Rv3064c Family assigned · medium auto-curated

H37Rv Rv3064c · MTBC0 mtbc0_003256 · 141 aa · 3451189–3451614 (-) · RefSeq NP_217580.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)integral membrane protein
MTBC0 PGAP re-annotationDoxX family protein
Revised (this work)DoxX family protein. Pfam: DoxX (PF07681.18).

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

Curated reference (UniProt)

UniProt I6XG31 TrEMBL · unreviewed · Inferred from homology
UniProt nameProbable conserved integral membrane protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionmembrane
Orthologous groupCOG2259
KEGG orthology K15977

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 0.118 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 1 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.45% of strains (656) · 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
DoxXPF07681.18 3.5e-1317–94 DoxX

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

Closest characterised functional partner: mmr (multidrug resistance protein Mmr), medium confidence from genomic context alone (score 594 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3065 mmr multidrug resistance protein Mmr 593 594 ctx neighborhood:577
Rv3868 eccA1 ESX-1 secretion system protein EccA1 578 579 database:576
Rv0282 eccA3 ESX-3 secretion system protein EccA 577 578 database:576
Rv0435c ATPase 576 576 database:576
Rv3066 DeoR family transcriptional regulator 551 551 ctx neighborhood:550
Rv0908 ctpE metal cation transporter ATPase E 481 481
Rv0425c ctpH metal cation transporting ATPase H 481 481
Rv1997 ctpF cation transporter ATPase F 479 480
Rv0107c ctpI cation-transporter ATPase I 479 480
Rv3413c rsdA anti-sigma-D factor RsdA 470 470 ctx cooccurence:470
Rv1305 atpE ATP synthase subunit C 433 433 database:417
Rv0732 secY preprotein translocase SecY 402 365
Rv2182c 1-acylglycerol-3-phosphate O-acyltransferase 575 282 textmining:434
Rv3484 cpsA hyp hypothetical protein 576 159 textmining:517
Rv3483c hyp hypothetical protein 687 142 textmining:651

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: integral membrane protein
  • MTBC0 PGAP product: DoxX family protein
  • Pfam (hmmscan --cut_ga): DoxX PF07681.18 (E=4e-13)
  • (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_217580.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DoxX (PF07681.18)
  • 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 COG2259
  • Curated reference: UniProt I6XG31 (TrEMBL, unreviewed; Inferred from homology)
  • 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 — 30 functional partner(s); context anchor mmr
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003256|Rv3064c|
MVKDLDRRLAGCLPAVLSLFRLVYGLLFAGYGSMILFGWPVTSAQPVEFGSWPGWYAGVIELVAGLLIATGLFTRAVAFVASGEMAVAYFWMHQPYALWPIGGPPDGNGGTPAILFCFGFFLLVFTGGGIYSIDARRTVTA