EFL1

Summary: Conserved ribosome-maturation GTPase activity.

Reason: The current PTHR42908 tree places human EFL1 at PTN002534018 beneath PTN000562745, and the literal ancestral IBD matches this source assertion. Its target alignment reproduces all 1,120 canonical residues. Current experimental donor records include EFL1 itself, which is valid descendant support rather than circular evidence. Human EFL1 biochemistry independently demonstrates GTP hydrolysis. The family also contains other GTPases; the reviewed EFL1 branch has separate losses of elongation-factor and elongation-process assertions, not a loss of GTPase activity.

Summary: Human EFL1 hydrolyzes GTP during ribosome maturation.

Reason: The original experiments use recombinant human EFL1 expressed in yeast and measure phosphate release from GTP. The 60S subunit stimulates activity, and SBDS further stimulates it in the ribosome-containing reaction; H96A provides a catalytic control. The expression host does not change the human construct identity. These assays support GTPase activity without establishing that both current natural splice products have equivalent activity.

Summary: The electronic mapping agrees with the conserved GTPase mechanism.

Reason: InterPro IPR000795 matches the human target at residues 17–272 and maps the translational-type GTP-binding domain to GTPase activity. ARBA00026818 independently has a sufficient current FunFam condition, 3.30.70.240:FF:000006, that is present in the official target record. The actual human hydrolysis experiments corroborate both mapped inputs; this is not inferred merely from an unrelated family name.

Summary: Direct human EFL1–SBDS binding is retained.

Reason: The full original Methods and Figure 6 describe titration of purified human EFL1 into fluorescently labeled human SBDS, with a saturating wild-type interaction and much weaker binding to SBDS S143L. Human EFL1 was produced in yeast; the paper also uses yeast EFL1 for much of its nucleotide-kinetics analysis, which is kept separate from this explicitly human pair assay. The current IntAct export did not recover this dated record, but that does not negate the directly inspected experiment. SBDS promotes nucleotide exchange on EFL1; this does not make EFL1 an exchange factor or establish SBDS as a catalytic enzyme for an enzyme-binding refinement. No informative supported binding child was identified, so the positive generic assertion is retained as non-core.

Summary: Human EFL1 binds SBDS in quantitative solution assays.

Reason: The original human-protein fluorescence-anisotropy experiments measure EFL1 binding to wild-type SBDS and domain or disease-variant constructs. IntAct EBI-21463457 / IM-27139-1 records fluorescence polarization spectroscopy (MI:0053), direct interaction, two human participants and an in-vitro host. Its SBDS-side tags, fragments and mutations must not be assigned to EFL1, whose recorded feature is a C-terminal His tag. The paper’s SAXS and two-hybrid domain modeling instead use yeast orthologs. This supports the positive pair without assigning an autonomous regulator activity to EFL1 or inferring a specific enzyme-binding class from SBDS’s exchange-factor role. The generic binding annotation is retained as non-core.

Summary: The SBDS-centered proximity association is retained with its assay limit.

Reason: IntAct EBI-56912423 / IM-30059-53 records human SBDS as the BioID-tagged bait and EFL1 as the prey in K562 cells, with proximity-dependent biotin identification (MI:1314), proximity interaction type and spoke expansion. The original study compares biotin-treated pulldowns with matched controls lacking a biotin pulse. This record supports a protein neighborhood association, not an independently measured binary interface or a new EFL1 post-transcriptional regulatory activity. Direct EFL1–SBDS binding is separately established by the 2015 and 2018 studies. The positive imported association is retained as generic non-core binding; no more specific partner class has been established.

Summary: GTP binding is an intrinsic part of the EFL1 catalytic cycle.

Reason: Current target-specific InterPro matches place IPR000795 at residues 17–272 and IPR005225 at 19–161. Their GTP-binding mappings agree with the human EFL1 GTPase reaction and nucleotide-dependent ribosome maturation experiments. This is substrate binding within the established GTPase mechanism, not evidence for a separate signaling-GTPase function or equal activity of both splice products.

Summary: Cytosol is the compartment of the principal maturation reaction.

