Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
| MTBC0 PGAP re-annotation | winged helix-turn-helix transcriptional regulator |
| Revised (this work) | Winged helix-turn-helix transcriptional regulator. Pfam: HxlR (PF01638.24). |
Auto-curated: this verdict and function were generated by rules from
PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P71983
TrEMBL · unreviewed
· Predicted
|
| UniProt name | HTH hxlR-type domain-containing protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
| eggNOG description | HxlR-like helix-turn-helix |
| Orthologous group | COG1733 |
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)
pseudogene candidate
| pN/pS |
0.274 · purifying
|
| Polymorphic sites (≥ 0.1% of strains) |
4 synonymous, 3 missense, 0 nonsense, 1 frameshift
|
| Disruption |
1 distinct premature-stop/frameshift site(s); most common in
2.23% of strains
(3239) · clonal
|
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 |
HxlR | PF01638.24 |
9.6e-27 | 16–101 |
HxlR-like helix-turn-helix |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
Rv1931c |
transcriptional regulator |
910 |
911 |
coexpression:860 |
Rv1724c hyp |
hypothetical protein |
882 |
882 ctx |
neighborhood:882 |
Rv1189 sigI |
ECF RNA polymerase sigma factor SigI |
871 |
872 |
coexpression:833 |
Rv3055 |
TetR family transcriptional regulator |
872 |
869 |
coexpression:850 |
Rv3167c |
TetR family transcriptional regulator |
863 |
860 |
coexpression:839 |
Rv3328c sigJ |
ECF RNA polymerase sigma factor SigJ |
858 |
859 |
coexpression:822 |
Rv1151c cobB |
NAD-dependent protein deacylase |
858 |
858 |
coexpression:850 |
Rv3736 |
AraC/XylS family transcriptional regulator |
853 |
853 |
coexpression:853 |
Rv0377 |
HTH-type transcriptional regulator |
857 |
851 |
coexpression:851 |
Rv3263 |
DNA methylase |
848 |
848 |
coexpression:848 |
Rv2488c |
LuxR family transcriptional regulator |
851 |
846 |
coexpression:846 |
Rv1267c embR |
transcriptional regulator EmbR |
846 |
846 |
coexpression:846 |
Rv2788 sirR |
transcriptional repressor SirR |
844 |
844 |
coexpression:844 |
Rv0212c nadR |
transcriptional regulator NadR |
840 |
840 |
coexpression:815 |
Rv0117 oxyS |
oxidative stress response regulatory protein OxyS |
841 |
836 |
coexpression:835 |
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: hypothetical protein
- MTBC0 PGAP product: winged helix-turn-helix transcriptional regulator
- Pfam (hmmscan --cut_ga): HxlR PF01638.24 (E=1e-26)
- (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_216241.1)
- Domains: Pfam-A via hmmscan --cut_ga — HxlR (PF01638.24)
- 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
COG1733
- Curated reference: UniProt
P71983
(TrEMBL, unreviewed; Predicted)
- 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 —
87 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001837|Rv1725c|
MQPYGQYCPVARAAELLGDRWTLLIVRELLFGPLRFTEIERGLPGISRSVLAQRLRRLQHDRIIEAVPEHTGGGYRFTVAGEELRPVLQTLGDWVSRWLMADPTPAECDPELLTLWISRRVNTEALPGRRVVVEFRYHGERPLWAWLVLEPGDISVCLHDPCLPVDLTVRGHPRDLYRVYSGRSTLAAEISAERIELDGLPAMRRAFPSWMAWSPFAPAMRQAVVSVDQMPEAHGG
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