Rv2576c Family assigned · medium auto-curated

H37Rv Rv2576c · MTBC0 mtbc0_002743 · 154 aa · 2923770–2924234 (-) · RefSeq NP_217092.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)membrane protein
MTBC0 PGAP re-annotationhypothetical protein
Revised (this work)Contains Rv2576c_beta (PF27168.1) domain(s); putative function inferred from the domain architecture.

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

Curated reference (UniProt)

UniProt P9WL83 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv2576c

UniProt still lists this protein as Uncharacterized protein Rv2576c; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

Orthologous group2AVKT
Gene Ontology (7) GO:0005575, GO:0005576, GO:0005618, GO:0005623, GO:0030312, GO:0044464, GO:0071944

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 0.688 · 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
Rv2576c_betaPF27168.1 4.3e-3354–149 Rv2576c beta-sandwich domain

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

PartnerProductScoreNo text-miningChannels (≥400)
Rv2577 hyp hypothetical protein 536 536 ctx neighborhood:536
Rv0130 htdZ 3-hydroxyl-thioester dehydratase 479 44 textmining:478

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: membrane protein
  • MTBC0 PGAP product: hypothetical protein
  • Pfam (hmmscan --cut_ga): Rv2576c_beta PF27168.1 (E=4e-33)
  • (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_217092.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Rv2576c_beta (PF27168.1)
  • 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 2AVKT
  • Curated reference: UniProt P9WL83 (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 — 2 functional partner(s)
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002743|Rv2576c|
MPAGVGNASGSVLDMTSVRTVPSAVALVTFAGAALSGVIPAIARADPVGHQVTYTVTTTSDLMANIRYMSADPPSMAAFNADSSKYMITLHTPIAGGQPLVYTATLANPSQWAIVTASGGLRVNPEFHCEIVVDGQVVVSQDGGSGVQCSTRPW