ARL2BP

Summary: Transcriptional output does not establish a locus-specific coactivator mechanism.

Reason: The actual original Methods and Results establish STAT3 binding, nuclear retention, and cytokine-dependent reporter/endogenous SOCS3 output. The current coactivator definition requires action through a DNA-bound transcription factor at a genomic locus. BART recruitment or action at such a locus was not established; the authors discuss retention and leave stabilization of STAT3-DNA binding as a possibility. Retain the experimental context while flagging the stronger molecular interpretation, without declaring the transcriptional phenotype false.

Summary: The original human BART comparator experiment supports small GTPase binding to ARL2.

Reason: The original PMID:11847227 construct Methods identifies human BART and ARL2/ARL3 cDNAs, and its Results/Figure 4A directly reports BART association with ARL2 in affinity pull-down experiments. This resolves the source-specific IPI assertion and supports the more informative small-GTPase binding term. The experiment uses BART as a positive control in the RP2 study; its tubulin-GAP results must not be transferred to BART. The normal publication record remains abstract-only, while the original-body locator and result are recorded in the linked notes.

Proposed replacements: small GTPase binding

Summary: The original human BART comparator experiment supports small GTPase binding to ARL3.

Reason: The original PMID:11847227 construct Methods identifies human BART and ARL2/ARL3 cDNAs, and its Results/Figure 4A directly reports BART association with ARL3 in affinity pull-down experiments. This resolves the source-specific IPI assertion and supports the more informative small-GTPase binding term. The experiment uses BART as a positive control in the RP2 study; its tubulin-GAP results must not be transferred to BART. The normal publication record remains abstract-only, while the original-body locator and result are recorded in the linked notes.

Proposed replacements: small GTPase binding

Summary: Refine the demonstrated ARL2 association to small GTPase binding.

Reason: The original STAT3 study directly tests BART association with ARL2 and nucleotide-state mutants in 293T cells. This supports the more informative small-GTPase binding term; it does not establish that BART hydrolyzes GTP or acts as an ARL2 GAP.

Proposed replacements: small GTPase binding

Summary: Refine the demonstrated STAT3 association to transcription-factor binding.

Reason: Original Y2H, deletion mapping, and endogenous 293T co-IP support BART association with STAT3, a DNA-binding transcription factor. Human BART was explicitly tested in the Y2H reconstruction; some other constructs and rescue experiments have distinct species scope. The specific partner class is supported, without assigning intrinsic DNA binding or a locus-specific coactivator mechanism to BART.

Proposed replacements: DNA-binding transcription factor binding

Summary: The human complex structure supports small GTPase binding.

Reason: The cited human ARL2-GTP–BART crystal structure and interface mutagenesis directly support small-GTPase binding. This is an effector/regulator contact, not evidence that ARL2BP itself is a GTPase.

Proposed replacements: small GTPase binding

Summary: The curated ARL2 interaction supports the more specific small GTPase binding term.

Reason: PMID:21988832 describes a human liver interaction survey using high-stringency yeast two-hybrid screening and network integration. Its complete cached abstract and targeted screen Results were read; the exact ARL2BP–ARL2 configuration and pair-specific validation were not inspected. A liver-focused survey does not by itself establish endogenous liver-cell binding. The original IPI record names ARL2, a small monomeric GTPase. Retaining that curated interaction is consistent with independently established ARL2BP binding to ARL2; refining it to small GTPase binding specifies only the recorded partner class. It does not establish the uninspected assay details, directness, nucleotide state, compartment or physiological consequence.

Proposed replacements: small GTPase binding

Summary: The curated ARL2 interaction supports the more specific small GTPase binding term.

Reason: PMID:25416956 describes a systematic human binary-interaction map based on large-scale yeast two-hybrid work. The complete cached abstract and available Discussion were read, while the configuration and pair-level validation of this ARL2BP–ARL2 record remain uninspected. The original IPI record names ARL2, a small monomeric GTPase. Retaining that curated interaction is consistent with independently established ARL2BP binding to ARL2; refining it to small GTPase binding specifies only the recorded partner class. It does not establish the uninspected assay details, directness, nucleotide state, compartment or physiological consequence.

