Rv3485c Resolved · high auto-curated

H37Rv Rv3485c · MTBC0 - · 314 aa · 3904622–3905566 (-) · RefSeq NP_218002.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)short-chain type dehydrogenase/reductase
MTBC0 PGAP re-annotation
Revised (this work)Short-chain type dehydrogenase/reductase. Pfam: SDR (PF23441.1), KR (PF08659.17), adh_short (PF00106.32), 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 O06348 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable short-chain type dehydrogenase/reductase

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Q Secondary metabolites biosynthesis, transport and catabolism
eggNOG descriptionDehydrogenase
Orthologous groupCOG1028

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 0.348 · purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 4 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 5.2e-0745–290 SDR-like rossmann domain
KRPF08659.17 5.5e-1747–209 KR domain
adh_shortPF00106.32 1.5e-4448–239 short chain dehydrogenase
EpimerasePF01370.28 7.3e-0549–215 NAD dependent epimerase/dehydratase family
adh_short_C2PF13561.13 4.3e-5855–287 Enoyl-(Acyl carrier protein) reductase

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

Closest characterised functional partner: Rv2129c (oxidoreductase), high confidence from genomic context alone (score 769 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2524c fas fatty acid synthase 828 802 coexpression:511 experimental:475
Rv2129c oxidoreductase 769 769 ctx cooccurence:762
Rv3502c 3-oxoacyl-ACP reductase 751 751 ctx cooccurence:751
Rv0547c oxidoreductase 704 693 ctx cooccurence:651
Rv1882c short-chain type dehydrogenase/reductase 689 690 ctx cooccurence:673
Rv3548c short-chain type dehydrogenase/reductase 682 682 ctx cooccurence:679
Rv0945 oxidoreductase 677 666 ctx cooccurence:618
Rv0148 short-chain type dehydrogenase/reductase 590 590 ctx cooccurence:589
Rv0073 glutamine ABC transporter ATP-binding protein 605 587 database:431
Rv2564 glnQ glutamine ABC transporter ATP-binding protein 601 583 database:431
Rv3486 hyp hypothetical protein 554 554 ctx neighborhood:490
Rv1937 oxygenase 593 545
Rv3728 membrane protein 556 532 database:431
Rv2299c htpG chaperone protein HtpG 539 520 database:450
Rv0125 pepA serine protease PepA 528 517

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): short-chain type dehydrogenase/reductase
  • Pfam (hmmscan --cut_ga): SDR PF23441.1 (E=5e-07), KR PF08659.17 (E=6e-17), adh_short PF00106.32 (E=2e-44), Epimerase PF01370.28 (E=7e-05), adh_short_C2 PF13561.13 (E=4e-58)
  • (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_218002.1)
  • Domains: Pfam-A via hmmscan --cut_ga — SDR (PF23441.1), KR (PF08659.17), adh_short (PF00106.32), 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 COG1028
  • Curated reference: UniProt O06348 (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 — 84 functional partner(s); context anchor Rv2129c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3485c|
MNSRAPRNLAVSSPSAQVTGRMVQNGENLFQFRREGPQVQLSFQDRTYLVTGGGSGIGKGVAAGLVAAGAAVMIVGRNPDKLAAAVKDIEALKTGAIGYEPADITDEEQTLRVVDAATAWHGRLHGVVHCAGGSQTIGPITQIDSQAWRRTVDLNVNGTMYVLKHAARELVRGGGGSFVGISSIAASNTHRWFGAYGVTKSAVDHMMKLAADELGPSWVRVNSIRPGLIRTDLVVPVTESPELSADYRVCTPLPRVGEVEDVANLAMFLLSDAASWITGQVINVDGGHMLRRGPDFSPMLEPVFGADGLRGVVG