Rv0569 Family assigned · medium
H37Rv Rv0569 · MTBC0 mtbc0_000599 ·
88 aa · 664554–664820 (+) ·
RefSeq NP_215083.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | DUF1918 domain-containing protein |
| Revised (this work) | DosR (dormancy survival regulon) protein; conserved hypothetical protein over-expressed under hypoxia. NMR solution structure determined (five antiparallel beta-sheets + one alpha-helix), structurally homologous to Rv2302; proposed to contribute to hypoxic signal transduction by binding DNA to up-regulate the adjacent Rv0570. Immunodominant Th1 latency antigen. Precise molecular function unfixed. |
Curated reference (UniProt)
| UniProt |
P9WM83
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized protein Rv0569 |
UniProt still lists this protein as Uncharacterized protein Rv0569; 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 (18) |
GO:0001666, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0006950, GO:0008150, GO:0009628, GO:0030312, GO:0036293 +6 more
|
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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
DUF1918 | PF08940.18 | 1.3e-26 | 1–58 | Domain of unknown function (DUF1918) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 64.3 (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 |
|---|---|---|---|---|
2a7y-assembly1_A |
1.00 | 0.67 | 3.3e-05 sig | 2a7y-assembly1_A Solution Structure of the Conserved Hypothetical Protein Rv2302 from the Bacterium Mycobacterium tuberculosis |
7hg5-assembly3_C |
0.82 | 0.49 | 1.5e-01 | 7hg5-assembly3_C PanDDA analysis group deposition -- Crystal structure of HRP-2 PWWP domain in complex with Z2142244288 |
5znp-assembly2_B |
0.72 | 0.57 | 2.3e-01 | 5znp-assembly2_B Crystal structure of PtSHL in complex with an H3K4me3 peptide |
5znr-assembly2_B |
0.69 | 0.65 | 5.5e-01 | 5znr-assembly2_B Crystal structure of PtSHL in complex with an H3K27me3 peptide |
2f5k-assembly6_F |
0.66 | 0.44 | 3.4e-01 | 2f5k-assembly6_F Crystal structure of the chromo domain of human MRG15 |
6bph-assembly1_A-2 |
0.57 | 0.52 | 5.5e-01 | 6bph-assembly1_A-2 Crystal structure of the chromodomain of RBBP1 |
7hh4-assembly2_B |
0.51 | 0.49 | 5.9e-01 | 7hh4-assembly2_B PanDDA analysis group deposition -- Crystal structure of HRP-2 PWWP domain in complex with Z1139246057 |
6bhe-assembly1_A |
0.47 | 0.53 | 1.0e+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: nrdZ (vitamin B12-dependent ribonucleoside-diphosphate reductase), high confidence from genomic context alone (score 822 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) |
|---|---|---|---|---|
Rv3132c devS |
two component sensor histidine kinase DevS | 904 | 870 | coexpression:803 |
Rv3133c devR |
two component transcriptional regulator DevR | 900 | 832 | coexpression:810 textmining:433 |
Rv0570 nrdZ |
vitamin B12-dependent ribonucleoside-diphosphate reductase | 822 | 822 ctx | neighborhood:724 |
Rv2005c |
universal stress protein | 819 | 819 | coexpression:774 |
Rv1736c narX |
nitrate reductase-like protein NarX | 615 | 615 | coexpression:615 |
Rv0568 cyp135B1 |
cytochrome P450 Cyp135B1 | 528 | 527 ctx | neighborhood:521 |
Rv2557 hyp |
hypothetical protein | 496 | 496 ctx | cooccurence:462 |
Rv3134c |
universal stress protein | 577 | 488 ctx | cooccurence:406 |
Rv2028c |
universal stress protein | 501 | 488 | |
Rv2624c |
universal stress protein | 481 | 481 | |
Rv2558 hyp |
hypothetical protein | 479 | 480 ctx | cooccurence:445 |
Rv1888c |
Rv1888c, (MTCY180.30), len: 186 aa. Possible transmembrane protein. | 473 | 474 ctx | cooccurence:466 |
Rv1738 hyp |
hypothetical protein | 795 | 470 ctx | cooccurence:462 textmining:630 |
Rv1907c hyp |
hypothetical protein | 457 | 457 ctx | cooccurence:451 |
Rv0080 hyp |
hypothetical protein | 447 | 448 ctx | cooccurence: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
- NMR solution structure; structural homolog of Rv2302 (Kim 2014, PMID 24275361)
- DosR regulon; immunodominant Th1-switching latency antigen (Kanaparthi 2022, PMID 35007662)
- 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_215083.1)
- 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 P9WM83 (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 64.3, low)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
39 functional partner(s); context anchor
nrdZ - Primary literature: Kim WJ, Son WS, Ahn DH, Im H, Ahn HC, Lee BJ (2014). Solution structure of Rv0569, potent hypoxic signal transduction protein, from Mycobacterium tuberculosis Tuberculosis (Edinb) 94(1):43-50. doi:10.1016/j.tube.2013.08.008 PMID:24275361
- Primary literature: Kanaparthi KJ, Afroz S, Minhas G, Moitra A, Khan RA, Medikonda J, Naz S, Cholleti SN, Banerjee S, Khan N (2022). Immunogenic profiling of Mycobacterium tuberculosis DosR protein Rv0569 reveals its ability to switch on Th1 based immunity Immunol Lett 242:27-36. doi:10.1016/j.imlet.2022.01.001 PMID:35007662
Ancestral MTBC0 protein sequence
>mtbc0_000599|Rv0569| MKAKVGDWLVIKGATIDQPDHRGLIIEVRSSDGSPPYVVRWLETDHVATVIPGPDAVVVTAEEQNAADERAQHRFGAVQSAILHARGT