Proposed replacements: small GTPase binding

Summary: The curated ARL2 interaction supports the more specific small GTPase binding term.

Reason: PMID:25502805 compares reference and disease-variant protein interactions, with Clone-seq and stability work including HEK293T experiments. The complete cached abstract and targeted Results were read, but the exact ARL2BP–ARL2 reference/variant assay and controls remain unresolved. Neither a mutant-only observation nor loss of a reference interaction is inferred. The original IPI record names ARL2, a small monomeric GTPase. Retaining that curated interaction is consistent with independently established ARL2BP binding to ARL2; refining it to small GTPase binding specifies only the recorded partner class. It does not establish the uninspected assay details, directness, nucleotide state, compartment or physiological consequence.

Proposed replacements: small GTPase binding

Summary: The curated ARL3 interaction supports the more specific small GTPase binding term.

Reason: PMID:26455799 contains new BARTL1–ARL3 structural experiments, a comparison with the earlier ARL2–BART structure, and new observations of variable BART ciliary localization in IMCD3 cells. The cached Introduction, targeted interaction/structure/localization Results and Discussion were read. The original BART–ARL3 IPI annotation is retained, while its exact pair-level assay and any relevant supplemental experiment remain uninspected; the BARTL1 structure is not reassigned to BART. The original IPI record names ARL3, a small monomeric GTPase. Retaining that curated interaction is consistent with independently established ARL2BP binding to ARL3; refining it to small GTPase binding specifies only the recorded partner class. It does not establish the uninspected assay details, directness, nucleotide state, compartment or physiological consequence.

Proposed replacements: small GTPase binding

Summary: The curated ARL2 interaction supports the more specific small GTPase binding term.

Reason: PMID:27107012 uses barcoded fusion-genetics yeast two-hybrid screening with reference sets and a centrosomal-protein matrix. The complete cached abstract and targeted method-principle, reference-set and network Results were read; which set, configuration and score support this exact ARL2BP–ARL2 record remain unresolved. The original IPI record names ARL2, a small monomeric GTPase. Retaining that curated interaction is consistent with independently established ARL2BP binding to ARL2; refining it to small GTPase binding specifies only the recorded partner class. It does not establish the uninspected assay details, directness, nucleotide state, compartment or physiological consequence.

Proposed replacements: small GTPase binding

Summary: The curated ARL3 interaction supports the more specific small GTPase binding term.

Reason: PMID:27173435 reports a ciliary interaction network using SF-TAP affinity purification and mass spectrometry in HEK293T cells. The complete cached abstract and targeted network Results were read. The exact ARL2BP–ARL3 bait/prey configuration, copurification mode and score remain uninspected; a direct binary interface is not inferred from network association. The original IPI record names ARL3, a small monomeric GTPase. Retaining that curated interaction is consistent with independently established ARL2BP binding to ARL3; refining it to small GTPase binding specifies only the recorded partner class. It does not establish the uninspected assay details, directness, nucleotide state, compartment or physiological consequence.

Proposed replacements: small GTPase binding

Summary: The specific PMID:27173435 association with UniProtKB:Q9Y6A4 remains unresolved.

Reason: Complete cached abstract and targeted SF-TAP affinity-purification/mass-spectrometry network Results. The ciliary network combines bait-prey and copurification relationships from HEK293T affinity purification. Exact ARL2BP–ARL3 and ARL2BP–CFAP20 records, association mode and scores remain uninspected. The network context is not automatically a direct binary binding assay. The original IPI source and partner are retained pending the source-specific observation; no contradictory result is established.

Summary: The curated ARL2 interaction supports the more specific small GTPase binding term.

