Rv0543c Family assigned · medium
H37Rv Rv0543c · MTBC0 mtbc0_000572 ·
100 aa · 639124–639426 (-) ·
RefSeq NP_215057.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | DUF3349 domain-containing protein |
| Revised (this work) | Member of the DUF3349 (PF11829) protein superfamily, found predominantly in Mycobacterium and Rhodococcus. The inaugural DUF3349 structure was solved for Rv0543c by NMR: a monomeric five-alpha-helix bundle (Buchko 2011); comparative structures show two structural subfamilies (Buchko 2020). Biological function unknown but family-restricted to these genera. |
Curated reference (UniProt)
| UniProt |
O06409
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 (DUF3349) |
| Orthologous group | 2E7QJ |
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 | 0.662 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 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 |
|---|---|---|---|---|
DUF3349 | PF11829.14 | 1.1e-33 | 4–92 | Protein of unknown function (DUF3349) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 63.1 (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 |
|---|---|---|---|---|
2kvc-assembly1_A |
1.00 | 0.83 | 8.4e-12 sig | 2kvc-assembly1_A Solution structure of the Mycobacterium tuberculosis protein Rv0543c, a member of the DUF3349 superfamily. Seattle Structural Genomics Center for Infectious Disease target MytuD.17112.a |
2lky-assembly1_A |
1.00 | 0.73 | 1.5e-07 sig | 2lky-assembly1_A Solution structure of MSMEG_1053, the second DUF3349 annotated protein in the genome of Mycobacterium smegmatis, Seattle Structural Genomics Center for Infectious Disease target MysmA.17112.b |
5m30-assembly1_A |
0.01 | 0.20 | 5.9e+00 | 5m30-assembly1_A Structure of TssK from T6SS EAEC in complex with nanobody nb18 |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: pitA (low-affinity inorganic phosphate transporter), high confidence from genomic context alone (score 848 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) |
|---|---|---|---|---|
Rv0545c pitA |
low-affinity inorganic phosphate transporter | 848 | 848 ctx | neighborhood:803 |
Rv0544c |
transmembrane protein | 808 | 808 ctx | neighborhood:803 |
Rv0542c menE |
2-succinylbenzoic acid--CoA ligase | 806 | 807 ctx | neighborhood:795 |
Rv0541c |
integral membrane protein | 797 | 797 ctx | neighborhood:792 |
Rv0547c |
oxidoreductase | 514 | 515 ctx | neighborhood:512 |
Rv0184 hyp |
hypothetical protein | 497 | 497 ctx | cooccurence:494 |
Rv0185 hyp |
hypothetical protein | 479 | 480 ctx | cooccurence:475 |
Rv3804c fbpA |
diacylglycerol acyltransferase/mycolyltransferase Ag85A | 439 | 439 ctx | cooccurence:432 |
Rv3256c hyp |
hypothetical protein | 436 | 436 ctx | cooccurence:428 |
Rv3454 |
Rv3454, (MTCY13E12.07), len: 422 aa. Probable conserved integral membrane protein, showing some similarity to various proteins (generally tr | 435 | 436 ctx | cooccurence:432 |
Rv0129c fbpC |
diacylglycerol acyltransferase/mycolyltransferase Ag85C | 431 | 432 ctx | cooccurence:428 |
Rv0546c hyp |
hypothetical protein | 410 | 410 ctx | neighborhood:406 |
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
- Inaugural DUF3349 superfamily NMR structure: 5-alpha-helix bundle (Buchko 2011, PMID 21144816)
- DUF3349 has two structural subfamilies; Mycobacterium/Rhodococcus-restricted (Buchko 2020, PMID 31658388)
- 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_215057.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF3349 (PF11829.14)
- 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
2E7QJ - Curated reference: UniProt O06409 (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 63.1, low)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
12 functional partner(s); context anchor
pitA - Primary literature: Buchko GW, Phan I, Myler PJ, Terwilliger TC, Kim CY (2011). Inaugural structure from the DUF3349 superfamily of proteins, Mycobacterium tuberculosis Rv0543c Arch Biochem Biophys 506(2):150-6. doi:10.1016/j.abb.2010.12.001 PMID:21144816
Ancestral MTBC0 protein sequence
>mtbc0_000572|Rv0543c| MNRFLTSIVAWLRAGYPEGIPPTDSFAVLALLCRRLSHDEVKAVANELMRLGDFDQIDIGVVITHFTDELPSPEDVERVRARLAAQGWPLDDVRDREEHA