Rv2021c Family assigned · medium auto-curated
H37Rv Rv2021c · MTBC0 mtbc0_002151 ·
101 aa · 2290418–2290723 (-) ·
RefSeq NP_216537.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | transcriptional regulator |
|---|---|
| MTBC0 PGAP re-annotation | XRE family transcriptional regulator |
| Revised (this work) | XRE family transcriptional regulator. Pfam: HTH_37 (PF13744.13), HTH_31 (PF13560.13), 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 |
O53467
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Putative antitoxin HigA2 |
| Curated function | Putative antitoxin component of a type II toxin-antitoxin (TA) system. Its cognate toxin would be HigB2. |
UniProt still lists this protein as Putative antitoxin HigA2; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
|---|---|
| eggNOG description | Helix-turn-helix domain |
| Orthologous group | COG1396 |
| Gene Ontology (27) |
GO:0002791, GO:0003674, GO:0003676, GO:0003677, GO:0005488, GO:0008150, GO:0010565, GO:0019216, GO:0019217, GO:0019222, GO:0031323, GO:0032879 +15 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) | 5 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 |
|---|---|---|---|---|
HTH_37 | PF13744.13 | 4.1e-10 | 33–92 | Helix-turn-helix domain |
HTH_31 | PF13560.13 | 7.6e-09 | 33–84 | Helix-turn-helix domain |
HTH_3 | PF01381.29 | 1.4e-10 | 35–88 | Helix-turn-helix |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2020c (Rv2020c, (MTV018.07c), len: 99 aa. Conserved hypothetical protein, nearly identical to C-terminal part of hypothetical protein RvD1-Rv2024c'), medium confidence from genomic context alone (score 555 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2022c higB2 hyp |
hypothetical protein | 998 | 981 ctx | neighborhood:786 fusion:648 cooccurence:771 textmining:912 |
Rv3182 higB3 hyp |
hypothetical protein | 954 | 781 ctx | cooccurence:768 textmining:800 |
Rv2023c hyp |
hypothetical protein | 703 | 703 ctx | neighborhood:701 |
Rv0744c |
transcriptional regulator | 580 | 580 | coexpression:580 |
Rv2020c |
Rv2020c, (MTV018.07c), len: 99 aa. Conserved hypothetical protein, nearly identical to C-terminal part of hypothetical protein RvD1-Rv2024c' | 555 | 555 ctx | neighborhood:552 |
Rv0332 hyp |
hypothetical protein | 520 | 494 | experimental:434 |
Rv0623 vapB30 |
antitoxin VapB30 | 651 | 469 ctx | cooccurence:445 |
Rv0366c hyp |
hypothetical protein | 473 | 445 | experimental:434 |
Rv2807 hyp |
hypothetical protein | 430 | 431 ctx | cooccurence:428 |
Rv3183 higA3 |
transcriptional regulator | 432 | 317 | |
Rv2515c hyp |
hypothetical protein | 400 | 312 | |
Rv1740 vapB34 |
antitoxin VapB34 | 495 | 286 | |
Rv2017 |
transcriptional regulator | 492 | 282 | |
Rv1956 higA |
antitoxin HigA | 839 | 219 | textmining:803 |
Rv1246c relE |
toxin RelE | 474 | 219 |
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: transcriptional regulator
- MTBC0 PGAP product: XRE family transcriptional regulator
- Pfam (hmmscan --cut_ga): HTH_37 PF13744.13 (E=4e-10), HTH_31 PF13560.13 (E=8e-09), HTH_3 PF01381.29 (E=1e-10)
- (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_216537.1)
- Domains: Pfam-A via hmmscan --cut_ga — HTH_37 (PF13744.13), HTH_31 (PF13560.13), 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 O53467 (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 —
36 functional partner(s); context anchor
Rv2020c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002151|Rv2021c| MAMTLRDMDAVRPVNREAVDRHKARMRDEVRAFRLRELRAAQSLTQVQVAALAHIRQSRVSSIENGDIGSAQVNTLRKYVSALGGELDITVRLGDETFTLA