Rv3760 Family assigned · medium auto-curated

H37Rv Rv3760 · MTBC0 - · 100 aa · 4205538–4205840 (+) · RefSeq NP_218277.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)membrane protein
MTBC0 PGAP re-annotation
Revised (this work)Membrane protein. Pfam: LapA_dom (PF06305.17).

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 O69726 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized membrane protein Rv3760

UniProt still lists this protein as Uncharacterized membrane protein Rv3760; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionmembrane
Orthologous groupCOG5416

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 0.0 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 0 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
LapA_domPF06305.17 2.2e-1043–94 Lipopolysaccharide assembly protein A domain

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

Closest characterised functional partner: proV (glycine betaine/carnitine/choline/L-proline ABC transporter ATP-binding protein ProV), high confidence from genomic context alone (score 775 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3758c proV glycine betaine/carnitine/choline/L-proline ABC transporter ATP-binding protein ProV 775 775 ctx neighborhood:768
Rv3759c proX glycine betaine/carnitine/choline/L-proline ABC transporter substrate-binding lipoprotein ProX 771 771 ctx neighborhood:768
Rv3756c proZ glycine betaine/carnitine/choline/L-proline ABC transporter permease ProZ 769 769 ctx neighborhood:768
Rv3757c proW glycine betaine/carnitine/choline/L-proline ABC transporter permease ProW 769 769 ctx neighborhood:768
Rv3755c hyp hypothetical protein 769 769 ctx neighborhood:768
Rv2216 epimerase family protein 421 422 coexpression:422
Rv1225c hyp hypothetical protein 418 419 coexpression:419
Rv1692 phosphatase 418 418 coexpression:418
Rv2869c rip zinc metalloprotease 413 414
Rv1624c membrane protein 407 408 coexpression:405
Rv3479 transmembrane protein 407 407
Rv0018c pstP phosphoserine/threonine phosphatase PstP 403 403 coexpression:403
Rv3461c rpmJ 50S ribosomal protein L36 402 402 coexpression:401
Rv3808c glfT2 galactofuranosyl transferase GlfT 400 400

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): membrane protein
  • Pfam (hmmscan --cut_ga): LapA_dom PF06305.17 (E=2e-10)
  • (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_218277.1)
  • Domains: Pfam-A via hmmscan --cut_ga — LapA_dom (PF06305.17)
  • 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 COG5416
  • Curated reference: UniProt O69726 (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 — 14 functional partner(s); context anchor proV
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3760|
MPGSVPGKAPEEPPVKFTRAAAVWSALIVGFLILILLLIFIAQNTASAQFAFFGWRWSLPLGVAILLAAVGGGLITVFAGTARILQLRRAAKKTHAAALR