Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | transcriptional repressor SirR |
|---|
| MTBC0 PGAP re-annotation | manganese-binding transcriptional regulator MntR |
|---|
| Revised (this work) | Manganese-binding transcriptional regulator MntR. Pfam: Fe_dep_repress (PF01325.26), Fe_dep_repr_C (PF02742.22), FeoA (PF04023.21). |
|---|
Auto-curated: this verdict and function were generated by rules from
PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6Y1Q2
SwissProt · reviewed
· Evidence at protein level
|
|---|
| UniProt name | Manganese-dependent transcriptional repressor MntR |
|---|
| Curated function | Transcriptional regulator that controls manganese homeostasis. Functions as a manganese-dependent transcriptional repressor, which directly regulates the expression of two transporters, MntH and the ABC transporter OppABCD (MntABCD). It also regulates genes that respond to metal ion deficiency such as the esx3 system. Its function is essential for survival of M.tuberculosis under conditions of high manganese availability, but it is dispensable during infection. Inhibits its own transcription. Is able to bind to a cis element upstream of the start codon of the Rv2787-mntR operon. Regulation of . |
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
|---|
| Preferred name | sirR |
|---|
| eggNOG description | iron dependent repressor |
|---|
| Orthologous group | COG1321 |
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| KEGG orthology |
K03709
|
|---|
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 |
0.997 · relaxed/neutral
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
2 synonymous, 5 missense, 1 nonsense, 2 frameshift
|
|---|
| Disruption |
3 distinct premature-stop/frameshift site(s); most common in
17.67% of strains
(25663) · 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 |
|---|
Fe_dep_repress | PF01325.26 |
7.4e-23 | 9–69 |
Iron dependent repressor, N-terminal DNA binding domain |
Fe_dep_repr_C | PF02742.22 |
3.5e-32 | 72–140 |
Iron dependent repressor, metal binding and dimerisation domain |
FeoA | PF04023.21 |
2.2e-12 | 156–226 |
FeoA domain |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv1725c hyp |
hypothetical protein |
844 |
844 |
coexpression:844 |
Rv3066 |
DeoR family transcriptional regulator |
830 |
830 |
coexpression:830 |
Rv3328c sigJ |
ECF RNA polymerase sigma factor SigJ |
827 |
826 |
coexpression:822 |
Rv2488c |
LuxR family transcriptional regulator |
833 |
824 |
coexpression:800 |
Rv1019 |
transcriptional regulator |
820 |
818 |
coexpression:817 |
Rv0273c |
transcriptional regulator |
810 |
807 |
coexpression:806 |
Rv1151c cobB |
NAD-dependent protein deacylase |
805 |
805 |
coexpression:802 |
Rv3263 |
DNA methylase |
804 |
804 |
coexpression:804 |
Rv3736 |
AraC/XylS family transcriptional regulator |
810 |
803 |
coexpression:803 |
Rv0691c mftR |
mycofactocin biosynthesis transcriptional regulator MftR |
803 |
800 |
coexpression:799 |
Rv0212c nadR |
transcriptional regulator NadR |
799 |
799 |
coexpression:751 |
Rv0624 vapC30 |
ribonuclease VapC30 |
798 |
798 |
coexpression:798 |
Rv1931c |
transcriptional regulator |
798 |
798 |
coexpression:793 |
Rv2175c |
DNA-binding protein |
797 |
797 |
coexpression:797 |
Rv1359 |
transcriptional regulator |
797 |
797 |
coexpression:797 |
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 repressor SirR
- MTBC0 PGAP product: manganese-binding transcriptional regulator MntR
- Pfam (hmmscan --cut_ga): Fe_dep_repress PF01325.26 (E=7e-23), Fe_dep_repr_C PF02742.22 (E=3e-32), FeoA PF04023.21 (E=2e-12)
- (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_217304.1)
- Domains: Pfam-A via hmmscan --cut_ga — Fe_dep_repress (PF01325.26), Fe_dep_repr_C (PF02742.22), FeoA (PF04023.21)
- 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
COG1321
- Curated reference: UniProt
I6Y1Q2
(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 —
83 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002967|Rv2788|sirR
MRADEEPGDLSAVAQDYLKVIWTAQEWSQDKVSTKMLAERIGVSASTASESIRKLAEQGLVDHEKYGAVTLTDSGRRAALAMVRRHRLLETFLVNELGYRWDEVHDEAEVLEHAVSDRLMARIDAKLGFPQRDPHGDPIPGADGQVPTPPARQLWACRDGDTGTVARISDADPQMLRYFASIGISLDSRLRVLARREFAGMISVAIDSADGATVDLGSPAAQAIWVVS
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