fdxB Resolved · high auto-curated

H37Rv Rv3554 · MTBC0 mtbc0_003771 · 685 aa · 4016362–4018419 (+) · RefSeq NP_218071.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)electron transfer protein FdxB
MTBC0 PGAP re-annotationfatty acid desaturase
Revised (this work)Fatty acid desaturase. Pfam: FA_desaturase (PF00487.31), FAD_binding_6 (PF00970.31), NAD_binding_1 (PF00175.27), Fer2 (PF00111.33).

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

Curated reference (UniProt)

UniProt P71846 TrEMBL · unreviewed · Evidence at protein level
UniProt namePossible electron transfer protein FdxB

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
Preferred namepaaE
eggNOG descriptionOxidoreductase FAD-binding domain
Orthologous groupCOG1018
KEGG orthology K02613
KEGG pathways map00360, map01120

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 0.497 · purifying
Polymorphic sites (≥ 0.1% of strains) 7 synonymous, 10 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.42% of strains (611) · 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)

PfamAccessioni-EvalueResiduesDescription
FA_desaturasePF00487.31 7.5e-3867–299 Fatty acid desaturase
FAD_binding_6PF00970.31 4.5e-11344–439 Oxidoreductase FAD-binding domain
NAD_binding_1PF00175.27 3.6e-15456–562 Oxidoreductase NAD-binding domain
Fer2PF00111.33 4.4e-15601–675 2Fe-2S iron-sulfur cluster binding domain

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

Closest characterised functional partner: Rv3553 (oxidoreductase), high confidence from genomic context alone (score 780 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1465 nitrogen fixation related protein 885 851 database:621
Rv3025c iscS cysteine desulfurase 867 848 experimental:422 database:621
Rv3825c pks2 phthioceranic/hydroxyphthioceranic acid synthase 914 802 experimental:759 textmining:586
Rv2940c mas multifunctional mycocerosic acid synthase 914 802 experimental:759 textmining:586
Rv1527c pks5 polyketide synthase 914 802 experimental:759 textmining:586
Rv2048c pks12 polyketide synthase 914 802 experimental:759 textmining:586
Rv2933 ppsC phthiocerol synthesis polyketide synthase type I PpsC 914 801 experimental:759 textmining:586
Rv1175c fadH NADPH dependent 2,4-dienoyl-CoA reductase FadH 901 786 experimental:430 database:568 textmining:558
Rv1663 pks17 polyketide synthase 841 781 experimental:759
Rv3553 oxidoreductase 798 780 ctx neighborhood:779
Rv0886 fprB ferredoxin/ferredoxin--NADP reductase 918 776 experimental:430 database:568 textmining:651
Rv1666c cyp139 cytochrome P450 Cyp139 781 754
Rv3106 fprA NADPH-ferredoxin reductase FprA 821 753 experimental:430 database:568
Rv3858c gltD glutamate synthase small subunit 818 752 experimental:430 database:568
Rv3153 nuoI NADH-quinone oxidoreductase subunit I 787 752 experimental:700

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 protein FdxB
  • MTBC0 PGAP product: fatty acid desaturase
  • Pfam (hmmscan --cut_ga): FA_desaturase PF00487.31 (E=7e-38), FAD_binding_6 PF00970.31 (E=4e-11), NAD_binding_1 PF00175.27 (E=4e-15), Fer2 PF00111.33 (E=4e-15)
  • (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_218071.1)
  • Domains: Pfam-A via hmmscan --cut_ga — FA_desaturase (PF00487.31), FAD_binding_6 (PF00970.31), NAD_binding_1 (PF00175.27), Fer2 (PF00111.33)
  • 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 COG1018
  • Curated reference: UniProt P71846 (TrEMBL, unreviewed; 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 — 153 functional partner(s); context anchor Rv3553
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003771|Rv3554|fdxB
MTDACQAEYAIAAMSTVEMDQAAPESAAHHPLPDPGESVPRLALPTIGIFLATLTAFVGSTTAYISGWIPFWVTIPVNAAVTFVMFTVVHDASHYAISSIRWVNGLFGRLAWLFVGPVVAFPAFGYIHIQHHRHSNDDEQDPDTFASHGSLWVLPLRWSMVEYFYIKYYLPRGRSRPVIEVAETLVMMTLFLTGLIVAIVTGNFWTLAIVFLIPQRIGLTVLAWWFDWLPHHGLEDTQRSNRYRATRNRVGAEWLFTPVLLSQNYHLVHHLHPSVPFYRYLRTWRRNEEAYLERNAAISTVFGQQLNPDEYRQWKELNGRLARLLPVRMPARSSSPHAVLHRIPVASVDPITADATLVTFAVPEALRDAFRFEPGQHVTVRTDLGGQGIRRNYSICAPATRAQLRIAVKHIPGGAFSTFVANELKAGDVLELMTPTGRFGTPLDPLHRKHYVGLVAGSGITPVLSILATTLEIETESRFTLIYGNRTKESTMFRAELDRLESRYADRLEILHVLSSEPLHTPELRGRIDRDKLTRWLTSTLRPAGVDEWFICGPLAMATAVRETLIEHGVDSERIHLELFYGFDTPPATRPSYAGATVTFTLSGQRAIFDLVPGDSILEGALGLRSDAPYACMGGACGTCRAKLIEGNVEMDHNFALRKAELDAGYILTCQSHPTTPFVAVDYDA