Rv0274 Family assigned · medium

H37Rv Rv0274 · MTBC0 mtbc0_000291 · 193 aa · 330804–331385 (+) · RefSeq NP_214788.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationVOC family protein
Revised (this work)VOC (vicinal-oxygen-chelate) / glyoxalase-bleomycin-resistance superfamily protein (Pfam Glyoxalase PF00903). Putative metalloenzyme (glyoxalase / dioxygenase-type chemistry); specific substrate not established.

Curated reference (UniProt)

UniProt O53680 TrEMBL · unreviewed · Evidence at protein level
UniProt nameConserved protein

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

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
eggNOG descriptionglyoxalase bleomycin resistance protein
Orthologous groupCOG0346

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 0.624 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 2 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.60% of strains (874) · 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)

PfamAccessioni-EvalueResiduesDescription
GlyoxalasePF00903.32 5.0e-2115–163 Glyoxalase/Bleomycin resistance protein/Dioxygenase superfamily
Glyoxalase_4PF13669.13 6.6e-0717–125 Glyoxalase/Bleomycin resistance protein/Dioxygenase superfamily

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

Closest characterised functional partner: Rv0273c (transcriptional regulator), high confidence from genomic context alone (score 900 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0273c transcriptional regulator 900 900 ctx neighborhood:773 cooccurence:575
Rv0272c hyp hypothetical protein 898 898 ctx neighborhood:598 cooccurence:753
Rv0271c fadE6 acyl-CoA dehydrogenase FadE6 685 673 ctx neighborhood:544
Rv3153 nuoI NADH-quinone oxidoreductase subunit I 676 656 coexpression:645
Rv0518 hyp hypothetical protein 586 585 ctx cooccurence:574
Rv3368c oxidoreductase 563 554 coexpression:415
Rv2032 acg NAD(P)H nitroreductase 538 528 coexpression:420
Rv3127 hyp hypothetical protein 537 526 coexpression:419
Rv0311 hyp hypothetical protein 523 523 ctx cooccurence:514
Rv0767c HTH-type transcriptional regulator 519 520 ctx cooccurence:519
Rv3148 nuoD NADH-quinone oxidoreductase subunit D 530 511 coexpression:497
Rv3316 sdhC succinate dehydrogenase cytochrome B-556 subunit 529 508 coexpression:505
Rv3131 NAD(P)H nitroreductase 509 499 coexpression:418
Rv2195 qcrA ubiquinol-cytochrome C reductase rieske iron-sulfur subunit 444 433 coexpression:431
Rv3593 lpqF lipoprotein LpqF 453 432 ctx cooccurence:427

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

  • MTBC0 PGAP product: 'VOC family protein'
  • Pfam: Glyoxalase PF00903 (E=5.0e-21), Glyoxalase_4 PF13669 (E=6.6e-07)

ESM Atlas signal (exploratory)

Ancestral protein hash c4591f310352618625ff9aa51466afe3 · 10 ESM-space neighbours (max similarity 0.888). SAE features are orienting indices, not validated domains.

#IndexActivationInterpretation
110352 1.01 Cupin/VOC beta-barrel core
213144 0.94 VOC/glyoxalase fold metal-binding core
36430 0.93 VOC/cupin metalloenzyme signature
412978 0.93 Metal-coordinating catalytic beta-strands
52557 0.91 VOC 2-His/acidic facial triad
6377 0.80 N-terminal VOC metal-ligating strand
79959 0.79 VOC metalloenzyme fold detector
89897 0.73 VOC fold metal-binding core

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_214788.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Glyoxalase (PF00903.32), Glyoxalase_4 (PF13669.13)
  • 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 COG0346
  • Curated reference: UniProt O53680 (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 — 37 functional partner(s); context anchor Rv0273c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000291|Rv0274|
MIKPHNTNTEFELGGINHVALVCSDMARTVDFYSNILGMPLIKALDLPGGQGQHFFFDAGNGDCVAFFWFADAPDRVPGLSSPVAIPGIGDITSAVSTMNHLAFHVPAERFDAYRQRLKDKGVRVGPVLNHDDSETQVSAVVHPGVYVRSFYFQDPDGITLEFACWTKEFTTSDAQAVPKTAADRRPPVAADR