Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
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| MTBC0 PGAP re-annotation | metal-sensitive transcriptional regulator |
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| Revised (this work) | Metal-sensing transcriptional regulator (Pfam Trns_repr_metal PF02583; CsoR/RcnR-like). Putative metalloregulator controlling metal-homeostasis genes in response to metal ions. |
|---|
Curated reference (UniProt)
| UniProt |
O07434
SwissProt · reviewed
· Evidence at protein level
|
|---|
| UniProt name | Copper-sensing transcriptional repressor RicR |
|---|
| Curated function | Under low copper conditions, represses the expression of lpqS, Rv2963, mymT, socA, socB, mmcO and its own expression. In the presence of copper, RicR dissociates from DNA, leading to the expression of the target genes. Members of the RicR regulon are important for copper resistance during infections and full virulence in a mouse model of infection. |
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Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
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| Preferred name | csoR |
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| eggNOG description | Metal-sensitive transcriptional repressor |
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| Orthologous group | COG1937 |
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| KEGG orthology |
K21600
|
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| Gene Ontology (59) |
GO:0000976, GO:0001067, GO:0001130, GO:0001217, GO:0003674, GO:0003676, GO:0003677, GO:0003690, GO:0003700, GO:0005488, GO:0005575, GO:0006355 +47 more
|
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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) |
1 synonymous, 0 missense, 0 nonsense, 0 frameshift
|
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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 |
|---|
Trns_repr_metal | PF02583.23 |
3.4e-30 | 11–91 |
Metal-sensitive transcriptional repressor |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner:
ilvD (dihydroxy-acid dehydratase),
high confidence from genomic context alone
(score 773 excluding text-mining).
This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv0189c ilvD |
dihydroxy-acid dehydratase |
773 |
773 ctx |
neighborhood:772 |
Rv0191 |
MFS-type transporter |
859 |
763 ctx |
neighborhood:759 textmining:434 |
Rv2259 mscR |
S-nitrosomycothiol reductase MscR |
484 |
464 |
coexpression:433 |
Rv3086 adhD |
alcohol dehydrogenase D |
480 |
460 |
coexpression:429 |
Rv0761c adhB |
alcohol dehydrogenase B |
480 |
460 |
coexpression:429 |
Rv0162c adhE1 |
zinc-type alcohol dehydrogenase subunit E |
480 |
460 |
coexpression:429 |
Rv0192 hyp |
hypothetical protein |
452 |
452 ctx |
neighborhood:449 |
Rv0129c fbpC |
diacylglycerol acyltransferase/mycolyltransferase Ag85C |
449 |
429 |
coexpression:411 |
Rv3804c fbpA |
diacylglycerol acyltransferase/mycolyltransferase Ag85A |
448 |
427 |
coexpression:409 |
Rv1288 hyp |
hypothetical protein |
453 |
426 |
coexpression:407 |
Rv0774c hyp |
hypothetical protein |
446 |
425 |
coexpression:407 |
Rv1639c hyp |
hypothetical protein |
446 |
425 |
coexpression:407 |
Rv3803c fbpD |
MPT51/MPB51 antigen |
446 |
425 |
coexpression:407 |
Rv1886c fbpB |
diacylglycerol acyltransferase/mycolyltransferase Ag85B |
446 |
425 |
coexpression:407 |
Rv3286c sigF |
RNA polymerase sigma factor SigF |
406 |
406 |
experimental:406 |
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
- MTBC0 PGAP product: 'metal-sensitive transcriptional regulator'
- Pfam: Trns_repr_metal PF02583 (E=3.4e-30)
ESM Atlas signal (exploratory)
Ancestral protein hash b2780861c6f503efd9cea59685ca7b08 ·
10 ESM-space neighbours (max similarity 0.933).
SAE features are orienting indices, not validated domains.
| # | Index | Activation | Interpretation |
|---|
| 1 | 9309 |
0.77 |
Solvent-exposed interaction patches |
| 2 | 13240 |
0.60 |
Amphipathic core helices |
| 3 | 1304 |
0.53 |
N-terminal first-folded block |
| 4 | 10679 |
0.48 |
Charged N-terminal subdomain activation |
| 5 | 12874 |
0.45 |
C-terminal assembly region |
| 6 | 3509 |
0.37 |
Terminal helix-to-IDR tails |
| 7 | 13156 |
0.36 |
Basic polar N-terminal leaders |
| 8 | 12554 |
0.35 |
Charged disordered interface loops |
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_214704.1)
- Domains: Pfam-A via hmmscan --cut_ga — Trns_repr_metal (PF02583.23)
- 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
COG1937
- Curated reference: UniProt
O07434
(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 —
31 functional partner(s); context anchor
ilvD
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000204|Rv0190|
MTAAHGYTQQKDNYAKRLRRVEGQVRGIARMIEEDKYCIDVLTQISAVTSALRSVALNLLDEHLSHCVTRAVAEGGPGADGKLAEASAAIARLVRS
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