Rv3694c Resolved · high auto-curated

H37Rv Rv3694c · MTBC0 mtbc0_003915 · 330 aa · 4160070–4161062 (-) · RefSeq NP_218211.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transmembrane protein
MTBC0 PGAP re-annotationstage II sporulation protein M
Revised (this work)Stage II sporulation protein M. Pfam: DUF8413 (PF28475.1), SpoIIM (PF01944.23).

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

Curated reference (UniProt)

UniProt O69662 TrEMBL · unreviewed · Evidence at protein level
UniProt namePossible conserved transmembrane protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionmembrane
Orthologous groupCOG1300

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 0.182 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 6 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
DUF8413PF28475.1 6.2e-224–75 Domain of unknown function (DUF8413)
SpoIIMPF01944.23 7.6e-44107–281 Stage II sporulation protein M

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

Closest characterised functional partner: Rv3695 (membrane protein), high confidence from genomic context alone (score 966 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3695 membrane protein 965 966 ctx neighborhood:782 cooccurence:774
Rv3693 membrane protein 838 807 ctx cooccurence:774
Rv3691 hyp hypothetical protein 791 792 ctx cooccurence:774
Rv3690 membrane protein 789 790 ctx cooccurence:773
Rv3689 transmembrane protein 752 752 ctx cooccurence:741
Rv3692 moxR2 methanol dehydrogenase transcriptional regulator MoxR 476 476 ctx cooccurence:431
Rv1078 pra hyp hypothetical protein 472 472
Rv0176 Mce associated transmembrane protein 458 458

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: stage II sporulation protein M
  • Pfam (hmmscan --cut_ga): DUF8413 PF28475.1 (E=6e-22), SpoIIM PF01944.23 (E=8e-44)
  • (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_218211.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF8413 (PF28475.1), SpoIIM (PF01944.23)
  • 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 COG1300
  • Curated reference: UniProt O69662 (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 — 8 functional partner(s); context anchor Rv3695
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003915|Rv3694c|
MDVDAFLLTNRGTWDRLDHLIKKRHSLSGAEIDELVELYQRVSTHLSMLRSASSDQLMTGRLSSLVARARSAVTGAHAPLTRTFIRFWTVSFPVVAYRTWRWWLATAVAFFAVVVLIGFWVAGSHEVQSAIGTPTEIDELVSHDVQSYYSEHPAASFALQVWVNNSWVATTCIAMSVVLGLPIPLVLFDNAANVGLIAGLMFQAGKGDFLLGLLLPHGLLELTAVFLAAAIGMRLGWSVISAGNRPRGQVLAEQGRGVVSVAVGLVGVFLVAGLIEAVVTPSPLPTFVRIAVGIIAEAVFLSYIGYFGRRAAQAGETGDMEDAPDVVPTG