Rv2656c Still unknown · low auto-curated

H37Rv Rv2656c · MTBC0 mtbc0_002830 · 130 aa · 3000863–3001255 (-) · RefSeq NP_217172.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)prophage protein
MTBC0 PGAP re-annotationDUF2742 domain-containing protein
Revised (this work)Conserved hypothetical protein; DUF domain(s) DUF2742. Function unknown.

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

Curated reference (UniProt)

UniProt P9WL49 SwissProt · reviewed · Predicted
UniProt nameUncharacterized protein Rv2656c

UniProt still lists this protein as Uncharacterized protein Rv2656c; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionProtein of unknown function (DUF2742)
Orthologous group2AYB0

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 0.729 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 2 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
DUF2742PF10888.15 2.5e-3835–128 Protein of unknown function (DUF2742)

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

Closest characterised functional partner: Rv2655c (prophage protein), high confidence from genomic context alone (score 830 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2655c prophage protein 831 830 ctx neighborhood:799
Rv2657c prophage protein 924 787 ctx neighborhood:785 textmining:657
Rv2654c antitoxin 921 784 ctx neighborhood:781 textmining:652
Rv2658c prophage protein 901 746 ctx neighborhood:746 textmining:629
Rv2659c prophage integrase 857 739 ctx neighborhood:738 textmining:479
Rv2653c toxin 724 578 ctx neighborhood:573
Rv2652c prophage protein 499 499 ctx neighborhood:496
Rv2660c hyp hypothetical protein 476 476 ctx neighborhood:461
Rv2661c hyp hypothetical protein 464 463 ctx neighborhood:461
Rv1398c vapB10 antitoxin VapB10 521 51 textmining:516
Rv2355 Probable transposase; Rv2355, (MTCY98.24), len: 328 aa. Probable IS6110 transposase. Identical to many other M. tuberculosis IS6110 transpos 548 44 textmining:547
Rv2278 Rv2278, (MTCY339.32c), len: 108 aa. Putative Transposase for IS6110 (fragment). Identical to many other M. tuberculosis IS6110 transposase s 548 44 textmining:547
Rv1511 gmdA GDP-D-mannose dehydratase GmdA 512 44 textmining:511
Rv0550c vapB3 antitoxin VapB3 511 44 textmining:510
Rv0718 rpsH 30S ribosomal protein S8 511 44 textmining:510

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: prophage protein
  • MTBC0 PGAP product: DUF2742 domain-containing protein
  • Pfam (hmmscan --cut_ga): DUF2742 PF10888.15 (E=3e-38)
  • (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_217172.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF2742 (PF10888.15)
  • 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 2AYB0
  • Curated reference: UniProt P9WL49 (SwissProt, reviewed; Predicted)
  • 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 — 18 functional partner(s); context anchor Rv2655c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002830|Rv2656c|
MTAVGGSPPTRRCPATEDRAPATVATPSSTDPTASRAVSWWSVHEYVAPTLAAAVEWPMAGTPAWCDLDDTDPVKWAAICDAARHWALRVETCQAASAEASRDVSAAADWPAVSREIQRRRDAYIRRVVV