dnaE2 Resolved · high auto-curated
H37Rv Rv3370c · MTBC0 - ·
1079 aa · 3781501–3784740 (-) ·
RefSeq NP_217887.3
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | error-prone DNA polymerase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Error-prone DNA polymerase. Pfam: PHP (PF02811.27), DNA_pol3_alpha (PF07733.19), DNA_pol3_finger (PF17657.7), HHH_6 (PF14579.13), tRNA_anti-codon (PF01336.32). |
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 |
P9WNT5
SwissProt · reviewed
· Evidence at transcript level
|
|---|---|
| UniProt name | Error-prone DNA polymerase |
| EC (curated) |
EC 2.7.7.7
|
| Curated function | DNA polymerase involved in damage-induced mutagenesis and translesion synthesis (TLS). It is not the major replicative DNA polymerase. Does not appear to be essential for chromosomal replication. May be involved in generating antibiotic resistance. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
L Replication, recombination and repair
|
|---|---|
| Preferred name | dnaE2 |
| eggNOG description | DNA polymerase involved in damage-induced mutagenesis and translesion synthesis (TLS). It is not the major replicative DNA polymerase |
| Orthologous group | COG0587 |
| EC number |
EC 2.7.7.7
|
| KEGG orthology |
K14162
|
| Gene Ontology (53) |
GO:0000731, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0006139, GO:0006259, GO:0006281, GO:0006301, GO:0006725, GO:0006807, GO:0006950 +41 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 | 0.521 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 11 synonymous, 16 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.12% of strains (180) · clonal |
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 |
|---|---|---|---|---|
PHP | PF02811.27 | 1.1e-31 | 48–219 | PHP domain |
DNA_pol3_alpha | PF07733.19 | 3.4e-84 | 338–582 | Bacterial DNA polymerase III alpha NTPase domain |
DNA_pol3_finger | PF17657.7 | 1.8e-55 | 585–749 | Bacterial DNA polymerase III alpha subunit finger domain |
HHH_6 | PF14579.13 | 8.9e-23 | 825–913 | Helix-hairpin-helix motif |
tRNA_anti-codon | PF01336.32 | 2.6e-06 | 992–1064 | OB-fold nucleic acid binding domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: otsB2 (trehalose 6-phosphate phosphatase), high confidence from genomic context alone (score 726 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3394c hyp |
hypothetical protein | 917 | 889 ctx | cooccurence:773 coexpression:450 |
Rv3395c hyp |
hypothetical protein | 958 | 879 ctx | cooccurence:762 coexpression:432 textmining:671 |
Rv0002 dnaN |
DNA polymerase III subunit beta | 905 | 858 | experimental:858 |
Rv2413c hyp |
hypothetical protein | 895 | 857 | experimental:829 |
Rv0054 ssb |
single-strand DNA-binding protein | 826 | 810 | experimental:773 |
Rv2478c hyp |
hypothetical protein | 824 | 809 | experimental:773 |
Rv3644c |
DNA polymerase | 805 | 787 | experimental:773 |
Rv3721c dnaZX |
DNA polymerase III subunit gamma/tau | 804 | 786 | experimental:773 |
Rv2116 lppK |
lipoprotein LppK | 792 | 773 | experimental:773 |
Rv3372 otsB2 |
trehalose 6-phosphate phosphatase | 725 | 726 ctx | neighborhood:725 |
Rv2191 hyp |
hypothetical protein | 873 | 625 | experimental:510 textmining:676 |
Rv3368c |
oxidoreductase | 580 | 581 ctx | neighborhood:463 |
Rv3711c dnaQ |
DNA polymerase III subunit epsilon | 674 | 525 | experimental:510 |
Rv3371 |
diacyglycerol O-acyltransferase | 521 | 521 ctx | neighborhood:500 |
Rv1537 dinX |
DNA polymerase IV | 842 | 508 | coexpression:425 textmining:693 |
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): error-prone DNA polymerase
- Pfam (hmmscan --cut_ga): PHP PF02811.27 (E=1e-31), DNA_pol3_alpha PF07733.19 (E=3e-84), DNA_pol3_finger PF17657.7 (E=2e-55), HHH_6 PF14579.13 (E=9e-23), tRNA_anti-codon PF01336.32 (E=3e-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_217887.3)
- Domains: Pfam-A via hmmscan --cut_ga — PHP (PF02811.27), DNA_pol3_alpha (PF07733.19), DNA_pol3_finger (PF17657.7), HHH_6 (PF14579.13), tRNA_anti-codon (PF01336.32)
- 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
COG0587 - Curated reference: UniProt P9WNT5 (SwissProt, reviewed; Evidence at transcript 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 —
42 functional partner(s); context anchor
otsB2 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3370c|dnaE2 MERVLNGKPRHAGVPAFDADGDVPRSRKRGAYQPPGRERVGSSVAYAELHAHSAYSFLDGASTPEELVEEAARLGLCALALTDHDGLYGAVRFAEAAAELDVRTVFGAELSLGATARTERPDPPGPHLLVLARGPEGYRRLSRQLAAAHLAGGEKGKPRYDFDALTEAAGGHWHILTGCRKGHVRQALSQGGPAAAQRALADLVDRFTPSRVSIELTHHGHPLDDERNAALAGLAPRFGVGIVATTGAHFADPSRGRLAMAMAAIRARRSLDSAAGWLAPLGGAHLRSGEEMARLFAWCPEAVTAAAELGERCAFGLQLIAPRLPPFDVPDGHTEDSWLRSLVMAGARERYGPPKSAPRAYSQIEHELKVIAQLRFPGYFLVVHDITRFCRDNDILCQGRGSAANSAVCYALGVTAVDPVANELLFERFLSPARDGPPDIDIDIESDQREKVIQYVYHKYGRDYAAQVANVITYRGRSAVRDMARALGFSPGQQDAWSKQVSHWTGQADDVDGIPEQVIDLATQIRNLPRHLGIHSGGMVICDRPIADVCPVEWARMANRSVLQWDKDDCAAIGLVKFDLLGLGMLSALHYAKDLVAEHKGIEVDLARLDLSEPAVYEMLARADSVGVFQVESRAQMATLPRLKPRVFYDLVVEVALIRPGPIQGGSVHPYIRRRNGVDPVIYEHPSMAPALRKTLGVPLFQEQLMQLAVDCAGFSAAEADQLRRAMGSKRSTERMRRLRGRFYDGMRALHGAPDEVIDRIYEKLEAFANFGFPESHALSFASLVFYSAWFKLHHPAAFCAALLRAQPMGFYSPQSLVADARRHGVAVHGPCVNASLAHATCENAGTEVRLGLGAVRYLGAELAEKLVAERTANGPFTSLPDLTSRVQLSVPQVEALATAGALGCFGMSRREALWAAGAAATGRPDRLPGVGSSSHIPALPGMSELELAAADVWATGVSPDSYPTQFLRADLDAMGVLPAERLGSVSDGDRVLIAGAVTHRQRPATAQGVTFINLEDETGMVNVLCTPGVWARHRKLAHTAPALLIRGQVQNASGAITVVAERMGRLTLAVGARSRDFR