Rv3486 Family assigned · medium auto-curated
H37Rv Rv3486 · MTBC0 mtbc0_003701 ·
149 aa · 3930354–3930803 (+) ·
RefSeq NP_218003.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | DoxX family protein |
| Revised (this work) | DoxX family protein. Pfam: DoxX (PF07681.18). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O06349
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized membrane protein Rv3486 |
UniProt still lists this protein as Uncharacterized membrane protein Rv3486; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | DoxX |
| Orthologous group | COG2259 |
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) pseudogene candidate
| pN/pS | n/a |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 0 synonymous, 1 missense, 0 nonsense, 2 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 1.10% of strains (1592) · 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 |
|---|---|---|---|---|
DoxX | PF07681.18 | 3.8e-16 | 11–89 | DoxX |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv3485c (short-chain type dehydrogenase/reductase), medium confidence from genomic context alone (score 554 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) |
|---|---|---|---|---|
Rv3884c eccA2 |
ESX-2 secretion system protein EccA | 578 | 579 | database:576 |
Rv3868 eccA1 |
ESX-1 secretion system protein EccA1 | 577 | 577 | database:576 |
Rv0282 eccA3 |
ESX-3 secretion system protein EccA | 576 | 577 | database:576 |
Rv3485c |
short-chain type dehydrogenase/reductase | 554 | 554 ctx | neighborhood:490 |
Rv0908 ctpE |
metal cation transporter ATPase E | 483 | 483 | |
Rv1997 ctpF |
cation transporter ATPase F | 481 | 481 | |
Rv0107c ctpI |
cation-transporter ATPase I | 480 | 481 | |
Rv0425c ctpH |
metal cation transporting ATPase H | 479 | 480 | |
Rv1305 atpE |
ATP synthase subunit C | 436 | 436 | database:417 |
Rv0732 secY |
preprotein translocase SecY | 403 | 366 |
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: DoxX family protein
- Pfam (hmmscan --cut_ga): DoxX PF07681.18 (E=4e-16)
- (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_218003.1)
- Domains: Pfam-A via hmmscan --cut_ga — DoxX (PF07681.18)
- 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
COG2259 - Curated reference: UniProt O06349 (SwissProt, reviewed; 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
Rv3485c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003701|Rv3486| MHAEGPPSVICIRLLVGLVFLSEGIQKFMYPDQLGPGRFERIGIPAATFFADLDGVVEIVCGTLVLLGLLTRVAAVPLLIDMVGAIVLTKLRALQPGGFLGVEGFWGMAHAARTDLSMLLGLIFLLWSGPGRWSLDRRLSKRATACGAR