Rv1257c Family assigned · medium auto-curated

H37Rv Rv1257c · MTBC0 mtbc0_001346 · 455 aa · 1413161–1414528 (-) · RefSeq NP_215773.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)oxidoreductase
MTBC0 PGAP re-annotationFAD-linked oxidase C-terminal domain-containing protein
Revised (this work)FAD-linked oxidase C-terminal domain-containing protein. Pfam: FAD_binding_4 (PF01565.29), FAD-oxidase_C (PF02913.25).

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

Curated reference (UniProt)

UniProt Q11061 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable oxidoreductase

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
eggNOG descriptionFAD linked
Orthologous groupCOG0277
EC number EC 1.1.2.4, EC 1.1.3.15
KEGG orthology K00102, K00104
KEGG pathways map00620, map00630, map01100, map01110, map01120, map01130

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 0.365 · purifying
Polymorphic sites (≥ 0.1% of strains) 4 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_4PF01565.29 1.4e-4241–179 FAD binding domain
FAD-oxidase_CPF02913.25 6.8e-69218–452 FAD linked oxidases, C-terminal domain

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

Closest characterised functional partner: tap (multidrug-efflux transporter), high confidence from genomic context alone (score 912 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2280 Rv2280, (MTCY339.30c), len: 459 aa. Probable dehydrogenase. Similar to D-lactate dehydrogenase (cytochrome) precursor e.g. G1061264 (587 aa) 920 920 database:900
Rv1837c glcB malate synthase 918 914 database:900
Rv1258c tap multidrug-efflux transporter 911 912 ctx neighborhood:881
Rv0467 icl1 isocitrate lyase 904 901 database:900
Rv1916 aceAb isocitrate lyase AceAb 903 900 database:900
Rv1915 aceAa isocitrate lyase AceAa 903 900 database:900
Rv2725c hflX GTP-binding protein HflX 862 862 coexpression:860
Rv0337c aspC aspartate aminotransferase 829 823 coexpression:821
Rv1905c aao D-amino acid oxidase 809 803 database:800
Rv1256c cyp130 cytochrome P450 Cyp130 778 777 ctx neighborhood:736
Rv1473 macrolide ABC transporter ATP-binding protein 751 751 coexpression:751
Rv1255c HTH-type transcriptional regulator 743 743 ctx neighborhood:732
Rv2415c hyp hypothetical protein 732 733 coexpression:732
Rv1551 plsB1 acyltransferase PlsB 622 606 database:549
Rv2482c plsB2 glycerol-3-phosphate acyltransferase 622 606 database:549

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-linked oxidase C-terminal domain-containing protein
  • Pfam (hmmscan --cut_ga): FAD_binding_4 PF01565.29 (E=1e-42), FAD-oxidase_C PF02913.25 (E=7e-69)
  • (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_215773.1)
  • Domains: Pfam-A via hmmscan --cut_ga — FAD_binding_4 (PF01565.29), FAD-oxidase_C (PF02913.25)
  • 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 Q11061 (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 — 45 functional partner(s); context anchor tap
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001346|Rv1257c|
MNTDVLAGLMAELPEGMVVTDPAVTDGYRQDRAFDPSAGKPLAIIRPRRTEEVQTVLRWASANQVPVVTRGAGSGLSGGATALDGGIVLSTEKMRDITVDPVTRTAVCQPGLYNAEVKEAAAEHGLWYPPDPSSFEICSIGGNIATNAGGLCCVKYGVTGDYVLGMQVVLANGTAVRLGGPRLKDVAGLSLTKLFVGSEGTLGVITEVTLRLLPAQNASSIVVASFGSVQAAVDAVLGVTGRLRPAMLEFMDSVAINAVEDTLRMDLDRDAAAMLVAGSDERGRAATEDAAVMAAVFAENGAIDVFSTDDPDEGEAFIAARRFAIPAVESKGALLLEDVGVPLPALGELVTGIARIAEERNLMISVIAHAGDGNTHPLLVYDPADAAMLERAHLAYGEIMDLAVGLGGTITGEHGVGRLKRPWLAGYLGPDVLALNQRIKQALDPQGILNPGSAI