mazF9 Resolved · high auto-curated

H37Rv Rv2801c · MTBC0 mtbc0_002980 · 118 aa · 3132582–3132938 (-) · RefSeq NP_217317.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)mRNA interferase MazF9
MTBC0 PGAP re-annotationtype II toxin-antitoxin system toxin endoribonuclease MazF9
Revised (this work)Type II toxin-antitoxin system toxin endoribonuclease MazF9. Pfam: PemK_toxin (PF02452.24).

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

Curated reference (UniProt)

UniProt P71650 SwissProt · reviewed · Evidence at protein level
UniProt nameEndoribonuclease MazF9
EC (curated) EC 3.1.-.-
Curated functionToxic component of a type II toxin-antitoxin (TA) system. Upon expression in E.coli and M.smegmatis inhibits cell growth and colony formation. Its toxic effect is neutralized by coexpression with cognate antitoxin MazE9. Acts as an mRNA interferase, specifically cleaving between U and C in UAC sequences. May cleave its cognate antitoxin's gene. In E.coli expression with non-cognate antitoxins VapB27 and VapB40 partially neutralizes the toxin.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
eggNOG descriptiontoxic component of a
Orthologous groupCOG2337
KEGG orthology K07171
Gene Ontology (52) GO:0003674, GO:0003824, GO:0004518, GO:0004519, GO:0004521, GO:0004540, GO:0006139, GO:0006401, GO:0006402, GO:0006725, GO:0006807, GO:0008150 +40 more

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) pseudogene candidate

pN/pS 0.272 · purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 2 missense, 2 nonsense, 0 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 2.58% of strains (3748) · 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
PemK_toxinPF02452.24 1.4e-283–113 PemK-like, MazF-like toxin of type II toxin-antitoxin system

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

Closest characterised functional partner: mazE9 (antitoxin MazE9), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2801A mazE9 antitoxin MazE9 999 1000 ctx neighborhood:882 cooccurence:767 experimental:999 textmining:655
Rv2063 mazE7 antitoxin MazE7 828 808 experimental:793
Rv2802c arginine/hypothetical protein 694 693 ctx neighborhood:676
Rv1991A mazE6 antitoxin MazE6 860 616 experimental:434 textmining:652
Rv2803 hyp hypothetical protein 491 491 ctx neighborhood:491
Rv1942c mazF5 toxin MazF5 881 449 ctx cooccurence:449 textmining:793
Rv3095 HTH-type transcriptional regulator 416 417 coexpression:417
Rv1725c hyp hypothetical protein 415 415 coexpression:415
Rv1103c mazE3 antitoxin MazE3 664 333 textmining:518
Rv1102c mazF3 mRNA interferase MazF3 855 297 textmining:803
Rv1991c mazF6 mRNA interferase MazF6 445 275
Rv2549c vapC20 ribonuclease VapC20 459 271
Rv0659c mazF2 toxin MazF2 616 250 textmining:510
Rv2829c vapC22 ribonuclease VapC22 508 245
Rv1495 mazF4 mRNA interferase MazF4 887 170 textmining:870

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: mRNA interferase MazF9
  • MTBC0 PGAP product: type II toxin-antitoxin system toxin endoribonuclease MazF9
  • Pfam (hmmscan --cut_ga): PemK_toxin PF02452.24 (E=1e-28)
  • (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_217317.1)
  • Domains: Pfam-A via hmmscan --cut_ga — PemK_toxin (PF02452.24)
  • 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 COG2337
  • Curated reference: UniProt P71650 (SwissProt, reviewed; 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 — 24 functional partner(s); context anchor mazE9
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002980|Rv2801c|mazF9
MMRRGEIWQVDLDPARGSEANNQRPAVVVSNDRANATATRLGRGVITVVPVTSNIAKVYPFQVLLSATTTGLQVDCKAQAEQIRSIATERLLRPIGRVSAAELAQLDEALKLHLDLWS