id: P23526
gene_symbol: AHCY
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  AHCY (adenosylhomocysteinase; S-adenosyl-L-homocysteine hydrolase, SAHH / AdoHcyase;
  EC 3.13.2.1) is an NAD+-dependent enzyme that catalyzes the reversible hydrolysis of
  S-adenosyl-L-homocysteine (SAH/AdoHcy) to L-homocysteine and adenosine. Each subunit
  binds one tightly associated NAD+ cofactor, and the active enzyme is a homotetramer.
  Because SAH is a potent product inhibitor of virtually all S-adenosyl-L-methionine
  (SAM)-dependent methyltransferases, AHCY continuously clears the SAH generated during
  cellular transmethylation reactions and thereby relieves this feedback inhibition,
  sustaining methylation capacity. In doing so it links the SAM/L-methionine cycle to
  homocysteine metabolism and one-carbon metabolism. The protein is predominantly
  cytosolic, with reported minor nuclear and endoplasmic-reticulum pools. In humans,
  loss of AHCY activity causes hypermethioninemia with S-adenosylhomocysteine hydrolase
  deficiency (SAHH deficiency; HMAHCHD), a metabolic disorder with elevated SAH, SAM and
  methionine and clinical features including failure to thrive, developmental/psychomotor
  delay, myopathy/myocardiopathy and hepatopathy.
alternative_products:
- name: '1'
  id: P23526-1
- name: '2'
  id: P23526-2
  sequence_note: VSP_045404
existing_annotations:
- term:
    id: GO:0004013
    label: adenosylhomocysteinase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      Core molecular function. AHCY is the S-adenosyl-L-homocysteine hydrolase that
      converts SAH to L-homocysteine + adenosine. The phylogenetic (IBA) call is
      consistent with direct experimental evidence (IDA, PMID:10933798) and with the
      UniProt catalytic-activity annotation.
    action: ACCEPT
    reason: >-
      Well-supported family-level enzymatic function; this is the defining activity of
      AHCY and its orthologs across eukaryotes and bacteria.
    supported_by:
    - reference_id: file:human/AHCY/AHCY-uniprot.txt
      supporting_text: "Reaction=S-adenosyl-L-homocysteine + H2O = L-homocysteine + adenosine"
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Cytosol is the principal site of AHCY activity, supported by phylogenetic
      inference and corroborated by direct immunofluorescence (IDA:HPA) and Reactome
      curation of the cytosolic AHCY:NAD+ tetramer.
    action: ACCEPT
    reason: >-
      Consistent across IBA, IDA and TAS lines; the SAH-hydrolysis reaction proceeds in
      the cytosol.
    supported_by:
    - reference_id: Reactome:R-HSA-174401
      supporting_text: >-
        Adenosylhomocysteinase (AHCY) is a tetrameric, NAD+-bound, cytosolic protein
        that regulates all adenosylmethionine-(AdoMet) dependent transmethylations by
        hydrolysing the feedback inhibitor adenosylhomocysteine (AdoHcy) to homocysteine
        (HCYS) and adenosine (Ade-Rib)
- term:
    id: GO:0033353
    label: L-methionine cycle
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      AHCY operates within the L-methionine/SAM cycle: by hydrolysing SAH it regenerates
      homocysteine (which can be remethylated to methionine) and relieves methyltransferase
      product inhibition, making it a core participant of this cycle.
    action: ACCEPT
    reason: >-
      Core biological-process context, supported phylogenetically and by the enzyme's
      established position in the methionine/one-carbon cycle. (Ontology label is now
      "L-methionine cycle"; UniProt still displays the older synonym "S-adenosylmethionine cycle".)
    supported_by:
    - reference_id: Reactome:R-HSA-174401
      supporting_text: >-
        Adenosylhomocysteinase (AHCY) is a tetrameric, NAD+-bound, cytosolic protein
        that regulates all adenosylmethionine-(AdoMet) dependent transmethylations by
        hydrolysing the feedback inhibitor adenosylhomocysteine (AdoHcy) to homocysteine
        (HCYS) and adenosine (Ade-Rib)
- term:
    id: GO:0004013
    label: adenosylhomocysteinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Electronic assignment of the core enzymatic activity via ARBA/RHEA/EC (EC 3.13.2.1,
      RHEA:21708). Redundant with, and consistent with, the IDA and IBA calls for the
      same term.
