Sdhaf2

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005759 mitochondrial matrix	IEA GO_REF:0000044	ACCEPT	Summary: Mitochondrial-matrix localization is consistent with the experimentally grounded Sdhaf2 mechanism and retention of the entire reference targeting peptide. This is a reasonable sequence-supported inference for the shorter product, not a localization assay of A0A494B8X4. Supporting Evidence: PMID:38569044 Restoration of Sdhaf2 normalized complex II activity, lipid oxidation, and insulin action in Drp1-KD myocytes. file:mouse/Sdhaf2/Sdhaf2-bioinformatics/RESULTS.md \| Transit peptide: Mitochondrion \| 1–27 \| 27 / 27 \| 27 \|
GO:0010719 negative regulation of epithelial to mesenchymal transition	IEA GO_REF:0000117	UNDECIDED	Summary: The mouse Sdhaf2 knockout phenotype directly supports negative regulation of EMT at the gene level. The selected product has an altered C-terminal region, and the study does not resolve whether it preserves the relevant activity. The electronic annotation is not dismissed as ARBA-derived, but it cannot be assigned as a core function of this product. Supporting Evidence: PMID:23983127 In SDH5 knock-out mice, lung epithelial cells exhibited elevated mesenchymal markers, which is characteristic of EMT. file:mouse/Sdhaf2/Sdhaf2-bioinformatics/RESULTS.md \| Transit peptide: Mitochondrion \| 1–27 \| 27 / 27 \| 27 \|
GO:0090090 negative regulation of canonical Wnt signaling pathway	IEA GO_REF:0000117	UNDECIDED	Summary: The SDH5-GSK3-beta/beta-catenin study supplies genuine primary evidence for negative Wnt regulation in the tested lung-cell context. This does not determine whether the alternative 135-residue mouse product retains the interaction and activity, so the precise product-level transfer remains uncertain. Supporting Evidence: PMID:23983127 SDH5 functions as a negative regulator of Wnt-β-catenin signaling. file:mouse/Sdhaf2/Sdhaf2-bioinformatics/RESULTS.md \| Transit peptide: Mitochondrion \| 1–27 \| 27 / 27 \| 27 \|

GO Term

Evidence

Action

Reason

GO:0005759 mitochondrial matrix

IEA
GO_REF:0000044

Summary: Mitochondrial-matrix localization is consistent with the experimentally grounded Sdhaf2 mechanism and retention of the entire reference targeting peptide. This is a reasonable sequence-supported inference for the shorter product, not a localization assay of A0A494B8X4.

Supporting Evidence:

PMID:38569044

Restoration of Sdhaf2 normalized complex II activity, lipid oxidation, and insulin action in Drp1-KD myocytes.

file:mouse/Sdhaf2/Sdhaf2-bioinformatics/RESULTS.md

| Transit peptide: Mitochondrion | 1–27 | 27 / 27 | 27 |

GO:0010719 negative regulation of epithelial to mesenchymal transition

IEA
GO_REF:0000117

UNDECIDED

Summary: The mouse Sdhaf2 knockout phenotype directly supports negative regulation of EMT at the gene level. The selected product has an altered C-terminal region, and the study does not resolve whether it preserves the relevant activity. The electronic annotation is not dismissed as ARBA-derived, but it cannot be assigned as a core function of this product.

Supporting Evidence:

PMID:23983127

In SDH5 knock-out mice, lung epithelial cells exhibited elevated mesenchymal markers, which is characteristic of EMT.

file:mouse/Sdhaf2/Sdhaf2-bioinformatics/RESULTS.md

| Transit peptide: Mitochondrion | 1–27 | 27 / 27 | 27 |

GO:0090090 negative regulation of canonical Wnt signaling pathway

IEA
GO_REF:0000117

UNDECIDED

Summary: The SDH5-GSK3-beta/beta-catenin study supplies genuine primary evidence for negative Wnt regulation in the tested lung-cell context. This does not determine whether the alternative 135-residue mouse product retains the interaction and activity, so the precise product-level transfer remains uncertain.

