ung Resolved · high auto-curated

H37Rv Rv2976c · MTBC0 mtbc0_003161 · 227 aa · 3353244–3353927 (-) · RefSeq NP_217492.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)uracil-DNA glycosylase
MTBC0 PGAP re-annotationuracil-DNA glycosylase
Revised (this work)Uracil-DNA glycosylase. Pfam: UDG (PF03167.26).

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

Curated reference (UniProt)

UniProt P9WFQ9 SwissProt · reviewed · Evidence at protein level
UniProt nameUracil-DNA glycosylase
EC (curated) EC 3.2.2.27
Curated functionExcises uracil residues from the DNA which can arise as a result of misincorporation of dUMP residues by DNA polymerase or due to deamination of cytosine.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
Preferred nameung
eggNOG descriptionExcises uracil residues from the DNA which can arise as a result of misincorporation of dUMP residues by DNA polymerase or due to deamination of cytosine
Orthologous groupCOG0692
EC number EC 3.2.2.27
KEGG orthology K03648
KEGG pathways map03410, map05340
Gene Ontology (34) GO:0003674, GO:0003824, GO:0004844, GO:0006139, GO:0006259, GO:0006281, GO:0006284, GO:0006285, GO:0006725, GO:0006807, GO:0006950, GO:0006974 +22 more

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 0.271 · purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 3 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
UDGPF03167.26 1.9e-1557–214 Uracil DNA glycosylase superfamily

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

Closest characterised functional partner: thiL (thiamine-monophosphate kinase), high confidence from genomic context alone (score 852 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2977c thiL thiamine-monophosphate kinase 851 852 ctx neighborhood:836
Rv0427c xthA exodeoxyribonuclease III protein XthA 852 807 database:743
Rv2979c resolvase 737 737 ctx neighborhood:721
Rv2978c tnpB transposase 730 729 ctx neighborhood:721
Rv2980 hyp hypothetical protein 728 728 ctx neighborhood:728
Rv0002 dnaN DNA polymerase III subunit beta 638 616 experimental:457
Rv2116 lppK lipoprotein LppK 636 613 experimental:457
Rv2192c trpD anthranilate phosphoribosyltransferase 592 592 ctx fusion:555
Rv3674c nth endonuclease III 613 571 ctx fusion:508
Rv0670 end endonuclease IV 566 434
Rv2737c recA recombinase A 500 345
Rv2467 pepN aminopeptidase PepN 591 294 textmining:446
Rv2697c dut deoxyuridine 5'-triphosphate nucleotidohydrolase 442 271
Rv1080c greA transcription elongation factor GreA 428 197
Rv3752c tadA cytidine/deoxycytidylate deaminase 434 190

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: uracil-DNA glycosylase
  • MTBC0 PGAP product: uracil-DNA glycosylase
  • Pfam (hmmscan --cut_ga): UDG PF03167.26 (E=2e-15)
  • (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_217492.1)
  • Domains: Pfam-A via hmmscan --cut_ga — UDG (PF03167.26)
  • 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 COG0692
  • Curated reference: UniProt P9WFQ9 (SwissProt, reviewed; 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 — 19 functional partner(s); context anchor thiL
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003161|Rv2976c|ung
MTARPLSELVERGWAAALEPVADQVAHMGQFLRAEIAAGRRYLPAGSNVLRAFTFPFDNVRVLIVGQDPYPTPGHAVGLSFSVAPDVRPWPRSLANIFDEYTADLGYPLPSNGDLTPWAQRGVLLLNRVLTVRPSNPASHRGKGWEAVTECAIRALAARAAPLVAILWGRDASTLKPMLAAGNCVAIESPHPSPLSASRGFFGSRPFSRANELLVGMGAEPIDWRLP