higA Resolved · high auto-curated
H37Rv Rv1956 · MTBC0 mtbc0_002071 ·
149 aa · 2221254–2221703 (+) ·
RefSeq NP_216472.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | antitoxin HigA |
|---|---|
| MTBC0 PGAP re-annotation | type II toxin-antitoxin system antitoxin HigA |
| Revised (this work) | Type II toxin-antitoxin system antitoxin HigA. Pfam: HTH_3 (PF01381.29). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WJA7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Antitoxin HigA1 |
| Curated function | Antitoxin component of an atypical, type II toxin-antitoxin chaperone (TAC) system. Upon expression in M.smegmatis neutralizes the effect of cognate toxin HigB1. Neutralization of HigB1 toxin in E.coli or M.marinum also requires SecB-like chaperone Rv1957, making this the first toxin-antitoxin chaperone (TAC) system. Antitoxin aggregation and degradation are prevented by the chaperone..; FUNCTION: In M.tuberculosis represses expression of the Rv1954A-higB1-higA1-Rv1957 operon promoter but not that of the higB1-higA1-Rv1957 operon. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
|---|---|
| eggNOG description | Helix-turn-helix |
| Orthologous group | COG1396 |
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 | 0.111 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 1 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 |
|---|---|---|---|---|
HTH_3 | PF01381.29 | 3.6e-11 | 43–92 | Helix-turn-helix |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: secBL (SecB-like chaperone), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1957 secBL |
SecB-like chaperone | 999 | 1000 ctx | neighborhood:882 coexpression:716 experimental:999 textmining:870 |
Rv1955 higB |
toxin HigB | 993 | 952 ctx | neighborhood:682 coexpression:731 experimental:484 textmining:880 |
Rv3347c PPE55 |
PPE family protein PPE55 | 682 | 683 ctx | cooccurence:681 |
Rv3350c PPE56 |
PPE family protein PPE56 | 677 | 677 ctx | cooccurence:676 |
Rv0355c PPE8 |
PPE family protein PPE8 | 675 | 676 ctx | cooccurence:674 |
Rv0836c hyp |
hypothetical protein | 669 | 669 ctx | cooccurence:667 |
Rv1004c |
membrane protein | 667 | 667 ctx | cooccurence:665 |
Rv0304c PPE5 |
PPE family protein PPE5 | 666 | 666 ctx | cooccurence:664 |
Rv1917c PPE34 |
PPE family protein PPE34 | 656 | 656 ctx | cooccurence:653 |
Rv1452c PE_PGRS28 |
PE-PGRS family protein PE_PGRS28 | 643 | 643 ctx | cooccurence:643 |
Rv3343c PPE54 |
PPE family protein PPE54 | 641 | 642 ctx | cooccurence:640 |
Rv1651c PE_PGRS30 |
PE-PGRS family protein PE_PGRS30 | 638 | 638 ctx | cooccurence:638 |
Rv0837c hyp |
hypothetical protein | 637 | 638 ctx | cooccurence:633 |
Rv2490c PE_PGRS43 |
PE-PGRS family protein PE_PGRS43 | 630 | 630 ctx | cooccurence:630 |
Rv1753c PPE24 |
PPE family protein PPE24 | 609 | 609 ctx | cooccurence:609 |
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: antitoxin HigA
- MTBC0 PGAP product: type II toxin-antitoxin system antitoxin HigA
- Pfam (hmmscan --cut_ga): HTH_3 PF01381.29 (E=4e-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_216472.1)
- Domains: Pfam-A via hmmscan --cut_ga — HTH_3 (PF01381.29)
- 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
COG1396 - Curated reference: UniProt P9WJA7 (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 —
69 functional partner(s); context anchor
secBL - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002071|Rv1956|higA MSIDFPLGDDLAGYIAEAIAADPSFKGTLEDAEEARRLVDALIALRKHCQLSQVEVAKRMGVRQPTVSGFEKEPSDPKLSTLQRYARALDARLRLVLEVPTLREVPTWHRLSSYRGSARDHQVRVGADKEILMQTNWARHISVRQVEVA