Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | transcriptional regulator |
| MTBC0 PGAP re-annotation | LuxR family transcriptional regulator |
| Revised (this work) | LuxR family transcriptional regulator. Pfam: HTH_77 (PF25872.1), GerE (PF00196.26). |
Auto-curated: this verdict and function were generated by rules from
PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53720
TrEMBL · unreviewed
· Evidence at protein level
|
| UniProt name | Probable transcriptional regulatory protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
| eggNOG description | involved in signal transduction (via phosphorylation) involved in transcriptional regulatory mechanism and in the regulation of secondary metabolites catalytic activity ATP a protein ADP a phosphoprotein |
| Orthologous group | COG2114 |
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 |
0.419 · purifying
|
| Polymorphic sites (≥ 0.1% of strains) |
11 synonymous, 13 missense, 0 nonsense, 2 frameshift
|
| Disruption |
2 distinct premature-stop/frameshift site(s); most common in
1.08% of strains
(1566) · 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_77 | PF25872.1 |
6.6e-07 | 437–512 |
Winged helix-turn-helix domain |
GerE | PF00196.26 |
3.7e-16 | 1025–1080 |
Bacterial regulatory proteins, luxR family |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
Rv2434c |
transmembrane protein |
686 |
653 |
experimental:440 |
Rv0104 hyp |
hypothetical protein |
644 |
622 |
experimental:440 |
Rv2564 glnQ |
glutamine ABC transporter ATP-binding protein |
643 |
601 |
experimental:447 |
Rv0073 |
glutamine ABC transporter ATP-binding protein |
643 |
600 |
experimental:447 |
Rv3728 |
membrane protein |
672 |
593 |
experimental:440 |
Rv3239c |
transmembrane transport protein |
672 |
593 |
experimental:440 |
Rv3132c devS |
two component sensor histidine kinase DevS |
638 |
583 |
|
Rv2565 |
NTE family protein |
624 |
575 |
experimental:440 |
Rv3899c hyp |
hypothetical protein |
585 |
569 ctx |
cooccurence:539 |
Rv3676 crp |
cAMP receptor protein |
583 |
557 |
experimental:440 |
Rv1675c cmr |
HTH-type transcriptional regulator Cmr |
583 |
557 |
experimental:440 |
Rv0998 |
acetyltransferase Pat |
582 |
556 |
experimental:440 |
Rv0845 narS |
sensor histidine kinase NarS |
572 |
553 |
|
Rv1354c hyp |
hypothetical protein |
803 |
550 ctx |
neighborhood:544 textmining:582 |
Rv2423 hyp |
hypothetical protein |
550 |
550 ctx |
cooccurence:544 |
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: LuxR family transcriptional regulator
- Pfam (hmmscan --cut_ga): HTH_77 PF25872.1 (E=7e-07), GerE PF00196.26 (E=4e-16)
- (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_214900.1)
- Domains: Pfam-A via hmmscan --cut_ga — HTH_77 (PF25872.1), GerE (PF00196.26)
- 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
COG2114
- Curated reference: UniProt
O53720
(TrEMBL, unreviewed; 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 —
44 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000406|Rv0386|
MSKLLPRGTVTLLLADVEGSTWLWETHPDDMGAAVARLDKAVSGVIAAHDGVRPVEQGEGDSFVLAFACASDAVAAALDLQRARLAPIRLRIGVHTGEVALRDEGNYAGPTINRTARLRDLAHGGQTVLSGVTESLVIDRLPDKAWLVDLGTHALRDLSRPERVMQLCHPELRIDFPPLRVANDDVAHGLPVHLTRFVGRGAQITEVHRLVTDNRLVTLTGAGGVGKTRLAAQLAAQIAGEFGRAWFVDLAPITDPDLVPVTVAGALGLHDQPGRSTTDTVLRFLGGRPALVVLDNCEHLLDATAALVLALVKACRGVRLLATCREPLRVEGEVSYRVPSLSLSDEAVEMFCYRAQRVRPDFRLTDDNSAAVTEICKRLDGLPLAIELAAARLRSMTLDEIIDGLRDRFALLTGGARTAAHRQQTLWASVDWSYTLLTEPERTLFRRLAVFVGCFFVDDAQAVACSGDVQRYQVLDEITLLVDKSLVMADDNSGRTCYRLCETMRHYALEKLSEAGEVDAVFARHRDYYTALAARVDNPGPSDYSHCLDQAETEIDNLRAAFVWNRENSDTEGALALASSLLRVWMTRGRIQEGRAWFDSILADENARHLEVAAAVRARALADKALLDIFVDAAAGMEQAQQALVIAREVDEPALLSRALTACGLIAVAVARADAAASYFAEAIDLARAVDDRWRLAQILTFQAVDAVVAGDPVAARPAAQEARELAAAIGDHSNALWCRWCLGYAQLMRGELAAAAAQFGEVVDEAEASQEVLHKANSLQGLAFALAYQGELSAARAAADAALEAAELGEYFAGMGYSALTTAALAAGDVQTAQHASEAAWRNLSLALPLSAAVQRAFNAQAALAGGDLSAARRWCDDAVQSMTGHHLAMALATRARIAVAEGKREEAERDAHKALACAAESGAHLDLPDVLECLAGLASDAGTHHAAARLFGAAEAIRQQIGSVRFAIYRSDYVQSVTALRDAMGEKDFDAAWAEGAALSIKETIAYAQRGHSWRKRPATGWESLTPTEIDVVRLVGEGLANKDIATRLFVSPRTVQTHLTHVYTKLGFTSRLQLAQAAARRT
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