mazE4 Resolved · medium auto-curated

H37Rv Rv1494 · MTBC0 mtbc0_001598 · 100 aa · 1696076–1696378 (+) · RefSeq NP_216010.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)antitoxin MazE4
MTBC0 PGAP re-annotationtype II toxin-antitoxin system antitoxin MazE4
Revised (this work)Type II toxin-antitoxin system antitoxin MazE4.

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

Curated reference (UniProt)

UniProt P9WJ91 SwissProt · reviewed · Evidence at protein level
UniProt nameProbable antitoxin MazE4
Curated functionAntitoxin component of a type II toxin-antitoxin (TA) system. In M.smegmatis neutralizes the toxic effect of mRNA interferase MazF4, its cognate toxin, on growth.

Functional vocabulary (eggNOG-mapper, orthology transfer)

Orthologous group2BSKF

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 0.813 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 5 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)

No Pfam-A domain above the gathering threshold (or not yet scanned).

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

Closest characterised functional partner: mazF4 (mRNA interferase MazF4), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1495 mazF4 mRNA interferase MazF4 999 1000 ctx neighborhood:882 experimental:999 textmining:594
Rv1496 meaB transport system kinase 803 802 ctx neighborhood:801
Rv1493 mutB methylmalonyl-CoA mutase large subunit 840 774 ctx neighborhood:772
Rv1492 mutA methylmalonyl-CoA mutase small subunit 775 774 ctx neighborhood:772
Rv1497 lipL esterase LipL 622 621 ctx neighborhood:619
Rv1491c TVP38/TMEM64 family membrane protein 500 501 ctx neighborhood:499
Rv1942c mazF5 toxin MazF5 404 405
Rv1991c mazF6 mRNA interferase MazF6 477 400
Rv1943c mazE5 antitoxin MazE5 635 55 textmining:630
Rv2493 vapB38 antitoxin VapB38 550 55 textmining:544
Rv3321c vapB44 antitoxin VapB44 527 53 textmining:522
Rv2547 vapB19 antitoxin VapB19 579 50 textmining:576
Rv2075c hyp hypothetical protein 406 47 textmining:403
Rv1114 vapC32 ribonuclease VapC32 654 46 textmining:653
Rv0301 vapC2 ribonuclease VapC2 517 46 textmining:515

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: antitoxin MazE4
  • MTBC0 PGAP product: type II toxin-antitoxin system antitoxin MazE4
  • (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_216010.1)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • 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 2BSKF
  • Curated reference: UniProt P9WJ91 (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 — 25 functional partner(s); context anchor mazF4
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001598|Rv1494|mazE4
MPFLVALSGIISGVRDHSMTVRLDQQTRQRLQDIVKGGYRSANAAIVDAINKRWEALHDEQLDAAYAAAIHDNPAYPYESEAERSAARARRNARQQRSAQ