Affinage mechanistic annotation for ACTR1A (human) Affinage Affinage (Claude Sonnet reading pass + Opus synthesis pass) 2 citations

Affinage mechanistic annotation for ACTR1A (human)

Current model (mechanistic narrative)

ACTR1A (alpha-centractin) is a subunit of the dynactin complex that additionally participates in innate immune signaling and is subject to post-translational regulation [PMID:31221720, PMID:41142317]. ACTR1A physically associates with TLR2 and is required for TLR2-mediated pro-inflammatory cytokine induction, since its knockdown reduces cytokine output downstream of the receptor PMID:31221720. ACTR1A is also an in vitro substrate of the SETD3 protein histidine methyltransferase, which methylates recombinant ACTR1A and contacts it in cells, extending SETD3's substrate repertoire beyond beta-actin to this dynactin subunit PMID:41142317. Beyond these findings, the structural basis of these interactions, the in-cell methylation site, and the link between ACTR1A modification and dynactin function have not been characterized in the available corpus.

Affinage mechanism profile (Affinage's own GO/Reactome grounding)

Dated findings (citation-anchored)

Year Confidence Finding PMIDs Journal
2019 Medium ACTR1A (alpha-centractin), a subunit of the dynactin complex, physically interacts with TLR2 and functions as a regulator of TLR2-mediated pro-inflammatory cytokine induction. The interaction was identified by cross-linking co-immunoprecipitation proteomics and validated by biochemical methods; RNA interference knockdown of ACTR1A reduced pro-inflammatory cytokine induction downstream of TLR2. PMID:31221720 Molecular & Cellular Proteomics
2025 Medium ACTR1A (alpha-centractin) is an in vitro substrate of the SETD3 protein histidine methyltransferase. SETD3 was identified as a proximal interactor of ACTR1A by TurboID proximity labeling, and recombinant SETD3 methylated ACTR1A in a radiochemical in vitro methylation assay, extending SETD3's known substrate repertoire beyond β-actin to this dynactin subunit. PMID:41142317 PeerJ

Citations