Rv3073c Still unknown · low auto-curated
H37Rv Rv3073c · MTBC0 mtbc0_003267 ·
118 aa · 3457693–3458049 (-) ·
RefSeq NP_217589.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | DUF488 domain-containing protein |
| Revised (this work) | Conserved hypothetical protein; DUF domain(s) DUF488-N3i, DUF488-N3a, DUF488. Function unknown. Foldseek best (non-significant) hit: 3ijd-assembly2_B-2 Uncharacterized protein Cthe_2304 from Clostridium (prob 0.04, TM 0.37). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WL11
SwissProt · reviewed
· Predicted
|
|---|---|
| UniProt name | Uncharacterized protein Rv3073c |
UniProt still lists this protein as Uncharacterized protein Rv3073c; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Protein of unknown function, DUF488 |
| Orthologous group | COG3189 |
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 | 0.641 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 4 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.11% of strains (164) · 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 |
|---|---|---|---|---|
DUF488-N3i | PF22752.2 | 2.2e-33 | 7–116 | Inactive DUF488-N3 subclade |
DUF488-N3a | PF22751.2 | 6.9e-21 | 7–116 | Active DUF488-N3 subclade |
DUF488 | PF04343.19 | 7.5e-27 | 9–115 | Domain of unknown function DUF488 |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 77.8 (confident). A confident model makes the fold comparison meaningful.
Best matches against the PDB, ranked by Foldseek homology probability. A high probability / TM-score suggests a shared fold; unless flagged sig (E < 0.01) these are fold hypotheses, not assignments.
| Target | Prob | TM | E-value | Description |
|---|---|---|---|---|
3ijd-assembly2_B-2 |
0.04 | 0.37 | 4.3e+00 | 3ijd-assembly2_B-2 Uncharacterized protein Cthe_2304 from Clostridium thermocellum binds two copies of 5-methyl-5,6,7,8-tetrahydrofolic acid |
3ijd-assembly2_A |
0.02 | 0.35 | 9.4e+00 | 3ijd-assembly2_A Uncharacterized protein Cthe_2304 from Clostridium thermocellum binds two copies of 5-methyl-5,6,7,8-tetrahydrofolic acid |
7w5r-assembly1_Q |
0.01 | 0.31 | 1.0e+01 | 7w5r-assembly1_Q KRAS G12V and peptide complex |
4phh-assembly3_C |
0.01 | 0.27 | 7.2e+00 | 4phh-assembly3_C Crystal structure of Ypt7 covalently modified with GNP |
4phh-assembly1_A |
0.01 | 0.28 | 8.8e+00 | 4phh-assembly1_A Crystal structure of Ypt7 covalently modified with GNP |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: udgB (uracil DNA glycosylase), medium confidence from genomic context alone (score 625 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) |
|---|---|---|---|---|
Rv3072c hyp |
hypothetical protein | 818 | 818 ctx | neighborhood:817 |
Rv1259 udgB |
uracil DNA glycosylase | 625 | 625 ctx | fusion:570 |
Rv3074 hyp |
hypothetical protein | 599 | 599 ctx | neighborhood:598 |
Rv3075c hyp |
hypothetical protein | 545 | 545 ctx | neighborhood:544 |
Rv1347c mbtK |
lysine N-acetyltransferase MbtK | 462 | 463 ctx | neighborhood:461 |
Rv3100c smpB |
SsrA-binding protein | 426 | 427 |
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: hypothetical protein
- MTBC0 PGAP product: DUF488 domain-containing protein
- Pfam (hmmscan --cut_ga): DUF488-N3i PF22752.2 (E=2e-33), DUF488-N3a PF22751.2 (E=7e-21), DUF488 PF04343.19 (E=8e-27)
- Foldseek best: 3ijd-assembly2_B-2 Uncharacterized protein Cthe_2304 from Clostridium thermocell (prob 0.04, E=4e+00, TM=0.37)
- (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_217589.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF488-N3i (PF22752.2), DUF488-N3a (PF22751.2), DUF488 (PF04343.19)
- 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
COG3189 - Curated reference: UniProt P9WL11 (SwissProt, reviewed; Predicted)
- Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
- Model confidence: ESMFold per-residue pLDDT (mean 77.8, confident)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
6 functional partner(s); context anchor
udgB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003267|Rv3073c| MVRETRVRVARVYEDIDPDDGQRVLVDRIWPHGIRKDDQRVGIWCKDVAPSKELREWYHHQPERFDEFASRYQEELHDSAALAELRKLTGRSVVTPVTATRHVARSHAAVLAQLLNGR