Reason: PMID:29997244 develops LuTHy, combining live-cell BRET and luminescence coprecipitation after lysis. The complete cached abstract, targeted Results and cellular assay Methods were read. Which readout and configuration support the exact ARL2BP–ARL2 record remain unresolved; positivity in both modes is not assumed. The original IPI record names ARL2, a small monomeric GTPase. Retaining that curated interaction is consistent with independently established ARL2BP binding to ARL2; refining it to small GTPase binding specifies only the recorded partner class. It does not establish the uninspected assay details, directness, nucleotide state, compartment or physiological consequence.

Proposed replacements: small GTPase binding

Summary: The curated ARL2 interaction supports the more specific small GTPase binding term.

Reason: PMID:31515488 compares missense-variant effects across human interaction pairs by yeast two-hybrid assays. The complete cached abstract and targeted variant-interaction Results were read, but the exact ARL2BP–ARL2 reference/variant profile was not inspected. No variant-specific functional failure is inferred. The original IPI record names ARL2, a small monomeric GTPase. Retaining that curated interaction is consistent with independently established ARL2BP binding to ARL2; refining it to small GTPase binding specifies only the recorded partner class. It does not establish the uninspected assay details, directness, nucleotide state, compartment or physiological consequence.

Proposed replacements: small GTPase binding

Summary: The curated ARL2 interaction supports the more specific small GTPase binding term.

Reason: PMID:32296183 combines repeated human interaction screens using different yeast two-hybrid configurations. The complete cached abstract and targeted screening Results were read. The exact ARL2BP–ARL2 assay version, bait/prey orientation and validation remain uninspected. The original IPI record names ARL2, a small monomeric GTPase. Retaining that curated interaction is consistent with independently established ARL2BP binding to ARL2; refining it to small GTPase binding specifies only the recorded partner class. It does not establish the uninspected assay details, directness, nucleotide state, compartment or physiological consequence.

Proposed replacements: small GTPase binding

Summary: The curated ARL3 interaction supports the more specific small GTPase binding term.

Reason: PMID:32296183 combines repeated human interaction screens using different yeast two-hybrid configurations. The complete cached abstract and targeted screening Results were read. The exact ARL2BP–ARL3 assay version, bait/prey orientation and validation remain uninspected. The original IPI record names ARL3, a small monomeric GTPase. Retaining that curated interaction is consistent with independently established ARL2BP binding to ARL3; refining it to small GTPase binding specifies only the recorded partner class. It does not establish the uninspected assay details, directness, nucleotide state, compartment or physiological consequence.

Proposed replacements: small GTPase binding

Summary: The specific PMID:32296183 association with UniProtKB:Q9Y6A4 remains unresolved.

Reason: Complete cached abstract and targeted three-version yeast-two-hybrid screening Results. HuRI combines repeated screens with different Y2H assay configurations. The exact ARL2BP records for ARL2, ARL3 and CFAP20, their assay versions and orientations, remain unresolved. The original IPI source and partner are retained pending the source-specific observation; no contradictory result is established.

Summary: The specific PMID:32814053 association with UniProtKB:O14901 remains unresolved.

Reason: Complete normal cached abstract; original full body/pair-level records unavailable in this read. This neurodegeneration network combines targeted yeast-two-hybrid work and literature interactions. The six ARL2BP records cannot yet be assigned to an original assay or a literature-derived entry, and their exact target-specific outcomes remain unverified. The original IPI source and partner are retained pending the source-specific observation; no contradictory result is established.

Summary: The specific PMID:32814053 association with UniProtKB:P06396 remains unresolved.

Reason: Complete normal cached abstract; original full body/pair-level records unavailable in this read. This neurodegeneration network combines targeted yeast-two-hybrid work and literature interactions. The six ARL2BP records cannot yet be assigned to an original assay or a literature-derived entry, and their exact target-specific outcomes remain unverified. The original IPI source and partner are retained pending the source-specific observation; no contradictory result is established.

Summary: The specific PMID:32814053 association with UniProtKB:P17987 remains unresolved.

