Rv2638 Resolved · high auto-curated

H37Rv Rv2638 · MTBC0 mtbc0_002808 · 148 aa · 2987966–2988412 (+) · RefSeq NP_217154.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationanti-sigma factor antagonist
Revised (this work)Anti-sigma factor antagonist. Pfam: STAS_2 (PF13466.13), STAS (PF01740.27).

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

Curated reference (UniProt)

UniProt I6X4W0 SwissProt · reviewed · Evidence at protein level
UniProt namePutative anti-anti-sigma factor Rv2638

UniProt still lists this protein as Putative anti-anti-sigma factor Rv2638; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category T Signal transduction mechanisms
eggNOG descriptionbut contains identity with a pfam01740 STAS domain. the STAS (after sulphate transporter and antisigma factor antagonist) domain is found in the C terminal region of sulphate transporters and bacterial antisigma factor antagonists. it has been Sug
Orthologous groupCOG1366

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 n/a
Polymorphic sites (≥ 0.1% of strains) 0 synonymous, 4 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
STAS_2PF13466.13 8.3e-0834–128 Mlab, STAS domain
STASPF01740.27 1.8e-2035–137 STAS domain

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

Closest characterised functional partner: rsbW (anti-sigma factor RsbW), high confidence from genomic context alone (score 846 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv1364c sigma factor regulatory protein 995 994 coexpression:929 experimental:859
Rv3287c rsbW anti-sigma factor RsbW 893 846 ctx cooccurence:452 coexpression:510 experimental:454
Rv3899c hyp hypothetical protein 699 700 ctx cooccurence:640
Rv1354c hyp hypothetical protein 710 692 coexpression:649
Rv2423 hyp hypothetical protein 666 667 ctx cooccurence:665
Rv1173 fbiC FO synthase 658 659 coexpression:648
Rv3434c transmembrane protein 652 653 ctx cooccurence:650
Rv2079 hyp hypothetical protein 651 651 ctx cooccurence:646
Rv0655 mkl ABC transporter ATP-binding protein 644 644 experimental:629
Rv1868 hyp hypothetical protein 639 639 ctx cooccurence:636
Rv2637 dedA transmembrane protein DedA 603 603 ctx neighborhood:528
Rv2778c hyp hypothetical protein 601 602 ctx cooccurence:599
Rv0169 mce1A Mce family protein Mce1A 588 571
Rv0172 mce1D Mce family protein Mce1D 571 571
Rv0048c membrane protein 565 565 ctx cooccurence:561

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: anti-sigma factor antagonist
  • Pfam (hmmscan --cut_ga): STAS_2 PF13466.13 (E=8e-08), STAS PF01740.27 (E=2e-20)
  • (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_217154.1)
  • Domains: Pfam-A via hmmscan --cut_ga — STAS_2 (PF13466.13), STAS (PF01740.27)
  • 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 COG1366
  • Curated reference: UniProt I6X4W0 (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 — 80 functional partner(s); context anchor rsbW
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002808|Rv2638|
MGLITTEPRSSPHPLSPRLVHELGDPHSTLRATTDGSGAALLIHAGGEIDGRNEHLWRQLVTEAAAGVTAPGPLIVDVTGLDFMGCCAFAALADEAQRCRCRGIDLRLVSHQPIVARIAEAGGLSRVLPIYPTVDTALGKGTAGPARC