fdhD Resolved · high auto-curated

H37Rv Rv2899c · MTBC0 mtbc0_003081 · 276 aa · 3229405–3230235 (-) · RefSeq NP_217415.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)formate dehydrogenase accessory protein FdhD
MTBC0 PGAP re-annotationformate dehydrogenase accessory sulfurtransferase FdhD
Revised (this work)Formate dehydrogenase accessory sulfurtransferase FdhD. Pfam: FdhD-NarQ (PF02634.22).

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

Curated reference (UniProt)

UniProt P9WNF1 SwissProt · reviewed · Evidence at protein level
UniProt nameSulfur carrier protein FdhD
Curated functionRequired for formate dehydrogenase (FDH) activity. Acts as a sulfur carrier protein that transfers sulfur from IscS to the molybdenum cofactor prior to its insertion into FDH.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
Preferred namefdhD
eggNOG descriptionRequired for formate dehydrogenase (FDH) activity. Acts as a sulfur carrier protein that transfers sulfur from IscS to the molybdenum cofactor prior to its insertion into FDH
Orthologous groupCOG1526
KEGG orthology K02379

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 0.184 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 1 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
FdhD-NarQPF02634.22 4.0e-7026–275 FdhD/NarQ family

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

Closest characterised functional partner: fdhF (formate dehydrogenase subunit alpha FdhF), high confidence from genomic context alone (score 972 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2900c fdhF formate dehydrogenase subunit alpha FdhF 988 972 ctx neighborhood:882 cooccurence:705 textmining:596
Rv2898c hyp hypothetical protein 729 729 ctx neighborhood:726
Rv2897c hyp hypothetical protein 728 729 ctx neighborhood:726
Rv2901c hyp hypothetical protein 673 674 ctx neighborhood:670
Rv0087 hycE formate hydrogenase HycE 712 547 ctx neighborhood:544
Rv2896c dprA hyp hypothetical protein 533 533 ctx neighborhood:531
Rv2902c rnhB ribonuclease HII 518 519 ctx neighborhood:512
Rv2903c lepB signal peptidase 489 489 ctx neighborhood:487
Rv0869c moaA2 molybdenum cofactor biosynthesis protein MoaA 523 459 coexpression:428
Rv2453c mobA molybdenum cofactor guanylyltransferase 675 456 textmining:428
Rv3150 nuoF NADH-quinone oxidoreductase subunit F 582 455
Rv3109 moaA1 cyclic pyranopterin monophosphate synthase 516 451 coexpression:420
Rv3323c moaX MoaD-MoaE fusion protein MoaX 574 401
Rv3025c iscS cysteine desulfurase 535 378
Rv0197 oxidoreductase 413 350

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 accessory protein FdhD
  • MTBC0 PGAP product: formate dehydrogenase accessory sulfurtransferase FdhD
  • Pfam (hmmscan --cut_ga): FdhD-NarQ PF02634.22 (E=4e-70)
  • (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_217415.1)
  • Domains: Pfam-A via hmmscan --cut_ga — FdhD-NarQ (PF02634.22)
  • 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 COG1526
  • Curated reference: UniProt P9WNF1 (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 — 16 functional partner(s); context anchor fdhF
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003081|Rv2899c|fdhD
MGYATAHRRVRHLSADQVITRPETLAVEEPLEIRVNGTPVTVTMRTPGSDFELVQGFLLAEGVVAHREDVLTVSYCGRRVEGNATGASTYNVLDVALAPGVKPPDVDVTRTFYTTSSCGVCGKASLQAVSQVSRFAPGGDPATVAADTLKAMPDQLRRAQKVFARTGGLHAAALFGVDGAMLAVREDIGRHNAVDKVIGWAFERDRIPLGASVLLVSGRASFELTQKALMAGIPVLAAVSAPSSLAVSLADASGITLVAFLRGDSMNVYTRADRIT