Rv3519 Family assigned · medium auto-curated

H37Rv Rv3519 · MTBC0 mtbc0_003735 · 236 aa · 3979227–3979937 (+) · RefSeq NP_218036.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationacetoacetate decarboxylase family protein
Revised (this work)Acetoacetate decarboxylase family protein. Pfam: ADC (PF06314.17).

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

Curated reference (UniProt)

UniProt O53564 TrEMBL · unreviewed · Evidence at protein level
UniProt nameAcetoacetate decarboxylase

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category Q Secondary metabolites biosynthesis, transport and catabolism
eggNOG descriptionAcetoacetate decarboxylase
Orthologous groupCOG4689

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 n/a
Polymorphic sites (≥ 0.1% of strains) 0 synonymous, 4 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.33% of strains (475) · 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
ADCPF06314.17 2.7e-3217–221 Acetoacetate decarboxylase (ADC)

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

Closest characterised functional partner: cyp142 (cytochrome P450 monooxygenase Cyp142), high confidence from genomic context alone (score 793 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3518c cyp142 cytochrome P450 monooxygenase Cyp142 805 793 ctx neighborhood:790
Rv3061c fadE22 acyl-CoA dehydrogenase FadE22 597 581 ctx cooccurence:580
Rv3412 hyp hypothetical protein 569 570 ctx cooccurence:555
Rv0771 4-carboxymuconolactone decarboxylase 562 562 ctx cooccurence:562
Rv0763c ferredoxin 555 555 ctx cooccurence:541
Rv1059 hyp hypothetical protein 508 509 ctx cooccurence:507
Rv0271c fadE6 acyl-CoA dehydrogenase FadE6 523 505 ctx cooccurence:502
Rv1786 ferredoxin 495 495 ctx cooccurence:479
Rv0585c integral membrane protein 457 457
Rv3803c fbpD MPT51/MPB51 antigen 437 438 ctx cooccurence:434
Rv0320 hyp hypothetical protein 435 435 ctx cooccurence:435
Rv1362c membrane protein 431 432 ctx cooccurence:428
Rv0498 hyp hypothetical protein 411 411 coexpression:410
Rv3521 hyp hypothetical protein 631 335 textmining:469
Rv3522 ltp4 lipid transfer protein 416 323

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: hypothetical protein
  • MTBC0 PGAP product: acetoacetate decarboxylase family protein
  • Pfam (hmmscan --cut_ga): ADC PF06314.17 (E=3e-32)
  • (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_218036.1)
  • Domains: Pfam-A via hmmscan --cut_ga — ADC (PF06314.17)
  • 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 COG4689
  • Curated reference: UniProt O53564 (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 — 18 functional partner(s); context anchor cyp142
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003735|Rv3519|
MPVSQHTIAGTVLTMPVRIRTANLHSAMFSVPADPAQRLIDYSGLRVCEYLPGKAIVMQMLVRYVDGDLGRYHEYGTAIMVNPPGTQRRGPRALTRAAAFIHHLPVDQVFTLEAGRTIWGFPKIMADFNVTDGRRFGFDVSADGRLIAGIEFSTGLPVPTLGWQMLKTYSHHDGVTREIPWEMKVSGLRARLGGARLRLGDHPYAKELASLGLPKRALLSQSAANVEMTFGDGHPI