Rv0250c Family assigned · low
H37Rv Rv0250c · MTBC0 mtbc0_000266 ·
97 aa · 302117–302410 (-) ·
RefSeq NP_214764.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | No Pfam domain above threshold, but Foldseek strongly matches a sensor / HD-domain fold (CpxA-like, prob 0.95, TM=0.88): a putative signal-transduction / sensor-associated module. Structure-based. |
Curated reference (UniProt)
| UniProt |
O53672
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized protein Rv0250c |
UniProt still lists this protein as Uncharacterized protein Rv0250c; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2DP0M |
|---|
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, 2 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)
No Pfam-A domain above the gathering threshold (or not yet scanned).
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 61.1 (low). Low-confidence model: the fold may be unreliable, so treat these structural hits with caution.
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 |
|---|---|---|---|---|
4biy-assembly1_B |
0.95 | 0.88 | 9.6e-01 | 4biy-assembly1_B Crystal structure of CpxAHDC (monoclinic form 2) |
4biy-assembly2_D |
0.89 | 0.71 | 6.9e-01 | 4biy-assembly2_D Crystal structure of CpxAHDC (monoclinic form 2) |
6ahx-assembly1_A-2 |
0.75 | 0.81 | 2.0e+00 | 6ahx-assembly1_A-2 Copper-Sensing Operon Regulator Protein (CsoRGz) |
7ls2-assembly1_b2 |
0.57 | 0.58 | 1.3e+00 | 7ls2-assembly1_b2 80S ribosome from mouse bound to eEF2 (Class I) |
6z6l-assembly1_Lh |
0.54 | 0.58 | 1.3e+00 | 6z6l-assembly1_Lh Cryo-EM structure of human CCDC124 bound to 80S ribosomes |
8ir1-assembly1_H |
0.51 | 0.57 | 1.3e+00 | 8ir1-assembly1_H human nuclear pre-60S ribosomal particle - State A |
8ink-assembly1_H |
0.38 | 0.58 | 2.1e+00 | 8ink-assembly1_H human nuclear pre-60S ribosomal particle - State D |
7nfx-assembly1_h |
0.28 | 0.59 | 3.4e+00 | 7nfx-assembly1_h Mammalian ribosome nascent chain complex with SRP and SRP receptor in early state A |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0249c (succinate dehydrogenase membrane anchor subunit), high confidence from genomic context alone (score 879 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) |
|---|---|---|---|---|
Rv0249c |
succinate dehydrogenase membrane anchor subunit | 940 | 879 ctx | neighborhood:787 cooccurence:451 textmining:527 |
Rv0248c |
succinate dehydrogenase flavoprotein subunit | 911 | 819 ctx | neighborhood:734 textmining:531 |
Rv0247c |
succinate dehydrogenase iron-sulfur subunit | 928 | 812 ctx | neighborhood:735 textmining:637 |
Rv0431 |
tuberculin-like peptide | 737 | 738 ctx | cooccurence:736 |
Rv3415c hyp |
hypothetical protein | 731 | 731 ctx | cooccurence:730 |
Rv2138 lppL |
lipoprotein LppL | 721 | 722 ctx | cooccurence:721 |
Rv0882 |
transmembrane protein | 716 | 717 ctx | cooccurence:715 |
Rv1632c hyp |
hypothetical protein | 704 | 705 ctx | cooccurence:701 |
Rv2743c hyp |
hypothetical protein | 704 | 704 ctx | cooccurence:700 |
Rv0556 |
transmembrane protein | 655 | 655 ctx | cooccurence:653 |
Rv2732c |
transmembrane protein | 640 | 640 ctx | cooccurence:640 |
Rv2360c hyp |
hypothetical protein | 627 | 627 ctx | cooccurence:625 |
Rv1109c hyp |
hypothetical protein | 626 | 626 ctx | cooccurence:621 |
Rv1081c |
membrane protein | 624 | 624 ctx | cooccurence:622 |
Rv3212 hyp |
hypothetical protein | 623 | 623 ctx | cooccurence:621 |
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: 'hypothetical protein'
- Pfam: none above threshold
- Foldseek on the ESMFold model: strong match to a CpxA-like sensor / HD-domain fold (TM=0.88)
ESM Atlas signal (exploratory)
Ancestral protein hash ca27799c8163182369fb3521d1974fcd ·
10 ESM-space neighbours (max similarity 0.957).
SAE features are orienting indices, not validated domains.
| # | Index | Activation | Interpretation |
|---|---|---|---|
| 1 | 1448 |
0.54 | Chromatin DNA-binding and scaffold domains |
| 2 | 1101 |
0.49 | Acidic N-terminal disordered region |
| 3 | 16 |
0.46 | Modified peptide core detector |
| 4 | 8102 |
0.45 | Membrane-proximal PTM-rich IDRs |
| 5 | 8724 |
0.45 | Amphipathic helical packing interfaces |
| 6 | 1688 |
0.43 | Acidic low-complexity interaction segments |
| 7 | 10164 |
0.42 | N-terminal helical assembly modules |
| 8 | 6600 |
0.42 | Disordered charged terminal tails |
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_214764.1)
- Domains: Pfam-A via hmmscan --cut_ga — none above threshold
- 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
2DP0M - Curated reference: UniProt O53672 (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 61.1, low)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
67 functional partner(s); context anchor
Rv0249c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000266|Rv0250c| MSTTAELAELHDLVGGLRRCVTALKARFGDNPATRRIVIDADRILTDIELLDTDVSELDLERAAVPQPSEKIAIPDTEYDREFWRDVDDEGVGGHRY