Rv0293c Resolved · high auto-curated

H37Rv Rv0293c · MTBC0 mtbc0_000312 · 400 aa · 360156–361358 (-) · RefSeq NP_214807.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationalpha/beta fold hydrolase
Revised (this work)Alpha/beta fold hydrolase. Pfam: Abhydrolase_1 (PF00561.27).

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

Curated reference (UniProt)

UniProt O53697 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 S Function unknown
eggNOG descriptionalpha beta
Orthologous groupCOG1073

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 0.518 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 5 missense, 1 nonsense, 1 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 0.20% of strains (287) · 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
Abhydrolase_1PF00561.27 1.4e-07170–307 alpha/beta hydrolase fold

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

Closest characterised functional partner: tam (trans-aconitate methyltransferase), high confidence from genomic context alone (score 778 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0294 tam trans-aconitate methyltransferase 778 778 ctx neighborhood:777
Rv1874 hyp hypothetical protein 697 698 ctx cooccurence:696
Rv3810 pirG cell surface protein 637 638 ctx cooccurence:618
Rv3775 lipE lipase LipE 617 617 ctx cooccurence:613
Rv2913c D-amino acid aminohydrolase 560 560 ctx cooccurence:558
Rv0982 mprB two component histidine-protein kinase/phosphatase MprB 559 560 coexpression:558
Rv3446c hyp hypothetical protein 533 534 ctx cooccurence:530
Rv2910c hyp hypothetical protein 531 532 ctx cooccurence:524
Rv2484c diacyglycerol O-acyltransferase 527 527 ctx cooccurence:522
Rv1275 lprC lipoprotein LprC 500 500 ctx cooccurence:481
Rv0518 hyp hypothetical protein 523 495 ctx cooccurence:483
Rv0383c ttfA hyp hypothetical protein 490 490 ctx cooccurence:465
Rv0221 diacyglycerol O-acyltransferase 498 478 ctx cooccurence:474
Rv2015c hyp hypothetical protein 468 468 ctx cooccurence:446
Rv3707c hyp hypothetical protein 466 466 ctx cooccurence:463

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: hypothetical protein
  • MTBC0 PGAP product: alpha/beta fold hydrolase
  • Pfam (hmmscan --cut_ga): Abhydrolase_1 PF00561.27 (E=1e-07)
  • (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_214807.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Abhydrolase_1 (PF00561.27)
  • 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 COG1073
  • Curated reference: UniProt O53697 (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 — 35 functional partner(s); context anchor tam
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000312|Rv0293c|
MSGTFTADAIGPPVPIPDVPGADAGAEGLPSRSVLSARQRILVESSAIADVALRTAVASVLSATVTPAVVANALRHVNEGSERSNLNFYAELAAAHDPAKSFPAPTELPKVTSRPASPLTEWVARGTVDNIAFASGFRAINPTMRQRWSALTANNIVHAQHWRHRDGPRPTLCVIHGFMGSSYLLNGLFFSLPWYYRSGYDVLLYTLPFHGQRAEKFSPFSGFGYFTSGLSGFAEAMAQAVYDFRSIVDYLRHIGVDRIALTGISLGGYTSALLASVESRLEAVIPNCPVVMPAKLFDEWFPANKLVKLGLRLTNISRDELIAGLAYHGPLNYRPLLPKDRRMIITGLGDRMAPPEHAVTLWKQWDRCALHWFPGSHLLHVSQLDYLRRMTVFLQGLMFD