Rv0029 Still unknown · low
H37Rv Rv0029 · MTBC0 mtbc0_000035 ·
365 aa · 32043–33140 (+) ·
RefSeq NP_214543.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | DUF5631 domain-containing protein |
| Revised (this work) | Conserved hypothetical protein; tandem DUF5631 + DUF5632 domains. Foldseek finds a significant structural match to Rv3899c (PDB 5IMU), another conserved hypothetical M. tuberculosis protein of unknown function (a proposed vaccine candidate): the fold is thus structurally characterised but the biological function remains unassigned. |
Curated reference (UniProt)
| UniProt |
P71599
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Transmembrane protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2A1TI |
|---|
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) pseudogene candidate
| pN/pS | 0.794 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 13 missense, 0 nonsense, 2 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 2.26% of strains (3276) · clonal |
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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
DUF5632 | PF18646.7 | 1.5e-35 | 165–243 | Family of unknown function (DUF5632) |
DUF5631 | PF18645.7 | 1.5e-36 | 268–361 | Family of unknown function (DUF5631) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 86.0 (confident). A confident model makes the fold comparison meaningful.
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 |
|---|---|---|---|---|
5imu-assembly1_A |
1.00 | 0.89 | 3.1e-16 sig | 5imu-assembly1_A A fragment of conserved hypothetical protein Rv3899c (residues 184-410) from Mycobacterium tuberculosis |
8ako-assembly1_B |
0.77 | 0.26 | 3.2e-03 sig | 8ako-assembly1_B Structure of EspB-EspK complex: the non-identical twin of the PE-PPE-EspG secretion mechanism. |
5zug-assembly1_F |
0.08 | 0.49 | 7.1e+00 | 5zug-assembly1_F Structure of the bacterial acetate channel SatP |
7z38-assembly1_D |
0.07 | 0.23 | 4.9e+00 | 7z38-assembly1_D Structure of the RAF1-HSP90-CDC37 complex (RHC-I) |
5d56-assembly1_A |
0.06 | 0.37 | 7.1e+00 | 5d56-assembly1_A In meso in situ serial X-ray crystallography structure of diacylglycerol kinase, DgkA, at 100 K |
5ku9-assembly2_B |
0.04 | 0.28 | 5.2e+00 | 5ku9-assembly2_B Crystal structure of MCL1 with compound 1 |
7nyx-assembly1_C |
0.04 | 0.23 | 8.3e+00 | 7nyx-assembly1_C Cryo-EM structure of the MukBEF-MatP-DNA monomer (closed conformation) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: eccC2 (ESX-2 type VII secretion system protein EccC), medium confidence from genomic context alone (score 551 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) |
|---|---|---|---|---|
Rv0030 hyp |
hypothetical protein | 798 | 798 ctx | neighborhood:792 |
Rv0028 hyp |
hypothetical protein | 730 | 731 ctx | neighborhood:728 |
Rv3372 otsB2 |
trehalose 6-phosphate phosphatase | 656 | 656 | coexpression:656 |
Rv0027 hyp |
hypothetical protein | 654 | 653 ctx | neighborhood:650 |
Rv2006 otsB1 |
trehalose-6-phosphate phosphatase OtsB | 652 | 653 | coexpression:653 |
Rv3894c eccC2 |
ESX-2 type VII secretion system protein EccC | 550 | 551 ctx | neighborhood:544 |
Rv0031 |
Rv0031, (MTCY10H4.31), len: 70 aa. Possible remnant of a transposase, showing partial similarity to mycobacterial transposases in a short ov | 510 | 510 ctx | neighborhood:507 |
Rv0182c sigG |
ECF RNA polymerase sigma factor SigG | 411 | 389 |
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
- MTBC0 PGAP product: 'DUF5631 domain-containing protein'
- Pfam (hmmscan --cut_ga): DUF5632 PF18646 (E=1.5e-35) + DUF5631 PF18645 (E=1.5e-36) -- two tandem domains of unknown function
- Foldseek on the ESMFold model: significant match to Rv3899c (PDB 5IMU), prob 1.00, E=3.1e-16, TM=0.89 -- a fold shared with another uncharacterised Mtb protein; weak secondary hit to the ESX EspB-EspK complex is non-conclusive
ESM Atlas signal (exploratory)
Ancestral protein hash a02a2d3e27dcbfe03c075cc12fd78de4.
SAE features are orienting indices, not validated domains.
| # | Index | Activation | Interpretation |
|---|---|---|---|
| 1 | 12612 |
1.30 | Secretion signals and low-complexity tracts |
| 2 | 1056 |
1.00 | C-terminal low-complexity disordered tails |
| 3 | 5883 |
0.97 | Mycobacterial PE/PGRS low-complexity repeats |
| 4 | 2267 |
0.97 | Pro/Gly-rich low-complexity repeats |
| 5 | 11576 |
0.82 | Long C-terminal appendages |
| 6 | 8959 |
0.80 | Long low-complexity IDRs |
| 7 | 12600 |
0.77 | Glycine-centric low-complexity and turns |
| 8 | 12453 |
0.76 | Secretion IDRs and toxic domains |
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_214543.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF5632 (PF18646.7), DUF5631 (PF18645.7)
- 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
2A1TI - Curated reference: UniProt P71599 (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 86.0, confident)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
8 functional partner(s); context anchor
eccC2 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000035|Rv0029| MAIFGRWSARQRLRRATRESLTIPTFSSSLDCTTRVIGGLWPAELSSNTAETATLAEHLKADLHRIVGSANDELMVIWRAGMADSTRRAEEDRVIDRARASAMRRVESAMRELRQITGRVPVEIPRMRGAGGSDLDTTRLMPAVTVVQPADQACTDWPVAAAEDDEARLQRLLAFVARQEPRLNWAVGVHADGTTVLVTDVAHGWIPPGIALPEGVRLLAPARRAGRAPELVGITTCCKTYTPGDSLRRAVDSTAPTSSVQPRALPAIAGLSVELGIATQRHDGLPKIVHAMATAAGNGAAAEEVDLLRVHVDTALHHVLAQYPRVDPALLLNCMLLAATERSVTGDPIAANYHFAWFRELDSRR