Rv1211 Family assigned · medium
H37Rv Rv1211 · MTBC0 - ·
75 aa · 1354243–1354470 (+) ·
RefSeq NP_215727.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Natively unfolded (intrinsically disordered) protein required for growth and pathogenesis; binds the calmodulin antagonist trifluoperazine (Kd 41 uM) in its C-terminal region while remaining unfolded. An earlier 'calmodulin-like Ca2+-binding protein (CAMLP)' assignment is CONTESTED: the structural study shows it does not bind Ca2+. A drug-interaction target of unfixed molecular function. |
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
O05312
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Conserved protein |
UniProt still lists this protein as Conserved protein; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Protein of unknown function (DUF3117) |
| Orthologous group | 2E39N |
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 | 0.0 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 0 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 |
|---|---|---|---|---|
DUF3117 | PF11314.14 | 2.5e-28 | 24–73 | Protein of unknown function (DUF3117) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 69.1 (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 |
|---|---|---|---|---|
1gut-assembly1_C |
0.98 | 0.70 | 2.5e-01 | 1gut-assembly1_C MopII from Clostridium pasteurianum (apo2) |
5inw-assembly2_B |
0.92 | 0.60 | 2.2e-01 | 5inw-assembly2_B Structure of reaction loop cleaved lamprey angiotensinogen |
1h9m-assembly1_A |
0.90 | 0.69 | 7.1e-01 | 1h9m-assembly1_A Two crystal structures of the cytoplasmic molybdate-binding protein ModG suggest a novel cooperative binding mechanism and provide insights into ligand-binding specificity. PEG-grown form with molybdate bound |
7xt7-assembly1_k |
0.90 | 0.66 | 4.6e-01 | 7xt7-assembly1_k RNA polymerase II elongation complex transcribing a nucleosome (EC49B) |
1o7l-assembly1_B |
0.87 | 0.73 | 7.5e-01 | 1o7l-assembly1_B Molybdate-activated form of ModE from Escherichia coli |
5inw-assembly1_A |
0.87 | 0.61 | 3.6e-01 | 5inw-assembly1_A Structure of reaction loop cleaved lamprey angiotensinogen |
1o7l-assembly2_D |
0.85 | 0.68 | 6.7e-01 | 1o7l-assembly2_D Molybdate-activated form of ModE from Escherichia coli |
8f2u-assembly1_E |
0.84 | 0.52 | 2.8e-01 | 8f2u-assembly1_E Human CCC complex |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: tagA (DNA-3-methyladenine glycosylase I TagA), high confidence from genomic context alone (score 756 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) |
|---|---|---|---|---|
Rv3678A hyp |
hypothetical protein | 773 | 773 ctx | cooccurence:770 |
Rv1209 hyp |
hypothetical protein | 757 | 757 ctx | neighborhood:754 |
Rv1210 tagA |
DNA-3-methyladenine glycosylase I TagA | 949 | 756 ctx | neighborhood:755 textmining:803 |
Rv1691 hyp |
hypothetical protein | 637 | 637 ctx | cooccurence:637 |
Rv1208 gpgS |
glucosyl-3-phosphoglycerate synthase | 552 | 551 ctx | neighborhood:549 |
Rv1207 folP2 |
dihydropteroate synthase | 551 | 550 ctx | neighborhood:549 |
Rv0883c sepH hyp |
hypothetical protein | 501 | 501 | |
Rv3660c ssd hyp |
hypothetical protein | 459 | 459 ctx | cooccurence:459 |
Rv3245c mtrB |
two component sensory histidine kinase MtrB | 425 | 426 ctx | cooccurence:422 |
Rv1205 log hyp |
hypothetical protein | 409 | 409 ctx | neighborhood:407 |
Rv3597c lsr2 |
iron-regulated H-NS-like protein | 408 | 409 | |
Rv1625c cya |
adenylate cyclase | 441 | 50 | textmining:436 |
Rv1264 |
adenylyl cyclase | 517 | 47 | textmining:514 |
Rv3645 |
transmembrane protein | 440 | 47 | textmining:437 |
Rv1832 gcvB |
glycine dehydrogenase | 439 | 47 | textmining:436 |
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
- Natively unfolded protein (size-exclusion, CD, NMR); binds trifluoperazine, NOT Ca2+ (Choo 2022, PMID 35468422)
- Earlier calmodulin-like/EF-hand claim contested (Koul 2009, PMID 19639701)
- Pfam DUF3117; required for growth
- 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_215727.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF3117 (PF11314.14)
- 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
2E39N - Curated reference: UniProt O05312 (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 69.1, low)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
21 functional partner(s); context anchor
tagA - Primary literature: Choo M, Oh S, Jo S, Jin X, Song Y, Wen H, Park S, Kang S (2022). Highly conserved protein Rv1211 in Mycobacterium tuberculosis is a natively unfolded protein that binds to a calmodulin antagonist, trifluoperazine Biochem Biophys Res Commun 610:182-187. doi:10.1016/j.bbrc.2022.04.045 PMID:35468422
- Primary literature: Koul S, Somayajulu A, Advani MJ, Reddy H (2009). A novel calcium binding protein in Mycobacterium tuberculosis - potential target for trifluoperazine Indian J Exp Biol 47(6):480-8. PMID:19639701
Ancestral MTBC0 protein sequence
>H37Rv|Rv1211| MLGADQARAGGPARIWREHSMAAMKPRTGDGPLEATKEGRGIVMRVPLEGGGRLVVELTPDEAAALGDELKGVTS