Rv1817 Family assigned · medium auto-curated

H37Rv Rv1817 · MTBC0 mtbc0_001931 · 487 aa · 2077683–2079146 (+) · RefSeq NP_216333.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)flavoprotein
MTBC0 PGAP re-annotationFAD-binding protein
Revised (this work)FAD-binding protein. Pfam: FAD_binding_2 (PF00890.31), DAO (PF01266.31), FAD_oxidored (PF12831.14).

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

Curated reference (UniProt)

UniProt Q50616 TrEMBL · unreviewed · Evidence at protein level
UniProt namePossible flavoprotein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
eggNOG descriptionSuccinate dehydrogenase fumarate reductase flavoprotein subunit
Orthologous groupCOG1053

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 0.133 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 10 synonymous, 4 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
FAD_binding_2PF00890.31 4.1e-4922–452 FAD binding domain
DAOPF01266.31 5.5e-1122–237 FAD dependent oxidoreductase
FAD_oxidoredPF12831.14 6.7e-0722–66 FAD dependent oxidoreductase

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

Closest characterised functional partner: hsaC (extradiol dioxygenase), high confidence from genomic context alone (score 833 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3316 sdhC succinate dehydrogenase cytochrome B-556 subunit 962 959 coexpression:650 experimental:707 database:621
Rv0760c hyp hypothetical protein 947 946 ctx cooccurence:476 database:900
Rv3537 kstD 3-oxosteroid 1-dehydrogenase 947 935 database:900
Rv1248c kgd multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase 937 918 coexpression:894
Rv0247c succinate dehydrogenase iron-sulfur subunit 881 875 coexpression:486 experimental:454 database:578
Rv1553 frdB fumarate reductase iron-sulfur subunit 881 875 coexpression:487 experimental:454 database:578
Rv3319 sdhB succinate dehydrogenase iron-sulphur protein subunit 881 875 coexpression:484 experimental:454 database:578
Rv3568c hsaC extradiol dioxygenase 848 833 ctx cooccurence:710
Rv3317 sdhD succinate dehydrogenase hydrophobic membrane anchor subunit 811 797 coexpression:647 experimental:430
Rv0310c hyp hypothetical protein 785 773 ctx cooccurence:582 coexpression:415
Rv3570c hsaA flavin-dependent monooxygenase oxygenase subunit HsaA 770 750 ctx cooccurence:710
Rv3526 kshA 3-ketosteroid-9-alpha-monooxygenase oxygenase subunit 738 725 ctx cooccurence:714
Rv2195 qcrA ubiquinol-cytochrome C reductase rieske iron-sulfur subunit 723 701 coexpression:646
Rv3150 nuoF NADH-quinone oxidoreductase subunit F 723 701 coexpression:650
Rv3148 nuoD NADH-quinone oxidoreductase subunit D 721 699 coexpression:652

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: flavoprotein
  • MTBC0 PGAP product: FAD-binding protein
  • Pfam (hmmscan --cut_ga): FAD_binding_2 PF00890.31 (E=4e-49), DAO PF01266.31 (E=5e-11), FAD_oxidored PF12831.14 (E=7e-07)
  • (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_216333.1)
  • Domains: Pfam-A via hmmscan --cut_ga — FAD_binding_2 (PF00890.31), DAO (PF01266.31), FAD_oxidored (PF12831.14)
  • 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 COG1053
  • Curated reference: UniProt Q50616 (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 — 85 functional partner(s); context anchor hsaC
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001931|Rv1817|
MSTDIPATVSAETVTSWSDDVDVTVIGFGIAGGCAAVSAAAAGARVLVLERAAAAGGTTALAGGHFYLGGGTTVQLATGHPDSPEEMYKYLVAVSREPDHDKIRAYCDGSVEHFNWLEGLGFQFERSYFPGKAVIQPNTEGLMFTGNEKVWPFLELAVPAPRGHKVPVPGDTGGAAMVIDLLLKRAASLGIQIRYETGATELIVDGTGKVTGVMWKRFSETGAIKAKSVIIAAGGFVMNPDMVAKYTPKLAEKPFVLGNTYDDGLGIRLGVSAGGATQHMDQMFITAPPYPPSILLTGIIVNKLGQRFVAEDSYHSRTAGFIMEQPDSAAYLIVDEAHLEHPKMPLVPLIDGWETVVEMEAALGIPPGNLAATLDRYNAYAARGADPDFHKQPEFLAAQDNGPWGAFDMSLGKAMYAGFTLGGLATSVDGQVLRDDGAVVAGLYAVGACASNIAQDGKGYASGTQLGEGSFFGRRAGAHAAARAQGM