Rv3085 Family assigned · medium auto-curated

H37Rv Rv3085 · MTBC0 mtbc0_003279 · 276 aa · 3472284–3473114 (+) · RefSeq NP_217601.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)oxidoreductase SadH
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 P9WGP9 SwissProt · reviewed · Evidence at transcript level
UniProt namePutative oxidoreductase SadH
EC (curated) EC 1.-.-.-
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 (13) GO:0008150, GO:0009268, GO:0009628, GO:0010447, GO:0040007, GO:0044110, GO:0044116, GO:0044117, GO:0044119, GO:0044403, GO:0044419, GO:0050896 +1 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 0.337 · purifying
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 3 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.19% of strains (272) · 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
adh_shortPF00106.32 1.7e-477–198 short chain dehydrogenase
KRPF08659.17 3.4e-1310–174 KR domain
adh_short_C2PF13561.13 1.5e-3313–215 Enoyl-(Acyl carrier protein) reductase

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

Closest characterised functional partner: mymA (FAD-containing monooxygenase MymA), high confidence from genomic context alone (score 989 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3083 mymA FAD-containing monooxygenase MymA 997 989 ctx neighborhood:882 coexpression:860 textmining:803
Rv3084 lipR acetyl-hydrolase LipR 997 983 ctx neighborhood:882 coexpression:860 textmining:870
Rv3086 adhD alcohol dehydrogenase D 991 959 ctx neighborhood:721 coexpression:860 textmining:810
Rv3088 tgs4 diacyglycerol O-acyltransferase 975 951 ctx neighborhood:616 coexpression:860 textmining:510
Rv3089 fadD13 long chain-fatty-acid--CoA ligase FadD13 973 945 ctx neighborhood:616 coexpression:863 textmining:542
Rv3087 diacyglycerol O-acyltransferase 970 941 ctx neighborhood:590 coexpression:862 textmining:511
Rv0233 nrdB ribonucleoside-diphosphate reductase subunit beta NrdB 687 687 coexpression:687
Rv0242c fabG4 3-oxoacyl-ACP reductase FabG 680 681 ctx cooccurence:672
Rv3549c short-chain type dehydrogenase/reductase 674 674 ctx cooccurence:665
Rv3082c virS HTH-type transcriptional regulator VirS 658 657 ctx neighborhood:602
Rv1714 oxidoreductase 644 645 ctx cooccurence:632
Rv1483 fabG1 3-oxoacyl-ACP reductase FabG 535 536 ctx cooccurence:526
Rv3502c 3-oxoacyl-ACP reductase 486 486 ctx cooccurence:472
Rv3049c monooxygenase 459 459 ctx cooccurence:400
Rv0976c hyp hypothetical protein 466 439

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: oxidoreductase SadH
  • MTBC0 PGAP product: SDR family NAD(P)-dependent oxidoreductase
  • Pfam (hmmscan --cut_ga): adh_short PF00106.32 (E=2e-47), KR PF08659.17 (E=3e-13), adh_short_C2 PF13561.13 (E=2e-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_217601.1)
  • 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 P9WGP9 (SwissProt, reviewed; Evidence at transcript 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 — 21 functional partner(s); context anchor mymA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003279|Rv3085|
MSSFEGKVAVITGAGSGIGRALALNLSEKRAKLALSDVDTDGLAKTVRLAQALGAQVKSDRLDVAEREAVLAHADAVVAHFGTVHQVYNNAGIAYNGNVDKSEFKDIERIIDVDFWGVVNGTKAFLPHVIASGDGHIVNISSLFGLIAVPGQSAYNAAKFAVRGFTEALRQEMLVARHPVKVTCVHPGGIKTAVARNATVADGEDQQTFAEFFDRRLALHSPEMAAKTIVNGVAKGQARVVVGLEAKAVDVLARIMGSSYQRLVAAGVAKFFPWAK