aofH Family assigned · medium auto-curated

H37Rv Rv3170 · MTBC0 mtbc0_003369 · 448 aa · 3563353–3564699 (+) · RefSeq NP_217686.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)flavin-containing monoamine oxidase
MTBC0 PGAP re-annotationflavin monoamine oxidase family protein
Revised (this work)Flavin monoamine oxidase family protein. Pfam: DAO (PF01266.31), Pyr_redox_2 (PF07992.21), FAD_binding_2 (PF00890.31), FAD_oxidored (PF12831.14), NAD_binding_8 (PF13450.13), Amino_oxidase (PF01593.31).

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

Curated reference (UniProt)

UniProt P9WQ15 SwissProt · reviewed · Evidence at protein level
UniProt namePutative flavin-containing monoamine oxidase AofH
EC (curated) EC 1.4.3.-

UniProt still lists this protein as Putative flavin-containing monoamine oxidase AofH; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
Preferred nameaofH
eggNOG description(mono)amine oxidase
Orthologous groupCOG1231
EC number EC 1.4.3.4
KEGG orthology K00274
KEGG pathways map00260, map00330, map00340, map00350, map00360, map00380, map00950, map00982, map01100, map01110, map04726, map04728, map05030, map05031, map05034
KEGG modules M00135
Gene Ontology (11) GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0016020, GO:0044424, GO:0044444, GO:0044464, GO:0071944

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) pseudogene candidate

pN/pS 0.476 · purifying
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 4 missense, 0 nonsense, 3 frameshift
Disruption 3 distinct premature-stop/frameshift site(s); most common in 17.45% of strains (25335) · 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
DAOPF01266.31 2.0e-129–383 FAD dependent oxidoreductase
Pyr_redox_2PF07992.21 1.2e-069–45 Pyridine nucleotide-disulphide oxidoreductase
FAD_binding_2PF00890.31 4.1e-079–46 FAD binding domain
FAD_oxidoredPF12831.14 3.2e-069–49 FAD dependent oxidoreductase
NAD_binding_8PF13450.13 2.3e-1412–76 NAD(P)-binding Rossmann-like domain
Amino_oxidasePF01593.31 1.3e-8317–444 Flavin containing amine oxidoreductase

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

Closest characterised functional partner: Rv3168 (aminoglycoside phosphotransferase), medium confidence from genomic context alone (score 628 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1703c methyltransferase 939 936 database:900
Rv2101 helZ helicase HelZ 918 910 experimental:442 database:844
Rv1530 adh alcohol dehydrogenase 913 908 database:900
Rv3293 pcd piperideine-6-carboxylic acid dehydrogenase 911 906 database:900
Rv1862 adhA alcohol dehydrogenase A 904 905 database:900
Rv0223c aldehyde dehydrogenase 909 904 database:900
Rv0147 aldehyde dehydrogenase 908 903 database:900
Rv0768 aldA aldehyde dehydrogenase AldA 908 903 database:900
Rv0162c adhE1 zinc-type alcohol dehydrogenase subunit E 901 902 database:900
Rv0761c adhB alcohol dehydrogenase B 901 901 database:900
Rv3169 hyp hypothetical protein 664 663 ctx neighborhood:617
Rv3168 aminoglycoside phosphotransferase 628 628 ctx neighborhood:540
Rv1660 pks10 chalcone synthase 530 512 experimental:506
Rv1372 pks18 alpha-pyrone synthesis polyketide synthase-like protein 527 509 experimental:506
Rv0902c prrB two component sensor histidine kinase PrrB 526 507 coexpression:507

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: flavin-containing monoamine oxidase
  • MTBC0 PGAP product: flavin monoamine oxidase family protein
  • Pfam (hmmscan --cut_ga): DAO PF01266.31 (E=2e-12), Pyr_redox_2 PF07992.21 (E=1e-06), FAD_binding_2 PF00890.31 (E=4e-07), FAD_oxidored PF12831.14 (E=3e-06), NAD_binding_8 PF13450.13 (E=2e-14), Amino_oxidase PF01593.31 (E=1e-83)
  • (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_217686.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DAO (PF01266.31), Pyr_redox_2 (PF07992.21), FAD_binding_2 (PF00890.31), FAD_oxidored (PF12831.14), NAD_binding_8 (PF13450.13), Amino_oxidase (PF01593.31)
  • 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 COG1231
  • Curated reference: UniProt P9WQ15 (SwissProt, reviewed; 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 — 47 functional partner(s); context anchor Rv3168
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003369|Rv3170|aofH
MTNPPWTVDVVVVGAGFAGLAAARELTRQGHEVLVFEGRDRVGGRSLTGRVAGVPADMGGSFIGPTQDAVLALATELGIPTTPTHRDGRNVIQWRGSARSYRGTIPKLSLTGLIDIGRLRWQFERIARGVPVAAPWDARRARELDDVSLGEWLRLVRATSSSRNLMAIMTRVTWGCEPDDVSMLHAARYVRAAGGLDRLLDVKNGAQQDRVPGGTQQIAQAAAAQLGARVLLNAAVRRIDRHGAGVTVTSDQGQAEAGFVIVAIPPAHRVAIEFDPPLPPEYQQLAHHWPQGRLSKAYAAYSTPFWRASGYSGQALSDEAPVFITFDVSPHADGPGILMGFVDARGFDSLPIEERRRDALRCFASLFGDEALDPLDYVDYRWGTEEFAPGGPTAAVPPGSWTKYGHWLREPVGPIHWASTETADEWTGYFDGAVRSGQRAAAEVAALL