Rv3278c Family assigned · medium auto-curated

H37Rv Rv3278c · MTBC0 mtbc0_003486 · 172 aa · 3682794–3683312 (-) · RefSeq NP_217795.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transmembrane protein
MTBC0 PGAP re-annotationPH domain-containing protein
Revised (this work)PH domain-containing protein. Pfam: bPH_2 (PF03703.21).

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

Curated reference (UniProt)

UniProt P96883 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable conserved transmembrane protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionBacterial PH domain
Orthologous groupCOG3428

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 0.082 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 4 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)

PfamAccessioni-EvalueResiduesDescription
bPH_2PF03703.21 7.2e-2082–155 Bacterial PH domain

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

Closest characterised functional partner: birA (bifunctional biotin operon repressor/biotin--[acetyl-CoA-carboxylase), high confidence from genomic context alone (score 823 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3279c birA bifunctional biotin operon repressor/biotin--[acetyl-CoA-carboxylase 822 823 ctx neighborhood:822
Rv3281 accE5 bifunctional protein acetyl-/propionyl-CoAcarboxylase subunit epsilon AccE 752 752 ctx neighborhood:748
Rv3280 accD5 propionyl-CoA carboxylase subunit beta 750 749 ctx neighborhood:748
Rv3282 hyp hypothetical protein 749 749 ctx neighborhood:748
Rv1227c transmembrane protein 633 585 coexpression:561
Rv1234 transmembrane protein 585 584 coexpression:498
Rv2744c 35kd_ag hyp hypothetical protein 523 524 ctx cooccurence:455
Rv3283 sseA thiosulfate sulfurtransferase SseA 490 489 ctx neighborhood:489
Rv2468c hyp hypothetical protein 477 478
Rv3284 hyp hypothetical protein 475 475 ctx neighborhood:474
Rv1638A hyp hypothetical protein 474 475
Rv0049 hyp hypothetical protein 472 472 ctx cooccurence:469
Rv1481 membrane protein 449 450 ctx cooccurence:432
Rv2062c cobN cobalamin biosynthesis protein CobN 446 447 coexpression:415
Rv3221A rshA anti-sigma factor RshA 445 446

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: PH domain-containing protein
  • Pfam (hmmscan --cut_ga): bPH_2 PF03703.21 (E=7e-20)
  • (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_217795.1)
  • Domains: Pfam-A via hmmscan --cut_ga — bPH_2 (PF03703.21)
  • 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 COG3428
  • Curated reference: UniProt P96883 (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 — 18 functional partner(s); context anchor birA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003486|Rv3278c|
MSYPENVLAAGEQVVLHRHPHWNRLIWPVVVLVLLTGLAAFGSGFVNSTPWQQIAKNVIHAVIWGIWLVIVGWLTLWPFLSWLTTHFVVTNRRVMFRHGVLTRSGIDIPLARINSVEFRDRIFERIFRTGTLIIESASQDPLEFYNIPRLREVHALLYHEVFDTLGSDESPS