DPYSL4

Summary: cytosol: a core subcellular location for DPYSL4 (cytoplasmic/cytoskeletal CRMP).

Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.

Summary: The curated NOT assertion for DPYSL4 concerns pyrimidine nucleobase catabolism specifically.

Reason: Retain the curated phylogenetic negation for the ancestral pyrimidine-degradation pathway, consistent with loss of its dihydropyrimidinase reaction and the characterized cytoskeletal role. No alternative structural or cofactor contribution to pyrimidine catabolism was identified. This does not imply exclusion from all nucleic-acid metabolism or from processes performed noncatalytically.

Summary: DPYSL4 lacks the conserved catalytic apparatus for ancestral dihydropyrimidinase-type cyclic-amide hydrolysis.

Reason: The target UniProt caution documents missing metal-cofactor ligands; the CRMP2 crystal structure and CRMP5 negative assay independently corroborate loss of this ancestral reaction in the CRMP subfamily. The OpenScientist report supplies residue-level comparisons, with direct-assay and paralog-inference limitations kept explicit. These data challenge retention of catalytic activity in this target, rather than the strength or number of phylogenetic donors.

Summary: NOT: DPYSL4 does not have dihydropyrimidinase activity. It belongs to the metallo-dependent hydrolase superfamily but lacks the conserved metal-cofactor-binding residues required for catalysis (UniProt CAUTION).

Reason: Retain the curated negation for dihydropyrimidinase chemistry and its lost ancestral metal center; this is not a universal negation of all possible catalytic activities.

Summary: cytoplasm: a core subcellular location for DPYSL4 (cytoplasmic/cytoskeletal CRMP).

Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.

Summary: Controlled mouse CRMP3 preparations show a distinct deacetylation activity, but intrinsic catalysis and transfer to human DPYSL4 remain unresolved.

Reason: PMID:23443259 provides positive mouse-CRMP3-associated deacetylation evidence: full-length protein, p54 and D-domain preparations were active, with full-length strongest; HEK293 EGFP fusions were purified using anti-EGFP, while Sf9 His6/S-tagged proteins used nickel affinity purification. EGFP/empty-vector, inactive C-terminal fragment, CRMP4-negative and HDAC6-positive controls, dose dependence and selective H4 effects strengthen the observation. However, the native-histone assay used a cell-lysate substrate preparation and the purified fractions were not shown to exclude another associated deacetylase; intrinsic catalytic attribution remains unresolved. The commercial Abnova reagent listed in Materials is not unambiguously linked to a particular assay/species, so it does not establish direct human-protein activity. The focused OpenScientist report correctly identifies enzyme-attribution and replication gaps, but its truncation-only account and host/tag conflation are incorrect. TSA sensitivity raises a possible associated-HDAC explanation without proving it. Loss of dihydropyrimidinase activity, including its curated NOT, does not negate every broader hydrolase activity. Retain UNDECIDED for this specific attribution question, rather than remove the term based on missing human tests or loss of the ancestral metal center.

Summary: Controlled mouse CRMP3 preparations show a distinct deacetylation activity, but intrinsic catalysis and transfer to human DPYSL4 remain unresolved.

Reason: PMID:23443259 provides positive mouse-CRMP3-associated deacetylation evidence: full-length protein, p54 and D-domain preparations were active, with full-length strongest; HEK293 EGFP fusions were purified using anti-EGFP, while Sf9 His6/S-tagged proteins used nickel affinity purification. EGFP/empty-vector, inactive C-terminal fragment, CRMP4-negative and HDAC6-positive controls, dose dependence and selective H4 effects strengthen the observation. However, the native-histone assay used a cell-lysate substrate preparation and the purified fractions were not shown to exclude another associated deacetylase; intrinsic catalytic attribution remains unresolved. The commercial Abnova reagent listed in Materials is not unambiguously linked to a particular assay/species, so it does not establish direct human-protein activity. The focused OpenScientist report correctly identifies enzyme-attribution and replication gaps, but its truncation-only account and host/tag conflation are incorrect. TSA sensitivity raises a possible associated-HDAC explanation without proving it. Loss of dihydropyrimidinase activity, including its curated NOT, does not negate every broader hydrolase activity. Retain UNDECIDED for this specific attribution question, rather than remove the term based on missing human tests or loss of the ancestral metal center.

Summary: The cited interaction evidence is retained as context, but the generic protein-binding term does not specify a molecular function.

Reason: PMID:21900206 reports protein interactions. Remove this uninformative GO:0005515 assertion under the annotation-reviewer policy; this does not reject the interaction or infer that the experiment assayed the wrong gene. A specific molecular function is not inferred from an interaction screen alone.

Summary: The cited interaction evidence is retained as context, but the generic protein-binding term does not specify a molecular function.

Reason: PMID:25416956 reports protein interactions. Remove this uninformative GO:0005515 assertion under the annotation-reviewer policy; this does not reject the interaction or infer that the experiment assayed the wrong gene. A specific molecular function is not inferred from an interaction screen alone.

Summary: The cited interaction evidence is retained as context, but the generic protein-binding term does not specify a molecular function.

Reason: PMID:32814053 reports protein interactions. Remove this uninformative GO:0005515 assertion under the annotation-reviewer policy; this does not reject the interaction or infer that the experiment assayed the wrong gene. A specific molecular function is not inferred from an interaction screen alone.

Summary: The cited interaction evidence is retained as context, but the generic protein-binding term does not specify a molecular function.

Reason: PMID:33961781 reports protein interactions. Remove this uninformative GO:0005515 assertion under the annotation-reviewer policy; this does not reject the interaction or infer that the experiment assayed the wrong gene. A specific molecular function is not inferred from an interaction screen alone.

Summary: The cited interaction evidence is retained as context, but the generic protein-binding term does not specify a molecular function.

Reason: PMID:40205054 reports protein interactions. Remove this uninformative GO:0005515 assertion under the annotation-reviewer policy; this does not reject the interaction or infer that the experiment assayed the wrong gene. A specific molecular function is not inferred from an interaction screen alone.

Summary: filamin binding: a specific molecular interaction consistent with DPYSL4's cytoskeletal-adapter role.

Reason: Filamin binding is a specific, experimentally demonstrated interaction (PMID:25358863) central to this CRMP's cytoskeletal-adapter role; retained as the representative core binding molecular function.

Summary: cytosol: a core subcellular location for DPYSL4 (cytoplasmic/cytoskeletal CRMP).

Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.

Summary: cytosol: a core subcellular location for DPYSL4 (cytoplasmic/cytoskeletal CRMP).

Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.

Summary: cytosol: a core subcellular location for DPYSL4 (cytoplasmic/cytoskeletal CRMP).

Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.

Summary: nervous system development: a core neuronal/cytoskeletal process for the CRMP family (DPYSL4 acts in semaphorin-driven cytoskeleton remodeling and neurite/axon development).

Reason: Core biological process for a CRMP-family cytoskeletal regulator.