Rv0393 Family assigned · low
H37Rv Rv0393 · MTBC0 - ·
441 aa · 472781–474106 (+) ·
RefSeq NP_214907.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Member of the conserved 13E12 (REP13E12) repeat protein family. RefSeq leaves it of unknown function. Identified as a conserved component (P95201) of M. tuberculosis extracellular vesicles, proposed as an MEV marker (Ryan 2025). The REP13E12 repeats serve as prophage (phiRv1) attachment sites. Molecular function unfixed. |
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 |
P95201
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | Conserved 13E12 repeat family protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
V Defense mechanisms
|
|---|---|
| eggNOG description | HNH endonuclease |
| Orthologous group | COG1403 |
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 | 1.036 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 14 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 |
|---|---|---|---|---|
DUF222 | PF02720.23 | 9.1e-47 | 100–281 | Domain of unknown function (DUF222) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ndhA (NADH dehydrogenase NdhA), medium confidence from genomic context alone (score 535 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) |
|---|---|---|---|---|
Rv1765c hyp |
hypothetical protein | 748 | 748 ctx | cooccurence:745 |
Rv1587c hyp |
hypothetical protein | 745 | 746 ctx | cooccurence:742 |
Rv2015c hyp |
hypothetical protein | 742 | 742 ctx | cooccurence:740 |
Rv0094c hyp |
hypothetical protein | 734 | 734 ctx | cooccurence:726 |
Rv3467 hyp |
hypothetical protein | 733 | 734 ctx | cooccurence:726 |
Rv1148c hyp |
hypothetical protein | 732 | 733 ctx | cooccurence:730 |
Rv1945 hyp |
hypothetical protein | 732 | 733 ctx | cooccurence:731 |
Rv3354 hyp |
hypothetical protein | 693 | 674 | experimental:470 |
Rv2564 glnQ |
glutamine ABC transporter ATP-binding protein | 663 | 631 | |
Rv3103c hyp |
hypothetical protein | 618 | 594 | experimental:512 |
Rv0073 |
glutamine ABC transporter ATP-binding protein | 617 | 581 | |
Rv0986 |
adhesion component ABC transporter ATP-binding protein | 598 | 578 | |
Rv1156 hyp |
hypothetical protein | 568 | 569 ctx | cooccurence:564 |
Rv1073 hyp |
hypothetical protein | 537 | 537 ctx | cooccurence:535 |
Rv0392c ndhA |
NADH dehydrogenase NdhA | 536 | 535 ctx | neighborhood:535 |
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
- Conserved 13E12 (REP13E12) repeat-family protein; MEV-associated marker (Ryan 2025, PMID 40256639)
- Curated from the literature crible (project 'Still unknown gene function', 2026-06-09)
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_214907.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF222 (PF02720.23)
- 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
COG1403 - Curated reference: UniProt P95201 (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 —
26 functional partner(s); context anchor
ndhA - Primary literature: Ryan JM, Shelton K, Dzieciatkowska M, Kruh-Garcia N, Dobos KM (2025). Establishment of minimum protein standards for Mycobacterium tuberculosis-derived extracellular vesicles through comparison of EV enrichment methods Mycobacteria 1(1):3. doi:10.1186/s44350-025-00003-8 PMID:40256639
Ancestral MTBC0 protein sequence
>H37Rv|Rv0393| MAVGRCAIPRFDQAASGSAINGGQVHLSDGSTSPARQLPAPWPGDAGAAAEGRAGVCCRGNRLPHVSDVGVSHRFDHRPAGVGAGGCRAGAAGAGLAVDDPGQLAAAIDRIVAVADPDAVRQVRERARDREVSIWNSADGMGEVYAQLYATDAQALDARLNALVATVCAGDPRSTDQRRADALGALAAGADRLACRCDNPDCAAEGRPVSAVVIHVVAEQASVKGHGQAPAALLGGDGLIPAELVAELAKTAGLQPIPVPAGTEPGYRPSVKLAAFVRARDLTCRAPGCDRPATQCDLDHTIAFADGGATHAANLKCLCRLHHLLATFCGWRAQQLPDGTVIWTLPGNQTYVTTPGSALLFPALCTPTGDPPAPEPARADRRGQRTAMMPRRASTRTQNRAHCIAAERHRNHQARRIAQAAVIATETHGPPPDPDDDPPPF