Rv0906 Resolved · high auto-curated

H37Rv Rv0906 · MTBC0 mtbc0_000960 · 372 aa · 1012158–1013276 (+) · RefSeq NP_215421.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationMBL fold metallo-hydrolase
Revised (this work)MBL fold metallo-hydrolase. Pfam: Lactamase_B_3 (PF13483.13), Lactamase_B_2 (PF12706.14).

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

Curated reference (UniProt)

UniProt P9WKP3 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv0906

UniProt still lists this protein as Uncharacterized protein Rv0906; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionBeta-lactamase superfamily domain
Orthologous groupCOG2220

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) pseudogene candidate

pN/pS 0.427 · purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 5 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 17.68% of strains (25674) · 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
Lactamase_B_3PF13483.13 2.1e-12107–303 Beta-lactamase superfamily domain
Lactamase_B_2PF12706.14 7.0e-52122–321 Beta-lactamase superfamily domain

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

Closest characterised functional partner: echA6 (enoyl-CoA hydratase EchA6), high confidence from genomic context alone (score 914 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0905 echA6 enoyl-CoA hydratase EchA6 914 914 ctx neighborhood:881
Rv0904c accD3 acetyl-CoAcarboxylase carboxyl transferase subunit beta 791 791 ctx neighborhood:790
Rv0908 ctpE metal cation transporter ATPase E 789 790 ctx neighborhood:787
Rv0907 hyp hypothetical protein 636 637 ctx neighborhood:620
Rv0909 antitoxin 582 583 ctx neighborhood:544
Rv0436c pssA CDP-diacylglycerol--serine O-phosphatidyltransferase 557 557 ctx cooccurence:543
Rv0437c psd phosphatidylserine decarboxylase 469 469
Rv0911 hyp hypothetical protein 452 453 ctx neighborhood:450
Rv0903c prrA two component transcriptional regulator PrrA 400 400
Rv3627c dacB hyp hypothetical protein 872 63 textmining:870
Rv3811 hyp hypothetical protein 870 41 textmining:870

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: MBL fold metallo-hydrolase
  • Pfam (hmmscan --cut_ga): Lactamase_B_3 PF13483.13 (E=2e-12), Lactamase_B_2 PF12706.14 (E=7e-52)
  • (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_215421.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Lactamase_B_3 (PF13483.13), Lactamase_B_2 (PF12706.14)
  • 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 COG2220
  • Curated reference: UniProt P9WKP3 (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 — 11 functional partner(s); context anchor echA6
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000960|Rv0906|
MVRRALRLAAGTASLAAGTWLLRALHGTPAALGADAASIRAVSEQSPNYRDGAFVNLDPASMFTLDREELRLIVWELVARHSASRPAAPIPLASPNIYRGDASRLAVSWFGHSTALLEIDGYRVLTDPVWSDRCSPSDVVGPQRLHPPPVQLAALPAVDAVVISHDHYDHLDIDTVVALVGMQRAPFLVPLGVGAHLRSWGVPQDRIVELDWNQSAQVDELTVVCVPARHFSGRFLSRNTTLWASWAFVGPNHRAYFGGDTGYTKSFTQIGADHGPFDLTLLPIGAYNTAWPDIHMNPEEAVRAHLDVTDSGSGMLVPVHWGTFRLAPHPWGEPVERLLAAAEPEHVTVAVPLPGQRVDPTGPMRLHPWWRL