Rv2980 Still unknown · low auto-curated
H37Rv Rv2980 · MTBC0 mtbc0_003165 ·
181 aa · 3357133–3357678 (+) ·
RefSeq NP_217496.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | DUF3515 domain-containing protein |
| Revised (this work) | Conserved hypothetical protein; DUF domain(s) DUF3515. Function unknown. Foldseek best (non-significant) hit: 5y39-assembly1_B Crystal structure of Ragulator complex (p18 76-145) (prob 0.38, TM 0.58). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P95115
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Possible conserved secreted protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Protein of unknown function (DUF3515) |
| Orthologous group | 2ECK0 |
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 | 0.396 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 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 |
|---|---|---|---|---|
DUF3515 | PF12028.14 | 1.0e-54 | 18–174 | Protein of unknown function (DUF3515) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 95.6 (very high). 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 |
|---|---|---|---|---|
5y39-assembly1_B |
0.38 | 0.58 | 4.5e-01 | 5y39-assembly1_B Crystal structure of Ragulator complex (p18 76-145) |
5x6u-assembly1_B |
0.33 | 0.58 | 5.8e-01 | 5x6u-assembly1_B Crystal structure of human heteropentameric complex |
5y3a-assembly1_B |
0.28 | 0.59 | 7.8e-01 | 5y3a-assembly1_B Crystal structure of Ragulator complex (p18 49-161) |
5y3a-assembly2_G |
0.25 | 0.56 | 7.8e-01 | 5y3a-assembly2_G Crystal structure of Ragulator complex (p18 49-161) |
6ehp-assembly1_B |
0.20 | 0.58 | 1.3e+00 | 6ehp-assembly1_B The crystal structure of the human LAMTOR complex |
8fw5-assembly1_D |
0.20 | 0.55 | 1.2e+00 | 8fw5-assembly1_D Chimeric HsGATOR1-SpGtr-SpLam complex |
5yk3-assembly2_B |
0.18 | 0.50 | 8.7e-01 | 5yk3-assembly2_B human Ragulator complex |
7yh1-assembly2_C |
0.15 | 0.61 | 2.3e+00 | 7yh1-assembly2_C Roadblock from Candidatus Prometheoarchaeum syntrophicum strain MK-D1 |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0556 (transmembrane protein), high confidence from genomic context alone (score 763 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) |
|---|---|---|---|---|
Rv0556 |
transmembrane protein | 763 | 763 ctx | cooccurence:763 |
Rv2446c |
integral membrane protein | 761 | 761 ctx | cooccurence:761 |
Rv3212 hyp |
hypothetical protein | 761 | 761 ctx | cooccurence:761 |
Rv3311 hyp |
hypothetical protein | 760 | 760 ctx | cooccurence:760 |
Rv1109c hyp |
hypothetical protein | 759 | 759 ctx | cooccurence:759 |
Rv3438 hyp |
hypothetical protein | 755 | 755 ctx | cooccurence:755 |
Rv0358 hyp |
hypothetical protein | 752 | 752 ctx | cooccurence:752 |
Rv1209 hyp |
hypothetical protein | 751 | 751 ctx | cooccurence:743 |
Rv1083 hyp |
hypothetical protein | 748 | 748 ctx | cooccurence:748 |
Rv3004 cfp6 |
low molecular weight protein antigen 6 | 740 | 740 ctx | cooccurence:740 |
Rv0419 lpqM |
lipoprotein peptidase LpqM | 735 | 735 ctx | cooccurence:735 |
Rv3850 hyp |
hypothetical protein | 735 | 735 ctx | cooccurence:735 |
Rv1166 lpqW |
monoacyl phosphatidylinositol tetramannoside-binding protein LpqW | 732 | 732 ctx | cooccurence:732 |
Rv2976c ung |
uracil-DNA glycosylase | 728 | 728 ctx | neighborhood:728 |
Rv2732c |
transmembrane protein | 721 | 721 ctx | cooccurence:721 |
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
- Legacy H37Rv annotation: hypothetical protein
- MTBC0 PGAP product: DUF3515 domain-containing protein
- Pfam (hmmscan --cut_ga): DUF3515 PF12028.14 (E=1e-54)
- Foldseek best: 5y39-assembly1_B Crystal structure of Ragulator complex (p18 76-145) (prob 0.38, E=5e-01, TM=0.58)
- (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_217496.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF3515 (PF12028.14)
- 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
2ECK0 - Curated reference: UniProt P95115 (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 95.6, very high)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
106 functional partner(s); context anchor
Rv0556 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003165|Rv2980| MTGESDGPPRAVLIAAAALAAAVIGVILVVAANRQPPERPVVIPAVPAPQATGPGCKALLAALPQRLGEYRRAPVAEPTTAGATAWRTGPNSTPVILRCGLDRPAEFVVGSAIQVVDRVQWFQVAAQNPDEPGRSTWYTVDRPVYVALTLPSGSGPTAIQELSDVIDHTIPAVPIDPAPAR