Rv3292 Family assigned · medium auto-curated

H37Rv Rv3292 · MTBC0 mtbc0_003500 · 415 aa · 3694408–3695655 (+) · RefSeq NP_217809.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationVOC family protein
Revised (this work)VOC family protein. Pfam: HGLS (PF07063.20).

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

Curated reference (UniProt)

UniProt P9WL01 SwissProt · reviewed · Evidence at protein level
UniProt name2-oxoadipate dioxygenase/decarboxylase
EC (curated) EC 1.13.11.93
Curated functionCatalyzes the decarboxylation and hydroxylation of 2-oxoadipate (2OA) to form D-2-hydroxyglutarate (D-2-HGA).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionDUF1338
Orthologous groupCOG5383

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 0.179 · 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
HGLSPF07063.20 2.8e-12116–370 2-oxoadipate dioxygenase/decarboxylase

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

Closest characterised functional partner: pcd (piperideine-6-carboxylic acid dehydrogenase), high confidence from genomic context alone (score 979 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3293 pcd piperideine-6-carboxylic acid dehydrogenase 978 979 ctx neighborhood:843 coexpression:799
Rv3291c lrpA transcriptional regulator LrpA 840 841 ctx neighborhood:790
Rv3290c lat L-lysine-epsilon aminotransferase 648 635 ctx neighborhood:526
Rv3289c transmembrane protein 539 539 ctx neighborhood:516
Rv3288c usfY hyp hypothetical protein 437 437 ctx neighborhood:406
Rv2476c gdh NAD-dependent glutamate dehydrogenase 412 412 coexpression:412
Rv3295 TetR family transcriptional regulator 403 403

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: hypothetical protein
  • MTBC0 PGAP product: VOC family protein
  • Pfam (hmmscan --cut_ga): HGLS PF07063.20 (E=3e-121)
  • (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_217809.1)
  • Domains: Pfam-A via hmmscan --cut_ga — HGLS (PF07063.20)
  • 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 COG5383
  • Curated reference: UniProt P9WL01 (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 — 7 functional partner(s); context anchor pcd
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003500|Rv3292|
MSRSKRLQTGQLRARFAAGLSAMYAAEVPAYGTLVEVCAQVNSDYLTRHRRAERLGSLQRVTAERHGAIRVGNPAELAAVADLFAAFGMLPVGYYDLRTAESPIPVVSTAFRPIDANELAHNPFRVFTSMLAIEDRRYFDADLRTRVQTFLARRQLFDPALLAQARAIAADGGCDADDAPAFVAAAVAAFALSREPVEKSWYDELSRVSAVAADIAGVGSTHINHLTPRVLDIDDLYRRMTERGITMIDTIQGPPRTDGPDVLLRQTSFRALAEPRMFRDEDGTVTPGILRVRFGEVEARGVALTPRGRERYEAAMAAADPAAVWATHFPSTDAEMAAQGLAYYRGGDPSAPIVYEDFLPASAAGIFRSNLDRDSQTGDGPDDAGYNVDWLAGAIGRHIHDPYALYDALAQEERR