Rv0398c Family assigned · low
H37Rv Rv0398c · MTBC0 mtbc0_000418 ·
213 aa · 480043–480684 (-) ·
RefSeq NP_214912.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | Secreted protein with a solved structure (PDB 7YD4, Rv0398c itself); fold characterised, precise function not established. |
Curated reference (UniProt)
| UniProt |
P95206
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Possible secreted protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2AUEU |
|---|
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 | 1.075 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 3 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)
No Pfam-A domain above the gathering threshold (or not yet scanned).
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 70.7 (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 |
|---|---|---|---|---|
7yd4-assembly1_A |
1.00 | 0.78 | 2.9e-22 sig | 7yd4-assembly1_A Crystal structure of an N terminal truncated secreted protein, Rv0398c from Mycobacterium tuberculosis |
4lrt-assembly1_B |
0.14 | 0.41 | 5.5e-01 | 4lrt-assembly1_B Crystal and solution structures of the bifunctional enzyme (Aldolase/Aldehyde dehydrogenase) from Thermomonospora curvata, reveal a cofactor-binding domain motion during NAD+ and CoA accommodation whithin the shared cofactor-binding site |
4jn6-assembly1_D |
0.12 | 0.38 | 5.8e-01 | 4jn6-assembly1_D Crystal Structure of the Aldolase-Dehydrogenase Complex from Mycobacterium tuberculosis HRv37 |
3vw8-assembly1_A |
0.07 | 0.32 | 1.1e+00 | 3vw8-assembly1_A Crystal structure of human c-Met kinase domain with its inhibitor |
4twn-assembly1_A |
0.06 | 0.33 | 1.6e+00 | 4twn-assembly1_A Human EphA3 Kinase domain in complex with Birb796 |
4mxc-assembly1_A |
0.04 | 0.38 | 4.3e+00 | 4mxc-assembly1_A Crystal structure of CMET in complex with novel inhibitor |
3n9h-assembly1_A |
0.03 | 0.65 | 6.7e+00 | 3n9h-assembly1_A Crystal Structural of mutant Y305A in the copper amine oxidase from hansenula polymorpha |
3nbb-assembly1_A |
0.03 | 0.64 | 6.7e+00 | 3nbb-assembly1_A Crystal structure of mutant Y305F expressed in E. coli in the copper amine oxidase from hansenula polymorpha |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: fadE7 (acyl-CoA dehydrogenase FadE7), high confidence from genomic context alone (score 887 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) |
|---|---|---|---|---|
Rv0400c fadE7 |
acyl-CoA dehydrogenase FadE7 | 887 | 887 ctx | neighborhood:881 |
Rv0399c lpqK |
lipoprotein LpqK | 882 | 882 ctx | neighborhood:881 |
Rv0401 |
transmembrane protein | 616 | 616 ctx | neighborhood:616 |
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
- MTBC0 PGAP product: hypothetical protein
- Foldseek best: 7yd4-assembly1_A Crystal structure of an N terminal truncated secreted protein, (prob 1.00, E=3e-22, TM=0.78)
- (structure-only promotion reviewed by hand, 2026-06-01)
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_214912.1)
- Domains: Pfam-A via hmmscan --cut_ga — none above threshold
- 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
2AUEU - Curated reference: UniProt P95206 (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 70.7, confident)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
3 functional partner(s); context anchor
fadE7 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000418|Rv0398c| MGVIARVVGVAACGLSLAVLAAAPTAGAEPTGALPPMTSSGSGPVIGDGDAALRQRISQQLFSFGDPTVQEVDGSDAAQFITAAAAVADRDVASVFLPLQRVLGCQQNTAGSGAGFGARAYRRTDGQWGGAMLVVAKSTVSDVDALKACVKSGWRKATAGTPTSMCNNGWTYPPFADTRRGEEGYFVLLAGTASDFCSAPNANYRTTASSWPG