Rv3725 Resolved · high auto-curated

H37Rv Rv3725 · MTBC0 - · 309 aa · 4170214–4171143 (+) · RefSeq NP_218242.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)oxidoreductase
MTBC0 PGAP re-annotation
Revised (this work)Oxidoreductase. Pfam: NmrA (PF05368.20), RmlD_sub_bind (PF04321.24), Epimerase (PF01370.28), Polysacc_synt_2 (PF02719.22), adh_short (PF00106.32), KR (PF08659.17), 3Beta_HSD (PF01073.26), GDP_Man_Dehyd (PF16363.12), NAD_binding_4 (PF07993.19), NAD_binding_10 (PF13460.13).

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 O69692 TrEMBL · unreviewed · Predicted
UniProt namePossible oxidoreductase

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category M Cell wall / membrane / envelope biogenesis
eggNOG descriptionPolysaccharide biosynthesis protein
Orthologous groupCOG0451

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 1.259 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 7 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 62.18% of strains (90297) · reference-fixed

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
NmrAPF05368.20 1.5e-096–80 NmrA-like family
RmlD_sub_bindPF04321.24 6.7e-076–122 RmlD substrate binding domain
EpimerasePF01370.28 1.6e-218–236 NAD dependent epimerase/dehydratase family
Polysacc_synt_2PF02719.22 6.8e-088–125 Polysaccharide biosynthesis protein
adh_shortPF00106.32 1.9e-068–170 short chain dehydrogenase
KRPF08659.17 3.9e-058–127 KR domain
3Beta_HSDPF01073.26 2.5e-149–128 3-beta hydroxysteroid dehydrogenase/isomerase family
GDP_Man_DehydPF16363.12 1.4e-099–122 GDP-mannose 4,6 dehydratase
NAD_binding_4PF07993.19 2.4e-1011–182 Male sterility protein
NAD_binding_10PF13460.13 3.8e-1312–126 NAD(P)H-binding

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

PartnerProductScoreNo text-miningChannels (≥400)
Rv0705 rpsS 30S ribosomal protein S19 817 818 experimental:463 database:574
Rv0682 rpsL 30S ribosomal protein S12 814 806 experimental:463 database:573
Rv0710 rpsQ 30S ribosomal protein S17 804 798 experimental:463 database:578
Rv0707 rpsC 30S ribosomal protein S3 803 796 experimental:463 database:578
Rv0721 rpsE 30S ribosomal protein S5 797 790 experimental:463 database:575
Rv0717 rpsN1 30S ribosomal protein S14 790 790 experimental:436 database:548
Rv2056c rpsN2 30S ribosomal protein S14 788 788 experimental:436 database:548
Rv0718 rpsH 30S ribosomal protein S8 794 787 experimental:463 database:578
Rv0700 rpsJ 30S ribosomal protein S10 789 785 experimental:463 database:557
Rv0702 rplD 50S ribosomal protein L4 787 781 experimental:463 database:575
Rv2785c rpsO 30S ribosomal protein S15 783 781 experimental:463 database:573
Rv2890c rpsB 30S ribosomal protein S2 779 771 experimental:463 database:573
Rv3459c rpsK 30S ribosomal protein S11 776 768 experimental:463 database:558
Rv3458c rpsD 30S ribosomal protein S4 771 766 experimental:463 database:555
Rv0683 rpsG 30S ribosomal protein S7 772 764 experimental:463 database:555

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): NmrA PF05368.20 (E=1e-09), RmlD_sub_bind PF04321.24 (E=7e-07), Epimerase PF01370.28 (E=2e-21), Polysacc_synt_2 PF02719.22 (E=7e-08), adh_short PF00106.32 (E=2e-06), KR PF08659.17 (E=4e-05), 3Beta_HSD PF01073.26 (E=3e-14), GDP_Man_Dehyd PF16363.12 (E=1e-09), NAD_binding_4 PF07993.19 (E=2e-10), NAD_binding_10 PF13460.13 (E=4e-13)
  • (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_218242.1)
  • Domains: Pfam-A via hmmscan --cut_ga — NmrA (PF05368.20), RmlD_sub_bind (PF04321.24), Epimerase (PF01370.28), Polysacc_synt_2 (PF02719.22), adh_short (PF00106.32), KR (PF08659.17), 3Beta_HSD (PF01073.26), GDP_Man_Dehyd (PF16363.12), NAD_binding_4 (PF07993.19), NAD_binding_10 (PF13460.13)
  • 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 COG0451
  • Curated reference: UniProt O69692 (TrEMBL, unreviewed; Predicted)
  • 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 — 76 functional partner(s)
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3725|
MQNATMRVLVTGGTGFVGGWTAKAIADAGHSVRFLVRNPARLKTSVAKLGVDVSDFAVADISDRDSVREALNGCDAVVHSAALVATDPRETSRMLSTNMAGAQNVLGQAVELGMDPIVHVSSFTALFRPNLATLSADLPVAGGTDGYGQSKAQIEIYARGLQDAGAPVNITYPGMVLGPPVGDQFGEAGEGVRSALWMHVIPGRGAAWLIVDVRDVAALHAALLESGRGPRRYTAGGHRIPVPELAKILGGSPAPRCWPSRCPIPRCVSRDRCWIKPGPICLSILRSPRQVCSTTHRCRSPTIRRAKKN