Rv2169c Still unknown · low auto-curated

H37Rv Rv2169c · MTBC0 mtbc0_002303 · 134 aa · 2457572–2457976 (-) · RefSeq NP_216685.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transmembrane protein
MTBC0 PGAP re-annotationDUF3040 domain-containing protein
Revised (this work)Conserved hypothetical protein; DUF domain(s) DUF3040. 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 O53503 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable conserved transmembrane protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionProtein of unknown function (DUF3040)
Orthologous group2E49S

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, 3 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
DUF3040PF11239.14 1.3e-281–86 Protein of unknown function (DUF3040)

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

Closest characterised functional partner: Rv2170 (GCN5-like N-acetyltransferase), high confidence from genomic context alone (score 776 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2170 GCN5-like N-acetyltransferase 776 776 ctx neighborhood:733
Rv2199c ctaF cytochrome c oxidase polypeptide 4 678 678 ctx cooccurence:676
Rv2680 hyp hypothetical protein 670 670 ctx cooccurence:670
Rv2194 qcrC ubiquinol-cytochrome C reductase cytochrome subunit C 643 643 ctx cooccurence:641
Rv2146c transmembrane protein 627 627 ctx cooccurence:612
Rv2256c hyp hypothetical protein 613 613 ctx cooccurence:609
Rv2166c mraZ transcriptional regulator MraZ 598 598 ctx neighborhood:593
Rv2229c hyp hypothetical protein 564 564 ctx cooccurence:564
Rv2219A membrane protein 534 535 ctx cooccurence:532
Rv2708c hyp hypothetical protein 533 534 ctx cooccurence:527
Rv2195 qcrA ubiquinol-cytochrome C reductase rieske iron-sulfur subunit 524 524 ctx cooccurence:521
Rv3208A TB9.4 hyp hypothetical protein 514 515 ctx cooccurence:513
Rv2171 lppM lipoprotein LppM 512 513 ctx neighborhood:511
Rv2219 transmembrane protein 511 512 ctx cooccurence:505
Rv0883c sepH hyp hypothetical protein 506 506 ctx cooccurence:503

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: transmembrane protein
  • MTBC0 PGAP product: DUF3040 domain-containing protein
  • Pfam (hmmscan --cut_ga): DUF3040 PF11239.14 (E=1e-28)
  • (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_216685.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF3040 (PF11239.14)
  • 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 2E49S
  • Curated reference: UniProt O53503 (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 — 57 functional partner(s); context anchor Rv2170
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002303|Rv2169c|
MPLSDHEQRMLDQIESALYAEDPKFASSVRGGGFRAPTARRRLQGAALFIIGLGMLVSGVAFKETMIGSFPILSVFGFVVMFGGVVYAITGPRLSGRMDRGGSAAGASRQRRTKGAGGSFTSRMEDRFRRRFDE