mazF5 Family assigned · medium auto-curated

H37Rv Rv1942c · MTBC0 mtbc0_002056 · 109 aa · 2213760–2214089 (-) · RefSeq NP_216458.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)toxin MazF5
MTBC0 PGAP re-annotationtype II toxin-antitoxin system PemK/MazF family toxin
Revised (this work)Type II toxin-antitoxin system PemK/MazF family toxin. 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 P95272 SwissProt · reviewed · Evidence at protein level
UniProt nameProbable endoribonuclease MazF5
EC (curated) EC 3.1.-.-
Curated functionToxic component of a type II toxin-antitoxin (TA) system. Upon expression in M.smegmatis inhibits colony formation. Its toxic effect is neutralized by coexpression with cognate antitoxin MazE5. Probably an endoribonuclease (By similarity).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category T Signal transduction mechanisms
Preferred namemazF5
eggNOG descriptionPemK-like, MazF-like toxin of type II toxin-antitoxin system
Orthologous groupCOG2337
KEGG orthology K07171
Gene Ontology (6) GO:0008150, GO:0040008, GO:0045926, GO:0048519, GO:0050789, GO:0065007

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 0.0 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 0 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
PemK_toxinPF02452.24 6.7e-147–103 PemK-like, MazF-like toxin of type II toxin-antitoxin system

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

Closest characterised functional partner: mazE5 (antitoxin MazE5), high confidence from genomic context alone (score 883 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1943c mazE5 antitoxin MazE5 957 883 ctx neighborhood:882 textmining:654
Rv1944c hyp hypothetical protein 802 802 ctx neighborhood:801
Rv2801A mazE9 antitoxin MazE9 803 782 ctx cooccurence:686
Rv0456A mazF1 toxin MazF1 854 669 ctx cooccurence:668 textmining:577
Rv1247c relB antitoxin RelB 626 611 ctx cooccurence:604
Rv2865 relF antitoxin RelF 648 610 ctx cooccurence:604
Rv1991A mazE6 antitoxin MazE6 656 607 experimental:434
Rv1102c mazF3 mRNA interferase MazF3 851 589 ctx cooccurence:586 textmining:652
Rv1246c relE toxin RelE 705 584 ctx cooccurence:572
Rv1945 hyp hypothetical protein 582 582 ctx neighborhood:581
Rv2063A mazF7 mRNA interferase MazF7 546 546 ctx cooccurence:546
Rv2866 relG toxin RelG 596 545 ctx cooccurence:534
Rv2801c mazF9 mRNA interferase MazF9 881 449 ctx cooccurence:449 textmining:793
Rv3407 vapB47 antitoxin VapB47 448 449 ctx cooccurence:444
Rv3095 HTH-type transcriptional regulator 414 415 coexpression:415

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: toxin MazF5
  • MTBC0 PGAP product: type II toxin-antitoxin system PemK/MazF family toxin
  • Pfam (hmmscan --cut_ga): PemK_toxin PF02452.24 (E=7e-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_216458.1)
  • 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 P95272 (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 — 19 functional partner(s); context anchor mazE5
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002056|Rv1942c|mazF5
MTALPARGEVWWCEMAEIGRRPVVVLSRDAAIPRLRRALVAPCTTTIRGLASEVVLEPGSDPIPRRSAVNLDSVESVSVAVLVNRLGRLADIRMRAICTALEVAVDCSR