tcrA Family assigned · medium auto-curated
H37Rv Rv0602c · MTBC0 - ·
253 aa · 699038–699799 (-) ·
RefSeq NP_215116.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | two component DNA binding transcriptional regulator TcrA |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Two component DNA binding transcriptional regulator TcrA. 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.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
O07776
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Transcriptional regulatory protein TcrA |
| Curated function | Member of the three-protein two-component system HK1/HK2/TcrA. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
T Signal transduction mechanisms
|
|---|---|
| Preferred name | tcrA |
| eggNOG description | Response regulator receiver domain |
| Orthologous group | COG0745 |
| KEGG orthology |
K02483
|
| Gene Ontology (35) |
GO:0000156, GO:0000160, GO:0003674, GO:0005575, GO:0005623, GO:0005886, GO:0007154, GO:0007165, GO:0008150, GO:0009966, GO:0009968, GO:0009987 +23 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 | 0.501 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 4 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 | 5.3e-31 | 25–134 | Response regulator receiver domain |
Trans_reg_C | PF00486.35 | 6.2e-23 | 168–242 | Transcriptional regulatory protein, C terminal |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0601c (two component sensor kinase HK2), high confidence from genomic context alone (score 967 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0601c |
two component sensor kinase HK2 | 987 | 967 ctx | neighborhood:700 cooccurence:616 coexpression:606 textmining:644 |
Rv0600c |
two component sensor kinase HK1 | 970 | 938 ctx | neighborhood:441 cooccurence:762 textmining:541 |
Rv0603 hyp |
hypothetical protein | 935 | 936 ctx | neighborhood:559 coexpression:860 |
Rv1032c trcS |
two component sensor histidine kinase TrcS | 899 | 872 ctx | cooccurence:706 |
Rv0902c prrB |
two component sensor histidine kinase PrrB | 944 | 870 ctx | cooccurence:700 textmining:594 |
Rv1675c cmr |
HTH-type transcriptional regulator Cmr | 877 | 870 | coexpression:854 |
Rv0982 mprB |
two component histidine-protein kinase/phosphatase MprB | 872 | 867 ctx | cooccurence:696 |
Rv3840 |
transcriptional regulator | 865 | 860 | coexpression:860 |
Rv3167c |
TetR family transcriptional regulator | 859 | 859 | coexpression:859 |
Rv3764c tcrY |
two component sensor kinase TcrY | 888 | 858 ctx | cooccurence:672 |
Rv1359 |
transcriptional regulator | 858 | 858 | coexpression:839 |
Rv0758 phoR |
two component system response sensor kinase PhoR | 877 | 852 ctx | cooccurence:742 |
Rv0490 senX3 |
two component sensor histidine kinase SenX3 | 889 | 850 ctx | cooccurence:737 |
Rv1776c |
transcriptional regulator | 848 | 848 | coexpression:848 |
Rv0691c mftR |
mycofactocin biosynthesis transcriptional regulator MftR | 848 | 848 | coexpression:848 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): two component DNA binding transcriptional regulator TcrA
- Pfam (hmmscan --cut_ga): Response_reg PF00072.31 (E=5e-31), Trans_reg_C PF00486.35 (E=6e-23)
- (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_215116.1)
- 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 O07776 (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 —
102 functional partner(s); context anchor
Rv0601c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0602c|tcrA MADETTMRAGRGPGRACGRVSGVRILVVEDEPKMTALLARALTEEGHTVDTVADGRHAVAAVDGGDYDAVVLDVMLPGIDGFEVCARLRRQRVWTPVLMLTARGAVTDRIAGLDGGADDYLTKPFNLDELFARLRALSRRGPIPRPPTLEAGDLRLDPSEHRVWRADTEIRLSHKEFTLLEALIRRPGIVHTRAQLLERCWDAAYEARSNIVDVYIRYLRDKIDRPFGVTSLETIRGAGYRLRKDGGRHALPR