Rv3677c Resolved · high auto-curated
H37Rv Rv3677c · MTBC0 mtbc0_003896 ·
264 aa · 4141088–4141882 (-) ·
RefSeq NP_218194.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | beta lactamase |
|---|---|
| MTBC0 PGAP re-annotation | MBL fold metallo-hydrolase |
| Revised (this work) | MBL fold metallo-hydrolase. Pfam: Lactamase_B (PF00753.34), Lactamase_B_2 (PF12706.14), WHD_BLACT (PF17778.8). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6XHY3
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Possible hydrolase |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | pksB_1 |
| 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 | 2.556 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 7 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.53% of strains (764) · 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 | 4.9e-13 | 35–193 | Metallo-beta-lactamase superfamily |
Lactamase_B_2 | PF12706.14 | 2.4e-06 | 53–132 | Beta-lactamase superfamily domain |
WHD_BLACT | PF17778.8 | 1.2e-05 | 230–261 | Beta-lactamase associated winged helix domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv3680 (anion transporter ATPase), high confidence from genomic context alone (score 781 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3678c hyp |
hypothetical protein | 891 | 891 ctx | neighborhood:882 |
Rv3678A hyp |
hypothetical protein | 869 | 869 ctx | neighborhood:867 |
Rv3680 |
anion transporter ATPase | 788 | 781 ctx | neighborhood:774 |
Rv3679 |
anion transporter ATPase | 783 | 776 ctx | neighborhood:774 |
Rv1561 vapC11 |
ribonuclease VapC11 | 765 | 765 | coexpression:765 |
Rv3040c hyp |
hypothetical protein | 656 | 656 ctx | cooccurence:445 |
Rv0331 |
dehydrogenase/reductase | 651 | 636 | database:583 |
Rv2533c nusB |
N utilization substance protein B | 558 | 558 | coexpression:553 |
Rv1637c hyp |
hypothetical protein | 530 | 530 ctx | cooccurence:529 |
Rv2260 hyp |
hypothetical protein | 462 | 463 ctx | cooccurence:456 |
Rv2367c ybeY |
endoribonuclease | 448 | 421 | |
Rv3455c truA |
tRNA pseudouridine synthase A | 428 | 407 | |
Rv2165c rsmH |
rRNA small subunit methyltransferase H | 404 | 405 | |
Rv0337c aspC |
aspartate aminotransferase | 417 | 396 | |
Rv3674c nth |
endonuclease III | 692 | 203 | textmining:630 |
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: beta lactamase
- MTBC0 PGAP product: MBL fold metallo-hydrolase
- Pfam (hmmscan --cut_ga): Lactamase_B PF00753.34 (E=5e-13), Lactamase_B_2 PF12706.14 (E=2e-06), WHD_BLACT PF17778.8 (E=1e-05)
- (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_218194.1)
- Domains: Pfam-A via hmmscan --cut_ga — Lactamase_B (PF00753.34), Lactamase_B_2 (PF12706.14), WHD_BLACT (PF17778.8)
- 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 I6XHY3 (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 —
27 functional partner(s); context anchor
Rv3680 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003896|Rv3677c| MSKTAESLTHPAYGQLRAVTDTASVLLADNPGLLTLDGTNTWVLRGPLSDELVVVDPGPDDDEHLARVAALGRIALVLISHRHGDHTSGIDKLVALTGAPVRAADPQFLRRDGETLTDGEVIDVAGLTITVLATPGHTADSLSFVLDDAVLTADTVLGCGTTVIDKEDGSLADYLESLHRLRGLGRRTVLPGHGPDLLDLEAIASGYLLHRHERLEQIRAALRDLGDDATVREVVEHVYLDVDEKLWNAAEWSVQAQLDYLRTR