Rv0377 Family assigned · medium auto-curated
H37Rv Rv0377 · MTBC0 mtbc0_000397 ·
321 aa · 457783–458748 (+) ·
RefSeq NP_214891.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | HTH-type transcriptional regulator |
|---|---|
| MTBC0 PGAP re-annotation | LysR family transcriptional regulator |
| Revised (this work) | LysR family transcriptional regulator. Pfam: HTH_1 (PF00126.34), LysR_substrate (PF03466.26). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WMF7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized HTH-type transcriptional regulator Rv0377 |
UniProt still lists this protein as Uncharacterized HTH-type transcriptional regulator Rv0377; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
|---|---|
| eggNOG description | Bacterial regulatory helix-turn-helix protein, lysR family |
| Orthologous group | COG0583 |
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 | 0.549 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 6 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.14% of strains (206) · 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 |
|---|---|---|---|---|
HTH_1 | PF00126.34 | 6.3e-16 | 5–61 | Bacterial regulatory helix-turn-helix protein, lysR family |
LysR_substrate | PF03466.26 | 5.2e-25 | 88–291 | LysR substrate binding domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0375c (carbon monoxyde dehydrogenase medium subunit), high confidence from genomic context alone (score 854 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0372c hyp |
hypothetical protein | 882 | 883 ctx | neighborhood:635 cooccurence:687 |
Rv0368c hyp |
hypothetical protein | 853 | 854 ctx | neighborhood:663 cooccurence:574 |
Rv0375c |
carbon monoxyde dehydrogenase medium subunit | 853 | 854 ctx | neighborhood:725 cooccurence:483 |
Rv1267c embR |
transcriptional regulator EmbR | 857 | 852 | coexpression:799 |
Rv1725c hyp |
hypothetical protein | 857 | 851 | coexpression:851 |
Rv0117 oxyS |
oxidative stress response regulatory protein OxyS | 847 | 848 | coexpression:803 |
Rv1776c |
transcriptional regulator | 879 | 832 | coexpression:785 |
Rv0691c mftR |
mycofactocin biosynthesis transcriptional regulator MftR | 831 | 829 | coexpression:778 |
Rv1773c |
transcriptional regulator | 836 | 828 | coexpression:744 |
Rv2488c |
LuxR family transcriptional regulator | 836 | 827 | coexpression:827 |
Rv0376c hyp |
hypothetical protein | 824 | 824 ctx | neighborhood:788 |
Rv3164c moxR3 |
methanol dehydrogenase transcriptional regulator MoxR | 828 | 822 | coexpression:822 |
Rv3167c |
TetR family transcriptional regulator | 825 | 819 | coexpression:797 |
Rv3055 |
TetR family transcriptional regulator | 825 | 819 | coexpression:797 |
Rv0369c |
membrane oxidoreductase | 815 | 815 ctx | neighborhood:663 cooccurence:472 |
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: HTH-type transcriptional regulator
- MTBC0 PGAP product: LysR family transcriptional regulator
- Pfam (hmmscan --cut_ga): HTH_1 PF00126.34 (E=6e-16), LysR_substrate PF03466.26 (E=5e-25)
- (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_214891.1)
- Domains: Pfam-A via hmmscan --cut_ga — HTH_1 (PF00126.34), LysR_substrate (PF03466.26)
- 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
COG0583 - Curated reference: UniProt P9WMF7 (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 —
84 functional partner(s); context anchor
Rv0375c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000397|Rv0377| MTPAQLRAYSAVVRLGSVRAAAAELGLSDAGVSMHVAALRKELDDPLFTRTGAGLAFTPGGLRLASRAVEILGLQQQTAIEVTEAAHGRRLLRIAASSAFAEHAAPGLIELFSSRADDLSVELSVHPTSRFRELICSRAVDIAIGPASESSIGSDGSIFLRPFLKYQIITVVAPNSPLAAGIPMPALLRHQQWMLGPSAGSVDGEIATMLRGLAIPESQQRIFQSDAAALEEVMRVGGATLAIGFAVAKDLAAGRLVHVTGPGLDRAGEWCVATLAPSARQPAVSELVGFISTPRCIQAMIRGSGVGVTRFRPKVHVTLWS