AHCY

Summary: The ancestral adenosylhomocysteinase activity agrees with the experimentally characterized human enzyme.

Reason: AHCY catalyzes SAH hydrolysis to adenosine and L-homocysteine. The cached PTHR23420 PAINT table places this IBD at PTN000602759, and the family member record includes human P23526. Human evidence among the descendant seeds is legitimate experimental grounding. The full phylogenetic alignment was not independently reconstructed; no target-specific catalytic loss contradicts the assertion.

Summary: Cytosol is an established compartment of the core AHCY enzyme.

Reason: The PAINT cytosolic IBD at PTN000602759 agrees with the human HPA assignment and the cytosolic Reactome reaction. The conserved metabolic compartment is retained without excluding a nuclear pool.

Summary: AHCY performs the SAH-to-homocysteine step of the L-methionine cycle.

Reason: The live GO definition includes interconversion of SAH, homocysteine, methionine and SAM. AHCY catalyzes one of these steps rather than merely responding to the pathway. The cached PAINT IBD at PTN000602759 supports the inherited process; it does not imply that AHCY itself remethylates homocysteine.

Summary: The combined EC/Rhea inference specifies the human SAH hydrolase reaction.

Reason: RHEA:21708 and EC:3.13.2.1 match the reversible hydrolysis curated in the human UniProt record. The activity is independently established; ARBA rule internals were not recovered and are not claimed to have been validated.

Summary: Endogenous AHCY occurs in the nucleus as well as the cytoplasm.

Reason: The original primary abstract directly reports endogenous nuclear AHCY and analyzes nucleocytoplasmic distribution using GFP constructs and AHCYL1 perturbation. Nuclear localization is retained as a compartment of the core enzyme; the source does not quantify a universally minor nuclear pool. Independent clock/chromatin work provides functional nuclear context, with mouse and human experiments distinguished in the notes.

Summary: The broad cytoplasm annotation describes an established AHCY compartment.

Reason: The original source resolution is supported by endogenous cytoplasmic localization and independent cytosol annotations. A broader compartment is still core; it need not be replaced by the finer cytosol term.

Summary: AHCY colocalizes with an ER marker in a tagged-expression experiment.

Reason: The externally recovered author manuscript of PMID:28647132, Results and Figure 6F, reports mCherry-AHCY colocalization with GFP-calreticulin 1 in HEK293T cells. This supports the curated ER compartment in the tested ectopic-expression context. It does not establish membrane topology, an ER-lumen pool or an ER-specific catalytic role.

Summary: AHCY was curated from melanosome-fraction proteomics; the target-level identification remains uninspected.

Reason: The human UniProt record traces this compartment to PMID:17081065. The main paper describes human melanoma-cell melanosome fractions and selected localization validation, but the AHCY-specific supplementary identification was not recovered. Cytosolic abundance is not evidence of contamination, and an organellar function is not required to support a localization annotation. The exact AHCY fraction evidence remains unresolved.

Summary: Generic protein binding from the human binary interaction map does not specify an AHCY molecular role.

Reason: Remove the uninformative generic term under the binding policy, without denying the reported interaction. The source chain names Q6AI12 (ANKRD40), Q92624 (APPBP2) and Q9BV19 (C1orf50). The accessible source establishes the screen design, while the individual AHCY pair/allele record was not independently recovered. Neither an adapter role nor catalytic regulation follows from the pair alone; no more informative MF replacement is justified by this source.

Summary: Generic protein binding from the Mendelian variant interaction-perturbation screen does not specify an AHCY molecular role.

Reason: Remove the uninformative generic term under the binding policy, without denying the reported interaction. The source chain names Q6AI12 (ANKRD40) and Q9BV19 (C1orf50). The accessible source establishes the screen design, while the individual AHCY pair/allele record was not independently recovered. Neither an adapter role nor catalytic regulation follows from the pair alone; no more informative MF replacement is justified by this source.

Summary: Generic protein binding from the BioPlex 2.0 affinity purification/mass spectrometry network does not specify an AHCY molecular role.

Reason: Remove the uninformative generic term under the binding policy, without denying the reported interaction. The source chain names Q6AI12 (ANKRD40) and Q9BV19 (C1orf50). The accessible source establishes the screen design, while the individual AHCY pair/allele record was not independently recovered. Neither an adapter role nor catalytic regulation follows from the pair alone; no more informative MF replacement is justified by this source.

Summary: Generic protein binding from the allele-frequency interaction-perturbation screen does not specify an AHCY molecular role.

Reason: Remove the uninformative generic term under the binding policy, without denying the reported interaction. The source chain names Q6AI12 (ANKRD40) and Q9BV19 (C1orf50). The accessible source establishes the screen design, while the individual AHCY pair/allele record was not independently recovered. Neither an adapter role nor catalytic regulation follows from the pair alone; no more informative MF replacement is justified by this source.

Summary: Generic protein binding from the HuRI binary interaction map does not specify an AHCY molecular role.

Reason: Remove the uninformative generic term under the binding policy, without denying the reported interaction. The source chain names Q9BV19 (C1orf50). The accessible source establishes the screen design, while the individual AHCY pair/allele record was not independently recovered. Neither an adapter role nor catalytic regulation follows from the pair alone; no more informative MF replacement is justified by this source.

Summary: Generic protein binding from the BioPlex 3.0 cell-line affinity purification/mass spectrometry networks does not specify an AHCY molecular role.

Reason: Remove the uninformative generic term under the binding policy, without denying the reported interaction. The source chain names Q6AI12 (ANKRD40) and Q9BV19 (C1orf50). The accessible source establishes the screen design, while the individual AHCY pair/allele record was not independently recovered. Neither an adapter role nor catalytic regulation follows from the pair alone; no more informative MF replacement is justified by this source.

