tcrX Resolved · high auto-curated
H37Rv Rv3765c · MTBC0 mtbc0_003989 ·
234 aa · 4235201–4235905 (-) ·
RefSeq NP_218282.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | two component transcriptional regulator TcrX |
|---|---|
| MTBC0 PGAP re-annotation | two-component system response regulator TcrX |
| Revised (this work) | Two-component system response regulator TcrX. Pfam: Response_reg (PF00072.31), Trans_reg_C (PF00486.35). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O69730
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable transcriptional regulatory protein TcrX |
| Curated function | Member of the two-component regulatory system TcrY/TcrX. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K TranscriptionT Signal transduction mechanisms
|
|---|---|
| Preferred name | tcrX |
| eggNOG description | transcriptional |
| Orthologous group | COG0745 |
| KEGG orthology |
K02483, K07672
|
| KEGG pathways |
map02020
|
| KEGG modules |
M00463
|
| Gene Ontology (33) |
GO:0006873, GO:0006875, GO:0006879, GO:0006950, GO:0007154, GO:0008150, GO:0009267, GO:0009605, GO:0009987, GO:0009991, GO:0010106, GO:0019725 +21 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 | 0.171 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 2 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 |
|---|---|---|---|---|
Response_reg | PF00072.31 | 7.9e-30 | 11–120 | Response regulator receiver domain |
Trans_reg_C | PF00486.35 | 3.4e-25 | 156–230 | Transcriptional regulatory protein, C terminal |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: tcrY (two component sensor kinase TcrY), high confidence from genomic context alone (score 985 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3764c tcrY |
two component sensor kinase TcrY | 993 | 985 ctx | neighborhood:793 cooccurence:772 coexpression:569 textmining:548 |
Rv1032c trcS |
two component sensor histidine kinase TrcS | 922 | 900 ctx | cooccurence:771 |
Rv0600c |
two component sensor kinase HK1 | 911 | 887 ctx | cooccurence:746 |
Rv0902c prrB |
two component sensor histidine kinase PrrB | 922 | 877 ctx | cooccurence:721 |
Rv0758 phoR |
two component system response sensor kinase PhoR | 880 | 859 ctx | cooccurence:748 |
Rv0982 mprB |
two component histidine-protein kinase/phosphatase MprB | 864 | 859 ctx | cooccurence:674 |
Rv0490 senX3 |
two component sensor histidine kinase SenX3 | 895 | 853 ctx | cooccurence:736 |
Rv3245c mtrB |
two component sensory histidine kinase MtrB | 795 | 741 ctx | cooccurence:549 |
Rv0601c |
two component sensor kinase HK2 | 752 | 689 | |
Rv2998A |
Rv2998A, len: 67 aa. Probable conserved hypothetical protein, (possibly gene fragment), highly similar to central part of two-component sens | 644 | 631 | |
Rv3365c hyp |
hypothetical protein | 593 | 578 | |
Rv3645 |
transmembrane protein | 548 | 520 | |
Rv1028c kdpD |
sensor protein KdpD | 594 | 511 | experimental:417 |
Rv2435c |
cyclase | 512 | 463 | experimental:444 |
Rv3151 nuoG |
NADH-quinone oxidoreductase subunit G | 461 | 427 | experimental:423 |
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: two component transcriptional regulator TcrX
- MTBC0 PGAP product: two-component system response regulator TcrX
- Pfam (hmmscan --cut_ga): Response_reg PF00072.31 (E=8e-30), Trans_reg_C PF00486.35 (E=3e-25)
- (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_218282.1)
- Domains: Pfam-A via hmmscan --cut_ga — Response_reg (PF00072.31), Trans_reg_C (PF00486.35)
- 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
COG0745 - Curated reference: UniProt O69730 (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 —
30 functional partner(s); context anchor
tcrY - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003989|Rv3765c|tcrX MRRADGQPVTVLVVDDEPVLAEMVSMALRYEGWNITTAGDGSSAIAAARRQRPDVVVLDVMLPDMSGLDVLHKLRSENPGLPVLLLTAKDAVEDRIAGLTAGGDDYVTKPFSIEEVVLRLRALLRRTGVTTVDSGAQLVVGDLVLDEDSHEVMRAGEPVSLTSTEFELLRFMMHNSKRVLSKAQILDRVWSYDFGGRSNIVELYISYLRKKIDNGREPMIHTLRGAGYVLKPAR