Rv3165c Still unknown · low auto-curated

H37Rv Rv3165c · MTBC0 mtbc0_003364 · 160 aa · 3558761–3559243 (-) · RefSeq NP_217681.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical 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 O53315 TrEMBL · unreviewed · Predicted
UniProt nameUncharacterized protein

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

Functional vocabulary (eggNOG-mapper, orthology transfer)

Orthologous group2A3DE

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, 1 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)

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

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

Closest characterised functional partner: moxR3 (methanol dehydrogenase transcriptional regulator MoxR), high confidence from genomic context alone (score 882 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3166c hyp hypothetical protein 908 908 ctx neighborhood:882
Rv3164c moxR3 methanol dehydrogenase transcriptional regulator MoxR 882 882 ctx neighborhood:881
Rv3162c integral membrane protein 843 843 ctx neighborhood:841
Rv3163c hyp hypothetical protein 841 841 ctx neighborhood:841
Rv3167c TetR family transcriptional regulator 609 609 ctx neighborhood:608
Rv3161c dioxygenase 513 513 ctx neighborhood:513
Rv3160c TetR family transcriptional regulator 512 512 ctx neighborhood:510
Rv3168 aminoglycoside phosphotransferase 439 440 ctx neighborhood:436
Rv3169 hyp hypothetical protein 424 424 ctx neighborhood:418
Rv1174c TB8.4 low molecular weight T-cell antigen 630 41 textmining:630
Rv0475 hbhA heparin binding hemagglutinin HbhA 525 41 textmining:525
Rv0288 esxH ESAT-6-like protein EsxH 440 41 textmining:440

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
  • (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_217681.1)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • 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 2A3DE
  • Curated reference: UniProt O53315 (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)
  • Model confidence: ESMFold per-residue pLDDT (mean 91.2, very high)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 12 functional partner(s); context anchor moxR3
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003364|Rv3165c|
MKRLIALGIFLIVGIELLALILHDRRLVLAGSGLALALVLLNVRRMLGNRDELTAAPDSDDLGEGLRRWLSNTETTIRWSESTRADWDRHLRPMLARRFEIATGHRQAKDPVAFAATGRMLFGDELWEWVNPNNVTHTGDRQPGPGRAALEEILQKLEQV