Rv3753c Family assigned · medium auto-curated

H37Rv Rv3753c · MTBC0 - · 166 aa · 4199721–4200221 (-) · RefSeq NP_218270.3

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)Contains Rv3753c (PF27101.1) 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.

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt O69720 SwissProt · reviewed · Evidence at protein level
UniProt nameProtein Rv3753c

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptiontRNA adenosine
Orthologous group2BM8T

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 1.055 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 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
Rv3753cPF27101.1 4.1e-5711–154 Rv3753c-like tRNA adenosine deaminase-associated protein

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

Closest characterised functional partner: tadA (cytidine/deoxycytidylate deaminase), high confidence from genomic context alone (score 873 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3752c tadA cytidine/deoxycytidylate deaminase 873 873 ctx neighborhood:867
Rv3013 hyp hypothetical protein 763 763 ctx cooccurence:763
Rv3754 tyrA prephenate dehydrogenase TyrA 759 759 ctx neighborhood:758
Rv3311 hyp hypothetical protein 743 744 ctx cooccurence:742
Rv3438 hyp hypothetical protein 717 718 ctx cooccurence:715
Rv2446c integral membrane protein 713 713 ctx cooccurence:713
Rv3212 hyp hypothetical protein 696 697 ctx cooccurence:695
Rv2219 transmembrane protein 691 692 ctx cooccurence:690
Rv2980 hyp hypothetical protein 689 689 ctx cooccurence:689
Rv1332 transcriptional regulator 686 687 ctx cooccurence:685
Rv0358 hyp hypothetical protein 678 678 ctx cooccurence:677
Rv0863 hyp hypothetical protein 676 676 ctx cooccurence:675
Rv0990c hyp hypothetical protein 665 665 ctx cooccurence:665
Rv2170 GCN5-like N-acetyltransferase 658 658 ctx cooccurence:657
Rv1166 lpqW monoacyl phosphatidylinositol tetramannoside-binding protein LpqW 638 638 ctx cooccurence:636

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): hypothetical protein
  • Pfam (hmmscan --cut_ga): Rv3753c PF27101.1 (E=4e-57)
  • (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_218270.3)
  • Domains: Pfam-A via hmmscan --cut_ga — Rv3753c (PF27101.1)
  • 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 2BM8T
  • Curated reference: UniProt O69720 (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 — 58 functional partner(s); context anchor tadA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3753c|
MQRPAADTPDGFGVAVVREEGRWRCSPMGPKALTSLRAAETELRELRSAGAVFGLLDVDDEFFVIVRPAPSGTRLLLSDATAALDYDIAAEVLDNLDAEIDPEDLEDADPFEEGDLGLLSDIGLPEAVLGVILDETDLYADEQLGRIAREMGFADQLSAVIDRLGR