end Resolved · high auto-curated

H37Rv Rv0670 · MTBC0 mtbc0_000709 · 252 aa · 773878–774636 (+) · RefSeq NP_215184.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)endonuclease IV
MTBC0 PGAP re-annotationdeoxyribonuclease IV
Revised (this work)Deoxyribonuclease IV. Pfam: AP_endonuc_2 (PF01261.31).

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

Curated reference (UniProt)

UniProt P9WQ13 SwissProt · reviewed · Evidence at protein level
UniProt nameProbable endonuclease 4
EC (curated) EC 3.1.21.2
Curated functionEndonuclease IV plays a role in DNA repair. It cleaves phosphodiester bonds at apurinic or apyrimidinic (AP) sites, generating a 3'-hydroxyl group and a 5'-terminal sugar phosphate.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
Preferred namenfo
eggNOG descriptionEndonuclease IV plays a role in DNA repair. It cleaves phosphodiester bonds at apurinic or apyrimidinic sites (AP sites) to produce new 5'-ends that are base-free deoxyribose 5-phosphate residues. It preferentially attacks modified AP sites created by bleomycin and neocarzinostatin
Orthologous groupCOG0648
EC number EC 3.1.21.2
KEGG orthology K01151
KEGG pathways map03410
Gene Ontology (31) GO:0003674, GO:0003824, GO:0003906, GO:0006139, GO:0006259, GO:0006281, GO:0006284, GO:0006725, GO:0006807, GO:0006950, GO:0006974, GO:0008081 +19 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) pseudogene candidate

pN/pS 1.348 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 4 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 7.70% of strains (11179) · 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
AP_endonuc_2PF01261.31 3.1e-4314–248 Xylose isomerase-like TIM barrel

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

Closest characterised functional partner: lpqP (lipoprotein LpqP), high confidence from genomic context alone (score 844 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0671 lpqP lipoprotein LpqP 844 844 ctx neighborhood:835
Rv0427c xthA exodeoxyribonuclease III protein XthA 951 826 experimental:825 textmining:732
Rv0672 fadE8 acyl-CoA dehydrogenase FadE8 769 769 ctx neighborhood:768
Rv0674 hyp hypothetical protein 766 766 ctx neighborhood:764
Rv0673 echA4 enoyl-CoA hydratase EchA4 766 766 ctx neighborhood:764
Rv0675 echA5 enoyl-CoA hydratase EchA5 765 765 ctx neighborhood:764
Rv0668 rpoC DNA-directed RNA polymerase subunit beta' 622 599 ctx neighborhood:544
Rv0669c neutral ceramidase 577 576 ctx neighborhood:558
Rv1156 hyp hypothetical protein 605 562 experimental:441
Rv0667 rpoB DNA-directed RNA polymerase subunit beta 545 545 ctx neighborhood:544
Rv3010c pfkA 6-phosphofructokinase 509 510 coexpression:494
Rv2529 hyp hypothetical protein 547 486 experimental:462
Rv0114 gmhB D-glycero-alpha-D-manno-heptose-1,7-bisphosphate 7-phosphatase 530 483
Rv3674c nth endonuclease III 768 480 experimental:441 textmining:572
Rv1870c hyp hypothetical protein 530 480 experimental:441

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: endonuclease IV
  • MTBC0 PGAP product: deoxyribonuclease IV
  • Pfam (hmmscan --cut_ga): AP_endonuc_2 PF01261.31 (E=3e-43)
  • (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_215184.1)
  • Domains: Pfam-A via hmmscan --cut_ga — AP_endonuc_2 (PF01261.31)
  • 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 COG0648
  • Curated reference: UniProt P9WQ13 (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 — 46 functional partner(s); context anchor lpqP
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000709|Rv0670|end
MLIGSHVSPTDPLAAAEAEGADVVQIFLGNPQSWKAPKPRDDAAALKAATLPIYVHAPYLINLASANNRVRIPSRKILQETCAAAADIGAAAVIVHGGHVADDNDIDKGFQRWRKALDRLETEVPVYLENTAGGDHAMARRFDTIARLWDVIGDTGIGFCLDTCHTWAAGEALTDAVDRIKAITGRIDLVHCNDSRDEAGSGRDRHANLGSGQIDPDLLVAAVKAAGAPVICETADQGRKDDIAFLRERTGS