Rv0366c Family assigned · medium auto-curated

H37Rv Rv0366c · MTBC0 mtbc0_000386 · 197 aa · 447584–448177 (-) · RefSeq NP_214880.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationzeta toxin family protein
Revised (this work)Zeta toxin family protein. Pfam: Zeta_toxin (PF06414.19), AAA_33 (PF13671.13).

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

Curated reference (UniProt)

UniProt O53701 TrEMBL · unreviewed · Inferred from homology
UniProt nameUDP-N-acetylglucosamine kinase
EC (curated) EC 2.7.1.176

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionZeta toxin
Orthologous groupCOG4185

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 0.721 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 2 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
Zeta_toxinPF06414.19 1.5e-144–156 Zeta toxin
AAA_33PF13671.13 4.6e-146–138 AAA domain

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

Closest characterised functional partner: Rv0369c (membrane oxidoreductase), medium confidence from genomic context alone (score 537 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0367c hyp hypothetical protein 984 847 ctx neighborhood:843 textmining:902
Rv0365c hyp hypothetical protein 968 766 ctx neighborhood:757 textmining:870
Rv0368c hyp hypothetical protein 937 537 ctx neighborhood:534 textmining:870
Rv0369c membrane oxidoreductase 537 537 ctx neighborhood:534
Rv2017 transcriptional regulator 693 451 experimental:434 textmining:465
Rv0465c ramB HTH-type transcriptional regulator 476 448 experimental:434
Rv0023 transcriptional regulator 476 448 experimental:434
Rv2745c clgR transcriptional regulator ClgR 475 447 experimental:434
Rv0474 HTH-type transcriptional regulator 475 447 experimental:434
Rv3183 higA3 transcriptional regulator 475 447 experimental:434
Rv3849 espR ESX-1 transcriptional regulator EspR 473 445 experimental:434
Rv2021c higA2 transcriptional regulator 473 445 experimental:434
Rv1129c prpR transcriptional regulator 473 445 experimental:434
Rv1113 vapB32 antitoxin VapB32 423 423 ctx cooccurence:423
Rv1114 vapC32 ribonuclease VapC32 403 403

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: hypothetical protein
  • MTBC0 PGAP product: zeta toxin family protein
  • Pfam (hmmscan --cut_ga): Zeta_toxin PF06414.19 (E=1e-14), AAA_33 PF13671.13 (E=5e-14)
  • (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_214880.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Zeta_toxin (PF06414.19), AAA_33 (PF13671.13)
  • 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 COG4185
  • Curated reference: UniProt O53701 (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 — 31 functional partner(s); context anchor Rv0369c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000386|Rv0366c|
MKRLDLVAGPNGAGKSTFVALTLAPLLPGIVFVNADEIAKQRWPDDPTSHAYQAAQVAADTRARLIDLGRPFIAETVFSHPSKLELIRTARTAGYTVVLHVLVIPEGLAVERVRHRVAAGGHDVPETKIRERHRRLAELVAQAITLADGATVYDNSRLAGPRIVAQFSGGGIIGRACWPSWTPPPLMSRWSNRPETA