nth Resolved · high auto-curated
H37Rv Rv3674c · MTBC0 mtbc0_003893 ·
245 aa · 4138987–4139724 (-) ·
RefSeq NP_218191.2
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | endonuclease III |
|---|---|
| MTBC0 PGAP re-annotation | endonuclease III |
| Revised (this work) | Endonuclease III. Pfam: HhH-GPD (PF00730.32), HHH (PF00633.30), EndIII_4Fe-2S (PF10576.15). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WQ11
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Endonuclease III |
| EC (curated) |
EC 4.2.99.18
|
| Curated function | DNA repair enzyme that has both DNA N-glycosylase activity and AP-lyase activity. The DNA N-glycosylase activity releases various damaged pyrimidines from DNA by cleaving the N-glycosidic bond, leaving an AP (apurinic/apyrimidinic) site. The AP-lyase activity cleaves the phosphodiester bond 3' to the AP site by a beta-elimination, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate. Has a preference for oxidized pyrimidines, such as thymine glycol (prefers 5S isomers) 5,6-dihydrouracil:G, 5-hydroxyuracil:G, 5-hydroxycytosine:G and urea:A. Cleaves ssDNA containing. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
L Replication, recombination and repair
|
|---|---|
| Preferred name | nth |
| eggNOG description | DNA repair enzyme that has both DNA N-glycosylase activity and AP-lyase activity. The DNA N-glycosylase activity releases various damaged pyrimidines from DNA by cleaving the N- glycosidic bond, leaving an AP (apurinic apyrimidinic) site. The AP-lyase activity cleaves the phosphodiester bond 3' to the AP site by a beta-elimination, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate |
| Orthologous group | COG0177 |
| EC number |
EC 4.2.99.18
|
| KEGG orthology |
K10773
|
| KEGG pathways |
map03410
|
| Gene Ontology (43) |
GO:0003674, GO:0003676, GO:0003677, GO:0003690, GO:0003824, GO:0005488, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0006139, GO:0006259 +31 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 | n/a |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 0 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
HhH-GPD | PF00730.32 | 4.7e-25 | 45–179 | HhH-GPD superfamily base excision DNA repair protein |
HHH | PF00633.30 | 4.1e-09 | 110–137 | Helix-hairpin-helix motif |
EndIII_4Fe-2S | PF10576.15 | 1.8e-04 | 198–214 | Iron-sulfur binding domain of endonuclease III |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv3673c (membrane-anchored thioredoxin-like protein), high confidence from genomic context alone (score 903 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3673c |
membrane-anchored thioredoxin-like protein | 903 | 903 ctx | neighborhood:881 |
Rv0427c xthA |
exodeoxyribonuclease III protein XthA | 823 | 799 | experimental:403 database:641 |
Rv3671c marP |
serine protease | 797 | 793 ctx | neighborhood:758 |
Rv3675 |
membrane protein | 855 | 779 ctx | neighborhood:779 |
Rv3672c hyp |
hypothetical protein | 617 | 597 ctx | neighborhood:591 |
Rv3676 crp |
cAMP receptor protein | 577 | 577 ctx | neighborhood:486 |
Rv2976c ung |
uracil-DNA glycosylase | 613 | 571 ctx | fusion:508 |
Rv0670 end |
endonuclease IV | 768 | 480 | experimental:441 textmining:572 |
Rv2239c hyp |
hypothetical protein | 438 | 439 ctx | cooccurence:428 |
Rv1613 trpA |
tryptophan synthase subunit alpha | 426 | 427 | coexpression:420 |
Rv0944 fpg2 |
formamidopyrimidine-DNA glycosylase | 548 | 418 | coexpression:418 |
Rv2924c fpg |
formamidopyrimidine-DNA glycosylase | 915 | 416 | coexpression:416 textmining:861 |
Rv2464c nei1 |
DNA glycosylase | 887 | 416 | coexpression:416 textmining:815 |
Rv3297 nei |
endonuclease VIII | 924 | 414 | coexpression:414 textmining:877 |
Rv2572c aspS |
aspartate--tRNA ligase | 404 | 404 |
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 III
- MTBC0 PGAP product: endonuclease III
- Pfam (hmmscan --cut_ga): HhH-GPD PF00730.32 (E=5e-25), HHH PF00633.30 (E=4e-09), EndIII_4Fe-2S PF10576.15 (E=2e-04)
- (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_218191.2)
- Domains: Pfam-A via hmmscan --cut_ga — HhH-GPD (PF00730.32), HHH (PF00633.30), EndIII_4Fe-2S (PF10576.15)
- 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
COG0177 - Curated reference: UniProt P9WQ11 (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 —
41 functional partner(s); context anchor
Rv3673c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003893|Rv3674c|nth MPGRWSAETRLALVRRARRMNRALAQAFPHVYCELDFTTPLELAVATILSAQSTDKRVNLTTPALFARYRTARDYAQADRTELESLIRPTGFYRNKAASLIGLGQALVERFGGEVPATMDKLVTLPGVGRKTANVILGNAFGIPGITVDTHFGRLVRRWRWTTAEDPVKVEQAVGELIERKEWTLLSHRVIFHGRRVCHARRPACGVCVLAKDCPSFGLGPTEPLLAAPLVQGPETDHLLALAGL