fpg Resolved · high auto-curated
H37Rv Rv2924c · MTBC0 mtbc0_003107 ·
289 aa · 3259598–3260467 (-) ·
RefSeq NP_217440.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | formamidopyrimidine-DNA glycosylase |
|---|---|
| MTBC0 PGAP re-annotation | DNA-formamidopyrimidine glycosylase |
| Revised (this work) | DNA-formamidopyrimidine 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 |
P9WNC3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Formamidopyrimidine-DNA glycosylase 1 |
| EC (curated) |
EC 3.2.2.23, 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 a preference for oxidized purines, such as 7,8-dihydro-8-oxoguanine (8-oxoG) when paired with C, G or T, as well as methyl-faPy (formanidopyrimidine residues) in poly(dG-dC) and spiroiminodihydantoin:C base pairs. Unlike its E.coli ortholog has no activity on 8-oxoG:A. 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 a. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
L Replication, recombination and repair
|
|---|---|
| Preferred name | fpg |
| eggNOG description | Involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. Acts as DNA glycosylase that recognizes and removes damaged bases. Has a preference for oxidized purines, such as 7,8-dihydro-8-oxoguanine (8-oxoG). 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 |
| Orthologous group | COG0266 |
| EC number |
EC 3.2.2.23, EC 4.2.99.18
|
| KEGG orthology |
K10563
|
| KEGG pathways |
map03410
|
| Gene Ontology (46) |
GO:0000702, GO:0003674, GO:0003676, GO:0003677, GO:0003690, GO:0003824, GO:0005488, GO:0005575, GO:0005623, GO:0005886, GO:0006139, GO:0006259 +34 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 | 0.733 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 4 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 | 1.1e-36 | 1–124 | Formamidopyrimidine-DNA glycosylase N-terminal domain |
H2TH | PF06831.20 | 6.5e-29 | 144–231 | Formamidopyrimidine-DNA glycosylase H2TH domain |
zf-FPG_IleRS | PF06827.21 | 4.2e-08 | 257–286 | Zinc finger found in FPG and IleRS |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: acyP (acylphosphatase), high confidence from genomic context alone (score 784 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0944 fpg2 |
formamidopyrimidine-DNA glycosylase | 946 | 926 | database:900 |
Rv1629 polA |
DNA polymerase I | 904 | 815 | coexpression:790 textmining:504 |
Rv2922A acyP |
acylphosphatase | 783 | 784 ctx | neighborhood:773 |
Rv2923c hyp |
hypothetical protein | 772 | 773 ctx | neighborhood:773 |
Rv2922c smc |
chromosome partition protein Smc | 769 | 770 ctx | neighborhood:765 |
Rv2926c hyp |
hypothetical protein | 887 | 711 ctx | neighborhood:711 textmining:628 |
Rv2925c rnc |
ribonuclease III | 841 | 711 ctx | neighborhood:711 textmining:474 |
Rv2921c ftsY |
signal recognition particle receptor FtsY | 714 | 689 ctx | neighborhood:673 |
Rv2927c sepIVA hyp |
hypothetical protein | 810 | 681 ctx | neighborhood:681 textmining:431 |
Rv1631 coaE |
dephospho-CoA kinase CoaE | 645 | 611 | coexpression:472 |
Rv2963 |
integral membrane protein | 534 | 534 ctx | neighborhood:529 |
Rv2090 |
5'-3' exonuclease | 694 | 446 | coexpression:428 textmining:471 |
Rv1870c hyp |
hypothetical protein | 449 | 418 | coexpression:418 |
Rv3674c nth |
endonuclease III | 915 | 416 | coexpression:416 textmining:861 |
Rv1156 hyp |
hypothetical protein | 445 | 414 | coexpression:414 |
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: formamidopyrimidine-DNA glycosylase
- MTBC0 PGAP product: DNA-formamidopyrimidine glycosylase
- Pfam (hmmscan --cut_ga): Fapy_DNA_glyco PF01149.30 (E=1e-36), H2TH PF06831.20 (E=6e-29), zf-FPG_IleRS PF06827.21 (E=4e-08)
- (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_217440.1)
- 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 P9WNC3 (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 —
56 functional partner(s); context anchor
acyP - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003107|Rv2924c|fpg MPELPEVEVVRRGLQAHVTGRTITEVRVHHPRAVRRHDAGPADLTARLRGARINGTDRRGKYLWLTLNTAGVHRPTDTALVVHLGMSGQMLLGAVPCAAHVRISALLDDGTVLSFADQRTFGGWLLADLVTVDGSVVPVPVAHLARDPLDPRFDCDAVVKVLRRKHSELKRQLLDQRVVSGIGNIYADEALWRAKVNGAHVAATLRCRRLGAVLHAAADVMREALAKGGTSFDSLYVNVNGESGYFERSLDAYGREGENCRRCGAVIRRERFMNRSSFYCPRCQPRPRK