Rv2017 Family assigned · medium auto-curated
H37Rv Rv2017 · MTBC0 mtbc0_002147 ·
346 aa · 2287611–2288651 (+) ·
RefSeq NP_216533.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | transcriptional regulator |
|---|---|
| MTBC0 PGAP re-annotation | ImmA/IrrE family metallo-endopeptidase |
| Revised (this work) | ImmA/IrrE family metallo-endopeptidase. Pfam: HTH_31 (PF13560.13), HTH_19 (PF12844.14), HTH_3 (PF01381.29), Peptidase_M78 (PF06114.20). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53463
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Transcriptional regulatory protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| eggNOG description | IrrE N-terminal-like domain |
| Orthologous group | COG1396 |
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 | 0.27 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 12 synonymous, 10 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_31 | PF13560.13 | 3.7e-12 | 4–62 | Helix-turn-helix domain |
HTH_19 | PF12844.14 | 1.4e-08 | 8–66 | Helix-turn-helix domain |
HTH_3 | PF01381.29 | 4.3e-16 | 11–61 | Helix-turn-helix |
Peptidase_M78 | PF06114.20 | 8.9e-27 | 154–264 | IrrE N-terminal-like domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: relE (toxin RelE), medium confidence from genomic context alone (score 449 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2016 hyp |
hypothetical protein | 927 | 846 ctx | neighborhood:809 textmining:544 |
Rv0792c |
transcriptional regulator | 788 | 775 | coexpression:744 |
Rv2912c |
TetR family HTH-type transcriptional regulator | 735 | 731 | coexpression:731 |
Rv1963c mce3R |
transcriptional repressor Mce3R | 734 | 730 | coexpression:730 |
Rv3066 |
DeoR family transcriptional regulator | 694 | 695 | coexpression:651 |
Rv2011c hyp |
hypothetical protein | 701 | 691 | coexpression:651 |
Rv3334 |
MerR family transcriptional regulator | 638 | 620 | coexpression:539 |
Rv0332 hyp |
hypothetical protein | 541 | 517 | experimental:434 |
Rv0767c |
HTH-type transcriptional regulator | 522 | 514 | coexpression:514 |
Rv2515c hyp |
hypothetical protein | 636 | 484 | |
Rv2018 vapB45 hyp |
hypothetical protein | 688 | 469 ctx | neighborhood:456 textmining:438 |
Rv3833 |
AraC family transcriptional regulator | 535 | 459 | coexpression:428 |
Rv0366c hyp |
hypothetical protein | 693 | 451 | experimental:434 textmining:465 |
Rv1246c relE |
toxin RelE | 511 | 449 ctx | cooccurence:413 |
Rv2019 vapC45 hyp |
hypothetical protein | 434 | 434 ctx | neighborhood:432 |
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: ImmA/IrrE family metallo-endopeptidase
- Pfam (hmmscan --cut_ga): HTH_31 PF13560.13 (E=4e-12), HTH_19 PF12844.14 (E=1e-08), HTH_3 PF01381.29 (E=4e-16), Peptidase_M78 PF06114.20 (E=9e-27)
- (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_216533.1)
- Domains: Pfam-A via hmmscan --cut_ga — HTH_31 (PF13560.13), HTH_19 (PF12844.14), HTH_3 (PF01381.29), Peptidase_M78 (PF06114.20)
- 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
COG1396 - Curated reference: UniProt O53463 (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 —
40 functional partner(s); context anchor
relE - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002147|Rv2017| MNGLGDVLAVARKARGLTQIELAELVGLTQPAINRYESGDRDPDQHIVAKLAEILGVTDDLLIHGNRFRGALAVDAHMRRHKTTKASAWRQLEARLNLLRVHASFLFEEVAINSEQHVPAFDPEFTAAEDAARLVRAQWRMPMGPVVNLTRWMEAAGCLVFEEDFATQRIDGLSQWVDDYPVMLINANAAPDRKRLTLAHELGHLVLHSTNPTENMETEATAFAAEFLMPESEIRPELRRLDLGKLLELKREWGVSMQALLERAYRMGLVSAEARTKLYKAMNARGWKTKEPGIESIVREKPSLPAHIGMTLRSRGFTDQQAAAIAGYANPADNPFRPEGGRLHAI