polA Resolved · high auto-curated

H37Rv Rv1629 · MTBC0 mtbc0_001737 · 904 aa · 1842629–1845343 (+) · RefSeq NP_216145.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)DNA polymerase I
MTBC0 PGAP re-annotationDNA polymerase I
Revised (this work)DNA polymerase I. Pfam: 5_3_exonuc_N (PF02739.23), 5_3_exonuc (PF01367.26), DNA_polI_exo1 (PF22619.3), DNA_pol_A (PF00476.27).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt P9WNU5 SwissProt · reviewed · Evidence at protein level
UniProt nameDNA polymerase I
EC (curated) EC 2.7.7.7
Curated functionIn addition to polymerase activity, this DNA polymerase exhibits 3'-5' and 5'-3' exonuclease activity.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
Preferred namepolA
eggNOG descriptionIn addition to polymerase activity, this DNA polymerase exhibits 5'-3' exonuclease activity
Orthologous groupCOG0258
EC number EC 2.7.7.7
KEGG orthology K02335
KEGG pathways map00230, map00240, map01100, map03030, map03410, map03420, map03440
Gene Ontology (61) GO:0003674, GO:0003824, GO:0003887, GO:0004518, GO:0004527, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005886, GO:0006139 +49 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 0.279 · purifying
Polymorphic sites (≥ 0.1% of strains) 15 synonymous, 12 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)

PfamAccessioni-EvalueResiduesDescription
5_3_exonuc_NPF02739.23 3.7e-5916–184 5'-3' exonuclease, N-terminal resolvase-like domain
5_3_exonucPF01367.26 2.6e-29186–279 5'-3' exonuclease, C-terminal SAM fold
DNA_polI_exo1PF22619.3 1.4e-08356–443 DNA polymerase I, ribonuclease H-like domain
DNA_pol_APF00476.27 1.2e-151526–900 DNA polymerase family A

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

Closest characterised functional partner: coaE (dephospho-CoA kinase CoaE), high confidence from genomic context alone (score 856 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0002 dnaN DNA polymerase III subunit beta 997 995 coexpression:414 experimental:970 database:630 textmining:508
Rv2116 lppK lipoprotein LppK 995 993 coexpression:414 experimental:970 database:630
Rv2737c recA recombinase A 996 987 coexpression:460 experimental:898 database:585 textmining:750
Rv1277 hyp hypothetical protein 989 980 experimental:836 database:844 textmining:494
Rv2529 hyp hypothetical protein 969 951 experimental:662 database:844 textmining:412
Rv1278 hyp hypothetical protein 952 919 experimental:432 database:844 textmining:430
Rv1329c dinG ATP-dependent helicase DinG 955 897 experimental:721 database:621 textmining:580
Rv2101 helZ helicase HelZ 930 863 experimental:538 database:660 textmining:513
Rv1252c lprE lipoprotein LprE 878 861 database:844
Rv1631 coaE dephospho-CoA kinase CoaE 922 856 ctx neighborhood:726 coexpression:405 textmining:488
Rv0938 ligD multifunctional non-homologous end joining DNA repair protein/ATP dependent DNA ligase LigD 949 850 experimental:454 database:569 textmining:680
Rv1630 rpsA 30S ribosomal protein S1 891 844 ctx neighborhood:710
Rv3062 ligB DNA ligase 901 842 experimental:454 database:569 textmining:405
Rv3731 ligC DNA ligase C 906 840 experimental:454 database:569 textmining:439
Rv2464c nei1 DNA glycosylase 865 816 coexpression:791

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 I
  • MTBC0 PGAP product: DNA polymerase I
  • Pfam (hmmscan --cut_ga): 5_3_exonuc_N PF02739.23 (E=4e-59), 5_3_exonuc PF01367.26 (E=3e-29), DNA_polI_exo1 PF22619.3 (E=1e-08), DNA_pol_A PF00476.27 (E=1e-151)
  • (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_216145.1)
  • Domains: Pfam-A via hmmscan --cut_ga — 5_3_exonuc_N (PF02739.23), 5_3_exonuc (PF01367.26), DNA_polI_exo1 (PF22619.3), DNA_pol_A (PF00476.27)
  • 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 COG0258
  • Curated reference: UniProt P9WNU5 (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 — 338 functional partner(s); context anchor coaE
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001737|Rv1629|polA
MVTTASAPSEDRAKPTLMLLDGNSLAFRAFYALPAENFKTRGGLTTNAVYGFTAMLINLLRDEAPTHIAAAFDVSRQTFRLQRYPEYKANRSSTPDEFAGQIDITKEVLGALGITVLSEPGFEADDLIATLATQAENEGYRVLVVTGDRDALQLVSDDVTVLYPRKGVSELTRFTPEAVVEKYGLTPRQYPDFAALRGDPSDNLPGIPGVGEKTAAKWIAEYGSLRSLVDNVDAVRGKVGDALRANLASVVRNRELTDLVRDVPLAQTPDTLRLQPWDRDHIHRLFDDLEFRVLRDRLFDTLAAAGGPEVDEGFDVRGGALAPGTVRQWLAEHAGDGRRAGLTVVGTHLPHGGDATAMAVAAADGEGAYLDTATLTPDDDAALAAWLADPAKPKALHEAKAAVHDLAGRGWTLEGVTSDTALAAYLVRPGQRSFTLDDLSLRYLRRELRAETPQQQQLSLLDDDDTDAETIQTTILRARAVIDLADALDAELARIDSTALLGEMELPVQRVLAKMESAGIAVDLPMLTELQSQFGDQIRDAAEAAYGVIGKQINLGSPKQLQVVLFDELGMPKTKRTKTGYTTDADALQSLFDKTGHPFLQHLLAHRDVTRLKVTVDGLLQAVAADGRIHTTFNQTIAATGRLSSTEPNLQNIPIRTDAGRRIRDAFVVGDGYAELMTADYSQIEMRIMAHLSGDEGLIEAFNTGEDLHSFVASRAFGVPIDEVTGELRRRVKAMSYGLAYGLSAYGLSQQLKISTEEANEQMDAYFARFGGVRDYLRAVVERARKDGYTSTVLGRRRYLPELDSSNRQVREAAERAALNAPIQGSAADIIKVAMIQVDKALNEAQLASRMLLQVHDELLFEIAPGERERVEALVRDKMGGAYPLDVPLEVSVGYGRSWDAAAH