Rv0368c Family assigned · medium auto-curated
H37Rv Rv0368c · MTBC0 mtbc0_000388 ·
403 aa · 448676–449887 (-) ·
RefSeq NP_214882.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | VWA domain-containing protein |
| Revised (this work) | VWA domain-containing protein. Pfam: VWA_CoxE (PF05762.21). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53703
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | VWFA domain-containing protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | VWA containing CoxE family protein |
| Orthologous group | COG3552 |
| KEGG orthology |
K07161
|
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 | 1.055 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 10 missense, 1 nonsense, 0 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.45% of strains (657) · clonal |
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 |
|---|---|---|---|---|
VWA_CoxE | PF05762.21 | 1.3e-75 | 171–391 | VWA domain containing CoxE-like protein |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0369c (membrane oxidoreductase), high confidence from genomic context alone (score 972 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) |
|---|---|---|---|---|
Rv0369c |
membrane oxidoreductase | 971 | 972 ctx | neighborhood:882 cooccurence:768 |
Rv0370c |
oxidoreductase | 947 | 946 ctx | neighborhood:773 cooccurence:770 |
Rv0372c hyp |
hypothetical protein | 944 | 945 ctx | neighborhood:773 cooccurence:748 |
Rv0373c |
carbon monoxyde dehydrogenase large subunit | 942 | 942 ctx | neighborhood:748 cooccurence:770 |
Rv0375c |
carbon monoxyde dehydrogenase medium subunit | 939 | 940 ctx | neighborhood:754 cooccurence:758 |
Rv0374c |
carbon monoxyde dehydrogenase small subunit | 870 | 870 ctx | neighborhood:760 cooccurence:452 |
Rv0371c hyp |
hypothetical protein | 863 | 863 ctx | neighborhood:773 |
Rv0377 |
HTH-type transcriptional regulator | 853 | 854 ctx | neighborhood:663 cooccurence:574 |
Rv0376c hyp |
hypothetical protein | 848 | 848 ctx | neighborhood:700 cooccurence:508 |
Rv2426c hyp |
hypothetical protein | 783 | 780 ctx | cooccurence:752 |
Rv0365c hyp |
hypothetical protein | 975 | 743 ctx | neighborhood:742 textmining:907 |
Rv0367c hyp |
hypothetical protein | 947 | 611 ctx | neighborhood:606 textmining:870 |
Rv0366c hyp |
hypothetical protein | 937 | 537 ctx | neighborhood:534 textmining:870 |
Rv2425c hyp |
hypothetical protein | 520 | 521 ctx | cooccurence:518 |
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: VWA domain-containing protein
- Pfam (hmmscan --cut_ga): VWA_CoxE PF05762.21 (E=1e-75)
- (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_214882.1)
- Domains: Pfam-A via hmmscan --cut_ga — VWA_CoxE (PF05762.21)
- 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
COG3552 - Curated reference: UniProt O53703 (TrEMBL, unreviewed; Predicted)
- Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
14 functional partner(s); context anchor
Rv0369c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000388|Rv0368c| MATPALLPGVDLAAFAAALAARLRDAGIPVSASGQASLVQALQQLVPRTPAALYWGARLTLVSRVDELATFDAVFASLFGVFGSAEPDGANRPPPPIAGPRTPVAGVGHRAKRRSCAAQAQNLPWDTRSLTMASAGQGGPSRTLPDVLPSRIVARADEPFDQFDPDDLRLLGAWLEATMARWPRRRSMRFESSPHGKRIDLRATMNASRSTGWESVLLARIRPRRRPRRVLLLCDVSRSMQPYAAIYLHLMRAAVLRRAGGHPEVFAFSTSLTRLTSVLSHRSAEMALHRANARVTDRYGGTFIGRSVAALLAPPHGNALRGAVVIIASDGWDSDPPDVLVHALTRVRRRAELLVWLNPRAAHPEFQPRAGSMAAALPYCDLFLPAHSLAGLHQLLLALAGAR