Rv3777 Resolved · high auto-curated

H37Rv Rv3777 · MTBC0 - · 328 aa · 4222694–4223680 (+) · RefSeq NP_218294.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)oxidoreductase
MTBC0 PGAP re-annotation
Revised (this work)Oxidoreductase. Pfam: ADH_N (PF08240.18), ADH_zinc_N (PF00107.33), ADH_zinc_N_2 (PF13602.13).

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 P72043 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable oxidoreductase

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
Preferred namecryz
eggNOG descriptionNAD(P)H quinone oxidoreductase
Orthologous groupCOG0604
EC number EC 1.6.5.5
KEGG orthology K00344

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 0.264 · purifying
Polymorphic sites (≥ 0.1% of strains) 7 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
ADH_NPF08240.18 1.3e-1926–109 Alcohol dehydrogenase GroES-like domain
ADH_zinc_NPF00107.33 5.5e-26151–266 Zinc-binding dehydrogenase
ADH_zinc_N_2PF13602.13 3.1e-21183–326 Zinc-binding dehydrogenase

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

Closest characterised functional partner: pks3 (polyketide beta-ketoacyl synthase), high confidence from genomic context alone (score 916 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1180 pks3 polyketide beta-ketoacyl synthase 917 916 ctx fusion:899
Rv2382c mbtC polyketide synthetase 916 916 ctx fusion:900
Rv2947c pks15 polyketide synthase 916 916 ctx fusion:900
Rv1664 pks9 polyketide synthase 867 866 ctx fusion:840
Rv1663 pks17 polyketide synthase 871 865 ctx fusion:835
Rv3776 hyp hypothetical protein 693 693 ctx neighborhood:625
Rv3774 echA21 enoyl-CoA hydratase EchA21 529 527 ctx neighborhood:460
Rv2932 ppsB phthiocerol synthesis polyketide synthase type I PpsB 552 523
Rv0405 pks6 membrane bound polyketide synthase 500 476
Rv3775 lipE lipase LipE 472 473 ctx neighborhood:470
Rv0182c sigG ECF RNA polymerase sigma factor SigG 435 433 coexpression:423
Rv2931 ppsA phthiocerol synthesis polyketide synthase type I PpsA 433 406
Rv3549c short-chain type dehydrogenase/reductase 835 180 textmining:807
Rv3560c fadE30 acyl-CoA dehydrogenase FadE30 599 157 textmining:544
Rv2272 transmembrane protein 810 78 textmining:803

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): ADH_N PF08240.18 (E=1e-19), ADH_zinc_N PF00107.33 (E=6e-26), ADH_zinc_N_2 PF13602.13 (E=3e-21)
  • (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_218294.1)
  • Domains: Pfam-A via hmmscan --cut_ga — ADH_N (PF08240.18), ADH_zinc_N (PF00107.33), ADH_zinc_N_2 (PF13602.13)
  • 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 COG0604
  • Curated reference: UniProt P72043 (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 — 21 functional partner(s); context anchor pks3
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3777|
MTIMRAVVAESSDRLVWQEVPDVSAGPGEVLIKVAASGVNRADVLQAAGKYPPPPGVSDIIGLEVSGIVAAVGPGVTEWSAGQEVCALLAGGGYAEYVAVPADQVLPIPPSVNLVDSAALPEVACTVWSNLVMTAHLRPGQLVLIHGGASGIGSHAIQVVRALAARVAITAGSPEKLELCRDLGAQITINYRDEDFVARLKQETDGSGADIILDIMGASYLDRNIDALATDGQLIVIGMQGGVKAELNLGKLLTKRARVIGTTLRARPVSGPHGKAAIAQAVAASVWPMIAANRVRPVIGTRLPIQQAAQAHELMLSGKTFGKILLTV