Aldh7a1 (mouse, Q9DBF1): ortholog comparison

Date: 2026-10-20

Inputs and method

orthologs.fasta: canonical UniProt sequences downloaded with
curl "https://rest.uniprot.org/uniprotkb/stream?query=accession:Q64057+OR+accession:Q2KJC9+OR+accession:Q803R9+OR+accession:Q28GS6+OR+accession:P49419+OR+accession:Q9DBF1&format=fasta"
(the zebrafish accession Q803R9 returned no entry and is absent).
compare_orthologs.py: global pairwise alignment of each ortholog to mouse
Q9DBF1 (Biopython PairwiseAligner, BLOSUM62, gap open -10, extend -0.5).
Raw output: compare_orthologs.out.
PANTHER 19.0 subfamily assignments were read from the release classification
files under .cache/panther/PTHR19.0_*, and PAINT IBD rows from
interpro/panther/PTHR43521/PTHR43521-paint.tsv.

Results

Ortholog	Identity to mouse	Catalytic Glu296 / Cys330	Residue at mouse 130
human P49419	0.883 (539 columns)	E296 / C330	S130
cow Q2KJC9	0.868	E296 / C330	S130
rat Q64057	0.941	E296 / C330	R130
Xenopus Q28GS6	0.810	E268 / C302	H102

Mouse window 125-135 is IQLLGRLVSLE; human is IQVLGSLVSLE.

Mouse R130 aligns to human Ser130 (Ser102 in the 511-residue human isoform 2
numbering), the residue annotated in human P49419 as phosphorylated by AMPK. In
human cells, phosphorylation at this site controls ALDH7A1 membrane recruitment
(PMID:31492851, PMID:40233740). Mouse and rat carry Arg and Xenopus carries His
at this position, so this AMPK site is not conserved in mouse.

Both catalytic residues (Glu296 and Cys330) are conserved in all orthologs
compared.

PANTHER 19.0 puts mouse Q9DBF1 in PTHR43521:SF1. Rat, cow, chicken, Xenopus,
Drosophila, C. elegans, Dictyostelium, Arabidopsis ALDH7B4 and several bacterial
members are also in SF1. Human P49419 is the only listed SF5 member. Mouse and
human are 88% identical across the full length, so this split looks like a
subfamily-HMM classification artifact, not functional divergence. The PAINT node
PTN000192435 contains both mouse and human and carries the IBDs for GO:0004043
and GO:0019477, seeded by MGI:108186, human P49419 and zebrafish. It also
carries IBDs for GO:0008802 and for the locations mitochondrion, cytosol,
nucleus, Golgi membrane and plasma membrane. No IBD at this node covers
ferroptosis, energy homeostasis or the membrane-transport regulation terms.

Interpretation limits

This is a pairwise comparison, not a phylogeny. A missing phosphosite shows the
human regulatory switch is absent in mouse. It does not show that mouse Aldh7a1
is never recruited to membranes, because other mechanisms could do this.