Summary: Generic protein binding from the OpenCell endogenous-tagging imaging and interaction resource does not specify an AHCY molecular role.

Reason: Remove the uninformative generic term under the binding policy, without denying the reported interaction. The source chain names Q6AI12 (ANKRD40). The accessible source establishes the screen design, while the individual AHCY pair/allele record was not independently recovered. Neither an adapter role nor catalytic regulation follows from the pair alone; no more informative MF replacement is justified by this source.

Summary: HPA immunofluorescence assigns AHCY to the cytosol.

Reason: Retain the curated human localization at its source resolution. Independent endogenous cytoplasmic observations and the cytosolic AHCY reaction corroborate this core compartment; the original HPA image panel was not independently re-scored.

Summary: Endogenous AHCY occurs in the nucleus as well as the cytoplasm.

Reason: The original primary abstract directly reports endogenous nuclear AHCY and analyzes nucleocytoplasmic distribution using GFP constructs and AHCYL1 perturbation. Nuclear localization is retained as a compartment of the core enzyme; the source does not quantify a universally minor nuclear pool. Independent clock/chromatin work provides functional nuclear context, with mouse and human experiments distinguished in the notes.

Summary: AHCY colocalizes with an ER marker in a tagged-expression experiment.

Reason: The externally recovered author manuscript of PMID:28647132, Results and Figure 6F, reports mCherry-AHCY colocalization with GFP-calreticulin 1 in HEK293T cells. This supports the curated ER compartment in the tested ectopic-expression context. It does not establish membrane topology, an ER-lumen pool or an ER-specific catalytic role.

Summary: The experimental catalytic assignment describes the defining AHCY reaction.

Reason: PMID:10933798 examines substrate-induced closure of the catalytic and NAD-binding domains. Its accessible abstract does not reproduce a complete hydrolysis assay, but the curated human IDA is independently consistent with the UniProt reaction and human structural evidence. Retain the established catalytic function with curator deference rather than treating abstract scope as a contradiction.

Summary: The expressed prostatic secretions in urine proteomics source requires an AHCY-specific identification audit.

Reason: The original HDA source establishes the sample and proteomics experiment, but its accessible text does not expose the AHCY identification, peptide specificity or enrichment controls. No contamination or absence is inferred from AHCY being cytosolic, and a known extracellular catalytic role is not a prerequisite for this location. The curator assignment remains unresolved pending the relevant supplementary record.

Summary: The disease Reactome event explicitly describes AHCY as cytosolic.

Reason: This source states the normal AHCY compartment while describing loss of hydrolysis in disease variants. The mutant reaction defect does not negate the protein location; normal catalytic function is supported separately.

Summary: AHCY was identified in the human urinary exosome preparation.

Reason: The externally recovered primary PMC2637050 Table 1 identifies AHCY with 10 unique peptides and 28 spectra (Pep and ID columns, respectively). The study profiled a low-density urinary membrane fraction consisting chiefly of exosomes. Retain the source-level detection as a contextual compartment; it does not establish an extracellular catalytic role or participation in exosome biogenesis.

Summary: The B-cell-derived exosomes proteomics source requires an AHCY-specific identification audit.

Reason: The externally recovered main paper describes RN B-cell exosome purification and the peptide/replicate criteria for the 539-protein list. AHCY-specific Supplementary Table 1 was not recovered, so its exact target identification remains unresolved. Sample purification alone does not verify that row; conversely, cytosolic abundance and lack of a known extracellular catalytic role do not refute the curator assignment.

Summary: The normal Reactome SAH hydrolysis event places the AHCY tetramer in the cytosol.

Reason: The cytosolic enzyme catalyzes this step directly. This traceable compartment statement agrees with the independent HPA and primary localization evidence.

Summary: The human full-length cDNA study is a traceable source for AHCY enzyme identity.

Reason: The abstract reports human placental cDNA sequence and a 432-residue protein, rather than an isolated kinetic experiment. Retain this TAS assignment because the same human enzyme activity is independently established; do not present the sequencing abstract as a direct catalytic assay.

Summary: AHCY directly forms L-homocysteine by hydrolyzing SAH.

Reason: Infer this product-forming process from the established human GO:0004013 IDA annotation and the explicit UniProt SAH-to-L-homocysteine reaction. PMID:10933798 is retained as the source of that catalytic annotation; the inference does not claim a newly inspected direct hydrolysis assay. AHCY itself forms the product. HAMAP AdoHcyase and Pseudomonas ahcY provide same-chemistry process comparators, while yeast MET17/HSU1 are other product-forming enzymes. The inspected parent pages place this biosynthesis term and L-methionine cycle as separate homocysteine-metabolism children; no ancestor/descendant relationship was found in those displayed is_a chains. No human de novo methionine synthesis is asserted.

Summary: Human AHCY directly binds the nicotinamide cofactor used in its catalytic cycle.

Reason: The human AHCY crystal structure associated with PMID:12590576 contains a bound nicotinamide cofactor; the primary RCSB 1LI4 deposition identifies human P23526 expressed in E. coli, rather than inferring protein species from the expression host. The paper describes the bound cofactors as NADH in the neplanocin-trapped state. GO:0051287 explicitly covers either NAD+ or NADH, and therefore captures the catalytic cofactor without restricting its oxidation state. This is direct binding evidence, not an inference from enzyme necessity. The indexed MGI comparative graph contains a rat Ahcy IDA precedent; the bacterial review's authored NEW is not treated as an independent curated precedent. No existing AHCY annotation is an ancestor or descendant of this nucleotide-binding term, and the cached GO-CAM index has no P23526 entry. Cofactor binding remains part of the integrated hydrolase core rather than a separate physiological function.