Rv1245c Family assigned · medium auto-curated

H37Rv Rv1245c · MTBC0 mtbc0_001334 · 276 aa · 1396242–1397072 (-) · RefSeq NP_215761.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)short-chain type dehydrogenase/reductase
MTBC0 PGAP re-annotationSDR family NAD(P)-dependent oxidoreductase
Revised (this work)SDR family NAD(P)-dependent oxidoreductase. Pfam: adh_short (PF00106.32), KR (PF08659.17), adh_short_C2 (PF13561.13).

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

Curated reference (UniProt)

UniProt O50460 TrEMBL · unreviewed · Evidence at protein level
UniProt namePutative oxidoreductase SadH
Curated functionRequired for maintaining the appropriate mycolic acid composition and permeability of the envelope on its exposure to acidic pH.

UniProt still lists this protein as Putative oxidoreductase SadH; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionBelongs to the short-chain dehydrogenases reductases (SDR) family
Orthologous groupCOG4221
Gene Ontology (57) GO:0000166, GO:0003674, GO:0003824, GO:0004303, GO:0005488, GO:0005496, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0006629 +45 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 0.515 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 3 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
adh_shortPF00106.32 5.9e-507–201 short chain dehydrogenase
KRPF08659.17 2.5e-1310–172 KR domain
adh_short_C2PF13561.13 5.9e-3313–229 Enoyl-(Acyl carrier protein) reductase

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

Closest characterised functional partner: kgd (multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase), high confidence from genomic context alone (score 722 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1248c kgd multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase 722 722 ctx neighborhood:720
Rv1249c membrane protein 684 684 ctx neighborhood:602
Rv3549c short-chain type dehydrogenase/reductase 680 680 ctx cooccurence:673
Rv1246c relE toxin RelE 654 653 ctx neighborhood:651
Rv1247c relB antitoxin RelB 652 652 ctx neighborhood:651
Rv1714 oxidoreductase 642 642 ctx cooccurence:629
Rv3049c monooxygenase 503 504 ctx cooccurence:445
Rv3502c 3-oxoacyl-ACP reductase 462 462 ctx cooccurence:449
Rv1393c monoxygenase 424 424 ctx cooccurence:418
Rv0976c hyp hypothetical protein 448 420
Rv1932 tpx 2-Cys peroxiredoxin 409 410 coexpression:410

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: short-chain type dehydrogenase/reductase
  • MTBC0 PGAP product: SDR family NAD(P)-dependent oxidoreductase
  • Pfam (hmmscan --cut_ga): adh_short PF00106.32 (E=6e-50), KR PF08659.17 (E=2e-13), adh_short_C2 PF13561.13 (E=6e-33)
  • (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_215761.1)
  • Domains: Pfam-A via hmmscan --cut_ga — adh_short (PF00106.32), KR (PF08659.17), adh_short_C2 (PF13561.13)
  • 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 COG4221
  • Curated reference: UniProt O50460 (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 — 11 functional partner(s); context anchor kgd
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001334|Rv1245c|
MEGFAGKVAVVTGAGSGIGQALAIELARSGAKVAISDVDTDGLADTEHRLKAISTPVKTDRLDVTEREAFLAYADAVNEHFGTVNQIYNNAGIAFTGDIEVSQFKDIERVMDVDFWGVVNGTKAFLPHLIASGDGHVINISSVFGLFSAPGQAAYNSAKFAVRGFTEALRQEMALAGHPVKVTTVHPGGVKTAIARNATAAEGLDQAELAETFDKRVAHLSPQRAAQIILTGVAKNKARVLVGVDAKVLDLVVRLTGSGYQRIFPIITGRLIPRPR