Affinage mechanistic annotation for C5orf46 (human) Affinage Affinage (Claude Sonnet reading pass + Opus synthesis pass) 3 citations

Affinage mechanistic annotation for C5orf46 (human)

Current model (mechanistic narrative)

C5ORF46 encodes AP-64, a small (64-amino-acid, ~7.2 kDa) anionic, amphiphilic, cysteine-free peptide detectable in human plasma that functions as a secreted antimicrobial peptide [PMID:31308252, PMID:33804835]. AP-64 exerts direct bactericidal activity against multiple Gram-negative bacteria in vitro and reduces E. coli O157:H7 infection in a mouse model PMID:33804835. Beyond its antibacterial role, no defined molecular mechanism, receptor, or binding partner has been characterized in the available corpus.

Affinage mechanism profile (its own GO/Reactome grounding)

Recorded for reference. The AIGR evaluation found this grounding is coarse (collapses to general parents) and can contradict the narrative — do not import these GO ids directly; re-ground from the narrative + PMIDs.

Dated findings (citation-anchored)

Year Confidence Finding PMIDs Journal
2021 Medium C5ORF46 encodes AP-64, a 64-amino-acid anionic amphiphilic peptide lacking cysteines (MW=7.2 kDa, pI=4.54) that exhibits direct antimicrobial activity against Gram-negative bacteria including E. coli DH5α, E. coli O157:H7, Vibrio cholerae, and Pseudomonas aeruginosa in vitro, and reduces E. coli O157:H7 infection in a mouse model. PMID:33804835 Biomolecules
2021 Low AP-64 (C5ORF46 protein product) exhibits cytotoxic effects against human T-cell lymphoma Jurkat and B-cell lymphoma Raji cells. PMID:33804835 Biomolecules
2019 Low C5ORF46 protein is detectable as a previously uncharacterized small protein (2–10 kDa range) in human plasma, identified by mass spectrometry using a small-protein enrichment assay. PMID:31308252 Molecular & Cellular Proteomics
2022 Low Knockdown of C5ORF46 in renal cancer cell lines reduced cell proliferation and migration and increased apoptosis in vitro; transcriptomic sequencing after knockdown implicated C5ORF46 in regulation of the malignant phenotype and immune microenvironment. PMID:35504177 Translational Oncology

Citations