Reason: Human EFL1 descends from PTN000562745, which carries the literal cytosol IBD. Current donor records retain cytosolic evidence for human EEF2 and bacterial BipA; the node placement is evaluated within the actual family tree rather than treated as a pairwise bacterial transfer. EFL1’s established action on late cytoplasmic 60S particles independently fits this localization. Acceptance does not assert exclusion from every other cellular pool.

Summary: Cytosolic ribosome assembly is the conserved EFL1 process.

Reason: The EFL1 lineage includes PTN000562912 and its exact GO:0042256 IBD, supported by human EFL1 and yeast RIA1/EFL1 evidence. Target self-membership is legitimate experimental grounding. EFL1 hydrolysis and conformational work help release eIF6, permitting translation-competent subunit joining. This is participation in assembly, not an inference solely from necessity. The broader assembly term is retained because the inspected work emphasizes late activation and subunit joining, not solely aggregation of components into a large subunit.

Summary: The current ARBA rule supports cytosolic ribosome assembly.

Reason: ARBA00085698 explicitly predicts GO:0042256. Its first sufficient condition combines FunFams 3.30.70.240:FF:000006 and 3.30.70.870:FF:000002 with Eukaryota; both FunFams and the lineage occur in the official EFL1 record. Direct human-factor reconstitution supports the same late maturation and subunit-joining role. The assertion is not used to imply a generic translation-elongation function.

Summary: EFL1 performs a late cytosolic ribosome-assembly step.

Reason: Recombinant human EFL1, human SBDS and GTP release eIF6 from pre-60S particles isolated from Sbds-deficient mouse liver; controls omitting either factor or a productive nucleotide do not support comparable release. Complementary human-factor/rabbit-subunit assays and yeast genetics support the maturation mechanism. The mouse mutation is in Sbds, not Efl1, and the imported IMP code remains unchanged. EFL1 supplies the GTPase-driven work that licenses joining, rather than merely being required as a passive substrate.

Summary: The supported ribosome interaction is with the large subunit.

Reason: PTN000562912 and its literal ribosome-binding IBD lie on the human EFL1 path; the human target is the valid experimental descendant supporting this assertion. The imported binding claim is sound, and human-factor sedimentation experiments plus structures specifically identify 60S large subunits. GO:0043023 is the verified child of ribosome binding and describes this resolved partner. This refinement does not require EFL1 to be a permanent ribosomal protein.

Proposed replacements: ribosomal large subunit binding

Summary: Human EFL1 binds the 60S ribosomal subunit.

Reason: The original sedimentation and salt-dependence experiments establish human EFL1 association with 60S subunits independently of SBDS. The later hybrid structures place human EFL1 on Dictyostelium 60S particles, corroborating the large-subunit specificity while retaining the mixed-species substrate and limited local-resolution boundaries. Replace the general ribosome-binding term with GO:0043023; preserve the source’s IMP evidence identity. The experiments do not imply stable membership of mature translating ribosomes.

Proposed replacements: ribosomal large subunit binding

Summary: GTP hydrolysis supports EFL1-mediated 60S maturation; the general metabolic-process annotation is retained as non-core.

Reason: Human EFL1 directly hydrolyzes GTP, so the broad GTP metabolic-process assertion is compatible with the measured reaction. Its informative biological role is cytosolic ribosome maturation, with GTP hydrolysis supplying the nucleotide cycle. Retain this chemical-process umbrella as non-core rather than implying that EFL1 independently controls cellular GTP production or pool homeostasis.

Summary: Association with a ribonucleoprotein particle is retained at broad resolution.

Reason: The literal GO:1990904 IBD at PTN000562745 is on the EFL1 lineage. Its donors include several ribosome- and spliceosome-associated family proteins; current donor-record absence for some exact terms does not invalidate the curator’s ancestral judgment. Human EFL1 participates transiently in a 60S–SBDS maturation complex, consistent with association with an RNA-containing particle. Retain this broad complex class as non-core without assigning EFL1 to spliceosomes, an early Urb2/Dbp6 pre-assembly complex, or the permanent structural complement of a mature ribosome.