est12 Resolved · high
H37Rv Rv1579c · MTBC0 mtbc0_001686 ·
104 aa · 1795270–1795584 (-) ·
RefSeq NP_216095.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | phage protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | EST12 (early secreted target, 12 kDa), a secreted effector encoded in region-of-difference RD3. RefSeq leaves it 'hypothetical'. Secreted EST12 binds the receptor for activated C kinase 1 (RACK1) and recruits the deubiquitinase UCHL5 to deubiquitinate NLRP3, triggering NLRP3-caspase-1-gasdermin-D pyroptosis and IL-1beta release; it also regulates Myc via RACK1-JNK-AP1. A crystal structure identifies Y80 as the RACK1-binding residue; ΔEST12 is more susceptible in vitro and in vivo (Qu 2020). |
Curated reference (UniProt)
| UniProt |
O06611
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable PhiRv1 phage protein |
Domains (Pfam, hmmscan --cut_ga)
No Pfam-A domain above the gathering threshold (or not yet scanned).
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv1580c (phage protein), high confidence from genomic context alone (score 776 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1580c |
phage protein | 776 | 776 ctx | neighborhood:773 |
Rv1581c |
phage protein | 754 | 754 ctx | neighborhood:752 |
Rv1578c |
phage protein | 563 | 563 ctx | neighborhood:557 |
Rv1582c |
phage protein | 445 | 445 ctx | neighborhood:436 |
Rv1584c |
phage protein | 439 | 439 ctx | neighborhood:436 |
Rv1583c |
phage protein | 438 | 438 ctx | neighborhood:436 |
STRING combines evidence channels (neighborhood, fusion, cooccurrence, coexpression, experimental, database, text-mining) into a 0–1000 score. The ctx badge marks edges carried by the genomic-context channels (conserved neighborhood, fusion, phylogenetic co-occurrence), which are independent of orthology and structure and the strongest signal for an unknown gene. The no text-mining column recomputes the score from data alone, so a link that does not depend on the literature is visible. Association is a function hypothesis, not proof: corroborate with the operon context and the primary literature before assigning a function.
Evidence
- Secreted RD3 effector; RACK1 ligand triggering NLRP3-pyroptosis-IL-1beta (Qu 2020, PMID 33097533)
- Crystal structure; Y80 = RACK1-binding residue
- Also drives RACK1-JNK-AP1-Myc inflammatory pathway (Wu 2022, PMID 36003390)
- Named EST12
- Curated from the literature crible (project 'Still unknown gene function', 2026-06-09)
Sources
- Ancestral sequence & coordinates: Harrison LB et al. (2024), An imputed ancestral reference genome for the MTBC, doi:10.1101/2023.09.07.556366
- Product annotation: NCBI PGAP on MTBC0; legacy from H37Rv NC_000962.3 (RefSeq NP_216095.1)
- Domains: Pfam-A via hmmscan --cut_ga — none above threshold
- Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
- Curated reference: UniProt O06611 (TrEMBL, unreviewed; Evidence at protein level)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
6 functional partner(s); context anchor
Rv1580c - Primary literature: Qu Z, Zhou J, Zhou Y, Xie Y, Jiang Y, Wu J, Luo Z, Liu G, Yin L, Zhang XL (2020). Mycobacterial EST12 activates a RACK1-NLRP3-gasdermin D pyroptosis-IL-1beta immune pathway Sci Adv 6(43):eaba4733. doi:10.1126/sciadv.aba4733 PMID:33097533
Ancestral MTBC0 protein sequence
>mtbc0_001686|Rv1579c|est12 MTPINRPLTNDERQLMHELAVQVVCSQTGCSPDAAVEALESFAKDGTLILRGDTENAYLEAGGNVLVHADRDWLAFHASYPGNDPLRDARPIEQDDDQGAGSPS