Rv2260 Resolved · high auto-curated
H37Rv Rv2260 · MTBC0 mtbc0_002403 ·
211 aa · 2559437–2560072 (+) ·
RefSeq NP_216776.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | MBL fold metallo-hydrolase |
| Revised (this work) | MBL fold metallo-hydrolase. Pfam: Lactamase_B (PF00753.34). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53534
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Metallo-beta-lactamase domain-containing protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Metallo-beta-lactamase superfamily |
| Orthologous group | COG0491 |
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 | 0.687 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
Lactamase_B | PF00753.34 | 8.2e-22 | 23–190 | Metallo-beta-lactamase superfamily |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mscR (S-nitrosomycothiol reductase MscR), high confidence from genomic context alone (score 958 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) |
|---|---|---|---|---|
Rv2259 mscR |
S-nitrosomycothiol reductase MscR | 959 | 958 ctx | neighborhood:882 cooccurence:633 |
Rv2258c |
transcriptional regulator | 705 | 705 ctx | neighborhood:692 |
Rv2257c hyp |
hypothetical protein | 704 | 695 ctx | neighborhood:689 |
Rv0360c hyp |
hypothetical protein | 649 | 650 ctx | cooccurence:648 |
Rv2256c hyp |
hypothetical protein | 645 | 645 ctx | neighborhood:644 |
Rv0331 |
dehydrogenase/reductase | 651 | 636 | database:583 |
Rv1117 hyp |
hypothetical protein | 519 | 520 ctx | cooccurence:509 |
Rv3677c |
beta lactamase | 462 | 463 ctx | cooccurence:456 |
Rv2643 arsC |
arsenic-transport integral membrane protein ArsC | 445 | 429 | |
Rv3455c truA |
tRNA pseudouridine synthase A | 419 | 397 | |
Rv2367c ybeY |
endoribonuclease | 424 | 396 |
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: MBL fold metallo-hydrolase
- Pfam (hmmscan --cut_ga): Lactamase_B PF00753.34 (E=8e-22)
- (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_216776.1)
- Domains: Pfam-A via hmmscan --cut_ga — Lactamase_B (PF00753.34)
- 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
COG0491 - Curated reference: UniProt O53534 (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 —
11 functional partner(s); context anchor
mscR - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002403|Rv2260| MAAIERVITHGTFELDGGSWEVDNNIWLVGDDSEVVVFDAAHHAAPIIDAVGGRKVVAVICTHGHNDHVTVAPELGTALDAPVLMHPGDAVLWRMTHPDKSFRAVSDGDAVRVGGTELRALHTPGHSPGSVCWYAPELGPGTGTVFSGDTLFAGGPGATGRSYSDFPTILRSISGRLGALPGDTVVHTGHGDSTTIGDEIVHYEEWVARGH