mazF6 Resolved · high auto-curated
H37Rv Rv1991c · MTBC0 mtbc0_002117 ·
114 aa · 2257918–2258262 (-) ·
RefSeq NP_216507.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | mRNA interferase MazF6 |
|---|---|
| MTBC0 PGAP re-annotation | type II toxin-antitoxin system toxin endoribonuclease MazF6 |
| Revised (this work) | Type II toxin-antitoxin system toxin endoribonuclease MazF6. 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 |
P9WII3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Endoribonuclease MazF6 |
| EC (curated) |
EC 3.1.27.-
|
| Curated function | Toxic component of a type II toxin-antitoxin (TA) system. Upon expression in E.coli and in M.smegmatis partially inhibits cell growth and colony formation; its toxic effect is neutralized by coexpression with cognate antitoxin MazE6. Acts as an mRNA interferase on ssRNA, cleaving between the second and third bases in the sequences CUCCU and UUCCU. Further experiments demonstrate that it digests between the first and second bases of UCCUU, yielding a 5'-hydroxyl end; digests M.tuberculosis mRNA (in coding as well as the 5'- and 3'-UTR regions) and 23S rRNA, digests E.coli 16S rRNA both alone an. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
L Replication, recombination and repair
|
|---|---|
| eggNOG description | Toxic component of a toxin-antitoxin (TA) module |
| Orthologous group | COG2337 |
| KEGG orthology |
K07171
|
| Gene Ontology (57) |
GO:0003674, GO:0003824, GO:0004518, GO:0004540, GO:0005575, GO:0005576, GO:0006139, GO:0006401, GO:0006402, GO:0006725, GO:0006807, GO:0008150 +45 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)
| pN/pS | 0.734 · 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
PemK_toxin | PF02452.24 | 2.3e-27 | 5–112 | PemK-like, MazF-like toxin of type II toxin-antitoxin system |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mazE6 (antitoxin MazE6), high confidence from genomic context alone (score 950 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1991A mazE6 |
antitoxin MazE6 | 990 | 950 ctx | neighborhood:882 experimental:434 textmining:820 |
Rv2801A mazE9 |
antitoxin MazE9 | 844 | 785 | experimental:677 |
Rv2063 mazE7 |
antitoxin MazE7 | 743 | 688 | experimental:677 |
Rv1990A |
Rv1990A, len: 111 aa. Possible dehydrogenase (fragment), similar to N-terminal part of several dehydrogenases and hypothetical proteins, e.g | 607 | 606 ctx | neighborhood:594 |
Rv1992c ctpG |
cation transporter ATPase G | 551 | 551 ctx | neighborhood:536 |
Rv1993c hyp |
hypothetical protein | 550 | 550 ctx | neighborhood:536 |
Rv2063A mazF7 |
mRNA interferase MazF7 | 528 | 528 ctx | cooccurence:528 |
Rv1994c cmtR |
HTH-type transcriptional regulator CmtR | 435 | 435 ctx | neighborhood:432 |
Rv1725c hyp |
hypothetical protein | 416 | 416 | coexpression:416 |
Rv3095 |
HTH-type transcriptional regulator | 414 | 415 | coexpression:415 |
Rv0456A mazF1 |
toxin MazF1 | 555 | 402 | |
Rv1494 mazE4 |
antitoxin MazE4 | 477 | 400 | |
Rv1495 mazF4 |
mRNA interferase MazF4 | 864 | 339 | textmining:803 |
Rv1960c parD1 |
antitoxin ParD1 | 415 | 337 | |
Rv1103c mazE3 |
antitoxin MazE3 | 762 | 334 | textmining:659 |
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 MazF6
- MTBC0 PGAP product: type II toxin-antitoxin system toxin endoribonuclease MazF6
- Pfam (hmmscan --cut_ga): PemK_toxin PF02452.24 (E=2e-27)
- (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_216507.1)
- 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 P9WII3 (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 —
34 functional partner(s); context anchor
mazE6 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002117|Rv1991c|mazF6 MVISRAEIYWADLGPPSGSQPAKRRPVLVIQSDPYNASRLATVIAAVITSNTALAAMPGNVFLPATTTRLPRDSVVNVTAIVTLNKTDLTDRVGEVPASLMHEVDRGLRRVLDL