    action: ACCEPT
    reason: >-
      Automated mapping is correct and matches the experimentally validated catalytic
      activity.
    supported_by:
    - reference_id: file:human/AHCY/AHCY-uniprot.txt
      supporting_text: "Reaction=S-adenosyl-L-homocysteine + H2O = L-homocysteine + adenosine"
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Electronic (UniProt SubCell) nuclear assignment. A nuclear pool of AHCY is
      experimentally observed (GFP-tagging, PMID:28647132) and is thought to act at sites
      of AdoMet-dependent methylation, but it is a secondary distribution rather than the
      principal catalytic compartment.
    action: KEEP_AS_NON_CORE
    reason: >-
      Real but minor localization; the dominant, functionally most relevant location is
      the cytosol.
    supported_by:
    - reference_id: PMID:28647132
      supporting_text: "AHCY is located both in cytoplasm and the nucleus."
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Electronic (UniProt SubCell) cytoplasmic assignment. This is the broader parent of
      the more specific and better-supported cytosol annotation.
    action: ACCEPT
    reason: >-
      Correct but less specific than cytosol; consistent with the enzyme's established
      cytoplasmic/cytosolic localization.
    supported_by:
    - reference_id: file:human/AHCY/AHCY-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Cytoplasm"
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Electronic (UniProt SubCell) ER assignment derived from the same GFP-tagging study
      (PMID:28647132) that reported an ER-associated pool. No ER-specific function of AHCY
      is established; the enzyme's catalysis is cytosolic.
    action: KEEP_AS_NON_CORE
    reason: >-
      Reported minor distribution, not a core functional location.
    supported_by:
    - reference_id: file:human/AHCY/AHCY-uniprot.txt
      supporting_text: "Endoplasmic reticulum"
- term:
    id: GO:0042470
    label: melanosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Electronic (UniProt SubCell) melanosome assignment traceable to high-throughput
      melanosome-fraction mass spectrometry (PubMed:17081065). This is co-purification of
      an abundant cytosolic enzyme in an organelle proteomics dataset, not an established
      site of AHCY function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Large-scale organelle proteomics identification; no evidence for a melanosome-specific
      role, and inclusion likely reflects abundance/co-fractionation.
    supported_by:
    - reference_id: file:human/AHCY/AHCY-uniprot.txt
      supporting_text: "melanosome fractions from stage I to stage IV"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: >-
      Bare "protein binding" from a proteome-scale binary interactome (Y2H) map. The
      IntAct partner captured here (e.g. ANKRD40/Q6AI12, APPBP2/Q92624, C1orf50/Q9BV19)
      is not functionally interpreted, and the term conveys no specific molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative "protein binding" from a high-throughput interactome screen; retained
      per policy (experimental IPI) but flagged as over-annotated because it does not
      describe AHCY's molecular function.
    supported_by:
    - reference_id: PMID:25416956
      supporting_text: >-
        we describe a systematic map of ?14,000 high-quality human binary
        protein-protein interactions
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25910212
  qualifier: enables
  review:
    summary: >-
      Bare "protein binding" from a large-scale interactome-perturbation study. No specific,
      functionally informative interaction for AHCY is defined.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative "protein binding" from a high-throughput screen; retained per policy
      but non-core and over-annotated.
    supported_by:
    - reference_id: PMID:25910212
      supporting_text: "Widespread macromolecular interaction perturbations in human genetic disorders."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: >-
      Bare "protein binding" from a large-scale interactome (protein-community) study;
      uninformative as a molecular-function statement for AHCY.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput interactome IPI with no specific functional interaction defined;
      retained but flagged as over-annotated.
    supported_by:
    - reference_id: PMID:28514442
      supporting_text: "Architecture of the human interactome defines protein communities and disease networks."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31515488
  qualifier: enables
  review:
    summary: >-
      Bare "protein binding" from a study of variant-driven interaction disruption;
      uninformative for AHCY's molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput interactome IPI; retained per policy but non-core and over-annotated.
