tusc2a notes

Setup and provenance

• Fetched with just fetch-gene on Q08BH0 (TrEMBL, zgc:153746, 111 aa); 4 GOA rows (ND root MF,
  3 IBA from mouse Tusc2). ZFIN ZDB-GENE-061013-612, Ensembl ENSDARG00000099817, chromosome 6.
• Deep research unavailable: Edison returned 402 Payment Required and the OpenAI key is
  invalid, so no -deep-research-*.md was generated. Literature searched by hand via Europe PMC
  (queries: "tusc2a", "tusc2b", zebrafish AND (tusc2 OR fus1),
  (TUSC2 OR FUS1) AND mitochondri* AND calcium, title searches for Fus1 and inflammation).
• "tusc2a" finds only a largemouth-bass heat-stress transcriptome; "tusc2b" finds nothing. No
  zebrafish study of either copy exists.
• Part of DANRE_DUPLICATION batch 4 (random sample, seed 20260928); paralog tusc2b. Ensembl
  Compara (REST, 2026-09-28) places the duplication at Osteoglossocephalai; gar ENSLOCG00000014230
  is a one-to-many orthologue of both copies; medaka one-to-one orthologues are
  ENSORLG00000027802 (tusc2a) and ENSORLG00000027402 (tusc2b).

Mammalian TUSC2 / FUS1 (ancestral function)

• Mitochondrial localization depends on myristoylation
  PMID:35181743
• Regulator of mitochondrial calcium uptake (mouse cells)
  PMID:24328503
  PMID:24328503
• The calcium-binding domain was predicted, not measured
  PMID:24328503
• Knockout mice: chronic inflammation, mitochondrial parameters changed
  PMID:22513871
• Motif conservation across metazoans (with AI modeling of an OSCP interface, a hypothesis)
  PMID:42314984

Own analysis

See RESULTS.md. The copies are 80.2% identical; both keep
Gly2 (myristoylation) and the exact DEDGDLAHEFYEE motif; relative rate not different (5 vs 9
unique changes). Expression: tusc2a is the larger maternal transcript and then drops to 1-2 TPM at
gastrulation; tusc2b is the main zygotic copy (26-51 TPM). In adult Bgee calls tusc2b is higher in
21 of 25 shared tissues; tusc2a's top calls are testis and ovarian follicle.

Curation decisions

• ND root MF: ACCEPT (MF genuinely unknown; calcium binding only predicted).
• mitochondrion (IBA): ACCEPT.
• regulation of mitochondrial membrane potential (IBA): ACCEPT.
• inflammatory response (IBA): MARK_AS_OVER_ANNOTATED (knockout consequence of mitochondrial
  dysfunction; the protein does not do the work of the inflammatory response).