mazF8 Resolved · medium auto-curated

H37Rv Rv2274c · MTBC0 mtbc0_002416 · 105 aa · 2572593–2572910 (-) · RefSeq NP_216790.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)toxin MazF8
MTBC0 PGAP re-annotationtoxin
Revised (this work)Toxin.

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

Curated reference (UniProt)

UniProt P9WIH7 SwissProt · reviewed · Uncertain
UniProt namePutative toxin MazF8
EC (curated) EC 3.1.-.-
Curated functionPutative toxic component of a type II toxin-antitoxin (TA) system, its cognate toxin is MaZE8. Probably an endoribonuclease (By similarity).

UniProt still lists this protein as Putative toxin MazF8; the revised annotation above is ahead of the current UniProt record.

Conservation & selection (intra-MTBC, 145 209 strains)

pN/pS 1.112 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 3 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: mazE8 (antitoxin MazE8), medium confidence from genomic context alone (score 668 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2274A mazE8 antitoxin MazE8 879 668 ctx neighborhood:668 textmining:653
Rv2275 cyclo(L-tyrosyl-L-tyrosyl) synthase 570 570 ctx neighborhood:556
Rv2276 cyp121 cytochrome P450 Cyp121 532 532 ctx neighborhood:525
Rv0656c vapC6 ribonuclease VapC6 575 51 textmining:571
Rv1720c vapC12 ribonuclease VapC12 523 47 textmining:520
Rv1397c vapC10 ribonuclease VapC10 520 44 textmining:519
Rv3905c esxF ESAT-6 like protein EsxF 437 44 textmining:436
Rv2138 lppL lipoprotein LppL 423 44 textmining:422
Rv1004c membrane protein 629 43 textmining:629
Rv2760c vapB42 antitoxin VapB42 440 42 textmining:440
Rv3289c transmembrane protein 629 41 textmining:629
Rv0996 transmembrane protein 546 41 textmining:546
Rv2526 vapB17 antitoxin VapB17 511 41 textmining:511
Rv3408 vapC47 ribonuclease VapC47 510 41 textmining:510
Rv2615c PE_PGRS45 PE-PGRS family protein PE_PGRS45 437 41 textmining:437

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 MazF8
  • MTBC0 PGAP product: toxin
  • (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_216790.1)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
  • Curated reference: UniProt P9WIH7 (SwissProt, reviewed; Uncertain)
  • 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 — 16 functional partner(s); context anchor mazE8
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002416|Rv2274c|mazF8
MSIARSAQPIGWISCPPKGGSSCCRCGGGYTHIFCVSAWTGLVVDLQAEQVRSVVTERLRRRIGRGAPILAGTLAPGVGLAAQNREFRQFTGRSAPPSATIAFGE