Rv3695 Family assigned · medium auto-curated

H37Rv Rv3695 · MTBC0 mtbc0_003916 · 310 aa · 4161154–4162086 (+) · RefSeq NP_218212.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)membrane protein
MTBC0 PGAP re-annotationRDD family protein
Revised (this work)RDD family protein. Pfam: RDD (PF06271.19).

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

Curated reference (UniProt)

UniProt O69663 TrEMBL · unreviewed · Evidence at protein level
UniProt namePossible conserved membrane protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionmembrane protein domain
Orthologous groupCOG1714

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 1.122 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 6 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
RDDPF06271.19 2.3e-1218–143 RDD family

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

Closest characterised functional partner: Rv3694c (transmembrane protein), high confidence from genomic context alone (score 966 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3694c transmembrane protein 965 966 ctx neighborhood:782 cooccurence:774
Rv3693 membrane protein 796 797 ctx cooccurence:774
Rv3691 hyp hypothetical protein 786 787 ctx cooccurence:774
Rv3690 membrane protein 785 785 ctx cooccurence:773
Rv3689 transmembrane protein 771 772 ctx cooccurence:758
Rv1274 lprB lipoprotein LprB 478 478 coexpression:469
Rv3692 moxR2 methanol dehydrogenase transcriptional regulator MoxR 412 412

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: membrane protein
  • MTBC0 PGAP product: RDD family protein
  • Pfam (hmmscan --cut_ga): RDD PF06271.19 (E=2e-12)
  • (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_218212.1)
  • Domains: Pfam-A via hmmscan --cut_ga — RDD (PF06271.19)
  • 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 COG1714
  • Curated reference: UniProt O69663 (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 — 7 functional partner(s); context anchor Rv3694c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003916|Rv3695|
MSEVVTGDAVVLDVQIAQLPVRAVSAVIDITIIFIGYILGLMLWATALTQFDEALTTAFLIIFTVLALVGYPLVWETATRGRSVGKIVMGLRVVSDDGGPERFRQALFRALASVVEIWMLLGSPAVICSMLSPKAKRVGDVFAGTVVVSERGPRLGPPPVMPPSLAWWASSLQLSGLTAGQAEVARQFLVRAPQLDPALREQMAYRIAGDVVARIAPPPPPGVPPQLVLAAVLAERHRRELLRLRPTLPPAGQAPWAQMAPHRGWPPGLSGATPWSPQQPVIPWPEPDPPPQAAPWPQQAPDGPGFSPPG