EML1

Summary: Inherited microtubule-cytoskeleton organization is consistent with EML1 molecular and cellular evidence.

Reason: The human leaf PTN002492439 descends from the literal PTN001010531 IBD for GO:0000226. The mouse Eml1 donor has experimental PMID:24859200 evidence, including disturbed spindle orientation and progenitor organization, while purified human EML1 binds microtubules in PMID:25740311. This is a structural microtubule-associated role, not an inferred enzyme activity; no relevant loss is recorded on the target ancestry.

Summary: The mouse-to-human organization transfer matches the conserved EML1 microtubule role.

Reason: The literal donor Q05BC3 is mouse Eml1, and its current experimental GO:0000226 record cites PMID:24859200. The source establishes an Eml1-dependent arrangement of progenitor mitotic structures, with human microtubule-binding corroboration from PMID:25740311. Retain the original Ensembl transfer and its source identifiers.

Summary: The reviewed similarity assertion captures EML1-dependent microtubule organization.

Reason: Q05BC3 is the verified mouse Eml1 ortholog and the experimental source is PMID:24859200. Conserved microtubule binding and the disrupted spindle organization phenotype provide a biological basis for this transfer. The conclusion does not depend on donor count or on changing the imported evidence code.

Summary: The calcium-binding claim cannot be resolved from the accessible original source.

Reason: The genuine PMID:9226380 abstract reports cloning and EMAP homology but does not describe a calcium-binding assay. Bounded original recovery did not yield operative full text. Neither WD-repeat architecture nor the historical 717-residue clone establishes calcium binding, and lack of an accessible assay does not establish its absence. Preserve the NAS assertion pending direct source verification.

Summary: The reported EML1–ISG20L2 interaction is supported but does not define its core molecular activity.

Reason: Human EML1–ISG20L2 association is corroborated by IntAct EBI-759235 from the cited two-hybrid screen. Retain the supported interaction as non-core; no evidence-backed, more specific molecular function is established for this pair. The assayed insert is not assigned to a particular natural EML1 product.

Summary: The reported EML1–ISG20L2 interaction is supported but does not define its core molecular activity.

Reason: IntAct EBI-2349951 and EBI-2350969 corroborate the cited human EML1–ISG20L2 pair in two-hybrid array and pooling assays. Retain non-core without assigning the partner exonuclease activity to EML1. The assayed insert is not assigned to a particular natural EML1 product.

Summary: The reported EML1–FXR1 interaction is supported but does not define its core molecular activity.

Reason: BioGRID 3018756 and 3018857 corroborate the exact EML1–FXR1 pair and PMID in two-hybrid and affinity-capture Western assays. Article Results support the screen/validation design; the original pair-level supplement was inaccessible. Retain the supported generic interaction as non-core, without inferring RNA-binding activity. The assayed insert is not assigned to a particular natural EML1 product.

Summary: The reported EML1–NUDC interaction is supported but does not define its core molecular activity.

Reason: IntAct EBI-9482705 records the EML1–NUDC association in the cited HEK293T LUMIER screen. Retain this generic interaction as non-core; cochaperone association does not establish cochaperone activity for EML1. The assayed insert is not assigned to a particular natural EML1 product.

Summary: The reported EML1–LAMP2 interaction is supported but does not define its core molecular activity.

Reason: IntAct EBI-25872768, EBI-26028485 and EBI-26182632 corroborate EML1 interaction with the specified LAMP2 partner P13473-2 in two-hybrid assays. Retain non-core, preserving the partner accession without inferring EML1 isoform specificity or lysosomal function. The assayed insert is not assigned to a particular natural EML1 product.

Summary: The reported EML1–STIP1 interaction is supported but does not define its core molecular activity.

Reason: IntAct EBI-25913540, EBI-26222510 and EBI-26068371 corroborate the cited human EML1–STIP1 pair in two-hybrid assays. Retain the generic interaction as non-core; association alone does not establish a chaperone role for EML1. The assayed insert is not assigned to a particular natural EML1 product.

