nei Resolved · high auto-curated
H37Rv Rv3297 · MTBC0 mtbc0_003505 ·
255 aa · 3703400–3704167 (+) ·
RefSeq NP_217814.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | endonuclease VIII |
|---|---|
| MTBC0 PGAP re-annotation | endonuclease VIII Nei2 |
| Revised (this work) | Endonuclease VIII Nei2. Pfam: Fapy_DNA_glyco (PF01149.30), H2TH (PF06831.20). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WNC1
SwissProt · reviewed
· Inferred from homology
|
|---|---|
| UniProt name | Endonuclease 8 2 |
| 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. Acts as a DNA glycosylase that recognizes and removes damaged bases. Has AP (apurinic/apyrimidinic) lyase activity and introduces nicks in the DNA strand. Cleaves the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'-phosphates (By similarity). Complements an E.coli nei nth double mutant. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
L Replication, recombination and repair
|
|---|---|
| Preferred name | nei |
| eggNOG description | Belongs to the FPG family |
| Orthologous group | COG0266 |
| EC number |
EC 4.2.99.18
|
| KEGG orthology |
K05522
|
| KEGG pathways |
map03410
|
| Gene Ontology (35) |
GO:0003674, GO:0003676, GO:0003677, GO:0003690, GO:0003824, GO:0005488, GO:0006139, GO:0006259, GO:0006281, GO:0006725, GO:0006807, GO:0006950 +23 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 | 1.066 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 6 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 | 2.0e-12 | 1–93 | Formamidopyrimidine-DNA glycosylase N-terminal domain |
H2TH | PF06831.20 | 3.6e-10 | 123–186 | Formamidopyrimidine-DNA glycosylase H2TH domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: lhr (ATP-dependent helicase), high confidence from genomic context alone (score 985 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3296 lhr |
ATP-dependent helicase | 996 | 985 ctx | neighborhood:881 coexpression:839 textmining:803 |
Rv2464c nei1 |
DNA glycosylase | 924 | 924 | database:900 |
Rv3555c hyp |
hypothetical protein | 820 | 820 | coexpression:817 |
Rv3295 |
TetR family transcriptional regulator | 819 | 819 ctx | neighborhood:818 |
Rv1629 polA |
DNA polymerase I | 864 | 815 | coexpression:790 |
Rv2191 hyp |
hypothetical protein | 834 | 803 | coexpression:797 |
Rv0944 fpg2 |
formamidopyrimidine-DNA glycosylase | 968 | 766 ctx | cooccurence:766 textmining:870 |
Rv3293 pcd |
piperideine-6-carboxylic acid dehydrogenase | 532 | 532 ctx | neighborhood:531 |
Rv1631 coaE |
dephospho-CoA kinase CoaE | 555 | 513 | coexpression:471 |
Rv3294c hyp |
hypothetical protein | 493 | 494 ctx | neighborhood:491 |
Rv2090 |
5'-3' exonuclease | 478 | 446 | coexpression:427 |
Rv1870c hyp |
hypothetical protein | 449 | 418 | coexpression:418 |
Rv1156 hyp |
hypothetical protein | 446 | 415 | coexpression:415 |
Rv3674c nth |
endonuclease III | 924 | 414 | coexpression:414 textmining:877 |
Rv1407 fmu |
16S rRNA m5C967 methyltransferase | 404 | 405 |
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 VIII
- MTBC0 PGAP product: endonuclease VIII Nei2
- Pfam (hmmscan --cut_ga): Fapy_DNA_glyco PF01149.30 (E=2e-12), H2TH PF06831.20 (E=4e-10)
- (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_217814.1)
- Domains: Pfam-A via hmmscan --cut_ga — Fapy_DNA_glyco (PF01149.30), H2TH (PF06831.20)
- 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 P9WNC1 (SwissProt, reviewed; Inferred from homology)
- 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 —
23 functional partner(s); context anchor
lhr - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003505|Rv3297|nei MPEGDTVWHTAATLRRHLAGRTLTRCDIRVPRFAAVDLTGEVVDEVISRGKHLFIRTGTASIHSHLQMDGSWRVGNRPVRVDHRARIILEANQQEQAIRVVGVDLGLLEVIDRHNDGAVVAHLGPDLLADDWDPQRAAANLIVAPDRPIAEALLDQRVLAGIGNVYCNELCFVSGVLPTAPVSAVADPRRLVTRARDMLWVNRFRWNRCTTGDTRAGRRLWVYGRAGQGCRRCGTLIAYDTTDERVRYWCPACQR