ProtNLM2 External predictions
View prediction review YAML · SIRT5-protnlm-predictions-review.yaml · Review status: COMPLETE
Assessment of 1 ProtNLM GO predictions for the selected horse SIRT5 protein, using mammalian experimental findings and an explicit comparison of the horse sequence.
Source documents: genes/human/SIRT5/SIRT5-uniprot.txt · genes/HORSE/SIRT5/SIRT5-bioinformatics/RESULTS.md · projects/PROTNLM_EVALUATION/mammal-benchmark/horse40-predictions.csv · genes/HORSE/SIRT5/SIRT5-hypotheses/horse40-nad-dependent-desuccinylation/openscientist.md
Review score: 2 = concordant with evidence; 1 = uncertain; 0 = discordant with evidence. This is an assessment score, not a model probability.
UNC — Uncertain Review score: 1/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: The selected horse sequence retains only part of the human SIRT5 cofactor-binding architecture. Human zinc-coordinating Cys207 and Cys212 align to Trp207 and Trp212 in F6S899, while Cys166/Cys169 are retained; the C-terminal region also diverges sharply and several NAD-binding segments are absent or altered. The OpenScientist report likewise flags F6S899 as a frameshifted exact sequence and names A0A9L0T9B1 as a candidate intact 310-aa horse SIRT5 isoform. The residual cysteines and family assignment do not establish a functional metal-binding site for F6S899 itself. Training-set membership is unknown.
Supporting Evidence:
- file:human/SIRT5/SIRT5-uniprot.txt: "CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and CC deglutarylase that specifically removes malonyl, succinyl and glutaryl CC groups on target proteins (PubMed:21908771, PubMed:22076378, CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to CC the regulation of blood ammonia levels during prolonged fasting: acts CC by mediating desuccinylation and deglutarylation of CPS1, thereby CC increasing CPS1 activity in response to elevated NAD levels during CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating CC its desuccinylation, leading to reduced reactive oxygen species CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent CC protein deacetylase activity; however this activity may not be CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) CC and a number of other proteins in vitro such as UOX. CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, CC ECO:0000269|PubMed:29180469}."
- file:HORSE/SIRT5/SIRT5-bioinformatics/RESULTS.md: "The horse sequence F6S899 (282 residues) aligns to human Q9NXA8 (310 residues) with 67.5% identity across 280 paired residues. Paired coverage is 90.32% of the human sequence and 99.29% of the horse sequence."
- file:HORSE/SIRT5/SIRT5-bioinformatics/RESULTS.md: "- BINDING: human [207] C → horse [207] W. ... - BINDING: human [212] C → horse [212] W."
- PMID:22076378: "We found that Sirt5 is an efficient protein lysine desuccinylase and demalonylase in vitro. The preference for succinyl and malonyl groups was explained by the presence of an arginine residue (Arg(105)) and tyrosine residue (Tyr(102)) in the acyl pocket of Sirt5."
- file:HORSE/SIRT5/SIRT5-hypotheses/horse40-nad-dependent-desuccinylation/openscientist.md: "The exact translated sequence of F6S899 as supplied would **not** produce a functional NAD-dependent desuccinylase, and the record should be flagged as a mispredicted/frameshifted model."