Summary: The reported EML1–CASP6 interaction is supported but does not define its core molecular activity.

Reason: IntAct EBI-25834583, EBI-25991661 and EBI-26145808 corroborate the cited human EML1–CASP6 pair in two-hybrid assays. Retain the interaction as non-core without assigning protease or apoptosis functions from partner identity alone. The assayed insert is not assigned to a particular natural EML1 product.

Summary: The reported EML1–NUDC interaction is supported but does not define its core molecular activity.

Reason: IntAct EBI-54741904 and the author BioPlex3 directed-edge data corroborate EML1 bait–NUDC prey association in HEK293T affinity-purification experiments. Retain non-core; copurification supports association rather than necessarily direct binding. The assayed insert is not assigned to a particular natural EML1 product.

Summary: Refine the broad cytoplasmic mapping to the supported cytosolic pool.

Reason: The imported SL-0086 mapping is broader than the retained cytosol annotation. Current mouse Q05BC3 has an experimental cytosol record from PMID:24859200; the study distinguishes soluble Eml1 from the microtubule-associated fraction, while human EML1 also associates with soluble tubulin in PMID:24706829. Use cytosol for this pool without excluding the separately supported microtubule, spindle or perinuclear locations. The historical imaging itself is not relabeled as a human endogenous fractionation assay.

Proposed replacements: cytosol

Summary: Refine the conserved broad cytoplasm assertion to cytosol.

Reason: The same verified Q05BC3 donor supports the more informative cytosol location, with soluble and microtubule-associated fractions distinguished in PMID:24859200. Human soluble-tubulin association is consistent with that pool. This is a cross-source review refinement, not a claim that the original similarity record resolved every cytoplasmic compartment.

Proposed replacements: cytosol

Summary: Retain the inferred cytosolic EML1 pool.

Reason: The literal mouse donor has a current IDA cytosol assertion grounded in PMID:24859200. Its soluble versus polymer-associated behavior, together with human EML1 soluble-tubulin association, supports this conserved location. This does not imply exclusive cytosolic residence or direct endogenous human localization in the donor paper.

Summary: Cytosol is a supported conserved location for soluble EML1.

Reason: The Q05BC3 experimental source and the human soluble-tubulin experiments support a cytosolic pool in addition to microtubule-bound protein. Preserve the ISS source and avoid converting tagged or biochemical preparations into an isoform-specific endogenous localization claim.

Summary: Refine generic cytoskeleton to the demonstrated microtubule location.

Reason: Human EML1 associates with cellular microtubules and purified EML1 binds microtubule polymers in PMID:25740311. These results support the specific microtubule component rather than an unspecified cytoskeletal structure. The refinement does not imply localization to actin or intermediate filaments.

Proposed replacements: microtubule

Summary: Human EML1 directly associates with microtubules.

Reason: PMID:25740311 shows human YFP-EML1 microtubule association in HeLa cells and binding of purified human EML1 to pig-brain microtubules by TIRF. Full-length and the 1–174 region bind polymer, whereas TAPE 167–815 and the 80–815 Δ-TD truncation do not. Preserve the assay and overexpression limits rather than generalizing an invariant endogenous distribution.

Summary: Retain the supported microtubule-associated EML1 assembly; no more specific complex is established.

Reason: The literal ARBA00044431 output is GO:0005875, defined as a multimeric complex connected to a microtubule. Human EML1 self-association and polymer binding in PMID:25740311 support that broad description. Exact current rule predicates were inspected, but target-specific FunFam clause matching was not independently established. Retain the biologically supported complex context without inventing a named stoichiometric complex; EML2/EML4 crystals, rather than EML1, establish the trimer geometry in that study.

Summary: Retain the broad microtubule-associated-complex context with later direct corroboration.

Reason: The original PMID:9226380 is available only as an abstract, so its precise complex evidence remains unverified. Independently, PMID:25740311 demonstrates EML1 self-association and microtubule binding, which supports the present broad complex definition. This corroboration supports retention without claiming that the older paper measured human oligomer stoichiometry.

