Rv1774 Resolved · high auto-curated

H37Rv Rv1774 · MTBC0 mtbc0_001888 · 446 aa · 2025843–2027183 (+) · RefSeq NP_216290.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)oxidoreductase
MTBC0 PGAP re-annotationFAD-binding oxidoreductase
Revised (this work)FAD-binding oxidoreductase. Pfam: FAD_binding_4 (PF01565.29).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt O33177 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable oxidoreductase

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
eggNOG descriptionFAD binding domain
Orthologous groupCOG0277

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 0.36 · purifying
Polymorphic sites (≥ 0.1% of strains) 8 synonymous, 9 missense, 0 nonsense, 2 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 0.54% of strains (788) · 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
FAD_binding_4PF01565.29 2.3e-3035–169 FAD binding domain

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

Closest characterised functional partner: Rv1773c (transcriptional regulator), medium confidence from genomic context alone (score 617 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1775 hyp hypothetical protein 989 921 ctx neighborhood:882 textmining:870
Rv1773c transcriptional regulator 616 617 ctx neighborhood:602
Rv1551 plsB1 acyltransferase PlsB 623 607 database:549
Rv2482c plsB2 glycerol-3-phosphate acyltransferase 620 604 database:549
Rv3633 hyp hypothetical protein 602 588 database:463
Rv3806c ubiA decaprenyl-phosphate phosphoribosyltransferase 590 570 database:552
Rv1310 atpD ATP synthase subunit beta 573 557 database:538
Rv1305 atpE ATP synthase subunit C 538 538 database:526
Rv1501 hyp hypothetical protein 545 529 database:463
Rv0694 mftD mycofactocin system heme/flavin oxidoreductase MftD 540 521
Rv1872c lldD2 L-lactate dehydrogenase 535 514
Rv3029c fixA electron transfer flavoprotein subunit beta 526 503
Rv3028c fixB electron transfer flavoprotein subunit alpha 522 498
Rv0440 groEL2 molecular chaperone GroEL 468 449
Rv1213 glgC glucose-1-phosphate adenylyltransferase 448 449 database:434

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
  • MTBC0 PGAP product: FAD-binding oxidoreductase
  • Pfam (hmmscan --cut_ga): FAD_binding_4 PF01565.29 (E=2e-30)
  • (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_216290.1)
  • Domains: Pfam-A via hmmscan --cut_ga — FAD_binding_4 (PF01565.29)
  • 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 COG0277
  • Curated reference: UniProt O33177 (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 — 35 functional partner(s); context anchor Rv1773c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001888|Rv1774|
MRALPAGRHFFRGSDGYEAARRGTVWHRRVPDRYPEVIVQAVSADDIVSAIRYATVNGHKVSVVSGGHSFAASHLRDGAVLLDVSRIDHASIDADKGRAVVGPGKGGSVLMAELEAQGLFFPGGHCRGVCLGGYLLQGGYGWNSRIYGPACESVIGLDVITADGAQIHCDADNHADLYWAARGAGPGFFGVVTSFYLKLYPRPATCGTSVYVYPFDLADEVFTWARAVSAEVDPRVELQALASRGEPSMGIDVPVISLASPAFADSPEEAEQALALFGTCPVVEQALVKVPYMPTDLPAWYDVAMTHYLSDHHYAVDNMWTSASAEDLLPGIRSILDTLPPHPAHFLWLNWGPCPPRQDMAYSIEADIYLALYGSWKDPADEAKYADWARSHMAAMSHLAVGIQLADENLGARPARFASDAAMAKLDRVRAEYDPDGLFNSWMGRI