lrpA Family assigned · medium auto-curated
H37Rv Rv3291c · MTBC0 mtbc0_003499 ·
150 aa · 3693925–3694377 (-) ·
RefSeq NP_217808.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | transcriptional regulator LrpA |
|---|---|
| MTBC0 PGAP re-annotation | transcriptional regulator LrpA |
| Revised (this work) | Transcriptional regulator LrpA. Pfam: HTH_24 (PF13412.13), HTH_AsnC-type (PF13404.13), AsnC_trans_reg (PF01037.29). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6YBQ3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | HTH-type transcriptional regulator LrpA |
| Curated function | Transcriptional regulator that probably plays an important role in M.tuberculosis persistence. Regulates the expression of several genes, including lat, rsmG, whiB2, lsr2 and Rv2011c. Acts by binding directly to the promoter region of the target genes. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
|---|---|
| Preferred name | lrp_3 |
| eggNOG description | AsnC family |
| Orthologous group | COG1522 |
| KEGG orthology |
K03719
|
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 | n/a |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 0 synonymous, 3 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_24 | PF13412.13 | 3.5e-13 | 5–52 | Winged helix-turn-helix DNA-binding |
HTH_AsnC-type | PF13404.13 | 8.5e-13 | 5–46 | AsnC-type helix-turn-helix domain |
AsnC_trans_reg | PF01037.29 | 7.1e-14 | 68–146 | Lrp/AsnC ligand binding domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: lat (L-lysine-epsilon aminotransferase), high confidence from genomic context alone (score 852 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3290c lat |
L-lysine-epsilon aminotransferase | 982 | 852 ctx | neighborhood:813 textmining:884 |
Rv3292 hyp |
hypothetical protein | 840 | 841 ctx | neighborhood:790 |
Rv3167c |
TetR family transcriptional regulator | 815 | 810 | coexpression:810 |
Rv1151c cobB |
NAD-dependent protein deacylase | 807 | 806 | coexpression:800 |
Rv0691c mftR |
mycofactocin biosynthesis transcriptional regulator MftR | 809 | 804 | coexpression:804 |
Rv0117 oxyS |
oxidative stress response regulatory protein OxyS | 813 | 803 | coexpression:803 |
Rv3293 pcd |
piperideine-6-carboxylic acid dehydrogenase | 809 | 802 ctx | neighborhood:764 |
Rv1960c parD1 |
antitoxin ParD1 | 802 | 802 | coexpression:802 |
Rv1359 |
transcriptional regulator | 802 | 802 | coexpression:802 |
Rv3840 |
transcriptional regulator | 800 | 800 | coexpression:800 |
Rv0603 hyp |
hypothetical protein | 799 | 799 | coexpression:799 |
Rv0212c nadR |
transcriptional regulator NadR | 805 | 798 | coexpression:798 |
Rv3830c |
TetR family transcriptional regulator | 803 | 798 | coexpression:798 |
Rv1267c embR |
transcriptional regulator EmbR | 798 | 798 | coexpression:798 |
Rv1740 vapB34 |
antitoxin VapB34 | 797 | 797 | coexpression:797 |
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 LrpA
- MTBC0 PGAP product: transcriptional regulator LrpA
- Pfam (hmmscan --cut_ga): HTH_24 PF13412.13 (E=4e-13), HTH_AsnC-type PF13404.13 (E=9e-13), AsnC_trans_reg PF01037.29 (E=7e-14)
- (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_217808.1)
- Domains: Pfam-A via hmmscan --cut_ga — HTH_24 (PF13412.13), HTH_AsnC-type (PF13404.13), AsnC_trans_reg (PF01037.29)
- 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
COG1522 - Curated reference: UniProt I6YBQ3 (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 —
67 functional partner(s); context anchor
lat - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003499|Rv3291c|lrpA MNEALDDIDRILVRELAADGRATLSELATRAGLSVSAVQSRVRRLESRGVVQGYSARINPEAVGHLLSAFVAITPLDPSQPDDAPARLEHIEEVESCYSVAGEESYVLLVRVASARALEDLLQRIRTTANVRTRSTIILNTFYSDRQHIP