mutY Resolved · high auto-curated

H37Rv Rv3589 · MTBC0 mtbc0_003808 · 304 aa · 4054170–4055084 (+) · RefSeq NP_218106.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)A/G-specific adenine glycosylase
MTBC0 PGAP re-annotationA/G-specific adenine glycosylase
Revised (this work)A/G-specific adenine glycosylase. Pfam: HhH-GPD (PF00730.32), HHH (PF00633.30).

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

Curated reference (UniProt)

UniProt P9WQ09 SwissProt · reviewed · Evidence at protein level
UniProt nameAdenine DNA glycosylase
EC (curated) EC 3.2.2.31
Curated functionAdenine glycosylase active on G:A and C:A mispairs, as well as processing 7,8-dihydro-8-oxoguanine:A (8-oxoG) mismatches. Minor activity against 8-oxoG:G and 8-oxo:T mismatches is also seen. Bind dsDNA oligonucleotides containing the above mismatches.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
Preferred namemutY
eggNOG descriptionadenine glycosylase
Orthologous groupCOG1194
KEGG orthology K03575
KEGG pathways map03410
Gene Ontology (32) GO:0003674, GO:0003824, GO:0005575, GO:0005623, GO:0005886, GO:0006139, GO:0006259, GO:0006281, GO:0006284, GO:0006725, GO:0006807, GO:0006950 +20 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 0.367 · purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 4 missense, 0 nonsense, 2 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 0.27% of strains (386) · 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
HhH-GPDPF00730.32 1.2e-1646–159 HhH-GPD superfamily base excision DNA repair protein
HHHPF00633.30 6.2e-07111–139 Helix-hairpin-helix motif

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

Closest characterised functional partner: canB (carbonic anhydrase), high confidence from genomic context alone (score 793 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0427c xthA exodeoxyribonuclease III protein XthA 903 865 experimental:428 database:771
Rv3588c canB carbonic anhydrase 857 793 ctx neighborhood:792
Rv3587c membrane protein 721 721 ctx neighborhood:713
Rv2116 lppK lipoprotein LppK 490 422 experimental:412
Rv0002 dnaN DNA polymerase III subunit beta 531 420 experimental:412
Rv3674c nth endonuclease III 939 382 textmining:906
Rv1316c ogt methylated-DNA--protein-cysteine methyltransferase 441 294
Rv1537 dinX DNA polymerase IV 609 210 textmining:526
Rv1108c xseA exodeoxyribonuclease VII large subunit 462 189
Rv3585 radA DNA repair protein RadA 418 177
Rv3671c marP serine protease 409 164
Rv2191 hyp hypothetical protein 479 157 textmining:408
Rv2985 mutT1 8-oxo-dGTP diphosphatase 651 140 textmining:611
Rv2464c nei1 DNA glycosylase 839 126 textmining:824
Rv0944 fpg2 formamidopyrimidine-DNA glycosylase 776 125 textmining:755

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: A/G-specific adenine glycosylase
  • MTBC0 PGAP product: A/G-specific adenine glycosylase
  • Pfam (hmmscan --cut_ga): HhH-GPD PF00730.32 (E=1e-16), HHH PF00633.30 (E=6e-07)
  • (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_218106.1)
  • Domains: Pfam-A via hmmscan --cut_ga — HhH-GPD (PF00730.32), HHH (PF00633.30)
  • 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 COG1194
  • Curated reference: UniProt P9WQ09 (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 — 50 functional partner(s); context anchor canB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003808|Rv3589|mutY
MPHILPEPSVTGPRHISDTNLLAWYQRSHRDLPWREPGVSPWQILVSEFMLQQTPAARVLAIWPDWVRRWPTPSATATASTADVLRAWGKLGYPRRAKRLHECATVIARDHNDVVPDDIEILVTLPGVGSYTARAVACFAYRQRVPVVDTNVRRVVARAVHGRADAGAPSVPRDHADVLALLPHRETAPEFSVALMELGATVCTARTPRCGLCPLDWCAWRHAGYPPSDGPPRRGQAYTGTDRQVRGRLLDVLRAAEFPVTRAELDVAWLTDTAQRDRALESLLADALVTRTVDGRFALPGEGF