Horse ALDH7A1 (antiquitin; alpha-aminoadipic semialdehyde dehydrogenase) is a member of the aldehyde dehydrogenase superfamily, family 7. A0A9L0R3Y5 is the full-length Ensembl canonical translation (566 aa) of horse gene ENSECAG00000010547. It contains every residue of human ALDH7A1 (P49419) with no internal gap and is 95.7% identical to it. The proton-acceptor glutamate, the nucleophilic cysteine, the NAD(+)-binding residues and the alpha-aminoadipic semialdehyde-binding residues characterized in the human enzyme are all conserved. By descent from the vertebrate ALDH7A1 node of the PTHR43521 family tree, the horse protein is inferred to be a homotetrameric NAD(+)-dependent dehydrogenase. Its main reaction would be the oxidation of alpha-aminoadipic semialdehyde (in equilibrium with delta-1-piperideine-6-carboxylate) to alpha-aminoadipate in L-lysine degradation. It would also oxidize betaine aldehyde, medium-chain aldehydes and lipid-peroxidation-derived aldehydes. In vertebrates the enzyme occurs in mitochondria (matrix) and cytosol, with nuclear and stress-recruited membrane pools. Compared with human and mouse, the horse canonical model carries a 27-residue arginine-rich N-terminal extension ahead of the conserved mitochondrial targeting region. None of these functions or locations has been measured on the horse protein itself.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000139 Golgi membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Golgi membrane is a PAINT-placed location of the vertebrate ALDH7A1 clade. Horse descends from that node. The location is inferred for horse, not observed. Reason: The SubCell line in this unreviewed entry is ARBA-derived, so it is not independent support. The location is nonetheless grounded evolutionarily. PAINT placed GO:0000139 at node PTN000192435, the vertebrate ALDH7A1 node whose seeds include zebrafish, and horse lies within that clade. In human cells, ALDH7A1 recruited to Golgi membranes converts NAD+ to NADH there (PMID:31492851). The membrane-associated pool is part of the enzyme's NADH-generating role. Horse retains all catalytic residues. The location is accepted as inferred. Supporting Evidence: file:HORSE/ALDH7A1__A0A9L0R3Y5/ALDH7A1__A0A9L0R3Y5-bioinformatics/RESULTS.md GO:0005829 cytosol, GO:0005634 nucleus, GO:0000139 Golgi membrane and GO:0005886 plasma membrane, seeded by human only PMID:31492851 simply incubating recombinant ALDH7A1 with Golgi membrane results in this NAD being converted to NADH |
| GO:0004029 aldehyde dehydrogenase (NAD+) activity | IEA GO_REF:0000120 | ACCEPT | Summary: Broad NAD+-dependent aldehyde oxidation. It is measured for the human ortholog and inferred for horse from full conservation of the catalytic and NAD-binding residues. Reason: Purified human ALDH7A1 oxidizes a range of aldehydes with NAD+ (PMID:20207735). Horse A0A9L0R3Y5 is in the same PANTHER family and ALDH7A1-like InterPro family. It shares 95.7% identity with the human enzyme. It conserves the proton acceptor, the nucleophilic cysteine and all NAD(+)-binding positions. PAINT places GO:0004029 at PTN000192422, an ancestor of the vertebrate node. The broad activity is accepted alongside the more specific AASA dehydrogenase activity. It covers substrates such as betaine aldehyde and lipid-peroxidation aldehydes, not only AASA. Supporting Evidence: PMID:20207735 Purified recombinant ALDH7A1 efficiently metabolized a number of aldehyde substrates file:HORSE/ALDH7A1__A0A9L0R3Y5/ALDH7A1__A0A9L0R3Y5-bioinformatics/RESULTS.md Result: all_sites_conserved = true. |
| GO:0004043 L-aminoadipate-semialdehyde dehydrogenase [NAD(P)+] activity | IEA GO_REF:0000120 | ACCEPT | Summary: The defining activity of ALDH7A1 is AASA/P6C oxidation to alpha-aminoadipate. It is inferred for horse from the PAINT vertebrate node and from conserved substrate-binding residues. Reason: This is the core catalytic function of the ALDH7A1 clade. Human enzyme assays and patient biochemistry establish it (PMID:20207735, PMID:16491085), as do mouse and zebrafish experiments. PAINT placed GO:0004043 at PTN000192435 from those three seeds, so the function is inherited across bony vertebrates, and horse is inside that clade. Horse retains the three residues that bind (S)-2-amino-6-oxohexanoate in the human enzyme (T358, G516, A517), the catalytic E323 and C357, and E454 (human E427, the PDE hot spot). No horse-specific evidence of loss exists. The ARBA source is not counted as support. Supporting Evidence: PMID:16491085 these mutations abolish the activity of antiquitin as a delta1-piperideine-6-carboxylate (P6C)-alpha-aminoadipic semialdehyde (alpha-AASA) dehydrogenase. PMID:20207735 including the osmolyte precursor, betaine aldehyde, lipid peroxidation-derived aldehydes, and the intermediate lysine degradation product, alpha-aminoadipic semialdehyde. file:interpro/panther/PTHR43521/PTHR43521-paint.tsv MGI:MGI:108186|UniProtKB:P49419|ZFIN:ZDB-GENE-030131-6129 file:HORSE/ALDH7A1__A0A9L0R3Y5/ALDH7A1__A0A9L0R3Y5-bioinformatics/RESULTS.md inherits the node's assertions unless there is horse-specific evidence of loss. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: An additional nuclear pool. PAINT places it at the vertebrate node from human data. It is not tied to a distinct nuclear function. Reason: The SubCell line is ARBA-derived, but PAINT placed GO:0005634 at PTN000192435 from human endothelial-cell localization (PMID:20207735), and horse descends from that node. The localization is accepted as inferred. It is not core because no nuclear catalytic role separate from the cytosolic and mitochondrial enzyme has been shown. Supporting Evidence: PMID:20207735 ALDH7A1 protein was found in the cytosol, nucleus, and mitochondria file:HORSE/ALDH7A1__A0A9L0R3Y5/ALDH7A1__A0A9L0R3Y5-bioinformatics/RESULTS.md GO:0005829 cytosol, GO:0005634 nucleus, GO:0000139 Golgi membrane and GO:0005886 plasma membrane, seeded by human only |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | ACCEPT | Summary: Mitochondrial ALDH7A1 is the lysine-catabolic form. PAINT places this location at the vertebrate node from mouse and human data. Horse import is inferred, with an unresolved N-terminal caveat. Reason: PAINT placed GO:0005739 at PTN000192435 with human and mouse seeds, and the human targeting-sequence isoform is mitochondrial (PMID:20207735). Horse conserves the human-equivalent transit region at residues 28..53. In the canonical model it is preceded by a 27-residue Arg-rich extension absent from human and mouse. Whether translation starts at the upstream methionine, and whether import is affected, is unverified. Since a presequence-like extension is unlikely to abolish targeting, the location is accepted as inferred rather than observed. Supporting Evidence: file:HORSE/ALDH7A1__A0A9L0R3Y5/ALDH7A1__A0A9L0R3Y5-bioinformatics/RESULTS.md GO:0005739 mitochondrion, seeded by mouse and human PMID:20207735 ALDH7A1 protein was found in the cytosol, nucleus, and mitochondria file:HORSE/ALDH7A1__A0A9L0R3Y5/ALDH7A1__A0A9L0R3Y5-bioinformatics/RESULTS.md horse ALDH7A1 is therefore inferred, not observed. |
| GO:0005759 mitochondrial matrix | IEA GO_REF:0000107 | ACCEPT | Summary: The matrix is where AASA oxidation occurs in lysine degradation. The location is transferred from mouse by Ensembl Compara. Reason: Ensembl Compara transfers this from mouse Aldh7a1, a seed of the same PAINT node that contains horse. Reactome curates the AASA-oxidizing catalyst as the mitochondrial-matrix ALDH7A1 tetramer (R-HSA-70941). The matrix is the specific compartment for the core lysine-catabolic step. It is retained as inferred for horse, with the same N-terminal caveat as the mitochondrion row. Supporting Evidence: Reactome:R-HSA-70941 Alpha-aminoadipic semialdehyde dehydrogenase (ALDH7A1) catalyzes the reaction of alpha-aminoadipic semialdehyde and NAD+ to form alpha-aminoadipate and NADH + H+ |
| GO:0005829 cytosol | IEA GO_REF:0000120 | ACCEPT | Summary: A cytosolic pool of ALDH7A1. PAINT places it at the vertebrate node from human data. Reason: Human ALDH7A1 has cytosolic and mitochondrial forms (PMID:20207735), and PAINT placed GO:0005829 at PTN000192435. The cytosolic pool oxidizes aldehydes and supplies the enzyme recruited to membranes. Horse is within the clade. Accepted as inferred. Supporting Evidence: PMID:20207735 ALDH7A1 protein was found in the cytosol, nucleus, and mitochondria file:HORSE/ALDH7A1__A0A9L0R3Y5/ALDH7A1__A0A9L0R3Y5-bioinformatics/RESULTS.md GO:0005829 cytosol, GO:0005634 nucleus, GO:0000139 Golgi membrane and GO:0005886 plasma membrane, seeded by human only |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: A membrane-associated pool that generates local NADH in human cells. PAINT places it at the vertebrate node. Reason: The SubCell line is ARBA-derived. However, PAINT placed GO:0005886 at PTN000192435 from human experimental data, and horse descends from that node. In human cells, membrane-recruited ALDH7A1 produces the NADH used by FSP1 (PMID:40233740). That process is not propagated by PAINT and is not asserted for horse here. The location itself is accepted as inferred. Supporting Evidence: PMID:40233740 this form of NADH is generated by aldehyde dehydrogenase 7A1 (ALDH7A1) to support FSP1 activity. file:HORSE/ALDH7A1__A0A9L0R3Y5/ALDH7A1__A0A9L0R3Y5-bioinformatics/RESULTS.md GO:0005829 cytosol, GO:0005634 nucleus, GO:0000139 Golgi membrane and GO:0005886 plasma membrane, seeded by human only |
