Rv2302 Family assigned · medium
H37Rv Rv2302 · MTBC0 mtbc0_002442 ·
80 aa · 2598562–2598804 (+) ·
RefSeq NP_216818.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | DUF1918 domain-containing protein |
| Revised (this work) | Conserved hypothetical protein with an NMR-determined solution structure: a five-strand antiparallel beta-sheet core with one C-terminal alpha-helix, with no high structural similarity to known proteins (a possible novel fold). Up-regulated under starvation and heat-shock; structural homolog of Rv0569. Biochemical function unknown. |
Curated reference (UniProt)
| UniProt |
P9WLD5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized protein Rv2302 |
UniProt still lists this protein as Uncharacterized protein Rv2302; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
T Signal transduction mechanisms
|
|---|---|
| eggNOG description | Domain of unknown function (DUF1918) |
| Orthologous group | COG2905 |
| Gene Ontology (6) |
GO:0005575, GO:0005618, GO:0005623, 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)
| pN/pS | 0.343 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 2 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.12% of strains (172) · 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 |
|---|---|---|---|---|
DUF1918 | PF08940.18 | 2.0e-27 | 1–58 | Domain of unknown function (DUF1918) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 89.9 (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 |
|---|---|---|---|---|
2a7y-assembly1_A |
1.00 | 0.56 | 9.6e-08 sig | 2a7y-assembly1_A Solution Structure of the Conserved Hypothetical Protein Rv2302 from the Bacterium Mycobacterium tuberculosis |
5znp-assembly2_B |
0.57 | 0.59 | 6.3e-01 | 5znp-assembly2_B Crystal structure of PtSHL in complex with an H3K4me3 peptide |
6bph-assembly1_A-2 |
0.51 | 0.60 | 1.7e+00 | 6bph-assembly1_A-2 Crystal structure of the chromodomain of RBBP1 |
7oh3-assembly1_T |
0.51 | 0.41 | 4.5e-01 | 7oh3-assembly1_T Nog1-TAP associated immature ribosomal particle population B from S. cerevisiae |
3oby-assembly1_A |
0.51 | 0.41 | 3.8e-01 | 3oby-assembly1_A Crystal structure of Archaeoglobus fulgidus Pelota reveals inter-domain structural plasticity |
7hg5-assembly3_C |
0.47 | 0.48 | 7.9e-01 | 7hg5-assembly3_C PanDDA analysis group deposition -- Crystal structure of HRP-2 PWWP domain in complex with Z2142244288 |
2f5k-assembly6_F |
0.38 | 0.46 | 1.3e+00 | 2f5k-assembly6_F Crystal structure of the chromo domain of human MRG15 |
6bhe-assembly1_A |
0.35 | 0.54 | 2.1e+00 | 6bhe-assembly1_A Crystal structure of SETDB1 with a modified H3 peptide |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: cut2 (cutinase), medium confidence from genomic context alone (score 627 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) |
|---|---|---|---|---|
Rv2301 cut2 |
cutinase | 627 | 627 ctx | neighborhood:560 |
Rv1888c |
Rv1888c, (MTCY180.30), len: 186 aa. Possible transmembrane protein. | 579 | 580 ctx | cooccurence:577 |
Rv2557 hyp |
hypothetical protein | 567 | 568 ctx | cooccurence:539 |
Rv1738 hyp |
hypothetical protein | 559 | 560 ctx | cooccurence:557 |
Rv2558 hyp |
hypothetical protein | 550 | 551 ctx | cooccurence:530 |
Rv2551c hyp |
hypothetical protein | 543 | 543 ctx | cooccurence:542 |
Rv2632c hyp |
hypothetical protein | 516 | 516 ctx | cooccurence:494 |
Rv0080 hyp |
hypothetical protein | 490 | 491 ctx | cooccurence:488 |
Rv3131 |
NAD(P)H nitroreductase | 481 | 480 ctx | cooccurence:476 |
Rv3134c |
universal stress protein | 458 | 459 ctx | cooccurence:450 |
Rv2027c dosT |
two component sensor histidine kinase DosT | 472 | 452 | |
Rv3132c devS |
two component sensor histidine kinase DevS | 463 | 442 | |
Rv2300c |
metallo-hydrolase | 418 | 418 ctx | neighborhood:416 |
Rv3127 hyp |
hypothetical protein | 415 | 413 ctx | cooccurence:409 |
Rv1014c pth |
peptidyl-tRNA hydrolase | 401 | 402 |
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
- NMR solution structure; novel fold (no Dali match); stress-induced (Buchko 2006, PMID 16885468)
- Structural homolog of Rv0569
- Pfam DUF1918
- Curated from the literature crible (project 'Still unknown gene function', 2026-06-09)
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_216818.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF1918 (PF08940.18)
- 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
COG2905 - Curated reference: UniProt P9WLD5 (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)
- Model confidence: ESMFold per-residue pLDDT (mean 89.9, confident)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
17 functional partner(s); context anchor
cut2 - Primary literature: Buchko GW, Kim CY, Terwilliger TC, Kennedy MA (2006). Solution structure of the conserved hypothetical protein Rv2302 from Mycobacterium tuberculosis J Bacteriol 188(16):5993-6001. doi:10.1128/JB.00460-06 PMID:16885468
Ancestral MTBC0 protein sequence
>mtbc0_002442|Rv2302| MHAKVGDYLVVKGTTTERHDQHAEIIEVRSADGSPPYVVRWLVNGHETTVYPGSDAVVVTATEHAEAEKRAAARAGHAAT