Rv0025 Still unknown · low
H37Rv Rv0025 · MTBC0 mtbc0_000030 ·
120 aa · 29227–29589 (+) ·
RefSeq NP_214539.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | DUF4226 domain-containing protein |
| Revised (this work) | Conserved hypothetical protein; DUF4226 domain-containing. Function unknown. |
Curated reference (UniProt)
| UniProt |
P9WMA1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized protein Rv0025 |
UniProt still lists this protein as Uncharacterized protein Rv0025; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Domain of unknown function (DUF4226) |
| Orthologous group | 2BA8J |
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 | 0.676 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 4 missense, 0 nonsense, 2 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 9.68% of strains (14052) · 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 |
|---|---|---|---|---|
DUF4226 | PF10774.16 | 3.7e-42 | 6–119 | Domain of unknown function (DUF4226) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 76.8 (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 |
|---|---|---|---|---|
6zw6-assembly1_G |
0.51 | 0.65 | 2.7e+00 | 6zw6-assembly1_G C16 symmetry: Bacterial Vipp1 and PspA are members of the ancient ESCRT-III membrane-remodeling superfamily. |
6nct-assembly1_B |
0.47 | 0.67 | 3.1e+00 | 6nct-assembly1_B Structure of p110alpha/niSH2 - vector data collection |
6zw5-assembly1_F |
0.30 | 0.64 | 4.5e+00 | 6zw5-assembly1_F C15 symmetry: Bacterial Vipp1 and PspA are members of the ancient ESCRT-III membrane-remodeling superfamily. |
4ovu-assembly1_B |
0.28 | 0.66 | 5.7e+00 | 4ovu-assembly1_B Crystal Structure of p110alpha in complex with niSH2 of p85alpha |
3hai-assembly2_D |
0.15 | 0.35 | 1.2e+00 | 3hai-assembly2_D Crystal structure of human PACSIN1 F-BAR domain (P21 lattice) |
8to0-assembly1_GU |
0.13 | 0.41 | 3.7e+00 | 8to0-assembly1_GU 48-nm repeating structure of doublets from mouse sperm flagella |
6ewy-assembly1_A |
0.08 | 0.45 | 8.2e+00 | 6ewy-assembly1_A RipA Peptidoglycan hydrolase (Rv1477, Mycobacterium tuberculosis) N-terminal domain |
7o3x-assembly1_C |
0.07 | 0.39 | 8.2e+00 | 7o3x-assembly1_C Structural basis for VIPP1 oligomerization and maintenance of thylakoid membrane integrity |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0023 (transcriptional regulator), high confidence from genomic context alone (score 833 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) |
|---|---|---|---|---|
Rv0023 |
transcriptional regulator | 833 | 833 ctx | neighborhood:826 |
Rv0022c whiB5 |
transcriptional regulator WhiB5 | 737 | 738 ctx | neighborhood:737 |
Rv0024 |
NLP/P60 family protein | 727 | 728 ctx | neighborhood:716 |
Rv0027 hyp |
hypothetical protein | 691 | 691 ctx | neighborhood:690 |
Rv0028 hyp |
hypothetical protein | 661 | 661 ctx | neighborhood:660 |
Rv0026 hyp |
hypothetical protein | 641 | 641 ctx | neighborhood:638 |
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: 'DUF4226 domain-containing protein' (a domain of unknown function)
- No literature hit in tbmonitor (2021-2026); remains genuinely uncharacterised
- Foldseek on the ESMFold model: weak, non-significant fold similarity to the PspA/Vipp1 (ESCRT-III) coiled-coil membrane-remodeling superfamily (prob 0.51, TM 0.65), convergent with the SAE coiled-coil features -- suggestive only
ESM Atlas signal (exploratory)
Ancestral protein hash 0bb7268e90bbe9fe8056a366027eaaed ·
10 ESM-space neighbours (max similarity 0.962).
SAE features are orienting indices, not validated domains.
| # | Index | Activation | Interpretation |
|---|---|---|---|
| 1 | 2916 |
1.32 | Secretion-targeting helical coiled-coils |
| 2 | 2267 |
1.24 | Pro/Gly-rich low-complexity repeats |
| 3 | 9670 |
1.04 | Elongated amphipathic coiled-coils |
| 4 | 5883 |
0.98 | Mycobacterial PE/PGRS low-complexity repeats |
| 5 | 5094 |
0.91 | N-terminal secretion-targeting helices |
| 6 | 8583 |
0.83 | N-terminal secretion helices |
| 7 | 5992 |
0.72 | Glycine-centered amphipathic helix-turn motifs |
| 8 | 15605 |
0.60 | Secretory coiled-coils and low-complexity linkers |
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_214539.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF4226 (PF10774.16)
- 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
2BA8J - Curated reference: UniProt P9WMA1 (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 76.8, 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
Rv0023 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000030|Rv0025| MSEQAGSSVAVIQERQALLARQHDAVAEADRELADVLASAHAAMRESVRRLDAIAAELDRAVPDQDQLAVDTPMGAREFQTFLVAKQREIVAVVAAAHELDRAKSAVLKRLRAQYTEPAR