Rv0036c Family assigned · medium
H37Rv Rv0036c · MTBC0 mtbc0_000041 ·
257 aa · 39155–39928 (-) ·
RefSeq NP_214550.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | TIGR03084 family metal-binding protein |
| Revised (this work) | Putative DinB/YfiT-like metal-dependent enzyme (Pfam DinB_2 PF12867, with MDMPI_N PF11716). The DinB superfamily is a versatile metal-binding four-helix bundle; PGAP annotates a TIGR03084-family metal-binding protein. Distinct from the Y-family DNA polymerases DinB1/DinB2 (Rv1537/Rv3056); the specific catalytic activity of Rv0036c is not established. |
Curated reference (UniProt)
| UniProt |
P9WM91
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized protein Rv0036c |
UniProt still lists this protein as Uncharacterized protein Rv0036c; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Wyosine base formation |
| Orthologous group | 28HG7 |
| Gene Ontology (8) |
GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0016020, GO:0030312, 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) pseudogene candidate
| pN/pS | 0.663 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 8 missense, 1 nonsense, 1 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 1.35% of strains (1957) · clonal |
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 |
|---|---|---|---|---|
MDMPI_N | PF11716.14 | 3.7e-31 | 11–147 | Mycothiol maleylpyruvate isomerase N-terminal domain |
DinB_2 | PF12867.13 | 1.8e-08 | 12–142 | DinB superfamily |
Wyosine_form | PF08608.18 | 7.3e-11 | 183–226 | Wyosine base formation |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0037c (MFS-type transporter), high confidence from genomic context alone (score 819 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) |
|---|---|---|---|---|
Rv0037c |
MFS-type transporter | 818 | 819 ctx | neighborhood:816 |
Rv0038 hyp |
hypothetical protein | 739 | 739 ctx | neighborhood:738 |
Rv0976c hyp |
hypothetical protein | 700 | 701 ctx | cooccurence:628 |
Rv0972c fadE12 |
acyl-CoA dehydrogenase fadE12 | 527 | 527 ctx | cooccurence:511 |
Rv2778c hyp |
hypothetical protein | 524 | 524 ctx | cooccurence:515 |
Rv0876c |
transmembrane protein | 517 | 517 ctx | cooccurence:514 |
Rv2912c |
TetR family HTH-type transcriptional regulator | 403 | 403 | |
Rv0931c pknD |
serine/threonine-protein kinase PknD | 546 | 53 | textmining:541 |
Rv0831c hyp |
hypothetical protein | 870 | 47 | textmining:870 |
Rv0941c hyp |
hypothetical protein | 868 | 47 | textmining:868 |
Rv0014c pknB |
serine/threonine-protein kinase PknB | 434 | 44 | textmining:433 |
Rv1507c hyp |
hypothetical protein | 437 | 42 | textmining:437 |
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: 'TIGR03084 family metal-binding protein'
- Pfam: MDMPI_N PF11716 (E=3.7e-31), DinB_2 PF12867 (E=1.8e-08), Wyosine_form PF08608 (E=7.3e-11) -- DinB-like metal-binding fold
- DinB family = metal-binding 4-helix bundle, enzymatically versatile; Rv0036c is NOT one of the characterised DinB DNA polymerases (Rv1537/Rv3056)
ESM Atlas signal (exploratory)
Ancestral protein hash db392d22b8c76b01f6c8aaf80c6e9232 ·
10 ESM-space neighbours (max similarity 0.910).
SAE features are orienting indices, not validated domains.
| # | Index | Activation | Interpretation |
|---|---|---|---|
| 1 | 16286 |
1.00 | Noncatalytic redox interfaces |
| 2 | 593 |
0.99 | Active-site metal-proximal helices |
| 3 | 4375 |
0.93 | Charged helix-capping pocket loop |
| 4 | 4851 |
0.87 | Amphipathic C-terminal interaction surfaces |
| 5 | 6050 |
0.86 | Aromatic–glycine hotspot motif |
| 6 | 3853 |
0.85 | Acidic amphipathic helix nucleators |
| 7 | 12426 |
0.69 | Active-site-adjacent scaffolding segments |
| 8 | 4287 |
0.66 | Non-heme diiron helical scaffolds |
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_214550.1)
- Domains: Pfam-A via hmmscan --cut_ga — MDMPI_N (PF11716.14), DinB_2 (PF12867.13), Wyosine_form (PF08608.18)
- 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
28HG7 - Curated reference: UniProt P9WM91 (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 —
12 functional partner(s); context anchor
Rv0037c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000041|Rv0036c| MADPGPFVADLRAESDDLDALVAHLPADRWADPTPAPGWTIAHQIGHLLWTDRVALTAVTDEAGFAELMTAAAANPAGFVDDAATELAAVSPAELLTDWRVTRGRLHEELLAVPDGRKLAWFGPPMSAASMATARLMETWAHGLDVADALGVIRPATQRLRSIAHLGVRTRDYAFIVNNLTPPAEPFLVELRGPSGDTWSWGPSDAAQRVTGSAEDFCFLVTQRRALSTLDVNAVGEDAQRWLTIAQAFAGPPGRGR