cmtR Family assigned · medium auto-curated
H37Rv Rv1994c · MTBC0 mtbc0_002121 ·
118 aa · 2261241–2261597 (-) ·
RefSeq NP_216510.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | HTH-type transcriptional regulator CmtR |
|---|---|
| MTBC0 PGAP re-annotation | Cd(II)/Pb(II)-sensing metalloregulatory transcriptional regulator CmtR |
| Revised (this work) | Cd(II)/Pb(II)-sensing metalloregulatory transcriptional regulator CmtR. Pfam: HTH_20 (PF12840.14), HTH_5 (PF01022.27). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WMI9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | HTH-type transcriptional regulator CmtR |
| Curated function | Metal-responsive transcriptional repressor for the cmt operon. Binding of cadmium or lead causes the repressor to dissociate from the DNA. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
|---|---|
| Preferred name | cmtR |
| eggNOG description | Transcriptional regulator |
| Orthologous group | COG0640 |
| KEGG orthology |
K21885
|
| Gene Ontology (40) |
GO:0003674, GO:0003676, GO:0003677, GO:0003700, GO:0005488, GO:0006355, GO:0008150, GO:0009889, GO:0010035, GO:0010038, GO:0010288, GO:0010468 +28 more
|
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 |
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-08 | 18–64 | Helix-turn-helix domain |
HTH_5 | PF01022.27 | 1.1e-16 | 20–64 | Bacterial regulatory protein, arsR family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ctpG (cation transporter ATPase G), high confidence from genomic context alone (score 780 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1992c ctpG |
cation transporter ATPase G | 892 | 780 ctx | neighborhood:663 textmining:533 |
Rv1993c hyp |
hypothetical protein | 935 | 684 ctx | neighborhood:680 textmining:805 |
Rv1995 hyp |
hypothetical protein | 732 | 539 ctx | neighborhood:528 textmining:443 |
Rv2640c |
ArsR family transcriptional regulator | 680 | 462 ctx | cooccurence:454 textmining:431 |
Rv2643 arsC |
arsenic-transport integral membrane protein ArsC | 511 | 438 | |
Rv1991c mazF6 |
mRNA interferase MazF6 | 435 | 435 ctx | neighborhood:432 |
Rv2358 smtB |
HTH-type transcriptional regulator SmtB | 797 | 433 ctx | cooccurence:429 textmining:658 |
Rv1991A mazE6 |
antitoxin MazE6 | 462 | 432 ctx | neighborhood:432 |
Rv3271c |
integral membrane protein | 419 | 391 | |
Rv1996 |
universal stress protein | 401 | 379 | |
Rv0827c kmtR |
HTH-type transcriptional regulator KmtR | 671 | 352 | textmining:513 |
Rv2034 |
ArsR family HTH-type transcriptional repressor | 552 | 313 | |
Rv0092 ctpA |
cation transporter ATPase A | 412 | 278 | |
Rv2641 cadI |
cadmium inducible protein CadI | 498 | 118 | textmining:455 |
Rv2025c |
cation efflux system protein | 480 | 83 | textmining:457 |
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 CmtR
- MTBC0 PGAP product: Cd(II)/Pb(II)-sensing metalloregulatory transcriptional regulator CmtR
- Pfam (hmmscan --cut_ga): HTH_20 PF12840.14 (E=4e-08), HTH_5 PF01022.27 (E=1e-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_216510.1)
- Domains: Pfam-A via hmmscan --cut_ga — HTH_20 (PF12840.14), HTH_5 (PF01022.27)
- 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 P9WMI9 (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 —
23 functional partner(s); context anchor
ctpG - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002121|Rv1994c|cmtR MLTCEMRESALARLGRALADPTRCRILVALLDGVCYPGQLAAHLGLTRSNVSNHLSCLRGCGLVVATYEGRQVRYALADSHLARALGELVQVVLAVDTDQPCVAERAASGEAVEMTGS