Rv0999 Family assigned · low
H37Rv Rv0999 · MTBC0 - ·
252 aa · 1115767–1116525 (+) ·
RefSeq NP_215514.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Lipoprotein / outer-membrane-associated protein (lipoprotein-like beta fold); structurally solved but functionally uncharacterised fold RefSeq leaves this locus uncharacterised. |
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 |
O05582
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | DUF5642 domain-containing protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2AQ7W |
|---|
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 | 0.25 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 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 |
|---|---|---|---|---|
DUF5642 | PF18702.8 | 4.7e-74 | 63–251 | Domain of unknown function (DUF5642) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 82.2 (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 |
|---|---|---|---|---|
4tmd-assembly1_A |
1.00 | 0.95 | 1.6e-24 sig | 4tmd-assembly1_A X-ray structure of Putative uncharacterized protein (Rv0999 ortholog) from Mycobacterium smegmatis |
4qdc-assembly1_A |
0.33 | 0.34 | 6.9e-02 | 4qdc-assembly1_A Crystal structure of 3-ketosteroid-9-alpha-hydroxylase 5 (KshA5) from R. rhodochrous in complex with FE2/S2 (INORGANIC) CLUSTER |
8c5w-assembly1_A |
0.25 | 0.38 | 2.5e-01 | 8c5w-assembly1_A Crystal Structure of Penicillin-binding Protein 3 (PBP3) from Staphylococcus Epidermidis in complex with Cefotaxime |
6mna-assembly1_A |
0.21 | 0.30 | 1.1e-01 | 6mna-assembly1_A Crystal structure of LpqN involved in cell envelope biogenesis of Mycobacterium tuberculosis |
4qdd-assembly1_A |
0.16 | 0.25 | 8.7e-02 | 4qdd-assembly1_A Crystal structure of 3-ketosteroid-9-alpha-hydroxylase 5 (KshA5) from R. rhodochrous in complex with 1,4-30Q-CoA |
6w3f-assembly2_B |
0.14 | 0.53 | 1.9e+00 | 6w3f-assembly2_B Rd1NTF2_05_I64F_A80G_T94P_D101K_L106W |
4ye5-assembly2_B |
0.14 | 0.42 | 1.1e+00 | 4ye5-assembly2_B The crystal structure of a peptidoglycan synthetase from Bifidobacterium adolescentis ATCC 15703 |
4wmc-assembly4_H |
0.13 | 0.32 | 2.9e-01 | 4wmc-assembly4_H OXA-48 covalent complex with Avibactam inhibitor |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0998 (acetyltransferase Pat), high confidence from genomic context alone (score 733 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) |
|---|---|---|---|---|
Rv0998 |
acetyltransferase Pat | 733 | 733 ctx | neighborhood:732 |
Rv0997 hyp |
hypothetical protein | 654 | 654 ctx | neighborhood:653 |
Rv2903c lepB |
signal peptidase | 544 | 47 | textmining:542 |
Rv0519c |
membrane protein | 870 | 46 | textmining:870 |
Rv2253 hyp |
hypothetical protein | 803 | 41 | textmining:803 |
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
- HHpred: top hit 4TMD uncharacterised SSGCID structure 99.94% E2.8e-24 (193 cols); then ~20 convergent hits all bacterial lipoproteins/OMP/secretion components 60-94% (LptM, YifL, M.tb LpqN/LpqE, BamC/E, TssJ, CagT/VirB7)
- HHpred web (MPI Bioinformatics Toolkit, profile-profile remote homology), interpreted in project 'Still unknown gene function', 2026-06-10. A fold/family-level assignment, not a demonstrated function.
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_215514.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF5642 (PF18702.8)
- 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
2AQ7W - Curated reference: UniProt O05582 (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 82.2, confident)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
5 functional partner(s); context anchor
Rv0998 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0999| MRPPLAPQFAADLLVKTVSTLRSSGAALGRLTTMRKAVLAVGSVCWLVGCSSGASSTTASTGDIAKVAEVKSGFGPEYTVTDVTPRAIDPGFFSARKLPDGLSFDPANCAQVAAGPQLPTGLQGNMAAVSAEGNGNRFVVIAVETSQPLPAPSPGKDCSKVTFSGTQLRGGIEVVDVPHIDGTQTLGVHRVLQAVVGGSARTGELYDYSARFGDYQVIVIANPLVIPGRPVARVDTQRARDLLVQAVAAVRG