blaC Resolved · high auto-curated
H37Rv Rv2068c · MTBC0 - ·
307 aa · 2325886–2326809 (-) ·
RefSeq NP_216584.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | beta-lactamase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Beta-lactamase. Pfam: Beta-lactamase2 (PF13354.13), Beta-lactamase (PF00144.30). |
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 |
P9WKD3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Beta-lactamase |
| EC (curated) |
EC 3.5.2.6
|
| Curated function | Extended spectrum beta-lactamase (ESBL) that inactivates beta-lactam antibiotics by hydrolyzing the amide group of the beta-lactam ring. Displays high levels of penicillinase and cephalosporinase activity as well as measurable activity with carbapenems, including imipenem and meropenem. Plays a primary role in the intrinsic resistance of M.tuberculosis to beta-lactam antibiotics. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
V Defense mechanisms
|
|---|---|
| Preferred name | blaC |
| eggNOG description | beta-lactamase |
| Orthologous group | COG2367 |
| EC number |
EC 3.5.2.6
|
| KEGG orthology |
K17836
|
| KEGG pathways |
map00311, map01130, map01501
|
| KEGG modules |
M00627, M00628
|
| Gene Ontology (47) |
GO:0003674, GO:0003824, GO:0005575, GO:0005576, GO:0005623, GO:0005886, GO:0006807, GO:0008150, GO:0008152, GO:0008800, GO:0009056, GO:0009308 +35 more
|
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 | 0.119 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 1 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 |
|---|---|---|---|---|
Beta-lactamase2 | PF13354.13 | 1.7e-44 | 44–299 | Beta-lactamase enzyme family |
Beta-lactamase | PF00144.30 | 1.4e-20 | 50–298 | Beta-lactamase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: sigC (ECF RNA polymerase sigma factor SigC), medium confidence from genomic context alone (score 655 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2067c hyp |
hypothetical protein | 778 | 777 ctx | neighborhood:772 |
Rv2069 sigC |
ECF RNA polymerase sigma factor SigC | 663 | 655 ctx | neighborhood:589 |
Rv2782c pepR |
zinc protease | 546 | 547 ctx | neighborhood:544 |
Rv2783c gpsI |
bifunctional guanosine pentaphosphate synthetase/polyribonucleotide nucleotidyltransferase | 478 | 478 ctx | neighborhood:473 |
Rv3044 fecB |
FeIII-dicitrate-binding periplasmic lipoprotein | 442 | 254 | |
Rv3364c hyp |
hypothetical protein | 706 | 195 | textmining:651 |
Rv1923 lipD |
lipase LipD | 705 | 182 | textmining:655 |
Rv1497 lipL |
esterase LipL | 525 | 166 | textmining:455 |
Rv3354 hyp |
hypothetical protein | 464 | 62 | textmining:453 |
Rv3775 lipE |
lipase LipE | 406 | 57 | |
Rv3627c dacB hyp |
hypothetical protein | 411 | 54 | textmining:403 |
Rv3763 lpqH |
lipoprotein LpqH | 541 | 49 | textmining:538 |
Rv3677c |
beta lactamase | 460 | 49 | textmining:456 |
Rv1922 |
lipoprotein | 400 | 48 | |
Rv0406c |
beta lactamase-like protein | 531 | 46 | textmining:529 |
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): beta-lactamase
- Pfam (hmmscan --cut_ga): Beta-lactamase2 PF13354.13 (E=2e-44), Beta-lactamase PF00144.30 (E=1e-20)
- (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_216584.1)
- Domains: Pfam-A via hmmscan --cut_ga — Beta-lactamase2 (PF13354.13), Beta-lactamase (PF00144.30)
- 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
COG2367 - Curated reference: UniProt P9WKD3 (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 —
19 functional partner(s); context anchor
sigC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2068c|blaC MRNRGFGRRELLVAMAMLVSVTGCARHASGARPASTTLPAGADLADRFAELERRYDARLGVYVPATGTTAAIEYRADERFAFCSTFKAPLVAAVLHQNPLTHLDKLITYTSDDIRSISPVAQQHVQTGMTIGQLCDAAIRYSDGTAANLLLADLGGPGGGTAAFTGYLRSLGDTVSRLDAEEPELNRDPPGDERDTTTPHAIALVLQQLVLGNALPPDKRALLTDWMARNTTGAKRIRAGFPADWKVIDKTGTGDYGRANDIAVVWSPTGVPYVVAVMSDRAGGGYDAEPREALLAEAATCVAGVLA