jefA Resolved · high auto-curated
H37Rv Rv2459 · MTBC0 mtbc0_002618 ·
508 aa · 2785102–2786628 (+) ·
RefSeq NP_216975.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | MFS-type transporter |
|---|---|
| MTBC0 PGAP re-annotation | multidrug efflux pump JefA |
| Revised (this work) | Multidrug efflux pump JefA. Pfam: MFS_1 (PF07690.22), Sugar_tr (PF00083.31). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WJW9
SwissProt · reviewed
· Evidence at transcript level
|
|---|---|
| UniProt name | Drug efflux pump JefA |
| Curated function | Involved in resistance to ethambutol and isoniazid. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolismG Carbohydrate transport and metabolismP Inorganic ion transport and metabolism
|
|---|---|
| eggNOG description | thought to be involved in a transport system across the membrane (perhaps drug transport) responsible for the translocation of the substrate across the membrane |
| Orthologous group | COG0477 |
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 | n/a |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 0 synonymous, 3 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.15% of strains (214) · 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 |
|---|---|---|---|---|
MFS_1 | PF07690.22 | 5.8e-51 | 14–404 | Major Facilitator Superfamily |
Sugar_tr | PF00083.31 | 3.2e-07 | 44–179 | Sugar (and other) transporter |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mmuM (homocysteine S-methyltransferase MmuM), medium confidence from genomic context alone (score 474 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2458 mmuM |
homocysteine S-methyltransferase MmuM | 475 | 474 ctx | neighborhood:463 |
Rv1250 |
MFS-type drug transporter | 432 | 335 | |
Rv3728 |
membrane protein | 507 | 330 | |
Rv2846c efpA |
MFS-type transporter EfpA | 542 | 320 | |
Rv0783c emrB |
multidrug resistance protein EmrB | 409 | 312 | |
Rv1258c tap |
multidrug-efflux transporter | 837 | 196 | textmining:806 |
Rv2209 |
integral membrane protein | 523 | 190 | textmining:436 |
Rv2942 mmpL7 |
transmembrane transport protein MmpL7 | 675 | 96 | textmining:656 |
Rv0696 mftF |
mycofactocin biosynthesis glycosyltransferase MftF | 404 | 85 | |
Rv3065 mmr |
multidrug resistance protein Mmr | 813 | 48 | textmining:812 |
Rv1819c bacA |
vitamin B12 transport ATP-binding protein BacA | 632 | 47 | textmining:630 |
Rv0755A |
Rv0755A, len: 61 aa. Putative transposase (possibly gene fragment), similar to C-terminal part of Q9EZM2|ISMav2|AF286339_1 putative transpos | 441 | 47 | textmining:438 |
Rv1217c |
tetronasin ABC transporter integral membrane protein | 432 | 44 | textmining:431 |
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: MFS-type transporter
- MTBC0 PGAP product: multidrug efflux pump JefA
- Pfam (hmmscan --cut_ga): MFS_1 PF07690.22 (E=6e-51), Sugar_tr PF00083.31 (E=3e-07)
- (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_216975.1)
- Domains: Pfam-A via hmmscan --cut_ga — MFS_1 (PF07690.22), Sugar_tr (PF00083.31)
- 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
COG0477 - Curated reference: UniProt P9WJW9 (SwissProt, reviewed; Evidence at transcript 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 —
13 functional partner(s); context anchor
mmuM - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002618|Rv2459|jefA MTPRQRLTVLATGLGIFMVFVDVNIVNVALPSIQKVFHTGEQGLQWAVAGYSLGMAAVLMSCALLGDRYGRRRSFVFGVTLFVVSSIVCVLPVSLAVFTVARVIQGLGAAFISVLSLALLSHSFPNPRMKARAISNWMAIGMVGAASAPALGGLMVDGLGWRSVFLVNVPLGAIVWLLTLVGVDESQDPEPTQLDWVGQLTLIPAVALIAYTIIEAPRFDRQSAGFVAALLLAAGVLLWLFVRHEHRAAFPLVDLKLFAEPLYRSVLIVYFVVMSCFFGTLMVITQHFQNVRDLSPLHAGLMMLPVPAGFGVASLLAGRAVNKWGPQLPVLTCLAAMFIGLAIFAISMDHAHPVALVGLTIFGAGAGGCATPLLHLGMTKVDDGRAGMAAGMLNLQRSLGGIFGVAFLGTIVAAWLGAALPNTMADEIPDPIARAIVVDVIVDSANPHAHAAFIGPGHRITAAQEDEIVLAADAVFVSGIKLALGGAAVLLTGAFVLGWTRFPRTPAS