Rv3900c Family assigned · medium
H37Rv Rv3900c · MTBC0 mtbc0_004133 ·
312 aa · 4409624–4410560 (-) ·
RefSeq NP_218417.1
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 (four-helical-bundle, WXG motif) RefSeq leaves this locus uncharacterised. |
Curated reference (UniProt)
| UniProt |
O05445
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | Conserved hypothetical alanine rich protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2A1TI |
|---|
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 | 0.443 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 11 synonymous, 14 missense, 0 nonsense, 5 frameshift |
| Disruption | 5 distinct premature-stop/frameshift site(s); most common in 2.46% of strains (3575) · convergent |
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: Rv3901c (membrane protein), medium confidence from genomic context alone (score 616 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) |
|---|---|---|---|---|
Rv3899c hyp |
hypothetical protein | 969 | 775 ctx | neighborhood:774 textmining:870 |
Rv3901c |
membrane protein | 617 | 616 ctx | neighborhood:614 |
Rv3898c hyp |
hypothetical protein | 503 | 503 ctx | neighborhood:498 |
Rv3897c hyp |
hypothetical protein | 495 | 495 ctx | neighborhood:490 |
Rv1662 pks8 |
polyketide synthase | 660 | 54 | textmining:656 |
Rv0945 |
oxidoreductase | 514 | 47 | textmining:511 |
Rv0944 fpg2 |
formamidopyrimidine-DNA glycosylase | 631 | 44 | textmining:630 |
Rv0943c |
monooxygenase | 511 | 41 | textmining:511 |
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): 14 concordant top hits all ESX/ESAT-6 family - EsxA/ESAT-6 3FAV, EsxB 6J19, EsxR 3H6P, PPE41 4W4K, WXG proteins - all ~97.5-97.9%, E 6.8e-4 to 0.017
- 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_218417.1)
- 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
2A1TI - Curated reference: UniProt O05445 (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 —
8 functional partner(s); context anchor
Rv3901c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_004133|Rv3900c| MVAADLPPGRWSAVLVGPWWPAPSAALRAAAQHWATWAMQKQELARNLISQHDLLLRNQGRTAEDLIGRYLRGAKSEVTKAEKYEIKKGAFNTAADAIDYLRSRLTGIAGEGNKEIDDVLASKKPLPEQLAEIQAIQTRCNADAANASRDAVDKVMTAMQEILEAEDIGDDPRTWARANGFNVDDAPPPRLIRENDLAALTGPGARGGSFGSVEGAGDLASPQSVGAGGFSGSGVQAACSQPAPRAIGASSRHASAGPVPPAPVVTTPAAATPPVIATGPPVAMPGGSLSPAALGQGVSPTSIGQSFATGMV