dinP Resolved · high auto-curated

H37Rv Rv3056 · MTBC0 mtbc0_003248 · 346 aa · 3438001–3439041 (+) · RefSeq NP_217572.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)DNA polymerase IV 2
MTBC0 PGAP re-annotationDNA polymerase IV
Revised (this work)DNA polymerase IV. Pfam: IMS (PF00817.26), 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 P9WNT1 SwissProt · reviewed · Inferred from homology
UniProt nameDNA polymerase IV 2
EC (curated) EC 2.7.7.7
Curated functionPoorly 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 namedinP
eggNOG descriptionPoorly 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 groupCOG0389
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 0.433 · purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 6 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.32% of strains (464) · 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)

PfamAccessioni-EvalueResiduesDescription
IMSPF00817.26 6.9e-4212–159 impB/mucB/samB family
IMS_CPF11799.14 1.3e-14248–343 impB/mucB/samB family C-terminal domain

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: Rv3055 (TetR family transcriptional regulator), high confidence from genomic context alone (score 876 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0002 dnaN DNA polymerase III subunit beta 919 907 experimental:766 database:612
Rv3055 TetR family transcriptional regulator 905 876 ctx neighborhood:876
Rv2116 lppK lipoprotein LppK 861 852 experimental:627 database:612
Rv2737c recA recombinase A 897 799 experimental:439 database:523 textmining:513
Rv3054c hyp hypothetical protein 778 778 ctx neighborhood:778
Rv3395c hyp hypothetical protein 730 701 coexpression:690
Rv1629 polA DNA polymerase I 815 674 database:553 textmining:456
Rv2101 helZ helicase HelZ 706 665 database:452
Rv1329c dinG ATP-dependent helicase DinG 689 656 database:577
Rv2090 5'-3' exonuclease 655 633 database:553
Rv1278 hyp hypothetical protein 662 628 database:548
Rv3868 eccA1 ESX-1 secretion system protein EccA1 635 622 database:569
Rv3062 ligB DNA ligase 781 619 database:521 textmining:451
Rv2720 lexA repressor LexA 832 601 experimental:463 textmining:598
Rv0938 ligD multifunctional non-homologous end joining DNA repair protein/ATP dependent DNA ligase LigD 750 597 database:521 textmining:407

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 2
  • MTBC0 PGAP product: DNA polymerase IV
  • Pfam (hmmscan --cut_ga): IMS PF00817.26 (E=7e-42), IMS_C PF11799.14 (E=1e-14)
  • (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_217572.1)
  • Domains: Pfam-A via hmmscan --cut_ga — IMS (PF00817.26), 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 P9WNT1 (SwissProt, reviewed; Inferred from homology)
  • 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 — 86 functional partner(s); context anchor Rv3055
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003248|Rv3056|dinP
MPTAAPRWILHVDLDQFLASVELLRHPELAGLPVIVGGNGDPTEPRKVVTCASYEARAYGVRAGMPLRTAARRCPEATFLPSNPAAYNAASEEVVALLRDLGYPVEVWGWDEAYLAVAPGTPDDPIEVAEEIRKVILSQTGLSCSIGISDNKQRAKIATGLAKPAGIYQLTDANWMAIMGDRTVEALWGVGPKTTKRLAKLGINTVYQLAHTDSGLLMSTFGPRTALWLLLAKGGGDTEVSAQAWVPRSRSHAVTFPRDLTCRSEMESAVTELAQRTLNEVVASSRTVTRVAVTVRTATFYTRTKIRKLQAPSTDPDVITAAARHVLDLFELDRPVRLLGVRLELA