CWF19L1

Reason: The actual PTHR12072 topology places the 538-residue human target below PTN000249204, with the literal GO:0000398 IBD and all source identifiers intact. The mouse donor is Cwf19l2 (MGI:1918023), not mouse Cwf19l1; the two fission-yeast proteins and budding-yeast Drn1 retain their separate identities. Independent human CWF19L1 experiments in PMID:39542248 provide co-IP with U5 snRNP/PRPF19 components, an E1A splicing reporter and RNA-seq/RT-PCR evidence of altered splicing after depletion. This supports participation in the spliceosomal process without assigning catalytic RNA cleavage or transferring the mouse fertility phenotype. The phylogenetic inference is not judged by donor count.

Reason: The positive interaction with human CWF19L2 (Q2TBE0) is supported by three literal IntAct records from PMID:32296183, including validated two-hybrid, array and prey-pooling records with exact sequence-based identifiers. CWF19L2 is a spliceosomal protein with an alternative-splicing role supported by mouse experiments and human ortholog annotation, and direct human late-spliceosome structural placement in PMID:30728453. GO:1990935 therefore describes the bound partner more informatively than generic protein binding. The current term has binding-only ancestry and does not assign RNA catalysis, an adaptor mechanism or activation of CWF19L2. The human proteins were tested in yeast; the curated sufficient CWF19L2 region is residues 155–893. The original target supplementary table was not independently recovered, and the class assignment does not claim that this particular interaction causes the CWF19L1 reporter phenotype.

Proposed replacements: splicing factor binding

Reason: The complete abstract of PMID:41422678 explicitly includes CWF19L1 in super-resolution imaging, despite foregrounding CWF19L2 in the title. The original Results, Methods and images were not recovered; this annotation is retained with curator deference and independent human nucleoplasmic localization from PMID:39542248. The CWF19L2 debranching assays in the abstract are not treated as direct CWF19L1 functional assays.

Reason: The current ARBA00026330 rule explicitly emits nucleus and matches the target at zero-based condition set 154 after evaluating all 1,293 branches against its actual taxonomy and cross-references. The original combined mapping also carries UniProt SL-0191. Human localization evidence independently supports nuclear residence; this broad source assertion is retained alongside the separately sourced nucleoplasm annotation.

Reason: The UniProt subcellular-location mapping SL-0190 is consistent with human CWF19L1 localization in PMID:39542248. The reported predominant nucleoplasmic localization supports this term. Failure to detect colocalization with several tested nuclear bodies in that experiment is not generalized to a universal exclusion from those compartments.

Reason: The current PAINT IBD is genuinely on the target path at PTN000249205 and is grounded in budding-yeast Drn1 (SGD:S000003325/P53255). In PMID:24919400, purified yeast Drn1 binds Dbr1 and enhances Dbr1-dependent turnover of a branched RNA substrate, whereas Drn1 alone does not cleave it. This matches the current definition of an RNA lariat debranching enzyme activator. Retain the considered ancestral inference with its actual experimental donor. Neither the human alternative-splicing study nor the CWF19L2-specific debranching study demonstrates this activity directly for human CWF19L1. Stable membership of the trapped post-release complex is not required for transient or soluble activation, so the separate uncertainty in row 6 does not invalidate this inference.

Reason: The authentic current PAINT tree and MSA place CWF19L1 beneath the stated IBD at PTN000249204; the literal donor identities and on-path positive assertion are valid. However, the actual human ILS study PMID:30728453 explicitly identifies CWF19L2 rather than CWF19L1 in the post-mRNA-release complexes. Its HeLa/MINX preparation uses excess dominant-negative PRP43 T429A and stabilization during purification, so it does not establish universal exclusion of CWF19L1. Fission-yeast PMID:24442611 Table 1 detects the L1-branch Mug161/Drn1 donor weakly in low salt, while Cwf19 is robust across preparations; zero quantitation is not proof of nonbinding. The newer human CWF19L1 co-IP/splicing study does not resolve this exact spliceosome stage. These source-specific tensions leave the inherited complex-membership assertion unresolved without claiming a wrong-gene source, global evolutionary loss or failure of the PAINT placement.