Rv3850 Family assigned · low auto-curated

H37Rv Rv3850 · MTBC0 mtbc0_004083 · 218 aa · 4348125–4348781 (+) · RefSeq NP_218367.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationDUF6474 family protein
Revised (this work)DUF6474 family protein.

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

Curated reference (UniProt)

UniProt P96227 TrEMBL · unreviewed · Evidence at protein level
UniProt nameConserved protein

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

Functional vocabulary (eggNOG-mapper, orthology transfer)

Orthologous group2E45H

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 0.631 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 5 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
DUF6474PF20079.5 8.5e-791–217 Family of unknown function (DUF6474)

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

Closest characterised functional partner: Rv3851 (membrane protein), high confidence from genomic context alone (score 960 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3851 membrane protein 960 960 ctx neighborhood:847 coexpression:751
Rv3849 espR ESX-1 transcriptional regulator EspR 854 813 ctx neighborhood:712
Rv3438 hyp hypothetical protein 777 777 ctx cooccurence:774
Rv1109c hyp hypothetical protein 775 775 ctx cooccurence:772
Rv2732c transmembrane protein 775 775 ctx cooccurence:772
Rv0556 transmembrane protein 774 775 ctx cooccurence:774
Rv3205c hyp hypothetical protein 773 773 ctx cooccurence:772
Rv2446c integral membrane protein 772 772 ctx cooccurence:771
Rv0358 hyp hypothetical protein 772 772 ctx cooccurence:771
Rv0475 hbhA heparin binding hemagglutinin HbhA 770 770 ctx cooccurence:768
Rv1166 lpqW monoacyl phosphatidylinositol tetramannoside-binding protein LpqW 769 769 ctx cooccurence:767
Rv0383c ttfA hyp hypothetical protein 767 767 ctx cooccurence:767
Rv3212 hyp hypothetical protein 765 765 ctx cooccurence:764
Rv3852 hns histone-like protein Hns 764 764 ctx neighborhood:763
Rv0996 transmembrane protein 763 764 ctx cooccurence:763

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: DUF6474 family protein
  • Pfam (hmmscan --cut_ga): DUF6474 PF20079.5 (E=9e-79)
  • (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_218367.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF6474 (PF20079.5)
  • 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 2E45H
  • Curated reference: UniProt P96227 (TrEMBL, unreviewed; 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 — 138 functional partner(s); context anchor Rv3851
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_004083|Rv3850|
MGLFGKRKSRATRRAEARAIKARAKLEAKLSAKNEARRIKAAQRAESKALKAQLKARRDSDRAALKVAEAELKVAREGKLLSPTRIRRLLTVSRLLAPILTPVIYRAAMAARGLIDQRRADQLGVPLAQIGRFSGHGARLSARVGGAERSLRMVQEKKPKDVETKQFVSAVTNRLTDLSAAVAAAEHMPAKRRRTAHSAISSQLDGIEADLMARLGLT