Rv1006 Family assigned · low

H37Rv Rv1006 · MTBC0 mtbc0_001081 · 567 aa · 1131050–1132753 (+) · RefSeq NP_215522.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationhypothetical protein
Revised (this work)Glycoside-hydrolase-like fold (GH2, PDB 5T99); putative glycosidase.

Curated reference (UniProt)

UniProt O05592 TrEMBL · unreviewed · Evidence at protein level
UniProt nameSecreted protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category G Carbohydrate transport and metabolism
eggNOG descriptionBeta-galactosidase
Orthologous groupCOG1874

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 0.558 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 5 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)

No Pfam-A domain above the gathering threshold (or not yet scanned).

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 82.4 (confident). A confident model makes the fold comparison meaningful.

Best matches against the PDB, ranked by Foldseek homology probability. A high probability / TM-score suggests a shared fold; unless flagged sig (E < 0.01) these are fold hypotheses, not assignments.

TargetProbTME-valueDescription
5t99-assembly2_B 1.00 0.46 4.4e-04 sig 5t99-assembly2_B Crystal structure of BuGH2Awt in complex with Galactoisofagomine
5t99-assembly1_A 1.00 0.47 1.0e-03 sig 5t99-assembly1_A Crystal structure of BuGH2Awt in complex with Galactoisofagomine
5t98-assembly2_B 1.00 0.44 1.1e-03 sig 5t98-assembly2_B Crystal structure of BuGH2Awt
3fn9-assembly2_C 0.99 0.50 2.6e-03 sig 3fn9-assembly2_C Crystal structure of putative beta-galactosidase from bacteroides fragilis
3bga-assembly1_B 0.99 0.41 3.9e-04 sig 3bga-assembly1_B Crystal structure of beta-galactosidase from Bacteroides thetaiotaomicron VPI-5482
5g50-assembly1_B 0.97 0.43 5.0e-03 sig 5g50-assembly1_B Vibrio cholerae scaffolding protein RbmA in complex with magnesium.
4kkq-assembly1_B 0.97 0.43 5.0e-03 sig 4kkq-assembly1_B Crystal structure of Vibrio cholerae RbmA (crystal form 1)
4be6-assembly1_A 0.95 0.42 3.7e-03 sig 4be6-assembly1_A V. cholera biofilm scaffolding protein RbmA

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

Closest characterised functional partner: Rv0180c (transmembrane protein), high confidence from genomic context alone (score 741 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv1435c hyp hypothetical protein 775 775 ctx cooccurence:774
Rv1868 hyp hypothetical protein 774 774 ctx cooccurence:774
Rv2047c hyp hypothetical protein 771 771 ctx cooccurence:770
Rv3033 hyp hypothetical protein 765 765 ctx cooccurence:764
Rv2114 hyp hypothetical protein 761 761 ctx cooccurence:759
Rv2598 hyp hypothetical protein 750 751 ctx cooccurence:749
Rv0180c transmembrane protein 741 741 ctx cooccurence:741
Rv3899c hyp hypothetical protein 738 739 ctx cooccurence:737
Rv1364c sigma factor regulatory protein 737 738 ctx cooccurence:736
Rv1005c pabB para-aminobenzoate synthase component I 786 726 ctx neighborhood:725
Rv3166c hyp hypothetical protein 714 714 ctx cooccurence:714
Rv1795 eccD5 ESX-5 type VII secretion system protein EccD 709 709 ctx cooccurence:705
Rv2571c transmembrane protein 702 703 ctx cooccurence:701
Rv2597 membrane protein 702 703 ctx cooccurence:701
Rv3263 DNA methylase 698 698 ctx cooccurence:695

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: hypothetical protein
  • Foldseek best: 5t99-assembly2_B Crystal structure of BuGH2Awt in complex with Galactoisofagomin (prob 1.00, E=4e-04, TM=0.46)
  • (structure-only promotion reviewed by hand, 2026-06-01)

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_215522.1)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • 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 COG1874
  • Curated reference: UniProt O05592 (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)
  • Model confidence: ESMFold per-residue pLDDT (mean 82.4, confident)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 92 functional partner(s); context anchor Rv0180c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001081|Rv1006|
MVLRSRKSTLGVVVCLALVLGGPLNGCSSSASHRGPLNAMGSPAIPSTAQEIPNPLRGQYEDLMEPLFPQGNPAQQRYPPWPASYDASLRVSWRQLQPTDPRTLPPDAPDDRKYDFSVIDNALTRLADRGMRLTLRVYAYSSCCKASYPDGTNIAIPDWERAIASTNTSYPGPATDPSTGVVQVVPNFNDSTYLNDFAQLLAALGRRYDGDERLSVFEFSGYGDFSENHVAYLRDTLGAPGPGPDESVATLGYYSQFRDQNITTASIKQLIAANVSAFPHTQLVTSPANPEIVRELFADEVTNKLAAPVGVRSDCLGVDAPLPAWAESSTSHYVQTKDPVVAALRQRLATAPVITEWCELPTGSSPRAYYEKGLRDVIRYHVSMTSSVNFPDQTATSPMDPALYLVWAQANAAAGYRYSVEAQPGSQALAGKVATISVTWTNYGAAAATEKWVPGYRLVDSTGQVVRTLPAAVDLKTLVSDQRGDRSSDQPTPASVAETVRVDLSGLPAGHYTLRAAIDWQQHKPNGSHVVNYPPMLLSRDGRDDSGFYPVATLDIPRDAQTAVNAS