Rv2581c Resolved · high auto-curated

H37Rv Rv2581c · MTBC0 mtbc0_002748 · 224 aa · 2929633–2930307 (-) · RefSeq NP_217097.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)glyoxalase II
MTBC0 PGAP re-annotationMBL 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 P9WMW3 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv2581c
EC (curated) EC 3.-.-.-

UniProt still lists this protein as Uncharacterized protein Rv2581c; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionZn-dependent
Orthologous groupCOG0491
EC number EC 3.1.2.6
KEGG orthology K01069
KEGG pathways map00620

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 0.528 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 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
Lactamase_BPF00753.34 5.2e-329–203 Metallo-beta-lactamase superfamily

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

Closest characterised functional partner: hisS (histidine--tRNA ligase), high confidence from genomic context alone (score 888 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2580c hisS histidine--tRNA ligase 888 888 ctx neighborhood:882
Rv2582 ppiB peptidyl-prolyl cis-trans isomerase B 651 650 ctx neighborhood:644
Rv0331 dehydrogenase/reductase 651 636 database:583
Rv3455c truA tRNA pseudouridine synthase A 423 401
Rv2165c rsmH rRNA small subunit methyltransferase H 400 400
Rv2367c ybeY endoribonuclease 425 398
Rv0390 hyp hypothetical protein 659 294 textmining:537
Rv1066 hyp hypothetical protein 658 293 textmining:537
Rv2047c hyp hypothetical protein 501 84 textmining:478
Rv1672c integral membrane transport protein 492 68 textmining:478

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: glyoxalase II
  • MTBC0 PGAP product: MBL fold metallo-hydrolase
  • Pfam (hmmscan --cut_ga): Lactamase_B PF00753.34 (E=5e-32)
  • (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_217097.1)
  • 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 P9WMW3 (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 — 10 functional partner(s); context anchor hisS
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002748|Rv2581c|
MLITGFPAGLLACNCYVLAERPGTDAVIVDPGQGAMGTLRRILDKNRLTPAAVLLTHGHIDHIWSAQKVSDTFGCPTYVHPADRFMLTDPIYGLGPRIAQLVAGAFFREPKQVVELDRDGDKIDLGGISVNIDHTPGHTRGSVVFRVLQATNNDKDIVFTGDTLFERAIGRTDLAGGSGRDLLRSIVDKLLVLDDSTVVLPGHGNSTTIGAERRFNPFLEGLSR