Rv2300c Resolved · high auto-curated
H37Rv Rv2300c · MTBC0 - ·
310 aa · 2572076–2573008 (-) ·
RefSeq NP_216816.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | metallo-hydrolase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | 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.
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 |
P9WLD7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable metallo-hydrolase Rv2300c |
| EC (curated) |
EC 3.-.-.-
|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Metallo-beta-lactamase superfamily |
| Orthologous group | COG0491 |
| Gene Ontology (6) |
GO:0005575, GO:0005623, GO:0005886, GO:0016020, GO:0044464, GO:0071944
|
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 | 0.684 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 2 missense, 0 nonsense, 2 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 0.23% of strains (338) · 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 |
|---|---|---|---|---|
Lactamase_B | PF00753.34 | 4.1e-16 | 68–266 | Metallo-beta-lactamase superfamily |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: htpG (chaperone protein HtpG), medium confidence from genomic context alone (score 594 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0331 |
dehydrogenase/reductase | 651 | 636 | database:583 |
Rv2299c htpG |
chaperone protein HtpG | 594 | 594 ctx | neighborhood:591 |
Rv2301 cut2 |
cutinase | 572 | 573 ctx | neighborhood:571 |
Rv1752 hyp |
hypothetical protein | 509 | 509 ctx | cooccurence:485 |
Rv2337c hyp |
hypothetical protein | 479 | 480 ctx | cooccurence:466 |
Rv2777c hyp |
hypothetical protein | 446 | 446 ctx | cooccurence:446 |
Rv2302 hyp |
hypothetical protein | 418 | 418 ctx | neighborhood:416 |
Rv2165c rsmH |
rRNA small subunit methyltransferase H | 400 | 401 | |
Rv3455c truA |
tRNA pseudouridine synthase A | 419 | 397 | |
Rv2367c ybeY |
endoribonuclease | 420 | 392 | |
Rv2048c pks12 |
polyketide synthase | 452 | 390 | |
Rv2946c pks1 |
polyketide synthase | 439 | 370 |
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): metallo-hydrolase
- Pfam (hmmscan --cut_ga): Lactamase_B PF00753.34 (E=4e-16)
- (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_216816.1)
- 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 P9WLD7 (SwissProt, reviewed; 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 —
12 functional partner(s); context anchor
htpG - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2300c| MVATRGRPCPTNFSRPQRPRVAGNGTKSQRCRGRLTTSMLGVAPEAKGPPVKVHHLNCGTMNAFGIALLCHVLLVETDDGLVLVDTGFGIQDCLDPGRVGLFRHVLRPAFLQAETAARQIEQLGYRTSDVRHIVLTHFDFDHIGGIADFPEAHLHVTAAEARGAIHAPSLRERLRYRRGQWAHGPKLVEHGPDGEPWRGFASAKPLDSIGTGVVLVPMPGHTRGHAAVAVDAGHRWVLHCGDAFYHRGTLDGRFRVPFVMRAEEKLLSYNRNQLRDNQARIVELHRRHDPDLLIVCAHDPDLYQLARDTA