Summary: Spindle organization is a supported cell-cycle context of the conserved microtubule role.

Reason: The Q05BC3 donor record cites PMID:24859200. Mouse Eml1 perturbation alters progenitor mitotic cleavage/spindle orientation, and tagged Eml1 is associated with spindle microtubules. In combination with its microtubule-binding role this supports contextual organization, while the detailed orientation mechanism and its endogenous human implementation remain unresolved.

Summary: Retain the conserved spindle-organization process as contextual.

Reason: PMID:24859200 supplies the mouse Eml1 experimental basis for this ISS assertion: abnormal mitotic orientation accompanies the Eml1 defect, with microtubule-associated protein localization. This is a specialized mitotic setting of the broader molecular role, not evidence for a separate catalytic spindle activity.

Summary: Eml1-dependent neuroblast proliferation is a developmental context, not a simple growth-promoting activity.

Reason: The current Q05BC3 experimental donor cites PMID:24859200, which measures BrdU/Ki-67 labeling, cell-cycle exit and ectopic dividing neural progenitors after Eml1 disruption. EML1 supplies a microtubule-associated contribution to orderly progenitor division; the phenotype includes prolonged cycling rather than loss of all proliferation. Retain contextual involvement without asserting that wild-type EML1 directly stimulates population expansion or that a human proliferation assay was performed.

Summary: Retain the experimentally grounded conserved neural-progenitor proliferation context.

Reason: The mouse source measures altered cycling and progenitor positioning, rather than merely counting marker-positive cells. Its microtubule/spindle connection supports the existing contextual process assignment. The direction of the mutant phenotype is not converted into a new positive or negative regulation annotation, and direct human cell-cycle effects are not claimed.

Summary: Brain development is a supported downstream setting of EML1 microtubule function.

Reason: The verified mouse donor carries an experimental PMID:24859200 brain-development assertion. That study combines cortical progenitor defects in mice with human EML1 disease alleles. Preserve the transfer as developmental context, without treating pathogenic necessity alone as an additional molecular activity or proposing a direct neuronal-migration function.

Summary: Human genetic and mouse mechanistic evidence support the brain-development annotation.

Reason: PMID:24859200 identifies human EML1 variants in severe cortical malformations and connects Eml1 perturbation in mice to ectopic progenitors and altered spindle orientation. The protein is a microtubule-associated contributor in this developmental setting; the human patients do not establish the precise cellular mechanism or natural-product specificity on their own.

Summary: Retain the conserved developmental consequence as non-core.

Reason: The Q05BC3 source is supported by mouse cortical experiments in PMID:24859200 and independently relevant human pathogenic alleles in the same study. This broad developmental process is less informative than the microtubule-binding molecular role and does not establish a separate signaling or neuronal-migration activity.

Summary: The inherited microtubule-binding activity is directly corroborated on human EML1.

Reason: The human leaf descends from the literal PTN000347035 IBD, with no relevant loss on its path. The recorded donor set contains human EML1, mouse Eml1, EML2/O95834 and fly DCX-EMAP/Q9VUI3; these identities are preserved. PMID:25740311 independently demonstrates human polymer binding. Inclusion of the target among experimental descendants is valid PAINT grounding, not circularity.

Summary: The combined electronic sources predict the experimentally verified polymer-binding activity.

Reason: ARBA00043642 literally outputs GO:0008017, and Q05BC3 has experimental polymer-binding evidence from PMID:24859200. Human purified-protein TIRF in PMID:25740311 independently supports the activity. Current rule predicates are retained, with exact target FunFam matching unresolved; correctness of the biological assertion does not require pretending that a rule clause was independently rerun.

Summary: EML1 microtubule binding is supported by polymer-sedimentation and independent human reconstitution.

