efpA Resolved · high auto-curated

H37Rv Rv2846c · MTBC0 mtbc0_003025 · 530 aa · 3173705–3175297 (-) · RefSeq NP_217362.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)MFS-type transporter EfpA
MTBC0 PGAP re-annotationmultidrug efflux MFS transporter EfpA
Revised (this work)Multidrug efflux MFS transporter EfpA. Pfam: MFS_1 (PF07690.22).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt P9WJY5 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized MFS-type transporter EfpA

UniProt still lists this protein as Uncharacterized MFS-type transporter EfpA; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
G Carbohydrate transport and metabolism
P Inorganic ion transport and metabolism
Preferred nameefpA
eggNOG descriptionMajor facilitator superfamily
Orthologous groupCOG0477
Gene Ontology (2) GO:0008150, GO:0040007

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 0.618 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 5 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)

PfamAccessioni-EvalueResiduesDescription
MFS_1PF07690.22 3.7e-4461–449 Major Facilitator Superfamily

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: cysG (multifunctional uroporphyrin-III C-methyltransferase/precorrin-2 oxidase/ferrochelatase), high confidence from genomic context alone (score 854 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2847c cysG multifunctional uroporphyrin-III C-methyltransferase/precorrin-2 oxidase/ferrochelatase 854 854 ctx neighborhood:853
Rv3801c fadD32 long-chain-fatty-acid--AMP ligase FadD32 823 770 coexpression:770
Rv2845c proS proline--tRNA ligase 740 740 ctx neighborhood:736
Rv2247 accD6 acetyl-/propionyl-CoA carboxylase subunit beta 830 731 coexpression:731
Rv2246 kasB 3-oxoacyl-ACP synthase 2 756 729 coexpression:729
Rv2245 kasA 3-oxoacyl-ACP synthase 1 876 716 coexpression:716 textmining:584
Rv2848c cobB cobyrinic acid A,C-diamide synthase 708 708 ctx neighborhood:708
Rv2849c cobO cob(I)alamin adenosyltransferase 708 708 ctx neighborhood:708
Rv2851c GCN5-like N-acetyltransferase 699 700 ctx neighborhood:698
Rv2850c magnesium chelatase 699 700 ctx neighborhood:698
Rv2852c mqo malate:quinone oxidoreductase 672 673 ctx neighborhood:668
Rv2854 hyp hypothetical protein 584 569 ctx neighborhood:569
Rv2855 mtr mycothione reductase 580 565 ctx neighborhood:565
Rv0412c glnX membrane protein 533 533 coexpression:533
Rv2243 fabD malonyl CoA-acyl carrier protein transacylase 564 442 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

  • Legacy H37Rv annotation: MFS-type transporter EfpA
  • MTBC0 PGAP product: multidrug efflux MFS transporter EfpA
  • Pfam (hmmscan --cut_ga): MFS_1 PF07690.22 (E=4e-44)
  • (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_217362.1)
  • Domains: Pfam-A via hmmscan --cut_ga — MFS_1 (PF07690.22)
  • 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 P9WJY5 (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 — 41 functional partner(s); context anchor cysG
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003025|Rv2846c|efpA
MTALNDTERAVRNWTAGRPHRPAPMRPPRSEETASERPSRYYPTWLPSRSFIAAVIAIGGMQLLATMDSTVAIVALPKIQNELSLSDAGRSWVITAYVLTFGGLMLLGGRLGDTIGRKRTFIVGVALFTISSVLCAVAWDEATLVIARLSQGVGSAIASPTGLALVATTFPKGPARNAATAVFAAMTAIGSVMGLVVGGALTEVSWRWAFLVNVPIGLVMIYLARTALRETNKERMKLDATGAILATLACTAAVFAFSIGPEKGWMSGITIGSGLVALAAAVAFVIVERTAENPVVPFHLFRDRNRLVTFSAILLAGGVMFSLTVCIGLYVQDILGYSALRAGVGFIPFVIAMGIGLGVSSQLVSRFSPRVLTIGGGYLLFGAMLYGSFFMHRGVPYFPNLVMPIVVGGIGIGMAVVPLTLSAIAGVGFDQIGPVSAIALMLQSLGGPLVLAVIQAVITSRTLYLGGTTGPVKFMNDVQLAALDHAYTYGLLWVAGAAIIVGGMALFIGYTPQQVAHAQEVKEAIDAGEL