Rv3612c Still unknown · low auto-curated
H37Rv Rv3612c · MTBC0 mtbc0_000273 ·
6 aa · 310302–310472 (-) ·
RefSeq NP_218129.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | Conserved hypothetical protein; no recognised domain. Function unknown. Foldseek best (non-significant) hit: 3j6b-assembly1_T Structure of the yeast mitochondrial large ribosomal (prob 0.11, TM 0.30). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6YGR2
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | Uncharacterized protein |
UniProt still lists this protein as Uncharacterized protein; the revised annotation above is ahead of the current UniProt record.
Conservation & selection (intra-MTBC, 145 209 strains)
| pN/pS | 0.367 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 2 missense, 0 nonsense, 0 frameshift |
pN/pS from segregating SNPs (singletons removed) normalised by possible sites. Low pN/pS = purifying selection (a strong signal that a "hypothetical" is a real, constrained gene). A high pN/pS is ambiguous: relaxed constraint or positive selection (drug resistance, antigenic variation) inflate it; e.g. rpoB/katG/pncA score high here for resistance, not loss of function. A clonal disruption (one allele over a clade) suggests lineage pseudogenisation; a convergent one (many independent alleles) is typical of resistance loss-of-function.
Domains (Pfam, hmmscan --cut_ga)
No Pfam-A domain above the gathering threshold (or not yet scanned).
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 38.8 (very low). Low-confidence model: the fold may be unreliable, so treat these structural hits with caution.
Best matches against the PDB, ranked by Foldseek homology probability. A high probability / TM-score suggests a shared fold; unless flagged sig (E < 0.01) these are fold hypotheses, not assignments.
| Target | Prob | TM | E-value | Description |
|---|---|---|---|---|
3j6b-assembly1_T |
0.11 | 0.30 | 2.3e+00 | 3j6b-assembly1_T Structure of the yeast mitochondrial large ribosomal subunit |
6ywv-assembly1_T |
0.06 | 0.29 | 4.4e+00 | 6ywv-assembly1_T The structure of the Atp25 bound assembly intermediate of the mitoribosome from Neurospora crassa |
6yxy-assembly1_A2 |
0.06 | 0.27 | 4.4e+00 | 6yxy-assembly1_A2 State B of the Trypanosoma brucei mitoribosomal large subunit assembly intermediate |
5ji0-assembly2_A |
0.04 | 0.36 | 9.7e+00 | 5ji0-assembly2_A PPARgamma-RXRalpha(S427F) heterodimer in complex with SRC-1, rosiglitazone, and 9-cis-retanoic acid |
6hix-assembly1_A2 |
0.04 | 0.27 | 7.4e+00 | 6hix-assembly1_A2 Cryo-EM structure of the Trypanosoma brucei mitochondrial ribosome - This entry contains the large mitoribosomal subunit |
6yxx-assembly1_A2 |
0.03 | 0.27 | 9.7e+00 | 6yxx-assembly1_A2 State A of the Trypanosoma brucei mitoribosomal large subunit assembly intermediate |
1ecw-assembly1_A |
0.03 | 0.29 | 9.7e+00 | 1ecw-assembly1_A CRYSTAL STRUCTURE OF SIMIAN IMMUNODEFICIENCY VIRUS MATRIX ANTIGEN (SIV MA) AT 293K. |
2x6k-assembly1_B |
0.02 | 0.21 | 7.4e+00 | 2x6k-assembly1_B THE CRYSTAL STRUCTURE OF THE DROSOPHILA CLASS III PI3-KINASE VPS34 IN COMPLEX WITH PI-103 |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: espD (ESX-1 secretion-associated protein EspD), high confidence from genomic context alone (score 854 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3614c espD |
ESX-1 secretion-associated protein EspD | 914 | 854 ctx | neighborhood:480 coexpression:730 textmining:440 |
Rv3613c hyp |
hypothetical protein | 848 | 830 ctx | neighborhood:700 coexpression:458 |
Rv3616c espA |
ESX-1 secretion-associated protein EspA | 868 | 630 | coexpression:514 textmining:658 |
Rv3615c espC |
ESX-1 secretion-associated protein EspC | 733 | 475 | textmining:514 |
Rv3875 esxA |
ESAT-6 protein EsxA | 444 | 54 | textmining:437 |
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
- Legacy H37Rv annotation: hypothetical protein
- MTBC0 PGAP product: hypothetical protein
- Foldseek best: 3j6b-assembly1_T Structure of the yeast mitochondrial large ribosomal subunit (prob 0.11, E=2e+00, TM=0.30)
- (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)
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_218129.1)
- Domains: Pfam-A via hmmscan --cut_ga — none above threshold
- Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
- Curated reference: UniProt I6YGR2 (TrEMBL, unreviewed; Predicted)
- Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
- Model confidence: ESMFold per-residue pLDDT (mean 38.8, very low)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
5 functional partner(s); context anchor
espD - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000273|Rv3612c| MVAVPS