fixA Family assigned · medium auto-curated

H37Rv Rv3029c · MTBC0 mtbc0_003220 · 266 aa · 3409380–3410180 (-) · RefSeq NP_217545.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)electron transfer flavoprotein subunit beta
MTBC0 PGAP re-annotationelectron transfer flavoprotein subunit beta/FixA family protein
Revised (this work)Electron transfer flavoprotein subunit beta/FixA family protein. Pfam: ETF (PF01012.28).

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

Curated reference (UniProt)

UniProt P9WNG7 SwissProt · reviewed · Evidence at protein level
UniProt nameElectron transfer flavoprotein subunit beta
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 nameetfB
eggNOG descriptionElectron transfer flavoprotein
Orthologous groupCOG2086
KEGG orthology K03521
Gene Ontology (25) GO:0003674, GO:0003824, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0006091, GO:0008150, GO:0008152 +13 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 0.169 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 2 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 6.2e-3625–214 Electron transfer flavoprotein domain

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

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

PartnerProductScoreNo text-miningChannels (≥400)
Rv3028c fixB electron transfer flavoprotein subunit alpha 999 1000 ctx neighborhood:827 fusion:807 cooccurence:774 coexpression:957 experimental:928 database:844 textmining:639
Rv1175c fadH NADPH dependent 2,4-dienoyl-CoA reductase FadH 996 995 experimental:994
Rv2500c fadE19 acyl-CoA dehydrogenase FadE19 905 901 ctx cooccurence:729 coexpression:406 experimental:418
Rv3274c fadE25 acyl-CoA dehydrogenase 897 893 ctx cooccurence:694 coexpression:432 experimental:418
Rv0975c fadE13 acyl-CoA dehydrogenase FadE13 865 860 ctx cooccurence:615 coexpression:408 experimental:418
Rv2789c fadE21 acyl-CoA dehydrogenase FadE21 851 845 ctx cooccurence:573 coexpression:410 experimental:418
Rv1933c fadE18 acyl-CoA dehydrogenase FadE18 846 840 ctx cooccurence:563 coexpression:406 experimental:418
Rv0215c fadE3 Rv0215c, (MTCY08D5.10c), len: 357 aa. Probable fadE3, acyl- dehydrogenase, similar to many e.g. ACDB_BACSU|P45857 acyl-CoA dehydrogenase fro 839 833 ctx cooccurence:542 coexpression:406 experimental:418
Rv3139 fadE24 acyl-CoA dehydrogenase 834 827 ctx cooccurence:523 coexpression:410 experimental:418
Rv1679 fadE16 acyl-CoA dehydrogenase FadE16 848 819 ctx cooccurence:499 coexpression:413 experimental:418
Rv2724c fadE20 acyl-CoA dehydrogenase FadE20 819 812 ctx cooccurence:483 coexpression:408 experimental:418
Rv0972c fadE12 acyl-CoA dehydrogenase fadE12 815 808 ctx cooccurence:470 coexpression:410 experimental:418
Rv3153 nuoI NADH-quinone oxidoreductase subunit I 833 800 coexpression:410 experimental:652
Rv3505 fadE27 acyl-CoA dehydrogenase FadE27 806 798 ctx cooccurence:450 coexpression:404 experimental:418
Rv3140 fadE23 acyl-CoA dehydrogenase FadE23 793 785 ctx cooccurence:407 coexpression:410 experimental:418

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 beta
  • MTBC0 PGAP product: electron transfer flavoprotein subunit beta/FixA family protein
  • Pfam (hmmscan --cut_ga): ETF PF01012.28 (E=6e-36)
  • (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_217545.1)
  • Domains: Pfam-A via hmmscan --cut_ga — ETF (PF01012.28)
  • 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 COG2086
  • Curated reference: UniProt P9WNG7 (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 — 138 functional partner(s); context anchor fixB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003220|Rv3029c|fixA
MTNIVVLIKQVPDTWSERKLTDGDFTLDREAADAVLDEINERAVEEALQIREKEAADGIEGSVTVLTAGPERATEAIRKALSMGADKAVHLKDDGMHGSDVIQTGWALARALGTIEGTELVIAGNESTDGVGGAVPAIIAEYLGLPQLTHLRKVSIEGGKITGERETDEGVFTLEATLPAVISVNEKINEPRFPSFKGIMAAKKKEVTVLTLAEIGVESDEVGLANAGSTVLASTPKPAKTAGEKVTDEGEGGNQIVQYLVAQKII