    supported_by:
    - reference_id: PMID:31515488
      supporting_text: >-
        Extensive disruption of protein interactions by genetic variants across the
        allele frequency spectrum in human populations.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: >-
      Bare "protein binding" from a reference binary interactome map; no specific,
      functionally informative AHCY interaction is defined.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput interactome IPI; retained per policy but over-annotated.
    supported_by:
    - reference_id: PMID:32296183
      supporting_text: "A reference map of the human binary protein interactome."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: >-
      Bare "protein binding" from a proteome-scale (BioPlex-type) affinity-MS interactome;
      uninformative for AHCY's specific molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput interactome IPI; retained per policy but over-annotated.
    supported_by:
    - reference_id: PMID:33961781
      supporting_text: "Dual proteome-scale networks reveal cell-specific remodeling of the human interactome."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  qualifier: enables
  review:
    summary: >-
      Bare "protein binding" from the OpenCell endogenous-tagging IP-MS/imaging resource.
      Informative for localization/interaction cartography at scale, but the term itself
      does not describe a specific AHCY molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput interactome IPI; retained per policy but over-annotated.
    supported_by:
    - reference_id: PMID:35271311
      supporting_text: >-
        we combined genome engineering, confocal live-cell imaging, mass spectrometry and
        data science to systematically map the localization and interactions of human proteins
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: >-
      Direct immunofluorescence localization (Human Protein Atlas) to the cytosol,
      consistent with the enzyme's known predominantly cytosolic distribution and its
      cytosolic SAH-hydrolysis activity.
    action: ACCEPT
    reason: >-
      Direct experimental support for the core cellular location.
    supported_by:
    - reference_id: file:human/AHCY/AHCY-uniprot.txt
      supporting_text: "GO:0005829; C:cytosol; IDA:HPA"
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: EXP
  original_reference_id: PMID:28647132
  qualifier: located_in
  review:
    summary: >-
      Experimental (GFP-tagging, fluorescence microscopy) demonstration that endogenous
      AHCY is present in both cytoplasm and nucleus, with disease mutations altering the
      nucleocytoplasmic ratio. The nuclear pool is a genuine but secondary distribution.
    action: KEEP_AS_NON_CORE
    reason: >-
      Real experimental localization but not the principal catalytic compartment; kept
      as non-core.
    supported_by:
    - reference_id: PMID:28647132
      supporting_text: "AHCY is located both in cytoplasm and the nucleus."
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: EXP
  original_reference_id: PMID:28647132
  qualifier: located_in
  review:
    summary: >-
      Experimental report (same GFP-tagging study) of an ER-associated AHCY pool. No
      ER-specific function is established.
    action: KEEP_AS_NON_CORE
    reason: >-
      Secondary localization from imaging; retained as non-core.
    supported_by:
    - reference_id: file:human/AHCY/AHCY-uniprot.txt
      supporting_text: "Endoplasmic reticulum"
- term:
    id: GO:0004013
    label: adenosylhomocysteinase activity
  evidence_type: IDA
  original_reference_id: PMID:10933798
  qualifier: enables
  review:
    summary: >-
      Direct experimental (IDA) evidence for the core adenosylhomocysteinase activity.
      This study characterizes substrate binding and the catalytic cycle of the
      homotetrameric enzyme and is the FUNCTION/CATALYTIC ACTIVITY reference in UniProt.
    action: ACCEPT
    reason: >-
      Strongest, direct experimental support for AHCY's defining molecular function.
    supported_by:
    - reference_id: PMID:10933798
      supporting_text: >-
        a reduction in the overall dimensions of the homotetrameric enzyme following
        substrate binding and oxidation observed in earlier crystallographic studies
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:23533145
  qualifier: located_in
  review:
    summary: >-
      High-throughput MS detection of AHCY in exosome preparations (prostatic-secretion
      urinary exosomes). AHCY is an abundant cytosolic protein routinely detected in
      exosome/secretome datasets; this is not evidence of a functional extracellular role.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Detection in a large-scale exosome proteome (co-isolation of an abundant cytosolic
      enzyme); not an established functional location.
