Rv3406 Resolved · high auto-curated

H37Rv Rv3406 · MTBC0 mtbc0_003620 · 295 aa · 3850769–3851656 (+) · RefSeq NP_217923.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)dioxygenase
MTBC0 PGAP re-annotationalpha-ketoglutarate-dependent sulfate ester dioxygenase
Revised (this work)Alpha-ketoglutarate-dependent sulfate ester dioxygenase. Pfam: TauD (PF02668.23).

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

Curated reference (UniProt)

UniProt P9WKZ1 SwissProt · reviewed · Evidence at protein level
UniProt nameAlpha-ketoglutarate-dependent sulfate ester dioxygenase
EC (curated) EC 1.14.11.77
Curated functionAlpha-ketoglutarate-dependent sulfate ester dioxygenase, which oxidizes medium-chain alkyl-sulfate esters. Shows preference for 2-ethylhexyl sulfate (2-EHS) in vitro, leading to the formation of succinate and 2-ethylhexanal. Has likely a role in sulfate scavenging in vivo..; FUNCTION: Also causes the inactivation of the 2-carboxyquinoxaline Ty38c (an antitubercular compound that inhibits DprE1) via oxidative decarboxylation, using Ty38c instead of alpha-ketoglutarate as a substrate. Is thus responsible for primary resistance of M.tuberculosis to Ty38c in vitro. Overexpression of Rv3406 causes .

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category Q Secondary metabolites biosynthesis, transport and catabolism
Preferred nametauD
eggNOG descriptiontaurine catabolism dioxygenase
Orthologous groupCOG2175
KEGG orthology K22303
Gene Ontology (26) GO:0000907, GO:0000908, GO:0003674, GO:0003824, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005886, GO:0006790, GO:0008150, GO:0008152 +14 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 0.827 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 5 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
TauDPF02668.23 6.1e-537–269 Taurine catabolism dioxygenase TauD, TfdA family

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

Closest characterised functional partner: Rv3405c (HTH-type transcriptional regulator), high confidence from genomic context alone (score 786 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3405c HTH-type transcriptional regulator 971 786 ctx neighborhood:786 textmining:870
Rv3408 vapC47 ribonuclease VapC47 668 669 ctx neighborhood:669
Rv3407 vapB47 antitoxin VapB47 668 669 ctx neighborhood:669
Rv0147 aldehyde dehydrogenase 629 506 database:428
Rv0458 aldehyde dehydrogenase 608 506 database:428
Rv2858c aldC aldehyde dehydrogenase AldC 525 506 database:428
Rv0768 aldA aldehyde dehydrogenase AldA 525 506 database:428
Rv1187 rocA pyrroline-5-carboxylate dehydrogenase RocA 525 506 database:428
Rv3293 pcd piperideine-6-carboxylic acid dehydrogenase 525 506 database:428
Rv0223c aldehyde dehydrogenase 525 506 database:428
Rv0753c mmsA methylmalonate-semialdehyde dehydrogenase 525 506 database:428
Rv0234c gabD1 succinate-semialdehyde dehydrogenase 525 506 database:428
Rv1731 gabD2 succinate-semialdehyde dehydrogenase 525 506 database:428
Rv2383c mbtB phenyloxazoline synthase 527 459 ctx neighborhood:434
Rv2693c integral membrane protein 470 436 coexpression:404

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: dioxygenase
  • MTBC0 PGAP product: alpha-ketoglutarate-dependent sulfate ester dioxygenase
  • Pfam (hmmscan --cut_ga): TauD PF02668.23 (E=6e-53)
  • (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_217923.1)
  • Domains: Pfam-A via hmmscan --cut_ga — TauD (PF02668.23)
  • 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 COG2175
  • Curated reference: UniProt P9WKZ1 (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 — 25 functional partner(s); context anchor Rv3405c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003620|Rv3406|
MTDLITVKKLGSRIGAQIDGVRLGGDLDPAAVNEIRAALLAHKVVFFRGQHQLDDAEQLAFAGLLGTPIGHPAAIALADDAPIITPINSEFGKANRWHTDVTFAANYPAASVLRAVSLPSYGGSTLWANTAAAYAELPEPLKCLTENLWALHTNRYDYVTTKPLTAAQRAFRQVFEKPDFRTEHPVVRVHPETGERTLLAGDFVRSFVGLDSHESRVLFEVLQRRITMPENTIRWNWAPGDVAIWDNRATQHRAIDDYDDQHRLMHRVTLMGDVPVDVYGQASRVISGAPMEIAG