Rv0063 Resolved · high auto-curated

H37Rv Rv0063 · MTBC0 mtbc0_000068 · 479 aa · 67031–68470 (+) · RefSeq NP_214577.1

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), BBE (PF08031.18).

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

Curated reference (UniProt)

UniProt O53608 TrEMBL · unreviewed · Evidence at protein level
UniProt namePossible oxidoreductase

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
eggNOG descriptionoxidoreductase
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 0.448 · purifying
Polymorphic sites (≥ 0.1% of strains) 14 synonymous, 16 missense, 1 nonsense, 3 frameshift
Disruption 4 distinct premature-stop/frameshift site(s); most common in 25.74% of strains (37372) · convergent

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 3.3e-3174–209 FAD binding domain
BBEPF08031.18 7.4e-08439–472 Berberine and berberine like

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

PartnerProductScoreNo text-miningChannels (≥400)
Rv3717 hyp hypothetical protein 837 837 coexpression:834
Rv2894c xerC tyrosine recombinase XerC 746 746 coexpression:746
Rv1435c hyp hypothetical protein 740 740 coexpression:740
Rv3414c sigD ECF RNA polymerase sigma factor SigD 734 734 coexpression:734
Rv3096 hyp hypothetical protein 730 730 coexpression:730
Rv3209 hyp hypothetical protein 716 716 coexpression:716
Rv1551 plsB1 acyltransferase PlsB 621 605 database:549
Rv2482c plsB2 glycerol-3-phosphate acyltransferase 620 604 database:549
Rv3806c ubiA decaprenyl-phosphate phosphoribosyltransferase 594 574 database:552
Rv1310 atpD ATP synthase subunit beta 573 558 database:538
Rv1305 atpE ATP synthase subunit C 539 539 database:526
Rv2154c ftsW lipid II flippase FtsW 533 533 coexpression:533
Rv1501 hyp hypothetical protein 545 529 database:463
Rv3633 hyp hypothetical protein 544 528 database:463
Rv0694 mftD mycofactocin system heme/flavin oxidoreductase MftD 537 517

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

  • Legacy H37Rv annotation: oxidoreductase
  • MTBC0 PGAP product: FAD-binding oxidoreductase
  • Pfam (hmmscan --cut_ga): FAD_binding_4 PF01565.29 (E=3e-31), BBE PF08031.18 (E=7e-08)
  • (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_214577.1)
  • Domains: Pfam-A via hmmscan --cut_ga — FAD_binding_4 (PF01565.29), BBE (PF08031.18)
  • 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 O53608 (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 — 44 functional partner(s)
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000068|Rv0063|
MAREISRQTFLRGAAGALAAGAVFGSVRATADPAASGWEALSSALGGKVLQPDDGPQFATAKQVFNTNYNGYTPAVIVTPTSQLDVQKAMAFAAANNLKVAPRGGGHSYVGASTANGAMVLDLRQLPGDINYDATTGRVTVTPATGLYAMHQVLAAAGRGIPTGTCPTVGVAGHALGGGLGANSRHAGLLCDQLTSASVVLPSGQAVTASATDHPDLFWALRGGGGGNFGVTTSLTFATFPSGDLDVVNLNFPPQSFAQVLVGWQNWLRTADRGSWALADATVDPLGTHCRILATCPAGSGGSVAAAIVSAVGTQPTGTENHTFNYLDLVRYLAVGNLNPSPLGYVGGSDVFTTITPATAQGIASAVDAFPRGAGRMLAIMHALDGALATVSPGATAFPWRRQSALVQWYVETSGSPSEATSWLNTAHQAVRAYSVGGYVNYLEVNQPPARYFGPNLSRLSAVRQKYDPSRVMFSGLNF