Rv3256c Resolved · medium auto-curated
H37Rv Rv3256c · MTBC0 mtbc0_003464 ·
346 aa · 3658418–3659458 (-) ·
RefSeq NP_217773.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | TobH protein |
| Revised (this work) | TobH protein. |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O05899
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)
| COG category |
K Transcription
|
|---|---|
| eggNOG description | Transcriptional regulator |
| Orthologous group | COG1737 |
| EC number |
EC 5.3.1.8, EC 5.3.1.9
|
| KEGG orthology |
K15916
|
| KEGG pathways |
map00010, map00030, map00051, map00500, map00520, map01100, map01110, map01120, map01130, map01200
|
| KEGG modules |
M00001, M00004, M00114
|
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 | 0.416 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 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).
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: manA (mannose-6-phosphate isomerase), high confidence from genomic context alone (score 945 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) |
|---|---|---|---|---|
Rv3255c manA |
mannose-6-phosphate isomerase | 989 | 945 ctx | neighborhood:881 coexpression:553 textmining:809 |
Rv3257c pmmA |
phosphomannomutase PmmA | 902 | 896 ctx | neighborhood:881 |
Rv2700 cei hyp |
hypothetical protein | 751 | 751 ctx | cooccurence:751 |
Rv2732c |
transmembrane protein | 749 | 749 ctx | cooccurence:740 |
Rv0556 |
transmembrane protein | 747 | 748 ctx | cooccurence:744 |
Rv0358 hyp |
hypothetical protein | 746 | 747 ctx | cooccurence:746 |
Rv3850 hyp |
hypothetical protein | 740 | 740 ctx | cooccurence:739 |
Rv2325c hyp |
hypothetical protein | 738 | 739 | coexpression:734 |
Rv3212 hyp |
hypothetical protein | 732 | 732 ctx | cooccurence:719 |
Rv1166 lpqW |
monoacyl phosphatidylinositol tetramannoside-binding protein LpqW | 731 | 731 ctx | cooccurence:720 |
Rv2446c |
integral membrane protein | 729 | 730 ctx | cooccurence:725 |
Rv3438 hyp |
hypothetical protein | 723 | 723 ctx | cooccurence:723 |
Rv3205c hyp |
hypothetical protein | 719 | 719 ctx | cooccurence:712 |
Rv0996 |
transmembrane protein | 710 | 710 ctx | cooccurence:707 |
Rv1109c hyp |
hypothetical protein | 702 | 703 ctx | cooccurence:701 |
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: TobH protein
- (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_217773.1)
- 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
COG1737 - Curated reference: UniProt O05899 (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)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
139 functional partner(s); context anchor
manA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003464|Rv3256c| MNVARAIDLEDTEGLIAADRGALLRAASMAGAQVRAIAAAADEGELDLLRGSDRPRSVIWVTGRGTAETAGTILASTLGAGAAEPIVLASAAPPWVGPLDVLIVAGDDPGDPALVGAAAIGVRRGARVVVVAPYEGPLRDSTAGRVAVLEPRLRVPDEFGLSRYLAAGLAALQTVDPKLRIDLASLADELDAEALRNSAGREVFTNPAKALAARVSGCQLALAGDNAATLALARHGSSVMLRIANQVVAATRLSDAVVALRAGTPPDALFHDEEIDGPAPQRLRVLALALAGERTVVAARVAGLDDAYLVAAEDVPELLDAPVGSGGAVLAVRLEMAAVYLRLVRG