Reason: Complete normal cached abstract; original full body/pair-level records unavailable in this read. This neurodegeneration network combines targeted yeast-two-hybrid work and literature interactions. The six ARL2BP records cannot yet be assigned to an original assay or a literature-derived entry, and their exact target-specific outcomes remain unverified. The original IPI source and partner are retained pending the source-specific observation; no contradictory result is established.

Summary: The specific PMID:32814053 association with UniProtKB:P22607 remains unresolved.

Reason: Complete normal cached abstract; original full body/pair-level records unavailable in this read. This neurodegeneration network combines targeted yeast-two-hybrid work and literature interactions. The six ARL2BP records cannot yet be assigned to an original assay or a literature-derived entry, and their exact target-specific outcomes remain unverified. The original IPI source and partner are retained pending the source-specific observation; no contradictory result is established.

Summary: The specific PMID:32814053 association with UniProtKB:P46379-2 remains unresolved.

Reason: Complete normal cached abstract; original full body/pair-level records unavailable in this read. This neurodegeneration network combines targeted yeast-two-hybrid work and literature interactions. The six ARL2BP records cannot yet be assigned to an original assay or a literature-derived entry, and their exact target-specific outcomes remain unverified. The original IPI source and partner are retained pending the source-specific observation; no contradictory result is established.

Summary: The specific PMID:32814053 association with UniProtKB:Q9Y649 remains unresolved.

Reason: Complete normal cached abstract; original full body/pair-level records unavailable in this read. This neurodegeneration network combines targeted yeast-two-hybrid work and literature interactions. The six ARL2BP records cannot yet be assigned to an original assay or a literature-derived entry, and their exact target-specific outcomes remain unverified. The original IPI source and partner are retained pending the source-specific observation; no contradictory result is established.

Summary: The curated ARL2 interaction supports the more specific small GTPase binding term.

Reason: PMID:33961781 compares affinity-purification/mass-spectrometry interactomes in 293T and HCT116 cells. The complete cached abstract and available Introduction/Discussion were read, while the ARL2BP–ARL2 bait/prey configuration, cell context and pair-level support remain uninspected. Availability of a full record does not imply that this target-specific assay was read. The original IPI record names ARL2, a small monomeric GTPase. Retaining that curated interaction is consistent with independently established ARL2BP binding to ARL2; refining it to small GTPase binding specifies only the recorded partner class. It does not establish the uninspected assay details, directness, nucleotide state, compartment or physiological consequence.

Proposed replacements: small GTPase binding

Summary: The curated ARL3 interaction supports the more specific small GTPase binding term.

Reason: PMID:33961781 compares affinity-purification/mass-spectrometry interactomes in 293T and HCT116 cells. The complete cached abstract and available Introduction/Discussion were read, while the ARL2BP–ARL3 bait/prey configuration, cell context and pair-level support remain uninspected. Availability of a full record does not imply that this target-specific assay was read. The original IPI record names ARL3, a small monomeric GTPase. Retaining that curated interaction is consistent with independently established ARL2BP binding to ARL3; refining it to small GTPase binding specifies only the recorded partner class. It does not establish the uninspected assay details, directness, nucleotide state, compartment or physiological consequence.

Proposed replacements: small GTPase binding

Summary: The specific PMID:33961781 association with UniProtKB:Q9Y6A4 remains unresolved.

Reason: Complete cached abstract and available Introduction/Discussion; source-specific pair results not inspected. BioPlex compares affinity-purification/mass-spectrometry interactomes in 293T and HCT116. Exact ARL2BP–ARL2, ARL3 and CFAP20 bait/prey configurations, cell contexts and support were not resolved. The full_text_available flag does not mean these exact records were inspected. The original IPI source and partner are retained pending the source-specific observation; no contradictory result is established.

Summary: Controlled observations support a nuclear ARL2BP pool.

