xthA Resolved · high auto-curated
H37Rv Rv0427c · MTBC0 - ·
291 aa · 516017–516892 (-) ·
RefSeq NP_214941.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | exodeoxyribonuclease III protein XthA |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Exodeoxyribonuclease III protein XthA. Pfam: Exo_endo_phos (PF03372.30). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
P96273
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable exodeoxyribonuclease III protein XthA |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
L Replication, recombination and repair
|
|---|---|
| Preferred name | xthA |
| eggNOG description | exodeoxyribonuclease III |
| Orthologous group | COG0708 |
| EC number |
EC 3.1.11.2
|
| KEGG orthology |
K01142
|
| KEGG pathways |
map03410
|
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 | 0.649 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 2 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 |
|---|---|---|---|---|
Exo_endo_phos | PF03372.30 | 1.8e-30 | 27–281 | Endonuclease/Exonuclease/phosphatase family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: def (polypeptide deformylase), high confidence from genomic context alone (score 894 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0429c def |
polypeptide deformylase | 952 | 894 ctx | neighborhood:881 textmining:566 |
Rv0428c |
GCN5-like N-acetyltransferase | 946 | 883 ctx | neighborhood:881 textmining:562 |
Rv3589 mutY |
A/G-specific adenine glycosylase | 903 | 865 | experimental:428 database:771 |
Rv2116 lppK |
lipoprotein LppK | 850 | 834 | experimental:414 database:653 |
Rv0002 dnaN |
DNA polymerase III subunit beta | 850 | 834 | experimental:414 database:653 |
Rv0670 end |
endonuclease IV | 951 | 826 | experimental:825 textmining:732 |
Rv1711 |
RNA pseudouridine synthase | 814 | 815 | coexpression:805 |
Rv2976c ung |
uracil-DNA glycosylase | 852 | 807 | database:743 |
Rv3674c nth |
endonuclease III | 823 | 799 | experimental:403 database:641 |
Rv1870c hyp |
hypothetical protein | 818 | 799 | experimental:403 database:641 |
Rv1156 hyp |
hypothetical protein | 818 | 799 | experimental:403 database:641 |
Rv1629 polA |
DNA polymerase I | 932 | 781 | database:662 textmining:703 |
Rv1317c alkA |
bifunctional regulatory protein/DNA repair enzyme AlkA | 894 | 759 | database:651 textmining:579 |
Rv2090 |
5'-3' exonuclease | 778 | 748 | database:662 |
Rv0938 ligD |
multifunctional non-homologous end joining DNA repair protein/ATP dependent DNA ligase LigD | 763 | 738 | database:644 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): exodeoxyribonuclease III protein XthA
- Pfam (hmmscan --cut_ga): Exo_endo_phos PF03372.30 (E=2e-30)
- (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_214941.1)
- Domains: Pfam-A via hmmscan --cut_ga — Exo_endo_phos (PF03372.30)
- 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
COG0708 - Curated reference: UniProt P96273 (TrEMBL, unreviewed; 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 —
71 functional partner(s); context anchor
def - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0427c|xthA MPDGTIDGGHPQRPASPRLRSPLLRLATWNVNSIRTRLDRVLDWLGRADVDVLAMQETKCPDGQFPALPLFELGYDVAHVGFDQWNGVAIASRVGLDDVRVGFDGQPSWSGKPEVAATTEARALGATCGGIRVWSLYVPNGRALDDPHYTYKLDWLAALRDTAEGWLRDDPAAPIALMGDWNIAPTDDDVWSTEFFAGCTHVSEPERKAFNAIVDAQFTDVVRPFTPGPGVYTYWDYTQLRFPKKQGMRIDFILGSPALAARVMDAQIVREERKGKAPSDHAPVLVDLHAG