Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | DNA polymerase IV |
|---|
| MTBC0 PGAP re-annotation | DNA polymerase IV |
|---|
| Revised (this work) | DNA polymerase IV. Pfam: IMS (PF00817.26), IMS_HHH (PF11798.15), IMS_HHH_1 (PF21999.3), IMS_C (PF11799.14). |
|---|
Auto-curated: this verdict and function were generated by rules from
PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WNT3
SwissProt · reviewed
· Evidence at protein level
|
|---|
| UniProt name | DNA polymerase IV 1 |
|---|
| EC (curated) |
EC 2.7.7.7
|
|---|
| Curated function | Poorly processive, error-prone DNA polymerase involved in untargeted mutagenesis. Copies undamaged DNA at stalled replication forks, which arise in vivo from mismatched or misaligned primer ends. These misaligned primers can be extended by PolIV. Exhibits no 3'-5' exonuclease (proofreading) activity. May be involved in translesional synthesis, in conjunction with the beta clamp from PolIII (By similarity). |
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
L Replication, recombination and repair
|
|---|
| Preferred name | dinB |
|---|
| eggNOG description | Poorly processive, error-prone DNA polymerase involved in untargeted mutagenesis. Copies undamaged DNA at stalled replication forks, which arise in vivo from mismatched or misaligned primer ends. These misaligned primers can be extended by PolIV. Exhibits no 3'-5' exonuclease (proofreading) activity. May be involved in translesional synthesis, in conjunction with the beta clamp from PolIII |
|---|
| Orthologous group | COG0389 |
|---|
| EC number |
EC 2.7.7.7
|
|---|
| KEGG orthology |
K02346
|
|---|
| Gene Ontology (11) |
GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0016020, GO:0044424, GO:0044444, 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 |
0.74 · relaxed/neutral
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
3 synonymous, 6 missense, 0 nonsense, 1 frameshift
|
|---|
| Disruption |
1 distinct premature-stop/frameshift site(s); most common in
0.19% of strains
(272) · 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 |
|---|
IMS | PF00817.26 |
2.2e-36 | 4–151 |
impB/mucB/samB family |
IMS_HHH | PF11798.15 |
1.7e-07 | 165–195 |
IMS family HHH motif |
IMS_HHH_1 | PF21999.3 |
2.5e-07 | 179–229 |
DNA polymerase-iota, thumb domain |
IMS_C | PF11799.14 |
2.4e-27 | 240–344 |
impB/mucB/samB family C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv0002 dnaN |
DNA polymerase III subunit beta |
941 |
907 |
experimental:766 database:612 |
Rv2116 lppK |
lipoprotein LppK |
862 |
853 |
experimental:627 database:612 |
Rv2737c recA |
recombinase A |
967 |
800 |
experimental:439 database:523 textmining:845 |
Rv3395c hyp |
hypothetical protein |
761 |
704 |
coexpression:693 |
Rv2720 lexA |
repressor LexA |
925 |
681 |
experimental:463 textmining:777 |
Rv1629 polA |
DNA polymerase I |
912 |
676 |
database:553 textmining:740 |
Rv1278 hyp |
hypothetical protein |
705 |
676 |
database:548 |
Rv2101 helZ |
helicase HelZ |
692 |
665 |
database:452 |
Rv2090 |
5'-3' exonuclease |
657 |
636 |
database:553 |
Rv1277 hyp |
hypothetical protein |
667 |
634 |
database:548 |
Rv1329c dinG |
ATP-dependent helicase DinG |
653 |
616 |
database:577 |
Rv0938 ligD |
multifunctional non-homologous end joining DNA repair protein/ATP dependent DNA ligase LigD |
731 |
606 |
database:521 |
Rv3646c topA |
DNA topoisomerase I |
644 |
585 |
database:548 |
Rv0435c |
ATPase |
589 |
574 |
database:569 |
Rv3884c eccA2 |
ESX-2 secretion system protein EccA |
586 |
571 |
database:569 |
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 IV
- MTBC0 PGAP product: DNA polymerase IV
- Pfam (hmmscan --cut_ga): IMS PF00817.26 (E=2e-36), IMS_HHH PF11798.15 (E=2e-07), IMS_HHH_1 PF21999.3 (E=2e-07), IMS_C PF11799.14 (E=2e-27)
- (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_216053.3)
- Domains: Pfam-A via hmmscan --cut_ga — IMS (PF00817.26), IMS_HHH (PF11798.15), IMS_HHH_1 (PF21999.3), IMS_C (PF11799.14)
- 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
COG0389
- Curated reference: UniProt
P9WNT3
(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 —
88 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001644|Rv1537|dinX
MLHLDMDAFFASVEQLTRPTLRGRPVLVGGLGGRGVVAGASYEARAYGARSAMPMHQARRLIGVTAVVLPPRGVVYGIASRRVFDTVRGLVPVVEQLSFDEAFAEPPQLAGAVAEDVETFCERLRRRVRDETGLIASVGAGSGKQIAKIASGLAKPDGIRVVRHAEEQALLSGLPVRRLWGIGPVAEEKLHRLGIETIGQLAALSDAEAANILGATIGPALHRLARGIDDRPVVERAEAKQISAESTFAVDLTTMEQLHEAIDSIAEHAHQRLLRDGRGARTITVKLKKSDMSTLTRSATMPYPTTDAGALFTVARRLLPDPLQIGPIRLLGVGFSGLSDIRQESLFADSDLTQETAAAHYVETPGAVVPAAHDATMWRVGDDVAHPELGHGWVQGAGHGVVTVRFETRGSGPGSARTFPVDTGDISNASPLDSLDWPDYIGQLSVEGSAGASAPTVDDVGDR
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