DARS2 notes

2026-09-08 paired human–horse review

DARS2 is the nuclear-encoded mitochondrial aspartate-tRNA ligase. It activates aspartate with ATP and transfers it to mitochondrial tRNA(Asp), supporting synthesis of mitochondrially encoded respiratory-chain proteins. The enzyme forms a homodimer and contains an N-terminal mitochondrial targeting sequence.

Substrate and compartment distinctions

Mitochondrial aspartate-tRNA synthetase must accommodate structurally unusual mitochondrial tRNA(Asp); the 2013 structure compares that accommodation with bacterial AspRS. Cross-aminoacylation of bacterial and mitochondrial tRNA(Asp) is a taxonomic/substrate-structure breadth claim, whereas acceptance of tRNA(Asn) is a different aminoacylation-specificity claim. The human GOA includes the latter, so the original experiments matter. The inspected 2013 full text did not settle that point and the 2005 characterization is abstract-only in the cache. Retaining uncertainty is appropriate. Matrix localization is the primary placement, but additional membrane-associated or extracellular activities cannot be dismissed just from that default.

Decisive inspected evidence

From PMID:15779907(https://pubmed.ncbi.nlm.nih.gov/15779907/):

Both belong to the expected class of synthetases, have a dimeric organization, and aminoacylate Escherichia coli tRNAs as well as in vitro transcribed human mitochondrial tRNAs.

Evidence inventory

Transfer to the selected horse protein

The exact target is A0A9L0SB67, not an arbitrary horse record with a matching name. The reproducible paired-sequence analysis records identity, coverage and internal gaps. It supports homology but is not a reciprocal orthology test. Molecular properties are transferred only with the relevant domain, targeting and paralog constraints. The prediction-time sequence is not independently verified.

Open evidence questions

The following annotation scopes need source-specific follow-up: aspartate-tRNA(Asn) ligase activity, mitochondrial membrane, obsolete mitochondrial asparaginyl-tRNA aminoacylation, protein binding. Experimental annotations are not removed merely because a cached abstract omits the gene or a specific assay. High-throughput protein-binding rows require their actual partner or complex context before replacement with an informative molecular function.

Research provenance: external Falcon/Edison was attempted with Perplexity fallback. Some requests returned HTTP 429 and fallback returned insufficient-quota HTTP 401; successful external reports are preserved separately. Primary-source manual synthesis is explicitly labeled manual where no external report was available.