifically in GMP salvage, and mechanistically
      AMP deaminase produces IMP (not GMP).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The term is a poor fit for AMP deaminase (which acts on AMP->IMP, upstream of, but not
      within, GMP salvage), and the cited paper foregrounds the erythrocyte AMPD3 isoform and
      the salvage network generally. Per curation policy this experimental annotation is not
      removed; the loose acts_upstream_of_or_within qualifier is retained but marked as an
      over-annotation for AMPD2.
    supported_by:
    - reference_id: PMID:29079593
      supporting_text: enhanced purine salvage reactions in human and mouse red blood cells
- term:
    id: GO:0052652
    label: cyclic purine nucleotide metabolic process
  evidence_type: IMP
  original_reference_id: PMID:23911318
  qualifier: involved_in
  review:
    summary: >-
      IMP annotation from the AMPD2/PCH9 study. That work demonstrates AMPD2's role in
      purine (AMP/IMP/GTP) nucleotide metabolism and guanine-nucleotide homeostasis, not in
      cyclic nucleotide (cAMP/cGMP) metabolism specifically, so the chosen term is a mismatch
      to the experimental readouts.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The phenotype (guanine/adenine nucleotide pool changes, translation initiation defect)
      supports purine-nucleotide metabolic terms rather than "cyclic purine nucleotide
      metabolic process". Experimental annotation, so not removed; marked over-annotated as
      the AMP/IMP/purine metabolic process terms better capture the finding.
    proposed_replacement_terms:
    - id: GO:0046033
      label: AMP metabolic process
    supported_by:
    - reference_id: PMID:23911318
      supporting_text: we identify AMPD2 as necessary for guanine nucleotide biosynthesis and protein translation
- term:
    id: GO:0003876
    label: AMP deaminase activity
  evidence_type: IGI
  original_reference_id: PMID:23911318
  qualifier: enables
  review:
    summary: >-
      Experimental (IGI) support for AMP deaminase activity: human AMPD2 functionally
      complements the yeast amd1 (AMP deaminase) mutant, and patient cells lacking AMPD2 lose
      80-90% of AMP deaminase activity. Core molecular function.
    action: ACCEPT
    reason: >-
      Directly demonstrates AMP deaminase activity for AMPD2 via cross-species genetic
      interaction/complementation and enzymatic assay of patient cells. This is the core
      function.
    supported_by:
    - reference_id: PMID:23911318
      supporting_text: which converts AMP to IMP
- term:
    id: GO:0006188
    label: IMP biosynthetic process
  evidence_type: IGI
  original_reference_id: PMID:23911318
  qualifier: acts_upstream_of_or_within
  review:
    summary: >-
      Experimental (IGI, yeast amd1 complementation) support that AMPD2 acts in production of
      IMP from AMP. Consistent with the core metabolic role of the enzyme.
    action: ACCEPT
    reason: >-
      Supported by functional complementation and by the direct chemistry of the reaction
      (AMP->IMP). Correct process for the gene.
    supported_by:
    - reference_id: PMID:23911318
      supporting_text: which converts AMP to IMP
- term:
    id: GO:0097009
    label: energy homeostasis
  evidence_type: IGI
  original_reference_id: PMID:23911318
  qualifier: acts_upstream_of_or_within
  review:
    summary: >-
      Experimental (IGI) support linking AMPD2 to cellular energy/purine homeostasis via the
      yeast amd1 complementation system and the demonstrated regulation of adenine/guanine
      nucleotide pools. A valid higher-level physiological role.
    action: KEEP_AS_NON_CORE
    reason: >-
      Downstream physiological role (setting the adenylate energy charge / purine pools)
      rather than the direct catalytic activity; retained as non-core.
    supported_by:
    - reference_id: PMID:23911318
      supporting_text: essential for cellular energy homeostasis and nucleic acid synthesis
- term:
    id: GO:0003876
    label: AMP deaminase activity
  evidence_type: NAS
  original_reference_id: PMID:8764830
  qualifier: enables
  review:
    summary: >-
      Author statement (NAS) of AMP deaminase activity from the AMPD2 gene cloning and
      characterization paper, which describes AMPD2 as a member of the AMP deaminase multigene
      family. Same core function as the IBA/IGI/IEA annotations.
    action: ACCEPT
    reason: >-
      Correct core molecular function; the cloning paper explicitly identifies AMPD2 as an AMP
      deaminase family gene. Redundant with stronger experimental evidence but accurate.
    supported_by:
    - reference_id: PMID:8764830
      supporting_text: "AMP deaminase (AMPD) is manifest through a multigene family in higher"
- term:
    id: GO:0006196
    label: AMP catabolic process
  evidence_type: IDA
  original_reference_id: PMID:23911318
  qualifier: involved_in
  review:
    summary: >-
      Proposed annotation for the most precise process term describing the AMPD2 reaction:
      catabolic breakdown of AMP (AMP -> IMP + ammonia). Directly supported by the
      demonstrated AMP deaminase activity and loss of that activity in patient cells.
    action: NEW
    reason: >-
      The AMP->IMP deamination is a breakdown of AMP and is best captured by AMP catabolic
      process. Existing annotations use the broader parent (AMP metabolic process, GO:0046033)
      and product-oriented terms (IMP biosynthetic process); adding the specific catabolic
      term makes the substrate-consuming role explicit. Supported experimentally.
    supported_by:
    - reference_id: PMID:23911318
      supporting_text: which converts AMP to IMP
    - reference_id: file:human/AMPD2/AMPD2-uniprot.txt
      supporting_text: "Catalyzes the deamination of AMP to IMP and plays an important role in"
core_functions:
- description: >-
    Cytosolic zinc-dependent hydrolytic deamination of AMP to IMP and ammonia, the committed
    step of the purine nucleotide cycle and AMP catabolism.
