Rv2159c Family assigned · medium auto-curated

H37Rv Rv2159c · MTBC0 mtbc0_002295 · 344 aa · 2448010–2449044 (-) · RefSeq NP_216675.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationcarboxymuconolactone decarboxylase family protein
Revised (this work)Carboxymuconolactone decarboxylase family protein. Pfam: CMD (PF02627.26).

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

Curated reference (UniProt)

UniProt O06218 SwissProt · reviewed · Evidence at protein level
UniProt nameAlkyl hydroperoxide reductase Rv2159c
EC (curated) EC 1.11.1.-
Curated functionInvolved in protection against oxidative stresses. May play a significant role in maintaining the cellular homeostasis during stress and virulence of M.tuberculosis. In vitro, catalyzes the decomposition of cumene hydroperoxide (CHP) to acetophenone.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category O Post-translational modification, protein turnover, chaperones
eggNOG descriptionAntioxidant protein with alkyl hydroperoxidase activity. Required for the reduction of the AhpC active site cysteine residues and for the regeneration of the AhpC enzyme activity
Orthologous groupCOG2128

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 0.959 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 10 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.14% of strains (199) · clonal

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
CMDPF02627.26 3.0e-0949–121 Carboxymuconolactone decarboxylase family

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

Closest characterised functional partner: Rv2160A (Rv2160A, len: 211 aa. Conserved hypothetical protein, possibly a TetR-family transcriptional regulator,similar to N-terminal half of AL51266), high confidence from genomic context alone (score 966 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2160A Rv2160A, len: 211 aa. Conserved hypothetical protein, possibly a TetR-family transcriptional regulator,similar to N-terminal half of AL51266 965 966 ctx neighborhood:799 coexpression:836
Rv2160c Rv2160c, (MTCY270.08), len: 113 aa. Conserved hypothetical protein, possibly a TetR-family transcriptional regulator, similar to C-terminal 978 843 coexpression:799 textmining:870
Rv2161c hyp hypothetical protein 978 842 coexpression:819 textmining:870
Rv2158c murE UDP-N-acetylmuramoylalanyl-D-glutamate--2,6-diaminopimelate ligase 847 784 ctx neighborhood:709
Rv2151c ftsQ cell division protein FtsQ 823 750 ctx neighborhood:700
Rv2156c murX phospho-N-acetylmuramoyl-pentappeptidetransferase 747 747 ctx neighborhood:709
Rv2157c murF UDP-N-acetylmuramoyl-tripeptide--D-alanyl-D-alanine ligase 752 746 ctx neighborhood:709
Rv2155c murD UDP-N-acetylmuramoylalanine--D-glutamate ligase 730 730 ctx neighborhood:709
Rv2153c murG UDP-N-acetylglucosamine--N-acetylmuramyl-(pentapeptide) pyrophosphoryl-undecaprenol-N-acetylglucosamine transferase 713 712 ctx neighborhood:699
Rv2154c ftsW lipid II flippase FtsW 711 703 ctx neighborhood:699
Rv2152c murC UDP-N-acetylmuramate--alanine ligase 703 703 ctx neighborhood:700
Rv2797c hyp hypothetical protein 586 586 ctx cooccurence:585
Rv3347c PPE55 PPE family protein PPE55 584 585 ctx cooccurence:582
Rv0355c PPE8 PPE family protein PPE8 575 575 ctx cooccurence:573
Rv1004c membrane protein 570 568 ctx cooccurence:540

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: carboxymuconolactone decarboxylase family protein
  • Pfam (hmmscan --cut_ga): CMD PF02627.26 (E=3e-09)
  • (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_216675.1)
  • Domains: Pfam-A via hmmscan --cut_ga — CMD (PF02627.26)
  • 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 COG2128
  • Curated reference: UniProt O06218 (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 — 66 functional partner(s); context anchor Rv2160A
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002295|Rv2159c|
MKFVNHIEPVAPRRAGGAVAEVYAEARREFGRLPEPLAMLSPDEGLLTAGWATLRETLLVGQVPRGRKEAVAAAVAASLRCPWCVDAHTTMLYAAGQTDTAAAILAGTAPAAGDPNAPYVAWAAGTGTPAGPPAPFGPDVAAEYLGTAVQFHFIARLVLVLLDETFLPGGPRAQQLMRRAGGLVFARKVRAEHRPGRSTRRLEPRTLPDDLAWATPSEPIATAFAALSHHLDTAPHLPPPTRQVVRRVVGSWHGEPMPMSSRWTNEHTAELPADLHAPTRLALLTGLAPHQVTDDDVAAARSLLDTDAALVGALAWAAFTAARRIGTWIGAAAEGQVSRQNPTG