Rv0049 Still unknown · low auto-curated
H37Rv Rv0049 · MTBC0 - ·
137 aa · 52831–53244 (+) ·
RefSeq NP_214563.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Conserved hypothetical protein; DUF domain(s) DUF5318. Function unknown. Foldseek best (non-significant) hit: 6ewl-assembly1_A Danio rerio CEP120 first C2 domain (C2A) (prob 0.20, TM 0.40). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
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 |
P9WM85
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized protein Rv0049 |
UniProt still lists this protein as Uncharacterized protein Rv0049; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Family of unknown function (DUF5318) |
| Orthologous group | 2CQNK |
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 | 0.378 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 1 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 |
|---|---|---|---|---|
DUF5318 | PF17249.9 | 8.4e-59 | 1–118 | Family of unknown function (DUF5318) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 81.3 (confident). 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 |
|---|---|---|---|---|
6ewl-assembly1_A |
0.20 | 0.40 | 7.0e-01 | 6ewl-assembly1_A Danio rerio CEP120 first C2 domain (C2A) |
6flj-assembly1_A |
0.16 | 0.42 | 8.5e-01 | 6flj-assembly1_A Crystal structure of Cep120 C2A_K76A mutant |
4icx-assembly2_B |
0.11 | 0.43 | 2.0e+00 | 4icx-assembly2_B N-terminal C2 domain of human CEP120 |
6p7b-assembly1_A |
0.10 | 0.77 | 3.9e+00 | 6p7b-assembly1_A Crystal structure of Fowlpox virus resolvase and substrate Holliday junction DNA complex |
4s1n-assembly1_A |
0.09 | 0.47 | 2.4e+00 | 4s1n-assembly1_A The crystal structure of phosphoribosylglycinamide formyltransferase from Streptococcus pneumoniae TIGR4 |
8gi2-assembly1_A |
0.08 | 0.30 | 7.5e-01 | 8gi2-assembly1_A Cryo-EM structure of Natrinema sp. J7-2 Type IV pilus |
1z7e-assembly1_B |
0.07 | 0.41 | 2.5e+00 | 1z7e-assembly1_B Crystal structure of full length ArnA |
1z7e-assembly1_D |
0.07 | 0.41 | 2.4e+00 | 1z7e-assembly1_D Crystal structure of full length ArnA |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: lprD (lipoprotein LprD), high confidence from genomic context alone (score 735 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) |
|---|---|---|---|---|
Rv1343c lprD |
lipoprotein LprD | 734 | 735 ctx | cooccurence:731 |
Rv2744c 35kd_ag hyp |
hypothetical protein | 704 | 705 ctx | cooccurence:703 |
Rv3013 hyp |
hypothetical protein | 692 | 693 ctx | cooccurence:692 |
Rv0051 |
transmembrane protein | 682 | 682 ctx | neighborhood:544 |
Rv1638A hyp |
hypothetical protein | 623 | 624 ctx | cooccurence:622 |
Rv3605c hyp |
hypothetical protein | 594 | 594 ctx | cooccurence:594 |
Rv0048c |
membrane protein | 587 | 587 ctx | neighborhood:584 |
Rv1209 hyp |
hypothetical protein | 585 | 585 ctx | cooccurence:579 |
Rv1481 |
membrane protein | 581 | 582 ctx | cooccurence:579 |
Rv2468c hyp |
hypothetical protein | 558 | 559 ctx | cooccurence:556 |
Rv0050 ponA1 |
bifunctional penicillin-insensitive transglycosylase/penicillin-sensitive transpeptidase | 665 | 551 ctx | neighborhood:544 |
Rv0053 rpsF |
30S ribosomal protein S6 | 546 | 547 ctx | neighborhood:544 |
Rv1332 |
transcriptional regulator | 542 | 543 ctx | cooccurence:538 |
Rv2091c |
membrane protein | 536 | 537 ctx | cooccurence:530 |
Rv0863 hyp |
hypothetical protein | 525 | 525 ctx | cooccurence:520 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): hypothetical protein
- Pfam (hmmscan --cut_ga): DUF5318 PF17249.9 (E=8e-59)
- Foldseek best: 6ewl-assembly1_A Danio rerio CEP120 first C2 domain (C2A) (prob 0.20, E=7e-01, TM=0.40)
- (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)
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_214563.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF5318 (PF17249.9)
- 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
2CQNK - Curated reference: UniProt P9WM85 (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 81.3, confident)
- 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
lprD - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0049| MDYTLRRRSLLAEVYSGRTGVSEVCDANPYLLRAAKFHGKPSRVICPICRKEQLTLVSWVFGEHLGAVSGSARTAEELILLATRFSEFAVHVVEVCRTCSWNHLVKSYVLGAARPARPPRGSGGTRTARNGARTASE