Supporting Evidence:

PMID:23983127

SDH5 functions as a negative regulator of Wnt-β-catenin signaling.

file:mouse/Sdhaf2/Sdhaf2-bioinformatics/RESULTS.md

| Transit peptide: Mitochondrion | 1–27 | 27 / 27 | 27 |

External Prediction Reviews

These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.

ProtNLM2 External predictions

View prediction review YAML · Sdhaf2-protnlm-predictions-review.yaml · Review status: COMPLETE

Mitochondrial targeting is supported by a retained transit peptide. The shorter Sdhaf2 product’s ability to promote SDHA flavinylation and respiratory-complex maturation remains uncertain.

Source documents: genes/mouse/Sdhaf2/Sdhaf2-protnlm-source.json · genes/mouse/Sdhaf2/Sdhaf2-notes.md

Review score: 2 = concordant with evidence; 1 = uncertain; 0 = discordant with evidence. This is an assessment score, not a model probability.

GO:0018293 protein-FAD linkage GO_BP

UNC — Uncertain Review score: 1/2

Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-10 · file:mouse/Sdhaf2/Sdhaf2-protnlm-source.json

Review rationale: Protein-FAD linkage is the established maturation role of SDHAF2, but the selected product’s altered C-terminal region has not been functionally tested. Preservation of the targeting peptide establishes a plausible compartment, not complete SDHA binding or flavinylation.

Supporting Evidence:

PMID:38569044: "Restoration of Sdhaf2 normalized complex II activity, lipid oxidation, and insulin action in Drp1-KD myocytes."
file:mouse/Sdhaf2/Sdhaf2-bioinformatics/RESULTS.md: "| Transit peptide: Mitochondrion | 1–27 | 27 / 27 | 27 |"

GO:0005759 mitochondrial matrix GO_CC

CNN — Correct but not novel Review score: 2/2

Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-10 · file:mouse/Sdhaf2/Sdhaf2-protnlm-source.json

Review rationale: The matrix compartment agrees with the gene-level mitochondrial mechanism and is independently supported by complete retention of the reference transit peptide. It overlaps the existing GOA compartment, without establishing literal training-set membership.

Supporting Evidence:

PMID:38569044: "Restoration of Sdhaf2 normalized complex II activity, lipid oxidation, and insulin action in Drp1-KD myocytes."
file:mouse/Sdhaf2/Sdhaf2-bioinformatics/RESULTS.md: "| Transit peptide: Mitochondrion | 1–27 | 27 / 27 | 27 |"

GO:0006121 mitochondrial electron transport, succinate to ubiquinone GO_BP

UNC — Uncertain Review score: 1/2

Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-10 · file:mouse/Sdhaf2/Sdhaf2-protnlm-source.json

Review rationale: Sdhaf2 enables assembly of the complex that carries out succinate-to-ubiquinone electron transport, but is not itself an electron-transfer subunit. A contribution to the process through assembly is plausible; for this altered product, preservation of that assembly function is unresolved.

Supporting Evidence:

PMID:38569044: "Restoration of Sdhaf2 normalized complex II activity, lipid oxidation, and insulin action in Drp1-KD myocytes."
file:mouse/Sdhaf2/Sdhaf2-bioinformatics/RESULTS.md: "| Transit peptide: Mitochondrion | 1–27 | 27 / 27 | 27 |"

📚 Additional Documentation

Bioinformatics Results

(RESULTS.md)

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Protnlm Function Review

(Sdhaf2-protnlm-function-review.md)

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Gene Description

Existing Annotations Review

References

Suggested Questions for Experts

External Prediction Reviews

ProtNLM2 External predictions

Deep Research

Falcon

📚 Additional Documentation

Notes

Bioinformatics Results

Protnlm Function Review

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