Rv2464c Family assigned · medium auto-curated
H37Rv Rv2464c · MTBC0 mtbc0_002625 ·
268 aa · 2791107–2791913 (-) ·
RefSeq NP_216980.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | DNA glycosylase |
|---|---|
| MTBC0 PGAP re-annotation | Fpg/Nei family DNA glycosylase |
| Revised (this work) | Fpg/Nei family DNA glycosylase. Pfam: Fapy_DNA_glyco (PF01149.30), H2TH (PF06831.20), zf-FPG_IleRS (PF06827.21). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WNB9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Endonuclease 8 1 |
| EC (curated) |
EC 3.2.2.-, EC 4.2.99.18
|
| Curated function | Involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. DNA glycosylase that recognizes and removes damaged pyrimidines. Excises Tg:A (thymine glycol, prefers 5R isomers), Tg:G, 5,6-dihydrouracil:G base pairs and urea:A, also excises oxidized purine derivatives guanidinohydantoin:C and spiroiminodihydantoin:C. Poorly cleaves dsDNA with uracil substitutions, thus also acting as a weak uracil-DNA glycosylase. Acts on DNA bubble and 3'-fork structures, suggesting a role in replication-associated DNA repair. Activity on 7,8-dihydro-8-oxoguanine (8-oxoG) is debated; a r. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
L Replication, recombination and repair
|
|---|---|
| Preferred name | nei1 |
| eggNOG description | Belongs to the FPG family |
| Orthologous group | COG0266 |
| EC number |
EC 3.2.2.23, EC 4.2.99.18
|
| KEGG orthology |
K05522, K10563
|
| KEGG pathways |
map03410
|
| Gene Ontology (47) |
GO:0000702, GO:0000703, GO:0003674, GO:0003676, GO:0003677, GO:0003690, GO:0003697, GO:0003824, GO:0003906, GO:0004844, GO:0005488, GO:0006139 +35 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 | 0.295 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 5 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 |
|---|---|---|---|---|
Fapy_DNA_glyco | PF01149.30 | 2.4e-08 | 1–94 | Formamidopyrimidine-DNA glycosylase N-terminal domain |
H2TH | PF06831.20 | 1.1e-27 | 126–214 | Formamidopyrimidine-DNA glycosylase H2TH domain |
zf-FPG_IleRS | PF06827.21 | 9.3e-06 | 240–267 | Zinc finger found in FPG and IleRS |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: rpiB (ribose-5-phosphate isomerase B), high confidence from genomic context alone (score 884 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3297 nei |
endonuclease VIII | 924 | 924 | database:900 |
Rv2465c rpiB |
ribose-5-phosphate isomerase B | 884 | 884 ctx | neighborhood:882 |
Rv1629 polA |
DNA polymerase I | 865 | 816 | coexpression:791 |
Rv2466c hyp |
hypothetical protein | 801 | 802 ctx | neighborhood:773 |
Rv2467 pepN |
aminopeptidase PepN | 715 | 715 ctx | neighborhood:701 |
Rv1631 coaE |
dephospho-CoA kinase CoaE | 554 | 512 | coexpression:470 |
Rv2090 |
5'-3' exonuclease | 484 | 451 | coexpression:433 |
Rv1156 hyp |
hypothetical protein | 448 | 417 | coexpression:417 |
Rv3674c nth |
endonuclease III | 887 | 416 | coexpression:416 textmining:815 |
Rv1870c hyp |
hypothetical protein | 448 | 416 | coexpression:416 |
Rv2924c fpg |
formamidopyrimidine-DNA glycosylase | 570 | 321 | |
Rv0944 fpg2 |
formamidopyrimidine-DNA glycosylase | 428 | 282 | |
Rv2737c recA |
recombinase A | 608 | 253 | textmining:497 |
Rv3296 lhr |
ATP-dependent helicase | 860 | 191 | textmining:835 |
Rv3589 mutY |
A/G-specific adenine glycosylase | 839 | 126 | textmining:824 |
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: DNA glycosylase
- MTBC0 PGAP product: Fpg/Nei family DNA glycosylase
- Pfam (hmmscan --cut_ga): Fapy_DNA_glyco PF01149.30 (E=2e-08), H2TH PF06831.20 (E=1e-27), zf-FPG_IleRS PF06827.21 (E=9e-06)
- (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_216980.1)
- Domains: Pfam-A via hmmscan --cut_ga — Fapy_DNA_glyco (PF01149.30), H2TH (PF06831.20), zf-FPG_IleRS (PF06827.21)
- 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
COG0266 - Curated reference: UniProt P9WNB9 (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
rpiB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002625|Rv2464c| MPEGHTLHRLARLHQRRFAGAPVSVSSPQGRFADSASALNGRVLRRASAWGKHLFHHYVGGPVVHVHLGLYGTFTEWARPTDGWLPEPAGQVRMRMVGAEFGTDLRGPTVCESIDDGEVADVVARLGPDPLRSDANPSSAWSRITKSRRPIGALLMDQTVIAGVGNVYRNELLFRHRIDPQRPGRGIGEPEFDAAWNDLVSLMKVGLRRGKIIVVRPEHDHGLPSYLPDRPRTYVYRRAGEPCRVCGGVIRTALLEGRNVFWCPVCQT