blaR Family assigned · medium auto-curated

H37Rv Rv1845c · MTBC0 mtbc0_001958 · 316 aa · 2113256–2114206 (-) · RefSeq NP_216361.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)sensor-transducer protein BlaR
MTBC0 PGAP re-annotationM56 family metallopeptidase
Revised (this work)M56 family metallopeptidase. Pfam: Peptidase_M48 (PF01435.25).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt P95164 TrEMBL · unreviewed · Inferred from homology
UniProt namePossible sensor-transducer protein BlaR

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category M Cell wall / membrane / envelope biogenesis
eggNOG descriptionZn-dependent protease with chaperone function
Orthologous groupCOG0501

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 0.321 · purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 3 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)

PfamAccessioni-EvalueResiduesDescription
Peptidase_M48PF01435.25 7.4e-08151–201 Peptidase family M48

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: blaI (transcriptional repressor BlaI), high confidence from genomic context alone (score 976 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1846c blaI transcriptional repressor BlaI 976 976 ctx neighborhood:869 cooccurence:772
Rv1844c gnd1 6-phosphogluconate dehydrogenase 848 848 ctx neighborhood:841
Rv1843c guaB1 inosine-5'-monophosphate dehydrogenase 826 819 ctx neighborhood:802
Rv1842c hyp hypothetical protein 716 716 ctx neighborhood:700
Rv1841c hyp hypothetical protein 712 713 ctx neighborhood:700
Rv0342 iniA isoniazid inductible protein IniA 663 644 database:643
Rv2001 hyp hypothetical protein 583 584 ctx cooccurence:583
Rv2673 aftC alpha-(1->3)-arabinofuranosyltransferase 553 553 ctx cooccurence:553
Rv1274 lprB lipoprotein LprB 564 537 ctx cooccurence:531
Rv0184 hyp hypothetical protein 531 532 ctx cooccurence:528
Rv1837c glcB malate synthase 516 516 ctx neighborhood:505
Rv0495c hyp hypothetical protein 515 515 ctx cooccurence:504
Rv2342 hyp hypothetical protein 505 505 ctx cooccurence:498
Rv3346c transmembrane protein 502 503 ctx cooccurence:500
Rv0466 hyp hypothetical protein 492 493 ctx cooccurence:490

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: sensor-transducer protein BlaR
  • MTBC0 PGAP product: M56 family metallopeptidase
  • Pfam (hmmscan --cut_ga): Peptidase_M48 PF01435.25 (E=7e-08)
  • (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_216361.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Peptidase_M48 (PF01435.25)
  • 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 COG0501
  • Curated reference: UniProt P95164 (TrEMBL, unreviewed; Inferred from homology)
  • 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 — 38 functional partner(s); context anchor blaI
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001958|Rv1845c|blaR
MSALAFTILAVLLAGPTPALLARATWPLRAPRAAMVLWQAIALAAVLSSFSAGIAIASRLLMPGPDGRPTTSFVGAAGRLGWPLWAAYITVFALTVLVGARLAVAVVRVATATRRRRAHHRMVVDLVGVGHNGALAQPCARARDLRVLDVAQPLAYCLPGVRSRVVVSEGTLTALADAEVAAILTHERAHLRARHDLVLEAFTAVHAAFPRLVRSANALGAVQLLVELLADDAAVRAAGRTPLARALVACASGRAPSGALAVGGPSTVLRVRRLSGRGNSAVLSAAAYLAAAAVLVVPTVALAVPWLTQLQRLFIA