Rv2449c Family assigned · medium auto-curated

H37Rv Rv2449c · MTBC0 mtbc0_002608 · 419 aa · 2774561–2775820 (-) · RefSeq NP_216965.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)trans-acting enoyl reductase
MTBC0 PGAP re-annotationtrans-acting enoyl reductase family protein
Revised (this work)Trans-acting enoyl reductase family protein. Pfam: Sacchrp_dh_NADP (PF03435.25).

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

Curated reference (UniProt)

UniProt O53176 SwissProt · reviewed · Evidence at protein level
UniProt namePutative trans-acting enoyl reductase Rv2449c
EC (curated) EC 1.3.1.-

UniProt still lists this protein as Putative trans-acting enoyl reductase Rv2449c; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred nameLYS1
eggNOG descriptionSaccharopine dehydrogenase
Orthologous groupCOG3268
KEGG orthology K12445
Gene Ontology (6) GO:0005575, GO:0005623, GO:0005886, GO:0016020, GO:0044464, GO:0071944

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 0.45 · purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 6 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
Sacchrp_dh_NADPPF03435.25 2.0e-1110–136 Saccharopine dehydrogenase NADP binding domain

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

Closest characterised functional partner: rpfE (resuscitation-promoting factor RpfE), medium confidence from genomic context alone (score 659 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2450c rpfE resuscitation-promoting factor RpfE 659 659 ctx neighborhood:596
Rv2448c valS valine--tRNA ligase 608 609 ctx neighborhood:599
Rv2447c folC folylpolyglutamate synthase FolC 603 603 ctx neighborhood:599
Rv2446c integral membrane protein 599 599 ctx neighborhood:599
Rv2445c ndkA nucleoside diphosphate kinase 523 523 ctx neighborhood:523
Rv0241c htdX 3-hydroxyacyl-thioester dehydratase HtdX 420 420 ctx cooccurence:403
Rv2451 hyp hypothetical protein 402 402 ctx neighborhood:402
Rv1484 inhA NADH-dependent enoyl-[ACP 427 57 textmining:418
Rv1544 ketoacyl reductase 603 55 textmining:598
Rv2928 tesA thioesterase TesA 431 41 textmining:431
Rv2382c mbtC polyketide synthetase 414 41 textmining:414

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: trans-acting enoyl reductase
  • MTBC0 PGAP product: trans-acting enoyl reductase family protein
  • Pfam (hmmscan --cut_ga): Sacchrp_dh_NADP PF03435.25 (E=2e-11)
  • (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_216965.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Sacchrp_dh_NADP (PF03435.25)
  • 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 COG3268
  • Curated reference: UniProt O53176 (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 — 11 functional partner(s); context anchor rpfE
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002608|Rv2449c|
MTATPREFDIVLYGATGFVGKLTAEYLARAGGDARIALAGRSTQRVLAVREALGESAQTWPILTADASLPSTLQAMAARAQVVVTTVGPYTRYGLPLVAACAAAGTDYADLTGEPMFMRNSIDLYHKQAADTGARIVHACGFDSVPSDLSVYALYHAAREDGAGELTDTNCVVRSFKGGFSGGTIASMLEVLSTASNDPDARRQLSDPYMLSPDRGAEPELGPQPDLPSRRGRRLAPELAGVWTAGFIMAPTNTRIVRRSNALLDWAYGRRFRYSETMSVGSTVLAPVVSVVGGGVGNAMFGLASRYIRLLPRGLVKRVVPKPGTGPSAAARERGYYRIETYTTTTTGARYLARMAQDGDPGYKATSVLLGECGLALALDRDKLSDMRGVLTPAAAMGDALLERLPAAGVSLQTTRLAS