Rv0385 Resolved · high auto-curated

H37Rv Rv0385 · MTBC0 mtbc0_000405 · 390 aa · 465497–466669 (+) · RefSeq NP_214899.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)monooxygenase
MTBC0 PGAP re-annotationFAD-binding oxidoreductase
Revised (this work)FAD-binding oxidoreductase. Pfam: Globin (PF00042.29), FAD_binding_6 (PF00970.31), NAD_binding_1 (PF00175.27).

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

Curated reference (UniProt)

UniProt Q7ARS9 TrEMBL · unreviewed · Evidence at protein level
UniProt namenitric oxide dioxygenase
EC (curated) EC 1.14.12.17

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
eggNOG descriptionBelongs to the globin family
Orthologous groupCOG0543

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 0.176 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 1 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
GlobinPF00042.29 1.7e-0926–125 Globin
FAD_binding_6PF00970.31 2.2e-19151–243 Oxidoreductase FAD-binding domain
NAD_binding_1PF00175.27 7.3e-05253–370 Oxidoreductase NAD-binding domain

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

Closest characterised functional partner: clpB (chaperone protein ClpB), medium confidence from genomic context alone (score 621 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2139 pyrD dihydroorotate dehydrogenase 958 953 coexpression:731 experimental:814
Rv0383c ttfA hyp hypothetical protein 859 846 ctx neighborhood:427 coexpression:669
Rv1385 pyrF orotidine 5'-phosphate decarboxylase 792 779 coexpression:733
Rv1384 carB carbamoyl-phosphate synthase large subunit 798 771 coexpression:731
Rv0382c pyrE orotate phosphoribosyltransferase 790 770 coexpression:671
Rv1371 membrane protein 835 751 database:661
Rv1380 pyrB aspartate carbamoyltransferase 775 746 coexpression:731
Rv1383 carA carbamoyl-phosphate synthase small subunit 777 745 coexpression:730
Rv1883c hyp hypothetical protein 760 732 coexpression:713
Rv2778c hyp hypothetical protein 760 732 coexpression:713
Rv1381 pyrC dihydroorotase 757 725 coexpression:709
Rv1382 hyp hypothetical protein 719 690 coexpression:676
Rv1379 pyrR bifunctional pyrimidine operon regulatory protein/uracil phosphoribosyltransferase 685 665 coexpression:646
Rv0384c clpB chaperone protein ClpB 620 621 ctx neighborhood:615
Rv0816c thiX thioredoxin ThiX 586 568 database:506

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: monooxygenase
  • MTBC0 PGAP product: FAD-binding oxidoreductase
  • Pfam (hmmscan --cut_ga): Globin PF00042.29 (E=2e-09), FAD_binding_6 PF00970.31 (E=2e-19), NAD_binding_1 PF00175.27 (E=7e-05)
  • (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_214899.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Globin (PF00042.29), FAD_binding_6 (PF00970.31), NAD_binding_1 (PF00175.27)
  • 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 COG0543
  • Curated reference: UniProt Q7ARS9 (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 — 65 functional partner(s); context anchor clpB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000405|Rv0385|
MGLEDRDALRVLQNAFKLDDPELVRRFYAHWFALDASVRDLFPPDMGAQRAAFGQALHWVYGELVAQRAEEPVAFLAQLGRDHRKYGVLPTQYDTLRRALYTTLRDYLGHPSRGAWTDAVDEAAGQSLNLIIGVMSGAADADDAPAWWDGTVVEHIRVSRDLAVARLQLDRPLHYYPGQYVNVHVPQCPRRWRYLSPAIPADPNGRIEFHVRVVPGGLVSNAIVGETRPGDRWRLSGPHGAFRVDRDGGDVLMVAGSTGLAPLRALIIDLSRFAVNPRVHLFFGARYACELYDLPTLWQIAAHNPWLSVSPVSEYNGDPAWAADYPDVSAPRGLHVRQTGRLPDVVSRYGGWGDRQILICGGPAMVRATKAALIAKGAPPERIQHDPLSR