Summary: Signal transduction is a broad inference without direct evidence for this DESRO cytokine.

Reason: Annotation is generic and not directly supported in DESRO; core function is cytokine activity.

Summary: K9IWR0 is lymphotoxin-alpha (UniProt RecName; PANTHER PTHR11471:SF31 LYMPHOTOXIN-ALPHA), a secreted TNF-superfamily cytokine that signals through TNFRSF1A/TNFR1, TNFRSF1B and TNFRSF14. Canonical NF-kappaB activation is the principal downstream output of that receptor engagement, and the propagation comes from the lymphotoxin-alpha node (PANTHER:PTN000158030), not from a broad family-level node.

Reason: Relaxed from MARK_AS_OVER_ANNOTATED on re-review. The previous rejection rested only on the absence of a Desmodus-specific experiment, which is not evidence against a supported phylogenetic inference. The protein carries the complete TNF-domain architecture (Pfam PF00229; InterPro IPR002960 TNF_beta) and is assigned to the lymphotoxin-alpha subfamily, and the review already accepts its cytokine activity (GO:0005125) and TNF receptor binding (GO:0005164); positive regulation of canonical NF-kappaB signalling is the established consequence of that receptor binding rather than an additional unsupported claim.

Summary: Lymphotoxin-alpha engages TNFR1, a death-domain receptor, and UniProt records that lymphotoxin is cytotoxic for a wide range of tumour cells in vitro and in vivo - the extrinsic, receptor-initiated apoptotic route. The propagation is from the lymphotoxin-alpha node (PANTHER:PTN000158030).

Reason: Relaxed from MARK_AS_OVER_ANNOTATED on re-review. The earlier rejection cited only the lack of a Desmodus-specific assay. The target has the full TNF ligand architecture and subfamily assignment, and the cytotoxic, TNFR1-mediated activity of lymphotoxin-alpha is the basis of the term; positive regulation of the extrinsic apoptotic signalling pathway follows from the accepted TNF receptor binding rather than extending beyond it.

Summary: UniProt describes this protein as a cytokine that binds TNF receptors.

Reason: UniProt functional description supports cytokine activity.

Summary: UniProt functional description indicates TNF receptor binding.

Reason: Functional description notes binding to TNF receptors.

Summary: A secreted cytokine; extracellular region is the appropriate location term.

Reason: UniProt indicates secretion; extracellular region is correct. GO has since obsoleted GO:0005615 extracellular space, the replacement previously proposed here, and merged it into GO:0005576 (replaced_by), so this term is now the correct location term.

Summary: UniProt annotates this protein as secreted.

Reason: Secreted localization is supported in UniProt.

Summary: Immune response is a broad inference without direct evidence in DESRO.

Reason: General immune response annotation is inferred and not directly supported.

Summary: Humoral immune response is a specific process inferred from orthology without direct DESRO evidence.

Reason: Specific humoral response evidence is lacking for this DESRO protein.

Summary: UniProt indicates membrane localization in addition to secretion.

Reason: Subcellular location includes membrane.