fdhF Family assigned · medium auto-curated

H37Rv Rv2900c · MTBC0 mtbc0_003082 · 779 aa · 3230235–3232574 (-) · RefSeq NP_217416.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)formate dehydrogenase subunit alpha FdhF
MTBC0 PGAP re-annotationFdhF/YdeP family oxidoreductase
Revised (this work)FdhF/YdeP family oxidoreductase. Pfam: Molybdopterin (PF00384.28), Molydop_binding (PF01568.28).

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

Curated reference (UniProt)

UniProt P9WJP9 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized oxidoreductase Rv2900c
EC (curated) EC 1.-.-.-

UniProt still lists this protein as Uncharacterized oxidoreductase Rv2900c; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
Preferred namefdhF
eggNOG descriptionBelongs to the prokaryotic molybdopterin-containing oxidoreductase family
Orthologous groupCOG0243
EC number EC 1.17.1.9
KEGG orthology K00123
KEGG pathways map00630, map00680, map01100, map01120, map01200
Gene Ontology (6) GO:0005575, GO:0005623, GO:0005886, GO:0016020, GO:0044464, GO:0071944

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 1.002 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 9 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
MolybdopterinPF00384.28 6.8e-23132–506 Molybdopterin oxidoreductase
Molydop_bindingPF01568.28 9.7e-07660–716 Molydopterin dinucleotide binding domain

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

Closest characterised functional partner: fdhD (formate dehydrogenase accessory protein FdhD), high confidence from genomic context alone (score 972 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2899c fdhD formate dehydrogenase accessory protein FdhD 988 972 ctx neighborhood:882 cooccurence:705 textmining:596
Rv2194 qcrC ubiquinol-cytochrome C reductase cytochrome subunit C 818 799 experimental:774
Rv0685 tuf elongation factor Tu 809 794 experimental:783
Rv2901c hyp hypothetical protein 674 675 ctx neighborhood:670
Rv2898c hyp hypothetical protein 577 576 ctx neighborhood:570
Rv2897c hyp hypothetical protein 577 576 ctx neighborhood:570
Rv3859c gltB glutamate synthase large subunit 769 575 experimental:420 textmining:481
Rv2896c dprA hyp hypothetical protein 575 574 ctx neighborhood:570
Rv2902c rnhB ribonuclease HII 532 533 ctx neighborhood:512
Rv2195 qcrA ubiquinol-cytochrome C reductase rieske iron-sulfur subunit 564 518 experimental:484
Rv2903c lepB signal peptidase 496 497 ctx neighborhood:487
Rv2895c viuB mycobactin utilization protein ViuB 480 480
Rv1162 narH nitrate reductase subunit beta 653 457 experimental:431
Rv3273 transmembrane carbonic anhydrase 413 384
Rv3153 nuoI NADH-quinone oxidoreductase subunit I 411 348

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: formate dehydrogenase subunit alpha FdhF
  • MTBC0 PGAP product: FdhF/YdeP family oxidoreductase
  • Pfam (hmmscan --cut_ga): Molybdopterin PF00384.28 (E=7e-23), Molydop_binding PF01568.28 (E=1e-06)
  • (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_217416.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Molybdopterin (PF00384.28), Molydop_binding (PF01568.28)
  • 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 COG0243
  • Curated reference: UniProt P9WJP9 (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 — 29 functional partner(s); context anchor fdhD
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003082|Rv2900c|fdhF
MYVEAVRWQRSAASRDVLADYDEQAVTVAPRKREAAGVRAVMVSLQRGMQQMGALRTAAALARLNQRNGFDCPGCAWPEEPGGRKLAEFCENGAKAVAEEATKRTVTAEFFARHSVAELSAKPEYWLSQQGRLAHPMVLRPGDDHYRPISWDAAYQLIAEQLNGLDSPDRAVFYTSGRTSNEAAFCYQLLVRSFGTNNLPDCSNMCHESSGAALTDSIGIGKGSVTIGDVEHADLIVIAGQNPGTNHPRMLSVLGKAKANGAKIIAVNPLPEAGLIRFKDPQKVNGVVGHGIPIADEFVQIRLGGDMALFAGLGRLLLEAEERVPGSVVDRSFVDNHCAGFDGYRRRTLQVGLDTVMDATGIELAQLQRVAAMLMASQRTVICWAMGLTQHAHAVATIGEVTNVLLLRGMIGKPGAGVCPVRGHSNVQGDRTMGIWEKMPEQFLAALDREFGITSPRAHGFDTVAAIRAMRDGRVSVFMGMGGNFASATPDTAVTEAALRRCALTVQVSTKLNRSHLVHGATALILPTLGRTDRDTRNGRKQLVSVEDSMSMVHLSRGSLHPPSDQVRSEVQIICQLARALFGPGHPVPWERFADDYDTIRDAIAAVVPGCDDYNHKVRVPDGFQLPHPPRDAREFRTSTGKANFAVNPLQWVPVPPGRLVLQTLRSHDQYNTTIYGLDDRYRGVKGGRRVVFINPADIETFGLTAGDRVDLVSEWTDGQGGLQERRAKDFLVVAYSTPVGNAAAYYPETNPLVPLDHTAAQSNTPVSKAIIVRLEPTA