Rv3848 Family assigned · medium auto-curated

H37Rv Rv3848 · MTBC0 mtbc0_004081 · 302 aa · 4346436–4347344 (+) · RefSeq NP_218365.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transmembrane protein
MTBC0 PGAP re-annotationTMEM165/GDT1 family protein
Revised (this work)TMEM165/GDT1 family protein. Pfam: GDT1 (PF01169.25).

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

Curated reference (UniProt)

UniProt P96229 TrEMBL · unreviewed · Evidence at protein level
UniProt nameGDT1 family protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionmembrane
Orthologous groupCOG2119

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 0.534 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 4 missense, 0 nonsense, 2 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 0.85% of strains (1232) · clonal

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
GDT1PF01169.25 3.1e-21107–180 Divalent cation/proton antiporter GDT1

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

Closest characterised functional partner: espR (ESX-1 transcriptional regulator EspR), medium confidence from genomic context alone (score 499 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3847 hyp hypothetical protein 536 536 ctx neighborhood:533
Rv3849 espR ESX-1 transcriptional regulator EspR 499 499 ctx neighborhood:496
Rv1909c furA ferric uptake regulation protein FurA 499 79 textmining:479
Rv2137c hyp hypothetical protein 490 44 textmining:489

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: TMEM165/GDT1 family protein
  • Pfam (hmmscan --cut_ga): GDT1 PF01169.25 (E=3e-21)
  • (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_218365.1)
  • Domains: Pfam-A via hmmscan --cut_ga — GDT1 (PF01169.25)
  • 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 COG2119
  • Curated reference: UniProt P96229 (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 — 4 functional partner(s); context anchor espR
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_004081|Rv3848|
MLAATLLSLGAVFLAELGDRSQLITMTYTLRYRWWVVLTGVAIAAFTVHGVAVAIGHFLGSTVPARPAACVSAIAFLIFAVWVWREDTASDSETSPTAAEPRLALFTVVSSFALAELGDKTTLATVTLASDHHWAGVWIGTTLGMILADGLAIGAGLLLHRRLPERLLQVLTGLLFLLFGLWLLFDDALGFRSVAIAVTAAVVLAAATTAVSVRVAQTRRRRPTAAATPEDDSTRPERSSVAPGHPGSILLPLPEVSLRGRRPPSGSPDERCADPGSKGGSRRISVGCWLPGVGRIRPTRSS