Rv3136A Still unknown · low auto-curated
H37Rv Rv3136A · MTBC0 - ·
110 aa · 3502945–3503277 (-) ·
RefSeq YP_007411850.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Conserved hypothetical protein; no recognised domain. Function unknown. Foldseek best (non-significant) hit: 7d8r-assembly2_C MITF HLHLZ structure (prob 0.41, TM 0.32). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
I6Y2Q7
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Conserved protein |
UniProt still lists this protein as Conserved protein; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2B18P |
|---|
Orthology-based transfer (eggNOG 5.0.2, diamond). EC/KO/GO/CAZy are computed annotations, not manual curation; cross-check against the primary literature before treating a specific reaction as established.
Conservation & selection (intra-MTBC, 145 209 strains)
| pN/pS | n/a |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 0 synonymous, 5 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 69.7 (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 |
|---|---|---|---|---|
7d8r-assembly2_C |
0.41 | 0.32 | 2.7e-01 | 7d8r-assembly2_C MITF HLHLZ structure |
7d8r-assembly2_D |
0.33 | 0.33 | 4.9e-01 | 7d8r-assembly2_D MITF HLHLZ structure |
7d8r-assembly1_A |
0.28 | 0.33 | 6.1e-01 | 7d8r-assembly1_A MITF HLHLZ structure |
8th5-assembly1_A |
0.16 | 0.69 | 7.2e+00 | 8th5-assembly1_A Crystal Structure of the G3BP1 NTF2-like domain bound to the IDR1 of SARS-CoV-2 nucleocapsid protein P13L mutant |
3rd4-assembly2_A |
0.15 | 0.39 | 1.6e+00 | 3rd4-assembly2_A Crystal structure of PROPEN_03304 from Proteus penneri ATCC 35198 Northeast Structural Genomics Consortium target id PvR55 |
8d0k-assembly1_A |
0.15 | 0.35 | 1.1e+00 | 8d0k-assembly1_A Human CST-DNA polymerase alpha/primase preinitiation complex bound to 4xTEL-foldback template - PRIM2C advanced PIC |
6yam-assembly1_j |
0.14 | 0.37 | 1.6e+00 | 6yam-assembly1_j Mammalian 48S late-stage translation initiation complex (LS48S+eIF3 IC) with beta-globin mRNA |
7ypo-assembly1_A |
0.11 | 0.38 | 2.9e+00 | 7ypo-assembly1_A Cryo-EM structure of baculovirus LEF-3 in complex with ssDNA |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: hisN (histidinol-phosphatase), high confidence from genomic context alone (score 778 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) |
|---|---|---|---|---|
Rv3137 hisN |
histidinol-phosphatase | 778 | 778 ctx | neighborhood:778 |
Rv3138 pflA |
pyruvate formate lyase activating protein PflA | 748 | 749 ctx | neighborhood:749 |
Rv3140 fadE23 |
acyl-CoA dehydrogenase FadE23 | 691 | 691 ctx | neighborhood:691 |
Rv3139 fadE24 |
acyl-CoA dehydrogenase | 495 | 495 ctx | neighborhood:495 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): hypothetical protein
- Foldseek best: 7d8r-assembly2_C MITF HLHLZ structure (prob 0.41, E=3e-01, TM=0.32)
- (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 YP_007411850.1)
- Domains: Pfam-A via hmmscan --cut_ga — none above threshold
- Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
- Controlled vocabulary: eggNOG-mapper 2.1.12 (Cantalapiedra et al. 2021,
doi:10.1093/molbev/msab293), eggNOG 5.0 DB
(Huerta-Cepas et al. 2019) — OG
2B18P - Curated reference: UniProt I6Y2Q7 (TrEMBL, unreviewed; Evidence at protein level)
- 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 69.7, low)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
4 functional partner(s); context anchor
hisN - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3136A| MGWEFGVLLILIAVLAVFLAPRLIPRGPRGDLASGTLLVTGVSPRPDAGGQQYVTIAGIITGPTVNEYAVYQRMAVDVDQWPTVGQILPVVYSPKNPDNWTFTPNGPPVG