Rv3851 Still unknown · low auto-curated

H37Rv Rv3851 · MTBC0 mtbc0_004084 · 94 aa · 4348793–4349077 (+) · RefSeq NP_218368.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)membrane protein
MTBC0 PGAP re-annotationhypothetical protein
Revised (this work)Conserved hypothetical protein; no recognised domain. 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 P96226 TrEMBL · unreviewed · Predicted
UniProt namePossible membrane protein

Conservation & selection (intra-MTBC, 145 209 strains)

pN/pS 0.0 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 0 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.12% of strains (172) · 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)

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

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

Closest characterised functional partner: hns (histone-like protein Hns), medium confidence from genomic context alone (score 562 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3850 hyp hypothetical protein 960 960 ctx neighborhood:847 coexpression:751
Rv3852 hns histone-like protein Hns 562 562 ctx neighborhood:558
Rv3849 espR ESX-1 transcriptional regulator EspR 531 531 ctx neighborhood:526
Rv3853 rraA RNase E regulator RraA 528 528 ctx neighborhood:523

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
  • (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_218368.1)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
  • Curated reference: UniProt P96226 (TrEMBL, unreviewed; 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 — 4 functional partner(s); context anchor hns
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_004084|Rv3851|
MTAIGMSHPPRVHRRVGGQRTALTAGIGLLLAALVLTTIANPPAAFAHTAQLSTATPAPAVAATDANDVPTWPFVVGTVAAVAVAALWAVRRGR