higB Resolved · high auto-curated
H37Rv Rv1955 · MTBC0 mtbc0_002070 ·
125 aa · 2220835–2221212 (+) ·
RefSeq NP_216471.2
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | toxin HigB |
|---|---|
| MTBC0 PGAP re-annotation | type II toxin-antitoxin system toxin HigB |
| Revised (this work) | Type II toxin-antitoxin system toxin HigB. Pfam: Gp49 (PF05973.21). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WJA5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable endoribonuclease HigB1 |
| EC (curated) |
EC 3.1.-.-
|
| Curated function | Toxic component of an atypical, type II toxin-antitoxin chaperone (TAC) system. Upon expression in M.smegmatis inhibits colony formation and cell growth. Ectopic expression in wild-type M.tuberculosis has no effect on cell growth; ectopic expression in a triple higB1-higA1-Rv1957 (delta TAC) disruption mutant causes growth arrest, killing a considerable proportion of the cells. Increased ectopic expression leads to decreased levels of IdeR- and Zur-regulated genes as well as cleavage within the mRNA region of tmRNA (transfer-mRNA), strongly suggesting it is an endoribonuclease; also degrades E. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Phage derived protein Gp49-like (DUF891) |
| Orthologous group | COG4679 |
| Gene Ontology (40) |
GO:0001666, GO:0003674, GO:0003824, GO:0004518, GO:0004519, GO:0004521, GO:0004540, GO:0006139, GO:0006725, GO:0006807, GO:0006950, GO:0008150 +28 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, 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
Gp49 | PF05973.21 | 1.5e-18 | 27–113 | Phage derived protein Gp49-like (DUF891) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: higA (antitoxin HigA), high confidence from genomic context alone (score 952 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1956 higA |
antitoxin HigA | 993 | 952 ctx | neighborhood:682 coexpression:731 experimental:484 textmining:880 |
Rv1957 secBL |
SecB-like chaperone | 970 | 783 ctx | neighborhood:695 textmining:870 |
Rv1954A |
Rv1954A, len: 100 aa. Hypothetical unknown protein. | 618 | 513 ctx | neighborhood:513 |
Rv1077 cbs |
cystathionine beta-synthase | 547 | 511 | experimental:484 |
Rv1843c guaB1 |
inosine-5'-monophosphate dehydrogenase | 542 | 505 | experimental:484 |
Rv2021c higA2 |
transcriptional regulator | 684 | 78 | textmining:672 |
Rv3183 higA3 |
transcriptional regulator | 471 | 78 | textmining:451 |
Rv1952 vapB14 |
antitoxin VapB14 | 591 | 76 | textmining:576 |
Rv1954c hyp |
hypothetical protein | 527 | 70 | textmining:513 |
Rv3384c vapC46 |
ribonuclease VapC46 | 447 | 64 | textmining:434 |
Rv1246c relE |
toxin RelE | 838 | 56 | textmining:836 |
Rv1102c mazF3 |
mRNA interferase MazF3 | 439 | 56 | textmining:431 |
Rv2829c vapC22 |
ribonuclease VapC22 | 444 | 55 | textmining:436 |
Rv2022c higB2 hyp |
hypothetical protein | 809 | 52 | textmining:807 |
Rv1991c mazF6 |
mRNA interferase MazF6 | 518 | 52 | textmining:513 |
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 HigB
- MTBC0 PGAP product: type II toxin-antitoxin system toxin HigB
- Pfam (hmmscan --cut_ga): Gp49 PF05973.21 (E=1e-18)
- (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_216471.2)
- Domains: Pfam-A via hmmscan --cut_ga — Gp49 (PF05973.21)
- 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
COG4679 - Curated reference: UniProt P9WJA5 (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 —
19 functional partner(s); context anchor
higA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002070|Rv1955|higB MPPPDPAAMGTWKFFRASVDGRPVFKKEFDKLPDQARAALIVLMQRYLVGDLAAGSIKPIRGDILELRWHEANNHFRVLFFRWGQHPVALTAFYKNQQKTPKTKIETALDRQKIWKRAFGDTPPI