Rv3046c Family assigned · medium
H37Rv Rv3046c · MTBC0 mtbc0_003238 ·
124 aa · 3428624–3428998 (-) ·
RefSeq NP_217562.1
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, predominant in Mycobacterium and Rhodococcus. RefSeq leaves it 'hypothetical protein'. The AlphaFold model superposes on the solved DUF3349 structure MSMEG_1053 (PDB 2lky; Foldseek prob 1.0, E 2e-4), a five-alpha-helix bundle; same superfamily as Rv0543c (already curated). Genus-restricted fold of unknown biochemical function. |
Curated reference (UniProt)
| UniProt |
I6YF16
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 | 0.704 · 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 | 4.2e-29 | 9–105 | Protein of unknown function (DUF3349) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 59.6 (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 | 0.67 | 3.0e-04 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 | 0.60 | 3.0e-04 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 |
6zmt-assembly1_S |
0.06 | 0.25 | 3.1e+00 | 6zmt-assembly1_S SARS-CoV-2 Nsp1 bound to a pre-40S-like ribosome complex |
8yho-assembly1_C |
0.04 | 0.32 | 9.0e+00 | 8yho-assembly1_C Cryo-EM structure of the trimeric HerA |
2cpt-assembly1_A |
0.03 | 0.17 | 2.9e+00 | 2cpt-assembly1_A Solution structure of MIT domain from human SKD1 |
7xiv-assembly1_B |
0.02 | 0.22 | 7.3e+00 | 7xiv-assembly1_B Structural insight into the interactions between Lloviu virus VP30 and nucleoprotein |
6zka-assembly1_Y |
0.02 | 0.19 | 7.3e+00 | 6zka-assembly1_Y Membrane domain of open complex I during turnover |
7zdj-assembly1_Y |
0.02 | 0.20 | 9.6e+00 | 7zdj-assembly1_Y Complex I from Ovis aries at pH5.5, Open state |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: papA3 (acyltransferase papA3), medium confidence from genomic context alone (score 436 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) |
|---|---|---|---|---|
Rv3256c hyp |
hypothetical protein | 483 | 483 ctx | cooccurence:480 |
Rv0184 hyp |
hypothetical protein | 476 | 476 ctx | cooccurence:476 |
Rv0185 hyp |
hypothetical protein | 447 | 448 ctx | cooccurence:446 |
Rv3847 hyp |
hypothetical protein | 445 | 445 ctx | cooccurence:440 |
Rv1182 papA3 |
acyltransferase papA3 | 435 | 436 ctx | cooccurence:432 |
Rv3047c hyp |
hypothetical protein | 416 | 416 ctx | neighborhood:416 |
Rv3824c papA1 |
acyltransferase | 409 | 410 ctx | cooccurence:408 |
Rv3454 |
Rv3454, (MTCY13E12.07), len: 422 aa. Probable conserved integral membrane protein, showing some similarity to various proteins (generally tr | 406 | 406 ctx | cooccurence:406 |
Rv3820c papA2 |
trehalose-2-sulfate acyltransferase | 403 | 404 ctx | cooccurence:402 |
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
- Pfam DUF3349 (PF11829)
- Foldseek -> DUF3349 structure MSMEG_1053 (2lky), prob 1.0, E 2e-4
- Same superfamily as Rv0543c (lit-crible)
- Structural homology: AlphaFold DB model + Foldseek vs PDB (project 'Still unknown gene function', phase5-7, 2026-06-10). A fold-level family assignment, not a demonstrated activity.
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_217562.1)
- 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 I6YF16 (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 59.6, low)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
9 functional partner(s); context anchor
papA3 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003238|Rv3046c| MTKTFSHPHFFRSVLRWLQVGYPEGVPGPDRVALLSLLRSTPLTEEQIGEVVRHFTENGSPAVADRVIDRDEIAEFISEVTHHDAGPENIQRVAGILAAAGWPLAGVDVGESESGSDRAPASQG