fixB Family assigned · medium auto-curated

H37Rv Rv3028c · MTBC0 mtbc0_003219 · 318 aa · 3408385–3409341 (-) · RefSeq NP_217544.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)electron transfer flavoprotein subunit alpha
MTBC0 PGAP re-annotationelectron transfer flavoprotein subunit alpha/FixB family protein
Revised (this work)Electron transfer flavoprotein subunit alpha/FixB family protein. Pfam: ETF (PF01012.28), ETF_alpha (PF00766.26).

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

Curated reference (UniProt)

UniProt P9WNG9 SwissProt · reviewed · Evidence at protein level
UniProt nameElectron transfer flavoprotein subunit alpha
Curated functionThe electron transfer flavoprotein serves as a specific electron acceptor for other dehydrogenases. It transfers the electrons to the main respiratory chain via ETF-ubiquinone oxidoreductase (ETF dehydrogenase) (By similarity).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
Preferred nameetfA
eggNOG descriptionElectron transfer flavoprotein
Orthologous groupCOG2025
KEGG orthology K03522
Gene Ontology (13) GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0016020, GO:0030312, GO:0044424, GO:0044444, GO:0044464 +1 more

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 0.248 · purifying
Polymorphic sites (≥ 0.1% of strains) 6 synonymous, 4 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
ETFPF01012.28 5.5e-304–174 Electron transfer flavoprotein domain
ETF_alphaPF00766.26 5.0e-35194–274 Electron transfer flavoprotein FAD-binding domain

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

Closest characterised functional partner: fixA (electron transfer flavoprotein subunit beta), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3029c fixA electron transfer flavoprotein subunit beta 999 1000 ctx neighborhood:827 fusion:807 cooccurence:774 coexpression:957 experimental:928 database:844 textmining:639
Rv3274c fadE25 acyl-CoA dehydrogenase 943 941 ctx cooccurence:694 coexpression:559 experimental:419
Rv1175c fadH NADPH dependent 2,4-dienoyl-CoA reductase FadH 950 933 experimental:922
Rv2500c fadE19 acyl-CoA dehydrogenase FadE19 928 925 ctx cooccurence:713 coexpression:410 experimental:419
Rv0975c fadE13 acyl-CoA dehydrogenase FadE13 884 879 ctx cooccurence:607 coexpression:411 experimental:419
Rv2724c fadE20 acyl-CoA dehydrogenase FadE20 872 867 ctx cooccurence:551 coexpression:412 experimental:419
Rv2789c fadE21 acyl-CoA dehydrogenase FadE21 870 865 ctx cooccurence:585 coexpression:416 experimental:419
Rv0215c fadE3 Rv0215c, (MTCY08D5.10c), len: 357 aa. Probable fadE3, acyl- dehydrogenase, similar to many e.g. ACDB_BACSU|P45857 acyl-CoA dehydrogenase fro 869 864 ctx cooccurence:550 coexpression:408 experimental:419
Rv0752c fadE9 acyl-CoA dehydrogenase FadE9 851 845 ctx cooccurence:466 coexpression:408 experimental:419
Rv1933c fadE18 acyl-CoA dehydrogenase FadE18 850 844 ctx cooccurence:567 coexpression:412 experimental:419
Rv1679 fadE16 acyl-CoA dehydrogenase FadE16 908 838 ctx cooccurence:534 coexpression:435 experimental:419 textmining:459
Rv3139 fadE24 acyl-CoA dehydrogenase 828 822 ctx cooccurence:504 coexpression:414 experimental:419
Rv3443c rplM 50S ribosomal protein L13 811 811 coexpression:811
Rv3505 fadE27 acyl-CoA dehydrogenase FadE27 816 809 ctx cooccurence:472 coexpression:410 experimental:419
Rv3140 fadE23 acyl-CoA dehydrogenase FadE23 803 794 ctx cooccurence:416 coexpression:414 experimental:419

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: electron transfer flavoprotein subunit alpha
  • MTBC0 PGAP product: electron transfer flavoprotein subunit alpha/FixB family protein
  • Pfam (hmmscan --cut_ga): ETF PF01012.28 (E=5e-30), ETF_alpha PF00766.26 (E=5e-35)
  • (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_217544.1)
  • Domains: Pfam-A via hmmscan --cut_ga — ETF (PF01012.28), ETF_alpha (PF00766.26)
  • 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 COG2025
  • Curated reference: UniProt P9WNG9 (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 — 172 functional partner(s); context anchor fixA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003219|Rv3028c|fixB
MAEVLVLVEHAEGALKKVSAELITAARALGEPAAVVVGVPGTAAPLVDGLKAAGAAKIYVAESDLVDKYLITPAVDVLAGLAESSAPAGVLIAATADGKEIAGRLAARIGSGLLVDVVDVREGGVGVHSIFGGAFTVEAQANGDTPVITVRAGAVEAEPAAGAGEQVSVEVPAAAENAARITAREPAVAGDRPELTEATIVVAGGRGVGSAENFSVVEALADSLGAAVGASRAAVDSGYYPGQFQVGQTGKTVSPQLYIALGISGAIQHRAGMQTSKTIVAVNKDEEAPIFEIADYGVVGDLFKVAPQLTEAIKARKG