agxta notes
Setup and provenance
- Fetched with
just fetch-gene on Q6DG86 (TrEMBL, 391 aa; synonym agxtl); 7 GOA rows (5 IBA, 2 IEA),
none with a PMID. ZFIN ZDB-GENE-040718-16, Ensembl ENSDARG00000052099, chromosome 6.
- The deleted TrEMBL entry F1QY24 (UniParc UPI00015A7661) that PMID:35295584 cites as "Agxta" has a sequence
that differs from Q6DG86 at a single position (checked by fetching UPI00015A7661 from UniParc), so it is the same
gene.
- Deep research unavailable: Edison returned 402 Payment Required and the OpenAI key is invalid. Literature
searched by hand via Europe PMC ((agxt OR agxta OR agxtb OR "alanine-glyoxylate aminotransferase") AND zebrafish,
"alanine:glyoxylate aminotransferase" AND (fish OR teleost ...), AGT targeting evolution queries).
- DANRE_DUPLICATION batch 4, random draw 11 (seed 20260928); paralog agxtb. PANTHER TGD_tree 1:1 pair
(PTHR21152); Ensembl Compara places the duplication at Osteoglossocephalai.
What is known about the zebrafish gene
- No experimental study of zebrafish agxta. The only specific statement is from a bioinformatic survey of the
zebrafish peroxisomal proteome:
PMID:35295584
and it contrasts agxtb
PMID:35295584
- ZFIN curated expression (Thisse high-throughput in situ, ZDB-PUB-040907-1): liver and pronephric duct from
the 20-25 somite stage to day 5 (bioinformatics output, section 9).
Background: vertebrate AGT (AGXT) and its targeting
- PLP-dependent class-V aminotransferase converting glyoxylate + L-alanine to glycine + pyruvate; also
serine:pyruvate aminotransferase. Deficiency in humans causes primary hyperoxaluria type 1
PMID:12899834.
- Organelle distribution varies between species and correlates with diet
PMID:21558762;
PMID:21558762.
- Mechanism in mammals: one gene, two start sites. The upstream start adds a cleavable MTS and the downstream
start makes a product that the C-terminal PTS1 sends to peroxisomes
PMID:21558762;
PMID:10723739.
- Human AGT is peroxisomal and its KKL PTS1 needs an internal ancillary signal that Xenopus AGT lacks
PMID:15911627.
- Mammal-wide study (685 genomes, cell assays) of MTS/PTS1 evolution; Xenopus AGT used as the exclusively
mitochondrial control
PMID:41781394.
- Fish biochemistry (species not named in the abstract): hepatic AGT in freshwater fish is in both organelles
PMID:8954944.
Purified mackerel liver AGT has AGT1-type substrate specificity
PMID:6697688.
See agxta-bioinformatics/RESULTS.md. Key points:
- agxta starts at the residue equivalent to the mammalian downstream (peroxisomal-form) Met; its 5' UTR and genomic
5' flank have an in-frame stop 16 codons upstream and no in-frame ATG, so no MTS-bearing isoform can be made.
- agxta ends SRV; agxtb has a 32-residue Arg-rich N-terminal extension that aligns with the gar extension and ends
SKA. Spotted gar (unduplicated outgroup) has both a 38-residue Arg-rich extension and a C-terminal SKV.
The pattern (a-copies without extension and with S[KR]V/NKM-type ends; b-copies with extension and mostly SKA
ends) recurs across the teleost panel.
- Catalytic Lys209 (PLP) and the substrate Arg360 of human AGXT are conserved in both copies.
- agxta evolves faster than agxtb relative to gar (59 vs 32 unique changes; chi2 8.01).
- Expression overlaps widely (liver, kidney, intestine, spleen, head kidney in Bgee), like gar (liver, mesonephros,
intestine). Larval whole-body TPM: agxtb higher than agxta at day 3-5.
GOA review decisions (summary)
- MF (AGT, SPT) IBA/IEA: accepted; catalytic residues conserved.
- Peroxisome IBA: accepted; this is the copy that keeps a C-terminal PTS1-like tripeptide and has no MTS.
- Glyoxylate catabolism and glycine biosynthesis IBA: accepted (peroxisomal glyoxylate detoxification is the
expected role of the peroxisomal copy), with the caveat that nothing has been measured in zebrafish.