ANKRD49 notes
- First described as FGIF (fetal globin-inducing factor). It has an N-terminal acidic domain with potent transactivation activity (yeast and COS assays) and three C-terminal ANK repeats, and it raises gamma-globin [PMID:11162141, PMID:16131492; abstracts]. Affinage missed this origin.
- Positive regulation of transcription (IDA ×2 and IBA): ACCEPT. The IBA node PTN009083995 is seeded only by ANKRD49 (NO_FAILURE_CORE). Nucleus (IEA, ISS, IC): ACCEPT. Mouse germ cells show predominantly nuclear ANKRD49 PMID:26043108.
- NEW GO:0003713 transcription coactivator activity (IDA, PMID:11162141): an acidic TAD plus the physical PKNOX1 interaction driving TGF-B1 PMID:41821002. Limits are stated: fusion-construct assays, and promoter occupancy not tested.
- Protein binding:
- HIF1AN ×5 → MODIFY to GO:0019899. FIH hydroxylates ankyrin repeats PMID:17003112; the pair is also seen by AP-MS.
- RAN → MODIFY to GO:0031267 small GTPase binding. GO:0008536 Ran GTPase binding is merged into GO:0031267. Source: the RaDAR RanGDP-ankyrin import study PMID:24855949.
- FKBPL ×5 → REMOVE: reproducible across AP-MS and Y2H, but no informative term fits; raised as a question.
- SMARCD1, ENKD1 (HuRI) → REMOVE.
- Phenotypes with no GO drawn: NF-kB-dependent autophagy in GC-1 cells and lung-cancer invasion/EMT.
Round 2 (reviewer, PR #4136)
- The coactivator row now quotes both decisive PKNOX1 results. In support: Flag-PKNOX1 ChIP enrichment is higher in ANKRD49-overexpressing cells ("ANKRD49 strengthens the interaction"). Against: ANKRD49 overexpression also raises PKNOX1 mRNA and protein, so the effect could be abundance rather than coactivation. (Superseded in round 3: the reporter did test this, see below.) The description and core function are softened accordingly, and the experiment now separates the two models.
- The HIF1AN rows have per-row provenance: one FIH screen plus four AP-MS studies, so 5 rows, not 4.
- GO:0008536 is now described as merged into GO:0031267.
- Cited PMID:37964204 and PMID:35775112 (LOW; signaling phenotypes). Added a SMARCD1/SWI-SNF suggested question.
Round 3 (reviewer, PR #4136)
- Correction: Fig. 7B of PMID:41821002 does test ANKRD49 on PKNOX1-driven reporter activity. With PKNOX1 from a plasmid, "co-expression of ANKRD49 further amplified this effect". The round-2 claim that it was untested came from the incomplete Methods; the reviewer withdrew it, and the sentence is removed.
- The limit is restated as nuclear PKNOX1 abundance (Fig. 8E, increased nuclear accumulation) versus activity. The description and core function now present ANKRD49 as a coactivator of PKNOX1.
- PMID:30798416 is cited (LOW), and the SMARCD1 removal reason is reworded.