Rv1751 Resolved · high auto-curated

H37Rv Rv1751 · MTBC0 - · 460 aa · 1979621–1981003 (+) · RefSeq NP_216267.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)oxidoreductase
MTBC0 PGAP re-annotation
Revised (this work)Oxidoreductase. Pfam: FAD_binding_3 (PF01494.26), NAD_binding_8 (PF13450.13).

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

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt O65936 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable oxidoreductase

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
H Coenzyme transport and metabolism
eggNOG descriptionCOG0654 2-polyprenyl-6-methoxyphenol hydroxylase and related FAD-dependent oxidoreductases
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) pseudogene candidate

pN/pS 0.723 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 7 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 1.66% of strains (2415) · 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
FAD_binding_3PF01494.26 1.5e-9053–394 FAD binding domain
NAD_binding_8PF13450.13 7.2e-0657–86 NAD(P)-binding Rossmann-like domain

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

Closest characterised functional partner: fadD1 (fatty-acid--CoA ligase FadD1), medium confidence from genomic context alone (score 571 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1752 hyp hypothetical protein 972 787 ctx neighborhood:759 textmining:878
Rv1814 erg3 membrane-bound C-5 sterol desaturase 639 612 coexpression:402
Rv1750c fadD1 fatty-acid--CoA ligase FadD1 581 571 ctx neighborhood:559
Rv2402 trehalase 544 544 ctx neighborhood:544
Rv2401A membrane protein 544 544 ctx neighborhood:544
Rv1749c integral membrane protein 437 438 ctx neighborhood:412
Rv1745c idi isopentenyl-diphosphate delta-isomerase 478 437 coexpression:437
Rv1666c cyp139 cytochrome P450 Cyp139 439 418
Rv3377c type B diterpene cyclase 447 403 coexpression:401
Rv0568 cyp135B1 cytochrome P450 Cyp135B1 420 399
Rv3059 cyp136 cytochrome P450 Cyp136 407 385
Rv1394c cyp132 cytochrome P450 Cyp132 405 383
Rv0136 cyp138 cytochrome P450 Cyp138 404 382
Rv2946c pks1 polyketide synthase 441 270

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): oxidoreductase
  • Pfam (hmmscan --cut_ga): FAD_binding_3 PF01494.26 (E=2e-90), NAD_binding_8 PF13450.13 (E=7e-06)
  • (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_216267.1)
  • Domains: Pfam-A via hmmscan --cut_ga — FAD_binding_3 (PF01494.26), NAD_binding_8 (PF13450.13)
  • 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 O65936 (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 — 14 functional partner(s); context anchor fadD1
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv1751|
MIATMPSMARRSRHDNKITTPAVDCLTIERLDSPASGAPQVTPYARALMGETTTCAIIGGGPAGMVLGLLLARAGVQVTLLEKHGDFLRDFRGDTVHPTTMRLLDELGLWERFAALPYSEVRTATLHSNGRAVTYIDFERLHQPYPYVAMVPQWDLLNLLAEAAQAEPSFTLRMKTEVTGLLREGGKVTGVRYQGAEGPGELRAELTVACDGRWSIARHEAGLKAREFPVNFDVWWFKLPREGDAEFSFLPRFSPGKGLGVIPREGYFQIAYLGPKGTDAQLRERGIEEFRRDVSELLPEATASVAALASMDEVKHLNVKVNRLRRWHIDGLLCIGDAAHAMSPVAGVGINLAVQDAVAAATILAEPLREHRVSSRHLAAVRRRRAFPTAVTQAVQRVLHRRLLGPLLQGRDPTPPAALLGLVERLPWLSAVPAYFVGVGVRPEHAPAFARRGPGNRKGP