ALDH7A1 is an antiquitin-family aldehyde dehydrogenase associated with lysine degradation and aldehyde detoxification. The selected horse sequence retains the catalytic glutamate and cysteine and the amino-terminal region corresponding to the human mitochondrial targeting peptide. It also contains an internal 18-residue deletion relative to canonical human ALDH7A1, so the substrate preferences and activity of this protein model require confirmation.
Summary: This extramitochondrial localization is not resolved for the selected precursor sequence.
Reason: Human ALDH7A1 has distinct mitochondrial and cytosolic isoforms and context-dependent nuclear/membrane pools. The selected horse sequence contains the N-terminal region corresponding to the human mitochondrial precursor; neither ARBA-derived localization text nor a gene-wide list of human compartments establishes this exact horse protein in the annotated compartment. Horse isoform and localization evidence is missing.
Summary: ALDH family chemistry is plausible, but catalytic competence of the internally deleted model remains unresolved.
Reason: The selected horse protein preserves the ALDH catalytic glutamate and cysteine and annotated nucleotide-binding residues. However, the internal deletion corresponding to human residues 65–82 removes part of a structured region. Conserved catalytic side chains alone do not establish an intact active fold or oligomer. Human biochemical evidence identifies the expected family chemistry, but model/structure verification or a direct assay is required to establish activity of this exact sequence.
Summary: The expected ALDH7A1 substrate/pathway assignment needs confirmation for the internally deleted protein model.
Reason: Human experiments support alpha-aminoadipic-semialdehyde oxidation, lysine degradation and betaine-aldehyde activity. The selected horse protein is ALDH7A1-like and retains catalytic residues but lacks human 65–82, including part of a structured N-terminal region. The consequence for substrate recognition and active folding is unresolved. Do not infer a different substrate from the deletion, but do not present exact substrate/pathway transfer as established for this model.
including the osmolyte precursor, betaine aldehyde, lipid peroxidation-derived aldehydes, and the intermediate lysine degradation product, alpha-aminoadipic semialdehyde.
Summary: This extramitochondrial localization is not resolved for the selected precursor sequence.
Reason: Human ALDH7A1 has distinct mitochondrial and cytosolic isoforms and context-dependent nuclear/membrane pools. The selected horse sequence contains the N-terminal region corresponding to the human mitochondrial precursor; neither ARBA-derived localization text nor a gene-wide list of human compartments establishes this exact horse protein in the annotated compartment. Horse isoform and localization evidence is missing.
Summary: The N-terminal targeting region supports mitochondrial localization by mammalian sequence inference.
Reason: The selected horse protein preserves the basic N-terminal segment corresponding to human mitochondrial precursor residues 1–26. This supports mitochondrial localization of this sequence, unlike a transfer based only on the name of a cytosolic isoform. Import and processing have not been measured in horse.
Summary: This extramitochondrial localization is not resolved for the selected precursor sequence.
Reason: Human ALDH7A1 has distinct mitochondrial and cytosolic isoforms and context-dependent nuclear/membrane pools. The selected horse sequence contains the N-terminal region corresponding to the human mitochondrial precursor; neither ARBA-derived localization text nor a gene-wide list of human compartments establishes this exact horse protein in the annotated compartment. Horse isoform and localization evidence is missing.
Summary: This extramitochondrial localization is not resolved for the selected precursor sequence.
Reason: Human ALDH7A1 has distinct mitochondrial and cytosolic isoforms and context-dependent nuclear/membrane pools. The selected horse sequence contains the N-terminal region corresponding to the human mitochondrial precursor; neither ARBA-derived localization text nor a gene-wide list of human compartments establishes this exact horse protein in the annotated compartment. Horse isoform and localization evidence is missing.
Summary: The expected ALDH7A1 substrate/pathway assignment needs confirmation for the internally deleted protein model.
Reason: Human experiments support alpha-aminoadipic-semialdehyde oxidation, lysine degradation and betaine-aldehyde activity. The selected horse protein is ALDH7A1-like and retains catalytic residues but lacks human 65–82, including part of a structured N-terminal region. The consequence for substrate recognition and active folding is unresolved. Do not infer a different substrate from the deletion, but do not present exact substrate/pathway transfer as established for this model.
including the osmolyte precursor, betaine aldehyde, lipid peroxidation-derived aldehydes, and the intermediate lysine degradation product, alpha-aminoadipic semialdehyde.
Summary: ALDH family chemistry is plausible, but catalytic competence of the internally deleted model remains unresolved.
Reason: The selected horse protein preserves the ALDH catalytic glutamate and cysteine and annotated nucleotide-binding residues. However, the internal deletion corresponding to human residues 65–82 removes part of a structured region. Conserved catalytic side chains alone do not establish an intact active fold or oligomer. Human biochemical evidence identifies the expected family chemistry, but model/structure verification or a direct assay is required to establish activity of this exact sequence.
Summary: The expected ALDH7A1 substrate/pathway assignment needs confirmation for the internally deleted protein model.
Reason: Human experiments support alpha-aminoadipic-semialdehyde oxidation, lysine degradation and betaine-aldehyde activity. The selected horse protein is ALDH7A1-like and retains catalytic residues but lacks human 65–82, including part of a structured N-terminal region. The consequence for substrate recognition and active folding is unresolved. Do not infer a different substrate from the deletion, but do not present exact substrate/pathway transfer as established for this model.
including the osmolyte precursor, betaine aldehyde, lipid peroxidation-derived aldehydes, and the intermediate lysine degradation product, alpha-aminoadipic semialdehyde.
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.
The exact glyceraldehyde-3-phosphate substrate prediction cannot be established from ALDH7A1 family membership or from experiments on other aldehydes. The selected horse model also has an internal deletion of unresolved functional consequence.
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: Human ALDH7A1 is an alpha-aminoadipic-semialdehyde dehydrogenase with experimentally demonstrated activity on several additional aldehydes. Those results establish ALDH chemistry but do not establish glyceraldehyde-3-phosphate oxidation. The selected horse sequence retains catalytic residues but has an internal 18-residue deletion, further limiting an exact substrate transfer. No target GOA overlap or direct glyceraldehyde-3-phosphate assay was found in the inspected evidence. The different canonical substrate alone does not prove the predicted reaction is impossible for a broad-specificity ALDH, so the prediction remains uncertain rather than receiving a confident paralog-error label.
Supporting Evidence:
PMID:20207735: "including the osmolyte precursor, betaine aldehyde, lipid peroxidation-derived aldehydes, and the intermediate lysine degradation product, alpha-aminoadipic semialdehyde."