dnaE1 Family assigned · medium auto-curated
H37Rv Rv1547 · MTBC0 mtbc0_001654 ·
1184 aa · 1757503–1761057 (+) ·
RefSeq NP_216063.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | DNA polymerase III subunit alpha |
|---|---|
| MTBC0 PGAP re-annotation | DNA polymerase III subunit alpha |
| Revised (this work) | DNA polymerase III subunit alpha. 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.
Curated reference (UniProt)
| UniProt |
P9WNT7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | DNA polymerase III subunit alpha |
| EC (curated) |
EC 2.7.7.7
|
| Curated function | DNA polymerase III is a complex, multichain enzyme responsible for most of the replicative synthesis in bacteria. Pol III also exhibits 3' to 5' exonuclease activity. The alpha chain is the DNA polymerase (By similarity). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
L Replication, recombination and repair
|
|---|---|
| Preferred name | dnaE |
| eggNOG description | DNA polymerase |
| Orthologous group | COG0587 |
| EC number |
EC 2.7.7.7
|
| KEGG orthology |
K02337
|
| KEGG pathways |
map00230, map00240, map01100, map03030, map03430, map03440
|
| KEGG modules |
M00260
|
| Gene Ontology (10) |
GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0008150, GO:0016020, GO:0030312, GO:0040007, GO:0044464, GO:0071944
|
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 | 0.162 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 14 synonymous, 7 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 |
|---|---|---|---|---|
PHP | PF02811.27 | 4.1e-48 | 12–198 | PHP domain |
DNA_pol3_alpha | PF07733.19 | 1.6e-92 | 320–590 | Bacterial DNA polymerase III alpha NTPase domain |
DNA_pol3_finger | PF17657.7 | 2.1e-62 | 593–762 | Bacterial DNA polymerase III alpha subunit finger domain |
HHH_6 | PF14579.13 | 1.1e-25 | 835–922 | Helix-hairpin-helix motif |
tRNA_anti-codon | PF01336.32 | 5.1e-08 | 1024–1100 | OB-fold nucleic acid binding domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: dnaG (DNA primase), medium confidence from genomic context alone (score 694 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0002 dnaN |
DNA polymerase III subunit beta | 993 | 988 | experimental:858 database:900 textmining:490 |
Rv2413c hyp |
hypothetical protein | 988 | 985 | experimental:829 database:900 |
Rv3721c dnaZX |
DNA polymerase III subunit gamma/tau | 983 | 982 | experimental:773 database:900 |
Rv3644c |
DNA polymerase | 983 | 982 | experimental:773 database:900 |
Rv2191 hyp |
hypothetical protein | 976 | 953 | experimental:510 database:900 textmining:515 |
Rv3711c dnaQ |
DNA polymerase III subunit epsilon | 956 | 952 | experimental:510 database:900 |
Rv0054 ssb |
single-strand DNA-binding protein | 843 | 829 | experimental:773 |
Rv1546 hyp |
hypothetical protein | 796 | 796 ctx | neighborhood:794 |
Rv2478c hyp |
hypothetical protein | 799 | 781 | experimental:773 |
Rv2116 lppK |
lipoprotein LppK | 792 | 773 | experimental:773 |
Rv2343c dnaG |
DNA primase | 864 | 694 ctx | cooccurence:610 textmining:576 |
Rv1544 |
ketoacyl reductase | 681 | 681 ctx | neighborhood:678 |
Rv2841c nusA |
transcription termination/antitermination protein NusA | 533 | 534 ctx | cooccurence:504 |
Rv3907c pcnA |
poly(A) polymerase PcnA | 514 | 512 ctx | cooccurence:496 |
Rv1543 |
oxidoreductase | 506 | 507 ctx | neighborhood:502 |
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 polymerase III subunit alpha
- MTBC0 PGAP product: DNA polymerase III subunit alpha
- Pfam (hmmscan --cut_ga): PHP PF02811.27 (E=4e-48), DNA_pol3_alpha PF07733.19 (E=2e-92), DNA_pol3_finger PF17657.7 (E=2e-62), HHH_6 PF14579.13 (E=1e-25), tRNA_anti-codon PF01336.32 (E=5e-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_216063.1)
- 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 P9WNT7 (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 —
65 functional partner(s); context anchor
dnaG - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001654|Rv1547|dnaE1 MSGSSAGSSFVHLHNHTEYSMLDGAAKITPMLAEVERLGMPAVGMTDHGNMFGASEFYNSATKAGIKPIIGVEAYIAPGSRFDTRRILWGDPSQKADDVSGSGSYTHLTMMAENATGLRNLFKLSSHASFEGQLSKWSRMDAELIAEHAEGIIITTGCPSGEVQTRLRLGQDREALEAAAKWREIVGPDNYFLELMDHGLTIERRVRDGLLEIGRALNIPPLATNDCHYVTRDAAHNHEALLCVQTGKTLSDPNRFKFDGDGYYLKSAAEMRQIWDDEVPGACDSTLLIAERVQSYADVWTPRDRMPVFPVPDGHDQASWLRHEVDAGLRRRFPAGPPDGYRERAAYEIDVICSKGFPSYFLIVADLISYARSAGIRVGPGRGSAAGSLVAYALGITDIDPIPHGLLFERFLNPERTSMPDIDIDFDDRRRGEMVRYAADKWGHDRVAQVITFGTIKTKAALKDSARIHYGQPGFAIADRITKALPPAIMAKDIPLSGITDPSHERYKEAAEVRGLIETDPDVRTIYQTARGLEGLIRNAGVHACAVIMSSEPLTEAIPLWKRPQDGAIITGWDYPACEAIGLLKMDFLGLRNLTIIGDAIDNVRANRGIDLDLESVPLDDKATYELLGRGDTLGVFQLDGGPMRDLLRRMQPTGFEDVVAVIALYRPGPMGMNAHNDYADRKNNRQAIKPIHPELEEPLREILAETYGLIVYQEQIMRIAQKVASYSLARADILRKAMGKKKREVLEKEFEGFSDGMQANGFSPAAIKALWDTILPFADYAFNKSHAAGYGMVSYWTAYLKANYPAEYMAGLLTSVGDDKDKAAVYLADCRKLGITVLPPDVNESGLNFASVGQDIRYGLGAVRNVGANVVGSLLQTRNDKGKFTDFSDYLNKIDISACNKKVTESLIKAGAFDSLGHARKGLFLVHSDAVDSVLGTKKAEALGQFDLFGSNDDGTGTADPVFTIKVPDDEWEDKHKLALEREMLGLYVSGHPLNGVAHLLAAQVDTAIPAILDGDVPNDAQVRVGGILASVNRRVNKNGMPWASAQLEDLTGGIEVMFFPHTYSSYGADIVDDAVVLVNAKVAVRDDRIALIANDLTVPDFSNAEVERPLAVSLPTRQCTFDKVSALKQVLARHPGTSQVHLRLISGDRITTLALDQSLRVTPSPALMGDLKELLGPGCLGS