Reason: The nuclear location mapping agrees with controlled BART nuclear staining in the actual PMID:16525022 text and the STAT3 retention work. The UniProt prose contains inconsistent negative and positive nuclear statements; direct nuclear observations are the relevant evidence. No constitutive or isoform-exclusive location is inferred.

Summary: Retain the corroborated nucleoplasmic localization.

Reason: The HPA nucleoplasm observation is consistent with independently controlled BART nuclear staining and the STAT3 retention mechanism. The original HPA assertion is retained; its individual image is not claimed re-inspected.

Summary: A predominant cytosolic pool supports the broader cytoplasm assignment.

Reason: A predominant cytosolic pool is explicitly reported in PMID:11809823. This supports the broader cytoplasm mapping and accommodates smaller mitochondrial and nuclear/ciliary pools.

Summary: Biochemical and imaging evidence support mitochondrial association.

Reason: Mitochondrial association is directly supported by fractionation, protection and imaging in PMID:11809823. Accept the broad electronic compartment without converting association into ANT transport chemistry or a matrix-specific location.

Summary: The inherited intermembrane-space assignment has experimental grounding.

Reason: The intermembrane-space IBA agrees with the actual indexed subfractionation Results and Figure 6 of PMID:11809823. Inclusion of ARL2BP itself among descendants is legitimate experimental grounding, not circularity. The exact PAINT node topology has not been independently reconstructed.

Summary: Original subfractionation identifies an intermembrane-space pool.

Reason: The original mitochondrial subfractionation Results explicitly identify most mitochondrial BART in the intermembrane space, with human sf295 and rat-brain preparations and matrix-retention controls. The existing human IDA is supported; this does not prove every cellular BART molecule occupies that compartment.

Summary: The location mapping agrees with intermembrane-space evidence.

Reason: The UniProt location mapping is consistent with the original mitochondrial subfractionation evidence. No membrane-spanning transporter activity or exclusively mitochondrial function is implied.

Summary: The exact model does not yet resolve the side occupied by ARL2BP.

Reason: The cached reaction describes ARL2-GTP–ARL2BP binding ANT1 at the mitochondrial inner membrane, but does not resolve the side occupied by ARL2BP. The full Reactome entity graph and source-specific matrix evidence were not inspected. Original BART intermembrane-space evidence is distinct; retain uncertainty rather than equating membrane association with matrix residence.

Summary: The reaction title and summary leave a compartment ambiguity.

Reason: This Reactome title names translocation to matrix, while its own summary describes movement into the intermembrane space. The exact participant topology and source evidence require inspection. Preserve the curated TAS assertion with this explicit compartment ambiguity; do not silently replace it using a title alone.

Summary: Nucleotide transport context does not establish the ARL2BP compartment.

Reason: The cached transport summary describes adenine-nucleotide exchange by SLC25A4/5/6 and the matrix ATP pool. It does not establish the compartment occupied by ARL2BP. The full participant model has not been inspected, so the matrix-specific TAS remains unresolved without assigning ANT transport activity to ARL2BP.

Summary: Retain centrosomal localization corroborated by independent experiments.

Reason: The HPA centrosome assertion agrees with independent endogenous BART microscopy and centrosome fractionation in PMID:16525022. Its individual HPA image was not independently inspected; the existing observation is biologically corroborated.

Summary: Controlled microscopy and fractionation establish centrosomal localization.

Reason: The original paper reports antigen-competed centrosomal BART staining across mammalian cell lines and enrichment in purified human HeLa centrosome fractions. These actual Results support the human IDA location without inferring tubulin polymerase chemistry.

Summary: The centrosome mapping agrees with experimental localization.

Reason: The electronic centrosome mapping agrees with independent controlled microscopy and biochemical enrichment of BART in centrosome fractions. It does not establish a mechanism for every centrosomal process.

Summary: Spindle-pole versus spindle-fiber scope leaves this electronic mapping unresolved.

