Rv2019 Family assigned · medium auto-curated

H37Rv Rv2019 · MTBC0 mtbc0_002149 · 138 aa · 2289602–2290018 (+) · RefSeq NP_216535.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationhypothetical protein
Revised (this work)Contains PIN_10 (PF18478.8) 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 O53465 SwissProt · reviewed · Evidence at protein level
UniProt namePutative ribonuclease VapC45
EC (curated) EC 3.1.-.-
Curated functionToxic component of a type II toxin-antitoxin (TA) system. An RNase. The cognate antitoxin is VapB45.

UniProt still lists this protein as Putative ribonuclease VapC45; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

Orthologous group2CNI4

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 0.252 · purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 3 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.26% of strains (372) · 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
PIN_10PF18478.8 9.2e-1413–94 PIN like domain

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

Closest characterised functional partner: Rv2017 (transcriptional regulator), medium confidence from genomic context alone (score 434 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2018 vapB45 hyp hypothetical protein 890 803 ctx neighborhood:802 textmining:464
Rv2017 transcriptional regulator 434 434 ctx neighborhood:432
Rv2016 hyp hypothetical protein 577 430 ctx neighborhood:427
Rv1246c relE toxin RelE 425 76 textmining:404
Rv3749c vapC50 hyp hypothetical protein 816 47 textmining:816
Rv3182 higB3 hyp hypothetical protein 656 47 textmining:654
Rv3358 relK toxin RelK 643 47 textmining:641
Rv0065 vapC1 ribonuclease VapC1 566 47 textmining:564
Rv3697c vapC48 ribonuclease VapC48 520 47 textmining:517
Rv1838c vapC13 ribonuclease VapC13 513 47 textmining:510
Rv2022c higB2 hyp hypothetical protein 631 46 textmining:630
Rv3357 relJ antitoxin RelJ 536 46 textmining:534
Rv0549c vapC3 ribonuclease VapC3 459 46 textmining:456
Rv0624 vapC30 ribonuclease VapC30 655 45 textmining:654
Rv2021c higA2 transcriptional regulator 544 45 textmining:543

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: hypothetical protein
  • Pfam (hmmscan --cut_ga): PIN_10 PF18478.8 (E=9e-14)
  • (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_216535.1)
  • Domains: Pfam-A via hmmscan --cut_ga — PIN_10 (PF18478.8)
  • 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 2CNI4
  • Curated reference: UniProt O53465 (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 — 29 functional partner(s); context anchor Rv2017
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002149|Rv2019|
MQPDRNLLADLDHIFVDRSLGAVQVPQLLRDAGFRLTTMREHYGETQAQSVSDHKWIAMTAECGWIGFHKDANIRRNAVERRTVLDTGARLFCVPRADILAEQVAARYIASLAAIARAARFPGPFIYTVHPSKIVRVL