Rv0945 Resolved · high auto-curated

H37Rv Rv0945 · MTBC0 - · 253 aa · 1054247–1055008 (+) · RefSeq NP_215460.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)oxidoreductase
MTBC0 PGAP re-annotation
Revised (this work)Oxidoreductase. Pfam: SDR (PF23441.1), adh_short (PF00106.32), KR (PF08659.17), Epimerase (PF01370.28), 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.

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt P9WGR7 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized oxidoreductase Rv0945
EC (curated) EC 1.-.-.-

UniProt still lists this protein as Uncharacterized oxidoreductase Rv0945; 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

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 0.451 · purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 5 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
SDRPF23441.1 1.4e-088–210 SDR-like rossmann domain
adh_shortPF00106.32 2.0e-439–202 short chain dehydrogenase
KRPF08659.17 8.9e-1210–173 KR domain
EpimerasePF01370.28 5.1e-0510–192 NAD dependent epimerase/dehydratase family
adh_short_C2PF13561.13 2.0e-2914–202 Enoyl-(Acyl carrier protein) reductase

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

Closest characterised functional partner: fpg2 (formamidopyrimidine-DNA glycosylase), high confidence from genomic context alone (score 883 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0944 fpg2 formamidopyrimidine-DNA glycosylase 976 883 ctx neighborhood:881 textmining:808
Rv3485c short-chain type dehydrogenase/reductase 677 666 ctx cooccurence:618
Rv0943c monooxygenase 914 637 ctx neighborhood:590 textmining:774
Rv3530c oxidoreductase 635 621 ctx cooccurence:570
Rv0769 oxidoreductase 628 614 ctx cooccurence:562
Rv1714 oxidoreductase 617 608 ctx cooccurence:549
Rv0927c oxidoreductase 672 593 ctx cooccurence:536
Rv2766c short-chain type dehydrogenase/reductase 594 579 ctx cooccurence:520
Rv1903 membrane protein 546 547 ctx neighborhood:544
Rv3391 acrA1 acyl-CoA-reductase AcrA 562 544 ctx cooccurence:539
Rv0825c hyp hypothetical protein 475 475 ctx cooccurence:474
Rv3734c tgs2 diacyglycerol O-acyltransferase 470 470 ctx cooccurence:455
Rv3740c diacyglycerol O-acyltransferase 468 468 ctx cooccurence:455
Rv3480c diacyglycerol O-acyltransferase 456 457 ctx cooccurence:427
Rv3502c 3-oxoacyl-ACP reductase 475 456

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): oxidoreductase
  • Pfam (hmmscan --cut_ga): SDR PF23441.1 (E=1e-08), adh_short PF00106.32 (E=2e-43), KR PF08659.17 (E=9e-12), Epimerase PF01370.28 (E=5e-05), adh_short_C2 PF13561.13 (E=2e-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_215460.1)
  • Domains: Pfam-A via hmmscan --cut_ga — SDR (PF23441.1), adh_short (PF00106.32), KR (PF08659.17), Epimerase (PF01370.28), 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 P9WGR7 (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 — 28 functional partner(s); context anchor fpg2
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0945|
MLTGVTRQKILITGASSGLGAGMARSFAAQGRDLALCARRTDRLTELKAELSQRYPDIKIAVAELDVNDHERVPKVFAELSDEIGGIDRVIVNAGIGKGARLGSGKLWANKATIETNLVAALVQIETALDMFNQRGSGHLVLISSVLGVKGVPGVKAAYAASKAGVRSLGESLRAEYAQRPIRVTVLEPGYIESEMTAKSASTMLMVDNATGVKALVAAIEREPGRAAVPWWPWAPLVRLMWVLPPRLTRRFA