Rv0181c Family assigned · medium
H37Rv Rv0181c · MTBC0 mtbc0_000194 ·
244 aa · 212625–213359 (-) ·
RefSeq NP_214695.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | pirin family protein |
| Revised (this work) | Pirin-family cupin metalloenzyme (Pfam Pirin PF02678 + Pirin_C_2 PF17954). A bicupin, often Fe-dependent (quercetinase / related dioxygenase chemistry); specific substrate not established. |
Curated reference (UniProt)
| UniProt |
P9WI85
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Putative quercetin 2,3-dioxygenase Rv0181c |
| EC (curated) |
EC 1.13.11.24
|
| Curated function | Putative quercetin 2,3-dioxygenase. |
UniProt still lists this protein as Putative quercetin 2,3-dioxygenase Rv0181c; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Belongs to the pirin family |
| Orthologous group | COG1741 |
| KEGG orthology |
K06911
|
| Gene Ontology (11) |
GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0016020, GO:0044424, GO:0044444, GO:0044464, GO:0071944
|
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, 7 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 |
|---|---|---|---|---|
Pirin | PF02678.23 | 8.2e-38 | 12–122 | Pirin |
Pirin_C_2 | PF17954.8 | 1.7e-06 | 156–235 | Quercetinase C-terminal cupin domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0180c (transmembrane protein), high confidence from genomic context alone (score 848 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0180c |
transmembrane protein | 968 | 848 ctx | neighborhood:846 textmining:803 |
Rv0182c sigG |
ECF RNA polymerase sigma factor SigG | 836 | 767 ctx | neighborhood:745 |
Rv0179c lprO |
lipoprotein LprO | 782 | 564 ctx | neighborhood:563 textmining:520 |
Rv0183 |
lysophospholipase | 840 | 557 ctx | neighborhood:557 textmining:653 |
Rv0185 hyp |
hypothetical protein | 474 | 474 ctx | neighborhood:459 |
Rv0184 hyp |
hypothetical protein | 474 | 474 ctx | neighborhood:461 |
Rv1364c |
sigma factor regulatory protein | 420 | 419 | coexpression:418 |
Rv0186 bglS |
beta-glucosidase BglS | 400 | 401 | |
Rv0654 |
carotenoid cleavage oxygenase | 583 | 183 | textmining:511 |
Rv0887c hyp |
hypothetical protein | 838 | 165 | textmining:814 |
Rv0886 fprB |
ferredoxin/ferredoxin--NADP reductase | 548 | 68 | textmining:535 |
Rv2010 vapC15 |
ribonuclease VapC15 | 587 | 55 | textmining:581 |
Rv0911 hyp |
hypothetical protein | 806 | 52 | textmining:804 |
Rv0234c gabD1 |
succinate-semialdehyde dehydrogenase | 678 | 47 | textmining:676 |
Rv2009 vapB15 |
antitoxin VapB15 | 654 | 47 | textmining:652 |
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
- MTBC0 PGAP product: 'pirin family protein'
- Pfam: Pirin PF02678 (E=8.2e-38), Pirin_C_2 PF17954 (E=1.7e-06)
ESM Atlas signal (exploratory)
Ancestral protein hash bb58cd8e96c547f3f1789973b1de72f9 ·
10 ESM-space neighbours (max similarity 0.919).
SAE features are orienting indices, not validated domains.
| # | Index | Activation | Interpretation |
|---|---|---|---|
| 1 | 14466 |
0.94 | Cupin/DSBH metal-binding scaffold |
| 2 | 14257 |
0.91 | Cupin/DSBH N-terminal entry cap |
| 3 | 12580 |
0.88 | Acidic His/Gly binding loop |
| 4 | 869 |
0.87 | Glycine/acidic ligand-sensing loops |
| 5 | 3059 |
0.85 | Histidine-acidic metal-binding motif |
| 6 | 12737 |
0.82 | Conserved ligand-facing beta hairpin |
| 7 | 5835 |
0.77 | Conserved functional core segments |
| 8 | 15646 |
0.74 | Cupin/CNBD ligand-binding loop |
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_214695.1)
- Domains: Pfam-A via hmmscan --cut_ga — Pirin (PF02678.23), Pirin_C_2 (PF17954.8)
- 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
COG1741 - Curated reference: UniProt P9WI85 (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 —
18 functional partner(s); context anchor
Rv0180c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000194|Rv0181c| MTATVEIRRAADRAVTTTSWLKSRHSFSFGDHYDPDNTHHGLLLVNNDDQMEPASGFDPHPHRDMEIVTWVLRGALRHQDSAGNSGVIYPGLAQRMSAGTGILHSEMNDSATEPVHFVQMWVIPDATGITASYQQQEIDDELLRAGLVTIASGIPGQDAALTLHNSSASLHGARLRPGATVSLPCAPFLHLFVAYGRLTLEGGGELADGDAVRFTDADARGLTANEPSEVLIWEMHAKLGDSAT