| GO:0008802 betaine-aldehyde dehydrogenase (NAD+) activity | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Betaine aldehyde is a measured substrate of the human enzyme. PAINT places the activity at the vertebrate node. It is an additional activity, not the defining one. Reason: Recombinant human ALDH7A1 oxidizes betaine aldehyde (PMID:20207735), and PAINT placed GO:0008802 at PTN000192435. The inference to horse is therefore phylogenetically grounded. The physiological contribution of ALDH7A1 to betaine synthesis is not quantified in any species, and it is secondary to AASA oxidation. Supporting Evidence: PMID:20207735 including the osmolyte precursor, betaine aldehyde, lipid peroxidation-derived aldehydes, and the intermediate lysine degradation product, alpha-aminoadipic semialdehyde. file:HORSE/ALDH7A1__A0A9L0R3Y5/ALDH7A1__A0A9L0R3Y5-bioinformatics/RESULTS.md GO:0008802 betaine-aldehyde dehydrogenase (NAD+) activity, seeded by human only |
| GO:0009063 amino acid catabolic process | IEA GO_REF:0000107 | MODIFY | Summary: True but general. The specific amino acid is lysine, and the review already carries L-lysine catabolic process. Reason: ALDH7A1 catalyzes a step of amino-acid catabolism, but the specific supported process is L-lysine catabolism. That is GO:0019477, which this gene already carries (accepted below) and which PAINT places at PTN000192435. Refine to that term. Proposed replacements: L-lysine catabolic process Supporting Evidence: file:HORSE/ALDH7A1__A0A9L0R3Y5/ALDH7A1__A0A9L0R3Y5-bioinformatics/RESULTS.md GO:0019477 L-lysine catabolic process, seeded by mouse, human and zebrafish experiments |
| GO:0016491 oxidoreductase activity | IEA GO_REF:0000002 | MODIFY | Summary: Correct at the level of the InterPro aldehyde dehydrogenase domain. The supported specific activity is NAD+-dependent aldehyde dehydrogenase. Reason: The InterPro aldehyde dehydrogenase domain and glutamate active-site signatures correctly identify an oxidoreductase. Family membership and conserved NAD-binding residues resolve this to GO:0004029 aldehyde dehydrogenase (NAD+) activity, which the gene already carries. Proposed replacements: aldehyde dehydrogenase (NAD+) activity Supporting Evidence: PMID:20207735 Purified recombinant ALDH7A1 efficiently metabolized a number of aldehyde substrates |
| GO:0019477 L-lysine catabolic process | IEA GO_REF:0000120 | ACCEPT | Summary: ALDH7A1 itself catalyzes the AASA-oxidation step of lysine degradation. PAINT places this at the vertebrate node from human, mouse and zebrafish experiments. Reason: This is direct participation: the enzyme performs the AASA/P6C to alpha-aminoadipate step. Human knockout neural progenitor cells accumulate AASA/P6C (PMID:36225138). PAINT placed GO:0019477 at PTN000192435 with three-species seeds. Horse is in the clade and conserves the catalytic and substrate-binding residues. Accepted as inferred for horse. Supporting Evidence: PMID:36225138 Quantitative analysis showed accumulation of PA and AASA/P6C in the antiquitin‐deficient NPC colonies but not in control cells file:interpro/panther/PTHR43521/PTHR43521-paint.tsv MGI:MGI:108186|UniProtKB:P49419|ZFIN:ZDB-GENE-030131-6129 |
| GO:0042802 identical protein binding | IEA GO_REF:0000107 | ACCEPT | Summary: Homotetramer assembly. It is part of the active enzyme architecture and is transferred from human by Ensembl Compara. Reason: Human ALDH7A1 is active as a tetramer, and mutations that impair oligomerization lower activity (PMID:38604394). Self-association is therefore functional, not an uninformative binding assertion. Horse conserves the human sequence at 95.7% identity across the full length. Accepted as inferred. Supporting Evidence: PMID:38604394 Because the tetramer is the active form of ALDH7A1, the defect in oligomerization explains the very low catalytic activity of R134S. |
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Download this section (compressed HTML)Q: Does horse ALDH7A1 translation initiate at the upstream methionine of the Ensembl canonical model (giving a 27-residue Arg-rich extension), and does this alter mitochondrial import relative to human and mouse?
Q: Is horse ALDH7A1 deficiency associated with pyridoxine-responsive seizures in foals, as in human pyridoxine-dependent epilepsy?
Experiment: Express recombinant horse ALDH7A1 and measure NAD+-dependent AASA/P6C and betaine aldehyde oxidation kinetics, to establish the core activity experimentally in this species.
Type: enzyme kinetics
Experiment: Map the N-terminus of endogenous horse ALDH7A1 by proteomics and test mitochondrial import of the long and short N-terminal forms in equine cells.
Type: subcellular localization
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