Rv0575c Resolved · high auto-curated

H37Rv Rv0575c · MTBC0 mtbc0_000605 · 388 aa · 672130–673296 (-) · RefSeq NP_215089.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)oxidoreductase
MTBC0 PGAP re-annotationFAD-binding domain
Revised (this work)FAD-binding domain. Pfam: FAD_binding_3 (PF01494.26).

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

Curated reference (UniProt)

UniProt O53772 TrEMBL · unreviewed · Evidence at protein level
UniProt namePossible oxidoreductase

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
H Coenzyme transport and metabolism
eggNOG descriptionFAD binding domain
Orthologous groupCOG0654

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 0.382 · purifying
Polymorphic sites (≥ 0.1% of strains) 6 synonymous, 7 missense, 0 nonsense, 4 frameshift
Disruption 4 distinct premature-stop/frameshift site(s); most common in 11.87% of strains (17241) · 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_3PF01494.26 3.2e-202–332 FAD binding domain

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

Closest characterised functional partner: Rv0576 (transcriptional regulator), medium confidence from genomic context alone (score 561 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1405c methyltransferase 766 758 coexpression:757
Rv1403c methyltransferase 726 716 coexpression:716
Rv1814 erg3 membrane-bound C-5 sterol desaturase 639 611 coexpression:401
Rv0576 transcriptional regulator 561 561 ctx neighborhood:552
Rv0573c pncB2 nicotinic acid phosphoribosyltransferase PncB2 577 552 ctx neighborhood:470
Rv0577 TB27.3 hyp hypothetical protein 554 544 ctx neighborhood:539
Rv2130c mshC cysteine:1D-myo-inosityl 2-amino-2-deoxy--D-glucopyranoside ligase 514 514 ctx neighborhood:511
Rv0574c hyp hypothetical protein 506 506 ctx neighborhood:483
Rv1181 pks4 polyketide beta-ketoacyl synthase 501 444
Rv1745c idi isopentenyl-diphosphate delta-isomerase 480 439 coexpression:439
Rv0062 celA1 cellulase CelA 425 426 ctx cooccurence:424
Rv1527c pks5 polyketide synthase 504 410
Rv3825c pks2 phthioceranic/hydroxyphthioceranic acid synthase 502 408
Rv2940c mas multifunctional mycocerosic acid synthase 498 403
Rv3377c type B diterpene cyclase 447 403 coexpression:401

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 domain
  • Pfam (hmmscan --cut_ga): FAD_binding_3 PF01494.26 (E=3e-20)
  • (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_215089.1)
  • Domains: Pfam-A via hmmscan --cut_ga — FAD_binding_3 (PF01494.26)
  • 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 COG0654
  • Curated reference: UniProt O53772 (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 — 24 functional partner(s); context anchor Rv0576
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000605|Rv0575c|
MKVAISGAGVAGAALAHWLQRTGHTPTVIERAPKFRTGGYMIDFWGVGYQVAKRMGITDQIAAAGYHMEHVRSVGPTGKVKADLGVDVFRRMVGDDFTSLPRGDLAAAIYTTIEDQVETIFDDSIATIDEHRDGVRLTFERTAPRDFDLVIGADGLHSNVRRLVFGPERDFEHYLGCKVAACVVDGYRPRDERSYVLYNTVDRQLARFALRGDRTMFLFVFRAEHDNPGVAPKDELRDQFGDVGWESRDILAALDDVEDLYFDVVSQIRMDRWSRGRVLLIGDAAGCISLLGGEGTGLAITEAYVLAGELARAGGDHRRAFDAYEKRLRPFIEGKQASAAKFIWFFATRTRFGLWFRNVAMRTMNFGPLATLFAGSVRDDFELPDYTW