Reason: This IEA is derived from UniProtKB-SubCell:SL-0251. The immutable UniProt record carries a positive spindle term but also states that BART was not detected on the mitotic spindle. Its localization reference, PMID:16525022, reports absent BART spindle staining under the tested conditions while detecting ARL3 on the spindle and BART at centrosomes and midbodies; antigen-competition, preimmune and secondary-antibody controls are described. GO:0031616 spindle pole centrosome is part of GO:0000922 spindle pole, which is part of GO:0005819 spindle. This specialized component is distinct from GO:0005813 general centrosome: not every centrosome is a spindle component. The paper reports BART at centrosomes throughout the cell cycle, with the BART all-stage images described as unpublished data. Thus the negative spindle-staining result does not conclusively exclude every structure encompassed by the broad GO component, while the positive general-centrosome observation does not establish spindle-pole localization or resolve this electronic mapping. Retain the mapping as uncertain and retain the independently supported centrosome and midbody annotations. No positive pole assertion, universal absence claim or NOT annotation is introduced.

Summary: Retain the independently supported cytosolic starting pool.

Reason: The Reactome translocation model starts from cytosolic ARL2BP, consistent with the predominant cytosolic pool measured in PMID:11809823. The destination-compartment ambiguity in the same event does not negate its independently supported cytosolic starting pool.

Summary: Cytosolic ARL2–ARL2BP association is consistent with localization evidence.

Reason: Cytosolic ARL2–ARL2BP association is consistent with the original predominant cytosolic localization and GTP-dependent interaction. This annotation supplies a compartment, not a claim that all binding occurs exclusively in cytosol.

Summary: Retain broad signaling context outside the specific molecular core.

Reason: The original effector study and later ARL3 co-GEF work are consistent with signaling, but this very broad process adds little mechanistic information. Retain it as context while representing the specific GTPase-regulatory activity and STAT3 retention separately; no new pathway is inferred.

Summary: Retain the midbody pool without inferring a cytokinesis mechanism.

Reason: Original controlled immunofluorescence identifies BART in the human HeLa midbody matrix and a somewhat different distribution in COS-7 cells. This is a supported additional localization. It does not establish a direct cytokinesis mechanism; the same study reports no observed BART-knockdown phenotype in its tested conditions.

Summary: The combined biochemical evidence supports GTPase regulation.

Reason: The original cited study establishes GTP-dependent ARL2 binding without GAP activity. Independently, the 2021 biochemical study demonstrates cooperative ARL3 exchange with ARL13B and stabilization of GTP-bound ARL3/ARL2. These are GTPase-regulatory activities under the current term definition. Preserve the old TAS source and distinguish the later mechanistic evidence; no autonomous GEF or GAP activity is asserted.

Summary: Retain the corroborated basal-body localization.

Reason: The HPA basal-body observation is consistent with the independently reviewed 2013 human ARPE19/nasal-cell localization evidence, alongside separate mouse photoreceptor localization. The original HPA image has not been re-inspected, and human and mouse observations are not conflated.

Summary: Retain the phospho-STAT3 consequence without assigning kinase activity.

Reason: In the actual original human-cell experiments, BART depletion reduces phospho-STAT3 and vanadate alters that effect. This supports maintenance of phosphorylation in the retention/signaling context, not intrinsic kinase activity or a demonstrated direct stimulation of phosphorylation chemistry. Retain the curated regulatory consequence as non-core.

Summary: Retain transcriptional effects as consequences of the retention mechanism.

Reason: The broad transcriptional consequence agrees with STAT3-dependent reporter and endogenous SOCS3 responses after BART depletion. Its electronic derivation from a coactivator annotation does not establish locus-specific coactivator action; retain the supported consequence as context, with nuclear retention as the more specific role.

Summary: Perturbation and rescue experiments support STAT3 nuclear retention.

Reason: The original human-cell depletion, zebrafish-BART rescue, live STAT3 imaging, and leptomycin-B experiments support maintenance of STAT3 nuclear localization. They distinguish retention from failure of nuclear entry. The exact stabilization mechanism remains a hypothesis, but the existing process assertion is directly supported.