hrcA Resolved · high auto-curated
H37Rv Rv2374c · MTBC0 mtbc0_002526 ·
343 aa · 2678255–2679286 (-) ·
RefSeq NP_216890.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | heat-inducible transcription repressor HrcA |
|---|---|
| MTBC0 PGAP re-annotation | heat-inducible transcriptional repressor HrcA |
| Revised (this work) | Heat-inducible transcriptional repressor HrcA. Pfam: HrcA (PF01628.28). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WMK3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Heat-inducible transcription repressor HrcA |
| Curated function | Negative regulator of class I heat shock genes (grpE-dnaK-dnaJ and groELS operons). Prevents heat-shock induction of these operons. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
|---|---|
| Preferred name | hrcA |
| eggNOG description | Negative regulator of class I heat shock genes (grpE- dnaK-dnaJ and groELS operons). Prevents heat-shock induction of these operons |
| Orthologous group | COG1420 |
| KEGG orthology |
K03705
|
| Gene Ontology (41) |
GO:0005575, GO:0005623, GO:0005886, GO:0006355, GO:0008150, GO:0009889, GO:0009890, GO:0009892, GO:0010468, GO:0010556, GO:0010558, GO:0010605 +29 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 | 0.444 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 6 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 |
|---|---|---|---|---|
HrcA | PF01628.28 | 5.8e-58 | 105–326 | HrcA protein C terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: dnaJ2 (chaperone protein DnaJ), high confidence from genomic context alone (score 933 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2373c dnaJ2 |
chaperone protein DnaJ | 971 | 933 ctx | neighborhood:790 coexpression:692 textmining:591 |
Rv0351 grpE |
stress response protein GrpE | 963 | 869 | coexpression:858 textmining:735 |
Rv2372c rsmE |
rRNA small subunit methyltransferase E | 825 | 795 ctx | neighborhood:784 |
Rv2375 hyp |
hypothetical protein | 766 | 766 ctx | neighborhood:766 |
Rv0352 dnaJ1 |
chaperone protein DnaJ | 842 | 711 | coexpression:676 textmining:478 |
Rv3446c hyp |
hypothetical protein | 773 | 688 | coexpression:677 |
Rv2461c clpP1 |
ATP-dependent CLP protease proteolytic subunit 1 | 722 | 685 | coexpression:685 |
Rv2264c hyp |
hypothetical protein | 770 | 684 | coexpression:673 |
Rv0350 dnaK |
chaperone protein DnaK | 944 | 683 | coexpression:672 textmining:833 |
Rv2460c clpP2 |
ATP-dependent CLP protease proteolytic subunit 2 | 757 | 682 | coexpression:682 |
Rv0312 hyp |
hypothetical protein | 768 | 681 | coexpression:670 |
Rv0757 phoP |
two component system response transcriptional positive regulator PhoP | 648 | 618 | experimental:550 |
Rv2366c |
transmembrane protein | 535 | 536 ctx | neighborhood:529 |
Rv0440 groEL2 |
molecular chaperone GroEL | 850 | 529 | coexpression:502 textmining:695 |
Rv3417c groEL1 |
chaperonin GroEL | 871 | 528 | coexpression:501 textmining:739 |
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: heat-inducible transcription repressor HrcA
- MTBC0 PGAP product: heat-inducible transcriptional repressor HrcA
- Pfam (hmmscan --cut_ga): HrcA PF01628.28 (E=6e-58)
- (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_216890.1)
- Domains: Pfam-A via hmmscan --cut_ga — HrcA (PF01628.28)
- 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
COG1420 - Curated reference: UniProt P9WMK3 (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 —
49 functional partner(s); context anchor
dnaJ2 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002526|Rv2374c|hrcA MGSADERRFEVLRAIVADFVATQEPIGSKSLVERHNLGVSSATVRNDMAVLEAEGYITQPHTSSGRVPTEKGYREFVDRLEDVKPLSSAERRAIQSFLESGVDLDDVLRRAVRLLAQLTRQVAVVQYPTLSTSTVRHLEVIALTPARLLMVVITDSGRVDQRIVELGDVIDDHQLAQLREILGQALEGKKLSAASVAVADLASQLGGAGGLGDAVGRAATVLLESLVEHTEERLLLGGTANLTRNAADFGGSLRSILEALEEQVVVLRLLAAQQEAGKVTVRIGHETASEQMVGTSMVSTAYGTAHTVYGGMGVVGPTRMDYPGTIASVAAVALYIGDVLGAR