Rv1290c Family assigned · low
H37Rv Rv1290c · MTBC0 mtbc0_001380 ·
521 aa · 1452521–1454086 (-) ·
RefSeq NP_215806.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | DUF2254 domain-containing protein |
| Revised (this work) | Polytopic integral membrane protein with 4 predicted transmembrane helices (DeepTMHMM). RefSeq leaves it 'hypothetical protein'. A topological feature consistent with a membrane transporter/permease or membrane-embedded enzyme; the transported substrate and molecular function are undetermined. |
Curated reference (UniProt)
| UniProt |
P9WM35
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized protein Rv1290c |
UniProt still lists this protein as Uncharacterized protein Rv1290c; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Predicted membrane protein (DUF2254) |
| Orthologous group | COG4325 |
| Gene Ontology (12) |
GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0008150, GO:0009405, GO:0044419, GO:0044424, GO:0044444, GO:0044464, GO:0051704
|
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 | 0.649 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 7 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 |
|---|---|---|---|---|
DUF2254 | PF10011.16 | 6.6e-104 | 69–438 | Predicted membrane protein (DUF2254) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 91.0 (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 |
|---|---|---|---|---|
5cwj-assembly1_A |
0.99 | 0.57 | 1.7e-01 | 5cwj-assembly1_A Crystal structure of de novo designed helical repeat protein DHR49 |
8f6q-assembly1_A |
0.60 | 0.50 | 1.6e+00 | 8f6q-assembly1_A CryoEM structure of designed modular protein oligomer C8-71 |
7exe-assembly1_A |
0.23 | 0.39 | 2.6e+00 | 7exe-assembly1_A Crystal structure of mouse 14-3-3zeta in complex with doubly phosphorylated ADAM22 peptide |
1zu2-assembly1_A |
0.21 | 0.31 | 1.4e+00 | 1zu2-assembly1_A Solution NMR structure of the plant Tom20 mitochondrial import receptor from Arabidopsis thaliana |
2xcc-assembly1_B |
0.15 | 0.32 | 2.1e+00 | 2xcc-assembly1_B Crystal structure of PcrH from Pseudomonas aeruginosa |
6e9t-assembly1_B |
0.15 | 0.29 | 1.8e+00 | 6e9t-assembly1_B DHF58 filament |
5k7v-assembly1_B |
0.13 | 0.21 | 1.1e+00 | 5k7v-assembly1_B Computational Design of Self-Assembling Cyclic Protein Homooligomers |
8yld-assembly1_v |
0.08 | 0.32 | 6.6e+00 | 8yld-assembly1_v State 4a (S4a) of yeast 80S ribosome bound to 2 tRNAs and open eEF3 and eEF2 during translocation |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1290A hyp |
hypothetical protein | 582 | 582 ctx | neighborhood:579 |
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
- DeepTMHMM: 4 transmembrane helices (type TM)
- Integral membrane topology (localisation feature, not a function)
- DeepTMHMM topology prediction (project 'Still unknown gene function', phase8, 2026-06-10). A topological feature, not a demonstrated molecular function.
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_215806.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF2254 (PF10011.16)
- 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
COG4325 - Curated reference: UniProt P9WM35 (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 91.0, very high)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 1 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001380|Rv1290c| MLQRSLGVNGRKLAMSARSAKRERKNASTAASKCYVVPPSARGWVHAYSVTATSMLNRRKAILDYLQGAVWVLPTFGVAIGLGSGAVLSMIPVKSGTLIDKLMFQGTPGDARGVLIVVSATMITTIGIVFSLTVLSLQIASSQFSVRLLRTFLRDVPNQVVLAIFACTFAYSTGGLHTVGEHRDGGAFIPKVAVTGSLALAFVSIAALIYFLHHLMHSIQIDTIMDKVRLRTLGLVDQLYPESDTADRQVETPPSPPADAVPLLAPHSGYLQTVDVDDIAELAAASRYTALLVTFVGDYVTAGGLLGWCWRRGTAPGAPGSDFPQRCLRHVHIGFERTLQQDIRFGLRQMVDIALRALSPALNDPYTAIQVVHHLSAVESVLASRALPDDVRRDRAGELLFWLPYPSFATYLHVGCAQIRRYGSREPLVLTALLQLLSAVAQNCVDPSRRVAVQTQIALVVRAAQREFADESDRAMVLGAAARATEVVERPGTLAPPPSTFGQVAAAQAAASTIRSADRDG