    supported_by:
    - reference_id: file:human/AHCY/AHCY-uniprot.txt
      supporting_text: "GO:0070062; C:extracellular exosome; HDA:UniProtKB"
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5579084
  qualifier: located_in
  review:
    summary: >-
      Reactome-traceable cytosolic location for AHCY, in the context of the reaction that
      is lost in AHCY deficiency (HMAHCHD). Consistent with the core cytosolic localization.
    action: ACCEPT
    reason: >-
      Author-traceable statement consistent with all other lines for the core location.
    supported_by:
    - reference_id: Reactome:R-HSA-5579084
      supporting_text: >-
        Adenosylhomocysteinase (AHCY) is a tetrameric, NAD+-bound, cytosolic protein
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:19056867
  qualifier: located_in
  review:
    summary: >-
      High-throughput MS detection in urinary exosomes (1132 proteins identified). Reflects
      co-isolation of an abundant cytosolic protein, not a functional secreted location.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Large-scale exosome proteomics; over-annotation of location for an abundant cytosolic
      enzyme.
    supported_by:
    - reference_id: PMID:19056867
      supporting_text: "the analysis identified 1132 proteins unambiguously"
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:20458337
  qualifier: located_in
  review:
    summary: >-
      High-throughput MS detection in B-cell-derived exosomes (539 proteins identified).
      Consistent with routine detection of an abundant cytosolic protein in exosome
      proteomes rather than a functional extracellular role.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Large-scale exosome proteomics; over-annotation of location.
    supported_by:
    - reference_id: PMID:20458337
      supporting_text: "identified 539 proteins, including known and not"
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-174401
  qualifier: located_in
  review:
    summary: >-
      Reactome-traceable cytosolic location for the active AHCY:NAD+ tetramer that
      hydrolyses AdoHcy. Consistent with the core cytosolic localization.
    action: ACCEPT
    reason: >-
      Author-traceable statement for the core location; consistent with IBA and IDA.
    supported_by:
    - reference_id: Reactome:R-HSA-174401
      supporting_text: >-
        Adenosylhomocysteinase (AHCY) is a tetrameric, NAD+-bound, cytosolic protein
- term:
    id: GO:0004013
    label: adenosylhomocysteinase activity
  evidence_type: TAS
  original_reference_id: PMID:2596825
  qualifier: enables
  review:
    summary: >-
      Author-traceable assignment of adenosylhomocysteinase activity accompanying the
      original human AHCY full-length cDNA/protein report. Consistent with the core MF.
    action: ACCEPT
    reason: >-
      Traceable statement for the defining enzymatic function; redundant with the stronger
      IDA evidence.
    supported_by:
    - reference_id: PMID:2596825
      supporting_text: >-
        Sequence of full length cDNA for human S-adenosylhomocysteine hydrolase.
- term:
    id: GO:0071269
    label: L-homocysteine biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:10933798
  qualifier: involved_in
  review:
    summary: >-
      Proposed new BP annotation reflecting the UniProt-curated pathway (L-homocysteine
      biosynthesis; L-homocysteine from S-adenosyl-L-homocysteine, step 1/1; UniPathway
      UPA00314/UER00076). This is the direct product-forming process of the AHCY-catalyzed
      reaction (SAH -> L-homocysteine + adenosine) and is more specific than the
      L-methionine cycle context (GO:0033353). Supported experimentally by the
      characterized catalytic activity (PMID:10933798).
    action: NEW
    reason: >-
      The direct enzymatic product process (L-homocysteine biosynthesis from SAH) is not
      captured in the current GOA set but is well established and is used in core_functions.
    supported_by:
    - reference_id: file:human/AHCY/AHCY-uniprot.txt
      supporting_text: "Reaction=S-adenosyl-L-homocysteine + H2O = L-homocysteine + adenosine"
core_functions:
- description: >-
    Adenosylhomocysteinase (S-adenosyl-L-homocysteine hydrolase): NAD+-dependent
    hydrolysis of S-adenosyl-L-homocysteine to L-homocysteine and adenosine, clearing the
    methyltransferase product inhibitor SAH and sustaining cellular transmethylation.