Reason: PMID:24859200 reports GST-EML1 binding to polymerized porcine tubulin, not to unpolymerized tubulin, and reduced association for a disease-linked mutant. The commercial GST reagent sequence/species is not explicit in the inspected Methods; mouse expression constructs are separately specified. Direct purified human EML1 binding in PMID:25740311 resolves the molecular claim without rewriting the original source or evidence code.

Summary: Retain the conserved microtubule-binding activity.

Reason: The mouse Q05BC3 donor has experimental PMID:24859200 evidence and is inside the same EML1 family placement as the human target. Human EML1 polymer binding is independently measured in PMID:25740311. No activity equivalence among untested natural splice products is inferred.

Summary: Refine the microtubule-cytoskeleton association to microtubules.

Reason: The original work distinguishes soluble Eml1 and detergent-resistant microtubule-associated protein; independently, human EML1 colocalizes with cellular microtubules and binds purified polymer in PMID:25740311. GO:0005874 is the specific structure resolved by these assays. Preserve the imported colocalizes_with relation and do not treat the commercial or tagged constructs as a uniquely identified natural isoform.

Proposed replacements: microtubule

Summary: The EML1 TAPE region associates with soluble alpha/beta tubulin.

Reason: PMID:24706829 uses human EML1 constructs expressed in HEK293F and cold, microtubule-depolymerizing conditions to test tubulin copurification. The TAPE-containing constructs bind, the N-terminal fragment does not, and a surface mutant loses association without the reported global fold disruption. This supports tubulin binding; it is not itself a polymer-binding assay or proof that soluble binding controls polymerization. This distinct core binding mode is included explicitly in the core-function description alongside N-terminal polymer binding. The two experimental activities remain separate even though the ontology places microtubule binding below tubulin binding.

Summary: Perinuclear enrichment is a supported cell-context location.

Reason: The SL-0198 mapping follows the current UniProt location comment, grounded by similarity to mouse Eml1. PMID:24859200 explicitly describes tagged protein enrichment in perinuclear regions of interphase cortical cells. Retain the contextual location without implying a PML body, organelle lumen or constitutive endogenous distribution.

Summary: The inherited mitotic-spindle association has source-grounded support.

Reason: PTN001010531 is on the human EML1 ancestry and its GO:0072686 IBD is grounded in mouse Eml1 and EML2/O95834. Mouse tagged Eml1 is enriched around spindle microtubules in PMID:24859200. This fits a mitotic context of microtubule binding, without assigning a spindle-only location or transferring EML2-specific experiments to human EML1 as direct assays.

Summary: Retain the conserved, cell-cycle-dependent spindle-pole location.

Reason: The literal Q05BC3 donor is experimentally annotated from PMID:24859200. Its Discussion explicitly reports tagged Eml1 enrichment at spindle poles during metaphase in neuronal progenitor cultures. This fits GO:0097431 and supports non-core retention of the conserved location. The study did not analyze endogenous Eml1 localization, so this is not a direct endogenous human assay or an exclusive location claim.

Summary: The mouse source explicitly supports tagged Eml1 enrichment at metaphase spindle poles.

Reason: PMID:24859200 Discussion describes tagged Eml1 at spindle poles during metaphase, in addition to the separately supported late-mitotic interzonal pool. Retain the exact ISS assertion as a contextual location. Preserve the cultured mouse progenitor and tagged-construct limits; neither endogenous human localization nor equivalence of the two natural human products is established.

Summary: Midzone enrichment is supported during late mitosis.

Reason: The Q05BC3 donor is experimentally annotated from PMID:24859200, whose Results explicitly describe tagged Eml1 puncta enriched between separating cells during telophase/cytokinesis. This matches the midzone definition and is retained as a conditional cell-cycle location, without asserting endogenous human imaging or exclusive residence.

Summary: Retain the conserved mitotic-midzone context.

Reason: The mouse source provides explicit telophase/cytokinesis midzone enrichment of tagged Eml1, consistent with the existing ISS inference and the conserved microtubule-associated molecular role. The conclusion is spatial and contextual, not a new claim that EML1 independently drives cytokinesis.