  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: PMID:23911318
    supporting_text: which converts AMP to IMP
  - reference_id: file:human/AMPD2/AMPD2-uniprot.txt
    supporting_text: "Catalyzes the deamination of AMP to IMP and plays an important role in"
- description: >-
    Regulation of adenine/guanine nucleotide pools and the adenylate energy charge: by
    deaminating AMP, AMPD2 relieves feedback inhibition of de novo purine synthesis and thereby
    sustains the guanine nucleotide (GTP) pool, important for GTP-dependent translation in neurons.
  molecular_function:
    id: GO:0003876
    label: AMP deaminase activity
  directly_involved_in:
  - id: GO:0046033
    label: AMP metabolic process
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: PMID:23911318
    supporting_text: we identify AMPD2 as necessary for guanine nucleotide biosynthesis and protein translation
  - reference_id: PMID:23911318
    supporting_text: dramatic reduction in guanine nucleotides, most remarkable for GTP, which was reduced by half
proposed_new_terms: []
suggested_questions:
- question: >-
    Do the four AMPD2 splice isoforms (differing mainly in N-terminal extension) differ in
    catalytic regulation, subcellular targeting, or tissue distribution?
- question: >-
    In post-mitotic neurons, where de novo purine synthesis is low, what is the precise
    mechanism by which AMPD2 loss depletes GTP and impairs translation initiation?
suggested_experiments:
- description: >-
    Isoform-resolved enzyme kinetics and allosteric regulation (by ATP, GTP, phosphate) of the
    four AMPD2 splice variants expressed and purified in parallel.
- description: >-
    Metabolic-flux (labeled-adenosine) analysis in AMPD2-null vs rescued human neurons to map
    how the AMP->IMP block redistributes purine flux toward or away from the guanine branch.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  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:21044950
  title: Genome-wide YFP fluorescence complementation screen identifies new regulators
    for telomere signaling in human cells.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      High-throughput telomere-signaling complementation screen; source of a binary AMPD2-TERF1
      interaction reported to IntAct. Does not establish a physiological AMPD2 function.
- id: PMID:23911318
  title: AMPD2 regulates GTP synthesis and is mutated in a potentially treatable neurodegenerative
    brainstem disorder.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Definitive functional paper: establishes AMPD2 (AMP->IMP) as required for guanine
      nucleotide/GTP homeostasis and translation, and identifies loss-of-function mutations as
      the cause of PCH9. Full text available and directly supports the core function.
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Proteome-scale Y2H interactome; source of an AMPD2-CCNDBP1 interaction in IntAct.
      Background interactome data, not a functional characterization of AMPD2.
- id: PMID:29079593
  title: Hypoxia modulates the purine salvage pathway and decreases red blood cell
    and supernatant levels of hypoxanthine during refrigerated storage.
  findings: []
  reference_review:
    relevance: LOW
    correctness: MISCITED
    review_notes: >-
      Study of erythrocyte purine metabolism centered on the RBC AMPD isoform (AMPD3) and the
      salvage/deamination network; cited for an AMPD2 GMP salvage IDA, but it does not establish
      AMPD2 in GMP salvage (AMP deaminase makes IMP, not GMP).
- id: PMID:31515488
  title: Extensive disruption of protein interactions by genetic variants across the
    allele frequency spectrum in human populations.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Variant/interactome study; source of an AMPD2-CCNDBP1 interaction in IntAct. Background
      interactome data.
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      BioPlex proteome-scale AP-MS interactome; source of an AMPD2-HIRIP3 interaction in IntAct.
- id: PMID:34819669
  title: A multi-scale map of cell structure fusing protein images and interactions.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Multi-scale cell-structure map; source of an AMPD2-HIRIP3 interaction in IntAct.
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Multimodal cell-map study; source of an AMPD2-HIRIP3 interaction in IntAct.
- id: PMID:8764830
  title: 'Cloning, sequence and characterization of the human AMPD2 gene: evidence
    for transcriptional regulation by two closely spaced promoters.'
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Original AMPD2 gene cloning/characterization; identifies AMPD2 as a member of the AMP
      deaminase multigene family (basis of the NAS AMP deaminase activity annotation).
      Abstract-only in cache.
- id: Reactome:R-HSA-76590
  title: AMP + H2O => IMP + NH4+ (AMPD)
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Reactome reaction for cytosolic AMP deaminase (AMP -> IMP + ammonia); basis of the cytosol
      TAS localization and consistent with the core catalytic function.
- id: file:human/AMPD2/AMPD2-uniprot.txt
  title: UniProtKB entry Q01433 (AMPD2_HUMAN)
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      UniProt record providing catalytic activity (EC 3.5.4.6; AMP + H2O + H+ = IMP + NH4+),
      zinc cofactor, homotetramer, cytosolic IMP-salvage pathway assignment, tissue specificity,
      interaction partners, and PCH9/SPG63 disease associations.