Rv0603 Family assigned · low
H37Rv Rv0603 · MTBC0 mtbc0_000633 ·
103 aa · 703408–703719 (+) ·
RefSeq NP_215117.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | Secreted protein with a solved NMR structure (PDB 2LRA, Rv0603); fold characterised, function not established. |
Curated reference (UniProt)
| UniProt |
O07775
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Possible exported protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2EQ52 |
|---|
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 | n/a |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 0 synonymous, 2 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 1.77% of strains (2572) · 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)
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 67.3 (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 |
|---|---|---|---|---|
2lra-assembly1_A |
1.00 | 0.67 | 3.7e-09 sig | 2lra-assembly1_A NMR Structure of Signal Sequence Deleted (SSD) Rv0603 Protein from Mycobacterium tuberculosis without N-terminal His-tag |
7ath-assembly1_AAA |
1.00 | 0.60 | 1.5e-02 | 7ath-assembly1_AAA Crystal structure of UipA |
2gu3-assembly1_A |
0.90 | 0.65 | 4.7e-01 | 2gu3-assembly1_A YpmB protein from Bacillus subtilis |
4fr9-assembly1_A |
0.72 | 0.50 | 2.2e-01 | 4fr9-assembly1_A Crystal structure of a BLIP-like protein (BF1215) from Bacteroides fragilis NCTC 9343 at 1.20 A resolution |
5igh-assembly1_A |
0.60 | 0.62 | 7.4e-01 | 5igh-assembly1_A Macrolide 2'-phosphotransferase type I |
4fma-assembly3_C |
0.14 | 0.50 | 4.5e+00 | 4fma-assembly3_C EspG structure |
8suc-assembly1_A |
0.13 | 0.62 | 4.2e+00 | 8suc-assembly1_A NHL-2 NHL domain |
2hxc-assembly1_A |
0.13 | 0.76 | 7.5e+00 | 2hxc-assembly1_A Crystal structure of the benzylamine complex of aromatic amine dehydrogenase in N-semiquinone form |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: tcrA (two component DNA binding transcriptional regulator TcrA), high confidence from genomic context alone (score 936 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) |
|---|---|---|---|---|
Rv0602c tcrA |
two component DNA binding transcriptional regulator TcrA | 935 | 936 ctx | neighborhood:559 coexpression:860 |
Rv0604 lpqO |
lipoprotein LpqO | 879 | 879 ctx | neighborhood:568 coexpression:731 |
Rv1675c cmr |
HTH-type transcriptional regulator Cmr | 850 | 850 | coexpression:850 |
Rv3167c |
TetR family transcriptional regulator | 841 | 841 | coexpression:841 |
Rv3082c virS |
HTH-type transcriptional regulator VirS | 827 | 827 | coexpression:827 |
Rv1151c cobB |
NAD-dependent protein deacylase | 827 | 827 | coexpression:827 |
Rv3840 |
transcriptional regulator | 826 | 826 | coexpression:826 |
Rv0691c mftR |
mycofactocin biosynthesis transcriptional regulator MftR | 822 | 822 | coexpression:822 |
Rv1267c embR |
transcriptional regulator EmbR | 819 | 819 | coexpression:819 |
Rv0117 oxyS |
oxidative stress response regulatory protein OxyS | 817 | 817 | coexpression:817 |
Rv1931c |
transcriptional regulator | 817 | 817 | coexpression:817 |
Rv1027c kdpE |
transcriptional regulator KdpE | 813 | 813 | coexpression:813 |
Rv0494 |
HTH-type transcriptional regulator | 813 | 813 | coexpression:813 |
Rv3830c |
TetR family transcriptional regulator | 810 | 810 | coexpression:810 |
Rv1190 hyp |
hypothetical protein | 810 | 810 | coexpression:810 |
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: hypothetical protein
- Foldseek best: 2lra-assembly1_A NMR Structure of Signal Sequence Deleted (SSD) Rv0603 Protein f (prob 1.00, E=4e-09, TM=0.67)
- (structure-only promotion reviewed by hand, 2026-06-01)
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_215117.1)
- 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
2EQ52 - Curated reference: UniProt O07775 (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 67.3, low)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
69 functional partner(s); context anchor
tcrA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000633|Rv0603| MNRIVQFGVSAVAAAAIGIGAGSGIAAAFDGEDEVTGPDADRARAAAVQAVPGGTAGEVETETGEGAAAYGVLVTRPDGTRVEVHLDRDFRVLDTEPADGDGG