id: F6S899
gene_symbol: SIRT5
taxon:
  id: NCBITaxon:9796
  label: Equus caballus
status: COMPLETE
description: 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
predictions:
- source_method: ProtNLM2
  source_version: UniProt API snapshot 2026-09-08
  predicted_term:
    id: GO:0046872
    label: metal ion binding
  predicted_term_type: GO_MF
  review:
    assessment: UNC
    confidence_score: 1
    summary: 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.
    supported_by:
    - reference_id: file:human/SIRT5/SIRT5-uniprot.txt
      supporting_text: '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}.'
    - reference_id: file:HORSE/SIRT5/SIRT5-bioinformatics/RESULTS.md
      supporting_text: 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.
    - reference_id: file:HORSE/SIRT5/SIRT5-bioinformatics/RESULTS.md
      supporting_text: "- BINDING: human [207] C \u2192 horse [207] W. ... - BINDING: human [212] C \u2192\
        \ horse [212] W."
    - reference_id: PMID:22076378
      supporting_text: '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.'
    - reference_id: file:HORSE/SIRT5/SIRT5-hypotheses/horse40-nad-dependent-desuccinylation/openscientist.md
      supporting_text: 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.
references:
- id: file:human/SIRT5/SIRT5-uniprot.txt
  title: UniProt record for human SIRT5
  findings: []
- id: file:HORSE/SIRT5/SIRT5-bioinformatics/RESULTS.md
  title: "SIRT5: horse\u2013human sequence comparison"
  findings: []
- id: PMID:22076378
  title: Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase.
  findings: []
- id: file:HORSE/SIRT5/SIRT5-hypotheses/horse40-nad-dependent-desuccinylation/openscientist.md
  title: 'OpenScientist hypothesis run: SIRT5 NAD-dependent desuccinylation'
  publication_type: DEEP_RESEARCH
  reference_review:
    relevance: HIGH
    review_notes: Substantive computational synthesis directly addressing the F6S899 model defect and
      identifying the A0A9L0T9B1 record as a candidate intact horse isoform. The report's broad frameshift
      conclusion agrees with the cached human-to-horse comparison, but its Cys241/Cys244 CDLC table row
      is not aligned with the human UniProt zinc-ligand numbering; treat the CDLC claim as a lost C-terminal
      motif, not a verified zinc-ligand pair, pending curator review.
  findings:
  - statement: OpenScientist found that F6S899 is a frameshifted SIRT5 model and recommended moving functional
      inference to an intact horse isoform such as A0A9L0T9B1.
    supporting_text: 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.