Rv3439c Family assigned · medium
H37Rv Rv3439c · MTBC0 mtbc0_003658 ·
467 aa · 3884145–3885548 (-) ·
RefSeq NP_217956.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | ESAT-6-like (WXG100) / ESX-PE-PPE superfamily protein associated with the Type VII (ESX) secretion system; conserved four-helical-bundle/WXG domain within a large (467 aa) protein RefSeq leaves this locus uncharacterised. |
Curated reference (UniProt)
| UniProt |
I6YC49
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Conserved hypothetical alanine and proline rich protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2ANA8 |
|---|
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 | 0.239 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 9 synonymous, 6 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).
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mrsA (phosphoglucosamine mutase), high confidence from genomic context alone (score 822 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) |
|---|---|---|---|---|
Rv3440c hyp |
hypothetical protein | 932 | 932 ctx | neighborhood:882 coexpression:449 |
Rv3441c mrsA |
phosphoglucosamine mutase | 822 | 822 ctx | neighborhood:816 |
Rv3903c cpnT hyp |
hypothetical protein | 732 | 732 | coexpression:732 |
Rv2759c vapC42 |
ribonuclease VapC42 | 730 | 730 | coexpression:730 |
Rv2760c vapB42 |
antitoxin VapB42 | 703 | 703 | coexpression:703 |
Rv3442c rpsI |
30S ribosomal protein S9 | 524 | 524 ctx | neighborhood:519 |
Rv3444c esxT |
ESAT-6 like protein EsxT | 513 | 513 | |
Rv3443c rplM |
50S ribosomal protein L13 | 450 | 450 ctx | neighborhood:445 |
Rv3911 sigM |
ECF RNA polymerase sigma factor SigM | 449 | 449 | coexpression:449 |
Rv3657c |
membrane protein | 441 | 441 | coexpression:441 |
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 (significant): 16 concordant top hits all ESX/ESAT-6 family ~97.8-98.1%, E 1.6e-4 to 2e-3 (ESXS, ESAT-6/EsxA 3FAV, EsxR, EsxB, PE family, MAB_3112/3113); aligned over the ~90-col conserved domain
- 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_217956.1)
- 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
2ANA8 - Curated reference: UniProt I6YC49 (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)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
10 functional partner(s); context anchor
mrsA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003658|Rv3439c| MADRLNVAERLAEGRPAAEHTQSYVRACHLVGYQHPDLTAYPAQIHDWYGSEDGLDLHALDADCAQLRAAASVLMEALRMERSQVAVLAAAWTGSGADAAVHFVQRHCETGNSVVTEVRAAAQRCESLRDNLWQLVDSKVATAIAIDERALAQRPAWLAAAEALTTEGADRPTAVEVVRQQIQPYVDDDVRNDWLTTMRSTTAGVAASYDAVTDQLASAPRAHFEIPDDLGPGRQPSPASVPAQPSATAAITPAAALPPPDPVPAVTSRPVTPSDFGSAPGDGSATPAGVGSAGGFGDAGGTGGLGGFAGLAGLANRIVDAVDSLLGSVAEQLGDPLAADNPPGAVDPFAEDAADNADDGDDAHPEEADEAAEPKEATEPDEADEVDDADESVPAERAQDVAEEATLPPVAEPPPPAAPPVAEPPPPVAAPAPPGAPEPANGPSPEALSEGATPCEIAADELPQAGP