  molecular_function:
    id: GO:0004013
    label: adenosylhomocysteinase activity
  directly_involved_in:
  - id: GO:0071269
    label: L-homocysteine biosynthetic process
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: PMID:10933798
    supporting_text: >-
      a reduction in the overall dimensions of the homotetrameric enzyme following
      substrate binding and oxidation observed in earlier crystallographic studies
  - reference_id: file:human/AHCY/AHCY-uniprot.txt
    supporting_text: "Reaction=S-adenosyl-L-homocysteine + H2O = L-homocysteine + adenosine"
- description: >-
    Participation in the L-methionine/S-adenosylmethionine cycle: by hydrolysing SAH,
    AHCY regenerates homocysteine and relieves feedback inhibition of SAM-dependent
    methyltransferases, coupling the methionine cycle to homocysteine and one-carbon
    metabolism.
  molecular_function:
    id: GO:0004013
    label: adenosylhomocysteinase activity
  directly_involved_in:
  - id: GO:0033353
    label: L-methionine cycle
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: Reactome:R-HSA-174401
    supporting_text: >-
      Adenosylhomocysteinase (AHCY) is a tetrameric, NAD+-bound, cytosolic protein
      that regulates all adenosylmethionine-(AdoMet) dependent transmethylations by
      hydrolysing the feedback inhibitor adenosylhomocysteine (AdoHcy) to homocysteine
      (HCYS) and adenosine (Ade-Rib)
references:
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: file:human/AHCY/AHCY-uniprot.txt
  title: UniProtKB entry P23526 (SAHH_HUMAN), Adenosylhomocysteinase
  findings: []
- id: PMID:10933798
  title: Substrate binding stabilizes S-adenosylhomocysteine hydrolase in a closed
    conformation.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified; IDA basis for GO:0004013 and UniProt FUNCTION/CATALYTIC ACTIVITY.
      Characterizes substrate-induced closed conformation of the homotetramer.
- id: PMID:19056867
  title: Large-scale proteomics and phosphoproteomics of urinary exosomes.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Large-scale exosome proteomics; AHCY detected among ~1132 proteins. Supports HDA
      exosome localization but not a functional secreted role.
- id: PMID:20458337
  title: MHC class II-associated proteins in B-cell exosomes and potential functional
    implications for exosome biogenesis.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Large-scale B-cell exosome proteomics (539 proteins). Supports HDA exosome
      detection only.
- id: PMID:23533145
  title: In-depth proteomic analyses of exosomes isolated from expressed prostatic
    secretions in urine.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Large-scale prostatic-secretion urinary exosome proteomics. Supports HDA exosome
      detection only.
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Proteome-scale binary interactome map; source of bare "protein binding" IPI. No
      specific functional AHCY interaction defined.
- id: PMID:25910212
  title: Widespread macromolecular interaction perturbations in human genetic disorders.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Large-scale interactome-perturbation study; source of bare "protein binding" IPI.
- id: PMID:2596825
  title: Sequence of full length cDNA for human S-adenosylhomocysteine hydrolase.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Original human AHCY full-length cDNA report; TAS basis for GO:0004013.
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease
    networks.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Large-scale interactome study; source of bare "protein binding" IPI.
- id: PMID:28647132
  title: Mutations in S-adenosylhomocysteine hydrolase (AHCY) affect its nucleocytoplasmic
    distribution and capability to interact with S-adenosylhomocysteine hydrolase-like
    1 protein.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      AHCY-specific study; EXP basis for nucleus/ER localization and for the AHCYL1
      interaction and disease-variant nucleocytoplasmic effects.
- 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: >-
      Large-scale variant/interaction study; source of bare "protein binding" IPI.
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Reference binary interactome (HuRI); source of bare "protein binding" IPI.
- 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: >-
      Proteome-scale affinity-MS interactome; source of bare "protein binding" IPI.
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      OpenCell endogenous-tagging IP-MS/imaging resource; source of bare "protein binding" IPI.
- id: Reactome:R-HSA-174401
  title: AHCY:NAD+ tetramer hydrolyses AdoHcy
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Reactome reaction for the core AHCY activity; TAS basis for cytosol localization.
- id: Reactome:R-HSA-5579084
  title: Defective AHCY does not hydrolyse AdoHcy
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Reactome reaction capturing loss of AHCY activity in HMAHCHD; TAS basis for cytosol.