Human SIRT5: Acidic lysine deacylation, not a generic strong deacetylase

Reference protein: Q9NXA8. This is a manual literature synthesis using fetched primary-publication text and the reviewed human UniProt record.

Reaction specificity

Purified human SIRT5 is an efficient lysine desuccinylase and demalonylase. Structural work identifies Tyr102 and Arg105 in an acyl pocket suited to negatively charged groups. The same study measured weak deacetylation, roughly 500-fold lower catalytic efficiency than SIRT1 on an acetyl-H3K9 peptide. A weak in-vitro activity is not equivalent to a core physiological deacetylation role. PMID:22076378(https://pubmed.ncbi.nlm.nih.gov/22076378/)

Compartment and substrates

Human SIRT5 localizes principally to mitochondria in the localization study. Nevertheless, localization should not be narrowed so far that all extramitochondrial observations are rejected. Substrate studies support roles outside a single metabolic pathway, and individual substrate/compartment claims need their own evidence. PMID:16079181(https://pubmed.ncbi.nlm.nih.gov/16079181/)

Regulatory consequences

SIRT5-dependent SHMT2 desuccinylation stimulates SHMT2 activity and serine catabolism in the reported cancer-cell systems. SOD1 desuccinylation is another reported substrate mechanism. These studies establish specific biochemical regulation; cell proliferation and tumor-growth outcomes are contextual consequences rather than replacement definitions of the enzyme. PMID:29180469(https://pubmed.ncbi.nlm.nih.gov/29180469/)

Exact horse sequence matters

The selected horse F6S899 protein retains Tyr102, Arg105 and His158 but differs at two zinc-coordinating cysteines and several C-terminal NAD-contact regions. Retention of one catalytic residue cannot establish an intact enzyme. The local reproducible comparison records C207W/C212W and the divergent tail. A transcript/translation-model problem is plausible but unproven; this should not be labeled an evolved horse pseudoenzyme without further evidence. PMID:22076378(https://pubmed.ncbi.nlm.nih.gov/22076378/)

Evidence access and research scope

The source caches distinguish full text from abstract-only access; unresolved experimental annotations should remain UNDECIDED until their supporting material is available. This synthesis focuses on the biochemical mechanism, localization, and evidence needed for the paired horse prediction assessment; it does not certify every existing GO annotation.