Rv2117 Family assigned · low auto-curated · to review
H37Rv Rv2117 · MTBC0 mtbc0_002249 ·
97 aa · 2404411–2404704 (+) ·
RefSeq NP_216633.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | DUF503 domain-containing protein |
| Revised (this work) | DUF503 domain-containing protein. |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed (flagged for human review).
Curated reference (UniProt)
| UniProt |
O33252
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | DUF503 domain-containing protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Protein of unknown function (DUF503) |
| Orthologous group | COG1550 |
| KEGG orthology |
K09764
|
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, 1 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 |
|---|---|---|---|---|
DUF503 | PF04456.18 | 1.9e-30 | 3–89 | Protein of unknown function (DUF503) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 91.5 (very high). 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 |
|---|---|---|---|---|
1j27-assembly1_A |
1.00 | 0.94 | 1.4e-08 sig | 1j27-assembly1_A Crystal structure of a hypothetical protein, TT1725, from Thermus thermophilus HB8 at 1.7A resolution |
7b90-assembly1_E |
1.00 | 0.69 | 3.8e-04 sig | 7b90-assembly1_E Circular permutant of ribosomal protein S6, P54-55 truncated, I8A mutant |
1q8b-assembly1_A |
1.00 | 0.57 | 9.9e-04 sig | 1q8b-assembly1_A Structural Genomics, protein YJCS |
3kg1-assembly3_A-2 |
1.00 | 0.52 | 5.0e-04 sig | 3kg1-assembly3_A-2 Crystal structure of SnoaB, a cofactor-independent oxygenase from Streptomyces nogalater, mutant N63A |
1wd6-assembly1_B |
1.00 | 0.58 | 3.6e-03 sig | 1wd6-assembly1_B crystal structure of JW1657 from Escherichia coli |
6wi5-assembly2_B |
1.00 | 0.59 | 2.7e-03 sig | 6wi5-assembly2_B De novo designed protein Foldit4 |
2n76-assembly1_A |
1.00 | 0.54 | 2.2e-03 sig | 2n76-assembly1_A Solution NMR Structure of De novo designed protein LFR1 1 with ferredoxin fold, Northeast Structural Genomics Consortium (NESG) Target OR414 |
3kng-assembly1_B |
0.99 | 0.50 | 1.7e-03 sig | 3kng-assembly1_B Crystal structure of SnoaB, a cofactor-independent oxygenase from Streptomyces nogalater, determined to 1.9 resolution |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: lppK (lipoprotein LppK), high confidence from genomic context alone (score 884 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) |
|---|---|---|---|---|
Rv2116 lppK |
lipoprotein LppK | 884 | 884 ctx | neighborhood:882 |
Rv2115c mpa |
proteasome-associated ATPase | 726 | 726 ctx | neighborhood:726 |
Rv2838c rbfA |
ribosome-binding factor RbfA | 714 | 695 | coexpression:644 |
Rv2839c infB |
translation initiation factor IF-2 | 607 | 581 | coexpression:511 |
Rv2840c hyp |
hypothetical protein | 420 | 421 |
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: DUF503 domain-containing protein
- Pfam (hmmscan --cut_ga): DUF503 PF04456.18 (E=2e-30)
- Foldseek best: 1j27-assembly1_A Crystal structure of a hypothetical protein, TT1725, from Therm (prob 1.00, E=1e-08, TM=0.94)
- (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_216633.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF503 (PF04456.18)
- 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
COG1550 - Curated reference: UniProt O33252 (TrEMBL, unreviewed; 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)
- Model confidence: ESMFold per-residue pLDDT (mean 91.5, very high)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
5 functional partner(s); context anchor
lppK - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002249|Rv2117| MWIGWLEFDVLLGDVRSLKQKRSVTRPLVAELQRKFSVSAAETGSHDLYRRAGIGVAVVSGDRSHAVDVLDNAERLVAAHPEFELLSVRRGLHRTDD