mazF3 Resolved · high auto-curated
H37Rv Rv1102c · MTBC0 mtbc0_001185 ·
103 aa · 1239100–1239411 (-) ·
RefSeq NP_215618.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | mRNA interferase MazF3 |
|---|---|
| MTBC0 PGAP re-annotation | type II toxin-antitoxin system toxin endoribonuclease MazF3 |
| Revised (this work) | Type II toxin-antitoxin system toxin endoribonuclease MazF3. 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 |
P9WIH9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Endoribonuclease MazF3 |
| EC (curated) |
EC 3.1.-.-
|
| Curated function | Toxic component of a type II toxin-antitoxin (TA) system. Acts as an mRNA and 23S rRNA interferase, cleaving predominantly after the first 2 Us in the sequence 5'-UUCCU-3'; in 23S rRNA only cleaves once in the ribosomal A site in dissociated but not intact ribosomes. Cleavage of 23S rRNA inhibits protein translation; the 23S rRNA region cleaved is involved in tRNA-binding in the A site, 30S and 50S subunit interaction and ribosome recycling factor association. Upon expression in E.coli and M.smegmatis inhibits cell growth and colony formation. It dramatically increases persister cell formation. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
T Signal transduction mechanisms
|
|---|---|
| Preferred name | mazF3 |
| eggNOG description | PemK-like, MazF-like toxin of type II toxin-antitoxin system |
| Orthologous group | COG2337 |
| KEGG orthology |
K07171
|
| Gene Ontology (92) |
GO:0003674, GO:0003824, GO:0004518, GO:0004519, GO:0004521, GO:0004540, GO:0006139, GO:0006355, GO:0006401, GO:0006402, GO:0006417, GO:0006725 +80 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 | n/a |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 0 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 | 2.6e-11 | 10–92 | PemK-like, MazF-like toxin of type II toxin-antitoxin system |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mazE3 (antitoxin MazE3), high confidence from genomic context alone (score 916 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1103c mazE3 |
antitoxin MazE3 | 960 | 916 ctx | neighborhood:882 textmining:546 |
Rv1104 |
Rv1104, (MTV017.57), len: 229 aa. Possible para-nitrobenzyl esterase (fragment; possibly first part). Similar to the N-terminal domain of ma | 622 | 622 ctx | neighborhood:620 |
Rv1991A mazE6 |
antitoxin MazE6 | 782 | 607 | experimental:434 textmining:468 |
Rv1942c mazF5 |
toxin MazF5 | 851 | 589 ctx | cooccurence:586 textmining:652 |
Rv2801A mazE9 |
antitoxin MazE9 | 568 | 563 | |
Rv3407 vapB47 |
antitoxin VapB47 | 548 | 549 ctx | cooccurence:543 |
Rv1101c hyp |
hypothetical protein | 535 | 535 ctx | neighborhood:528 |
Rv1725c hyp |
hypothetical protein | 503 | 503 | coexpression:420 |
Rv3408 vapC47 |
ribonuclease VapC47 | 639 | 488 ctx | cooccurence:472 |
Rv3384c vapC46 |
ribonuclease VapC46 | 522 | 444 ctx | cooccurence:438 |
Rv1962c vapC35 |
ribonuclease VapC35 | 436 | 435 ctx | cooccurence:430 |
Rv0456A mazF1 |
toxin MazF1 | 589 | 419 ctx | cooccurence:418 |
Rv3095 |
HTH-type transcriptional regulator | 416 | 417 | coexpression:417 |
Rv0659c mazF2 |
toxin MazF2 | 648 | 407 ctx | cooccurence:402 textmining:431 |
Rv2472 hyp |
hypothetical protein | 414 | 406 |
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 MazF3
- MTBC0 PGAP product: type II toxin-antitoxin system toxin endoribonuclease MazF3
- Pfam (hmmscan --cut_ga): PemK_toxin PF02452.24 (E=3e-11)
- (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_215618.1)
- 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 P9WIH9 (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 —
35 functional partner(s); context anchor
mazE3 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001185|Rv1102c|mazF3 MRPIHIAQLDKARPVLILTREVVRPHLTNVTVAPITTTVRGLATEVPVDAVNGLNQPSVVSCDNIQTIPVCDLGRQIGYLLASQEPALAEAIGNAFDLDWVVA