mazF4 Resolved · high auto-curated
H37Rv Rv1495 · MTBC0 mtbc0_001599 ·
105 aa · 1696375–1696692 (+) ·
RefSeq NP_216011.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | mRNA interferase MazF4 |
|---|---|
| MTBC0 PGAP re-annotation | type II toxin-antitoxin system toxin endoribonuclease MazF4 |
| Revised (this work) | Type II toxin-antitoxin system toxin endoribonuclease MazF4. 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 |
P9WII5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Endoribonuclease MazF4 |
| EC (curated) |
EC 3.1.-.-
|
| Curated function | Toxic component of a type II toxin-antitoxin (TA) system. Acts as an endoribonuclease (mRNA interferase) on single-strand mRNA, cleaving between the first and second bases in the sequence UCGCU. Overexpression in M.smegmatis but not E.coli inhibits growth, this effect is neutralized by coexpression with cognate toxin MazE4..; FUNCTION: Residues 29-56 inhibit ssDNA cleavage by DNA topoisomerase. This fragment does not have mRNA cleavage activity but it inhibits growth upon overexpression in M.smegmatis. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
T Signal transduction mechanisms
|
|---|---|
| eggNOG description | PemK-like, MazF-like toxin of type II toxin-antitoxin system |
| Orthologous group | COG2337 |
| KEGG orthology |
K07171
|
| Gene Ontology (13) |
GO:0008150, GO:0010911, GO:0032780, GO:0043086, GO:0043462, GO:0044092, GO:0050790, GO:0051336, GO:0051346, GO:0065007, GO:0065009, GO:2000371 +1 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 | 0.0 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
PemK_toxin | PF02452.24 | 2.6e-14 | 6–99 | PemK-like, MazF-like toxin of type II toxin-antitoxin system |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mazE4 (antitoxin MazE4), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1494 mazE4 |
antitoxin MazE4 | 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 | 827 | 773 ctx | neighborhood:772 |
Rv1492 mutA |
methylmalonyl-CoA mutase small subunit | 773 | 773 ctx | neighborhood:772 |
Rv3387 |
transposase | 629 | 630 ctx | cooccurence:628 |
Rv1497 lipL |
esterase LipL | 625 | 625 ctx | neighborhood:619 |
Rv1991A mazE6 |
antitoxin MazE6 | 638 | 607 | experimental:434 |
Rv2961 |
transposase | 575 | 575 ctx | cooccurence:575 |
Rv1034c |
Probable transposase (fragment); Rv1034c, (MTCY10G2.15), len: 129 aa. Probable IS1560 transposase fragment, similar to part of Rv3387|E12023 | 562 | 562 ctx | cooccurence:562 |
Rv1491c |
TVP38/TMEM64 family membrane protein | 500 | 501 ctx | neighborhood:499 |
Rv3386 |
transposase | 490 | 491 ctx | cooccurence:488 |
Rv0960 vapC9 |
ribonuclease VapC9 | 472 | 453 ctx | cooccurence:452 |
Rv0065 vapC1 |
ribonuclease VapC1 | 504 | 452 ctx | cooccurence:451 |
Rv1149 |
transposase | 437 | 437 ctx | cooccurence:436 |
Rv1042c |
IS2-like transposase | 437 | 437 ctx | cooccurence:436 |
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 MazF4
- MTBC0 PGAP product: type II toxin-antitoxin system toxin endoribonuclease MazF4
- Pfam (hmmscan --cut_ga): PemK_toxin PF02452.24 (E=3e-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_216011.1)
- 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 P9WII5 (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 —
37 functional partner(s); context anchor
mazE4 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001599|Rv1495|mazF4 MNAPLRGQVYRCDLGYGAKPWLIVSNNARNRHTADVVAVRLTTTRRTIPTWVAMGPSDPLTGYVNADNIETLGKDELGDYLGEVTPATMNKINTALATALGLPWP