agxtb notes

Setup and provenance

• Fetched with just fetch-gene on Q6PHK4 (TrEMBL, 423 aa; synonym agxt); 14 GOA rows (5 IBA, 2 IEA, 6 ISS from
  rat/mouse/human AGXT, 1 IDA from PMID:18618001). ZFIN ZDB-GENE-010302-3, Ensembl ENSDARG00000018478, chromosome 2.
• Deep research unavailable: Edison returned 402 Payment Required and the OpenAI key is invalid. Literature
  searched by hand via Europe PMC (same queries as agxta; see ../agxta/agxta-notes.md).
• DANRE_DUPLICATION batch 4, random draw 11 (seed 20260928); paralog agxta. The pair analysis lives in
  ../agxta/agxta-bioinformatics/ (RESULTS.md, output.txt).

What is known about the zebrafish gene

• No experimental study of the protein. Predicted MTS and no PTS1 in a bioinformatic survey
  PMID:35295584
  with the survey's explanation of what a mitochondrial AGT does
  PMID:35295584.
• The only experimental GOA row is an estrogen-response IDA from a whole-adult microarray study: an AGT probe was
  down-regulated in tissues of fish exposed to estrogenic compounds
  PMID:18618001. This is a transcript change,
  not a function; marked over-annotated.
• ZFIN curated expression: RT-PCR only (whole larva at long-pec; adult male kidney).

Background

See ../agxta/agxta-notes.md for AGT biochemistry and the evolution of its targeting. Key points for this copy:
the mitochondrial form of mammalian AGT comes from an upstream start that adds a cleavable MTS
PMID:21558762,
and mitochondrial AGT handles glyoxylate from hydroxyproline
PMID:21558762.

My analysis (../agxta/agxta-bioinformatics/RESULTS.md)

• 32-residue Arg-rich N-terminal extension (MMPRTVLSRCARLTQQVPLESALSGKQSVQRG) sharing a motif with the 38-residue
  gar AGXT extension; the annotated start is the first possible Met (in-frame genomic stop 20 codons upstream).
• C-terminus SKA, which does not fit the PTS1 consensus; SKA is also the end of most agxtb orthologues in the
  teleost panel, while gar ends SKV.
• Catalytic K209 and R360 (human numbering) conserved. agxtb is closer to gar than agxta (71.8% vs 61.5%) and has
  fewer lineage-specific changes (32 vs 59).
• Expression largely shared with agxta (liver, kidney, intestine, spleen); agxtb is the higher larval transcript
  (175 vs 50 TPM at day 5).

GOA review decisions (summary)

• MF rows (IBA, IEA, ISS) accepted; mitochondrion (ISS) accepted as the predicted location.
• Peroxisome IBA and ISS marked over-annotated: the copy lost the C-terminal PTS1 and kept the MTS; propagation
  review recorded on the IBA row. Not removed because nothing has been localized experimentally.
• Pyruvate biosynthetic process kept as non-core; estrogen response IDA marked over-annotated.