SHLD2

Review rationale: Mammalian SHLD2 experiments support this repair-process role, and the OpenScientist audit resolved the selected horse sequence as a justified orthology transfer. A likely C-terminal frameshift corrupts OB3, but it leaves the conserved SHLD3/REV7 recruitment segment and the OB1/OB2 ssDNA-binding execution module intact, so the horse model retains the apparatus that restricts DNA end resection and promotes NHEJ. This is a homology-based ISS/IBA transfer, not direct horse evidence.

Review rationale: HPA reports an additional actin-filament pool of human SHLD2 with supported antibody-based reliability, so this prediction is not contradicted merely by SHLD2 being a nuclear repair protein. However, the secondary localization is cell-line dependent and its targeting mechanism is uncharacterized; family membership and global sequence identity do not establish conservation of this particular pool in the selected horse isoform. The main nuclear localization has substantially stronger mechanistic support. A conserved targeting determinant or independent localization evidence is needed to resolve this exact transfer.

Review rationale: The selected horse protein belongs to the SHLD2 family and retains its OB-fold architecture; its alignment with human SHLD2 covers 94.9% of the human sequence with 70.2% identity among paired residues. Human SHLD2 recruitment to double-strand breaks and conserved shieldin domains support this location in horse. This is a supported transfer new relative to the frozen horse GOA, not a claim that the model training set lacked mammalian SHLD2 annotations.

Review rationale: The selected horse protein belongs to the SHLD2 family and retains its OB-fold architecture; its alignment with human SHLD2 covers 94.9% of the human sequence with 70.2% identity among paired residues. The human HPA nucleoplasmic signal agrees with nuclear damage-focus studies, supporting conservation of the principal nuclear compartment. This is a supported transfer new relative to the frozen horse GOA, not a claim that the model training set lacked mammalian SHLD2 annotations.

Review rationale: Mammalian SHLD2 experiments support this repair-process role, and the OpenScientist audit resolved the selected horse sequence as a justified orthology transfer. The likely OB3 frameshift should be verified against a corrected transcript, but the OB1/OB2 ssDNA-binding execution module and N-terminal recruitment segment are conserved, supporting the anti-resection mechanism that negatively regulates double-strand break repair by homologous recombination.

Review rationale: Mammalian SHLD2 and shieldin experiments connect this repair pathway to immunoglobulin class-switch recombination, but GO:0045830 is a tissue-restricted downstream immunological process. The OpenScientist audit supports transfer of the conserved OB1/OB2-dependent NHEJ and anti-HR repair module to horse SHLD2, but it did not evaluate GO:0045830 or provide horse B-cell or CSR evidence. This more specific process therefore remains unresolved until the conserved repair activity is tied to the relevant horse immune context.