Rv2499c Family assigned · medium auto-curated

H37Rv Rv2499c · MTBC0 mtbc0_002661 · 185 aa · 2836063–2836620 (-) · RefSeq NP_217015.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)oxidase regulatory-like protein
MTBC0 PGAP re-annotationMaoC family dehydratase
Revised (this work)MaoC family dehydratase. Pfam: MC_hydratase (PF19315.6), MaoC_dehydratas (PF01575.26).

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

Curated reference (UniProt)

UniProt I6Y9H2 TrEMBL · unreviewed · Evidence at protein level
UniProt namePossible oxidase regulatory-related protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
eggNOG descriptiondehydratase
Orthologous groupCOG2030

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 0.068 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 5 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
MC_hydratasePF19315.6 9.5e-1230–179 Mesaconyl-CoA hydratase
MaoC_dehydratasPF01575.26 4.0e-2939–159 MaoC like domain

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

Closest characterised functional partner: citE (citrate (pro-3S)-lyase subunit beta), high confidence from genomic context alone (score 993 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2498c citE citrate (pro-3S)-lyase subunit beta 998 993 ctx neighborhood:882 cooccurence:760 coexpression:761 textmining:816
Rv2500c fadE19 acyl-CoA dehydrogenase FadE19 998 990 ctx neighborhood:881 coexpression:844 textmining:815
Rv2502c accD1 acetyl-/propionyl-CoA carboxylase subunit beta 950 933 ctx neighborhood:881
Rv2501c accA1 acetyl/propionyl-CoA carboxylase subuit alpha 939 933 ctx neighborhood:881
Rv2503c scoB succinyl-CoA:3-ketoacid-CoA transferase subunit B 935 889 ctx neighborhood:881 textmining:438
Rv2504c scoA succinyl-CoA:3-ketoacid-CoA transferase subunit A 981 887 ctx neighborhood:881 textmining:845
Rv2506 TetR family transcriptional regulator 870 829 ctx neighborhood:714 cooccurence:413
Rv2495c bkdC branched-chain keto acid dehydrogenase E2 component 845 815 ctx neighborhood:723
Rv2497c bkdA 3-methyl-2-oxobutanoate dehydrogenase subunit alpha 807 784 ctx neighborhood:724
Rv2496c bkdB 3-methyl-2-oxobutanoate dehydrogenase subunit beta 736 737 ctx neighborhood:723
Rv3339c icd1 isocitrate dehydrogenase 651 636 database:476
Rv2505c fadD35 fatty-acid--CoA ligase FadD35 717 618 ctx neighborhood:567
Rv1223 htrA serine protease HtrA 575 576 database:498
Rv0983 pepD serine protease PepD 569 569 database:498
Rv3564 fadE33 acyl-CoA dehydrogenase FadE33 584 568

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: oxidase regulatory-like protein
  • MTBC0 PGAP product: MaoC family dehydratase
  • Pfam (hmmscan --cut_ga): MC_hydratase PF19315.6 (E=9e-12), MaoC_dehydratas PF01575.26 (E=4e-29)
  • (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_217015.1)
  • Domains: Pfam-A via hmmscan --cut_ga — MC_hydratase (PF19315.6), MaoC_dehydratas (PF01575.26)
  • 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 COG2030
  • Curated reference: UniProt I6Y9H2 (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 — 134 functional partner(s); context anchor citE
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002661|Rv2499c|
MTKHAGDRESDDAVSACRVAGSTVGRRILQRGLWFEEFQIGTTYLHRPGRTVTEADNVLFTTLTMNTQSLHLDAAWAGQQPGFRGERLVNSMFTLSTMVGLSVAQLTLGTIVANLGFSEVSFPKPVFHGDTLYAETVCTGKRESKSRPGEGIVTLEHIARNQHGEVVARAVRTTLVQKQSIKEAQ