nmtR Resolved · high auto-curated
H37Rv Rv3744 · MTBC0 mtbc0_003967 ·
120 aa · 4219561–4219923 (+) ·
RefSeq NP_218261.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | HTH-type transcriptional regulator NmtR |
|---|---|
| MTBC0 PGAP re-annotation | Ni(II)/Co(II)-sensing metalloregulatory transcriptional repressor NmtR |
| Revised (this work) | Ni(II)/Co(II)-sensing metalloregulatory transcriptional repressor NmtR. Pfam: HTH_20 (PF12840.14), HTH_5 (PF01022.27), HTH_IclR (PF09339.17), HTH_24 (PF13412.13). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O69711
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | HTH-type transcriptional regulator NmtR |
| Curated function | Represses transcription of ctpJ/nmtA, by binding to its promoter region. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
|---|---|
| Preferred name | nmtR |
| eggNOG description | helix_turn_helix, Arsenical Resistance Operon Repressor |
| Orthologous group | COG0640 |
| KEGG orthology |
K21886
|
| Gene Ontology (11) |
GO:0008150, GO:0010565, GO:0019216, GO:0019217, GO:0019222, GO:0031323, GO:0050789, GO:0050794, GO:0062012, GO:0065007, GO:0080090
|
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) | 3 synonymous, 0 missense, 0 nonsense, 0 frameshift |
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_20 | PF12840.14 | 3.8e-10 | 30–77 | Helix-turn-helix domain |
HTH_5 | PF01022.27 | 7.4e-16 | 33–76 | Bacterial regulatory protein, arsR family |
HTH_IclR | PF09339.17 | 1.3e-05 | 43–79 | IclR helix-turn-helix domain |
HTH_24 | PF13412.13 | 9.1e-05 | 43–76 | Winged helix-turn-helix DNA-binding |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ctpJ (cation transporter ATPase J), high confidence from genomic context alone (score 774 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3743c ctpJ |
cation transporter ATPase J | 889 | 774 ctx | neighborhood:580 textmining:532 |
Rv0894 |
transcriptional regulator | 731 | 731 | coexpression:731 |
Rv1359 |
transcriptional regulator | 703 | 703 | coexpression:703 |
Rv1469 ctpD |
cobalt/nickel-exporting P-type ATPase | 662 | 467 | |
Rv2359 zur |
zinc uptake regulation protein | 655 | 438 | textmining:413 |
Rv0081 |
HTH-type transcriptional regulator | 465 | 388 | |
Rv2643 arsC |
arsenic-transport integral membrane protein ArsC | 457 | 377 | |
Rv1674c |
transcriptional regulator | 656 | 285 | textmining:540 |
Rv0827c kmtR |
HTH-type transcriptional regulator KmtR | 438 | 276 | |
Rv2358 smtB |
HTH-type transcriptional regulator SmtB | 408 | 234 | |
Rv1470 trxA |
thioredoxin TrxA | 556 | 99 | textmining:528 |
Rv2641 cadI |
cadmium inducible protein CadI | 655 | 89 | textmining:638 |
Rv2640c |
ArsR family transcriptional regulator | 590 | 83 | textmining:572 |
Rv2025c |
cation efflux system protein | 872 | 80 | textmining:867 |
Rv2034 |
ArsR family HTH-type transcriptional repressor | 549 | 47 | textmining:547 |
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 NmtR
- MTBC0 PGAP product: Ni(II)/Co(II)-sensing metalloregulatory transcriptional repressor NmtR
- Pfam (hmmscan --cut_ga): HTH_20 PF12840.14 (E=4e-10), HTH_5 PF01022.27 (E=7e-16), HTH_IclR PF09339.17 (E=1e-05), HTH_24 PF13412.13 (E=9e-05)
- (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_218261.1)
- Domains: Pfam-A via hmmscan --cut_ga — HTH_20 (PF12840.14), HTH_5 (PF01022.27), HTH_IclR (PF09339.17), HTH_24 (PF13412.13)
- 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
COG0640 - Curated reference: UniProt O69711 (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 —
16 functional partner(s); context anchor
ctpJ - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003967|Rv3744|nmtR MGHGVEGRNRPSAPLDSQAAAQVASTLQALATPSRLMILTQLRNGPLPVTDLAEAIGMEQSAVSHQLRVLRNLGLVVGDRAGRSIVYSLYDTHVAQLLDEAIYHSEHLHLGLSDRHPSAG