dnaG Resolved · high auto-curated

H37Rv Rv2343c · MTBC0 mtbc0_002495 · 639 aa · 2645283–2647202 (-) · RefSeq NP_216859.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)DNA primase
MTBC0 PGAP re-annotationDNA primase
Revised (this work)DNA primase. Pfam: Zn_ribbon_DnaG (PF01807.26), DNAG_N (PF08275.18), Toprim_4 (PF13662.13), Toprim (PF01751.29), Toprim_2 (PF13155.13), DnaB_bind (PF10410.15), DnaG_DnaB_bind (PF08278.17).

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

Curated reference (UniProt)

UniProt P9WNW1 SwissProt · reviewed · Evidence at protein level
UniProt nameDNA primase
EC (curated) EC 2.7.7.101
Curated functionRNA polymerase that catalyzes the synthesis of short RNA molecules used as primers for DNA polymerase during DNA replication.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
Preferred namednaG
eggNOG descriptionRNA polymerase that catalyzes the synthesis of short RNA molecules used as primers for DNA polymerase during DNA replication
Orthologous groupCOG0358
KEGG orthology K02316
KEGG pathways map03030
Gene Ontology (8) GO:0005575, GO:0005623, GO:0005886, GO:0008150, GO:0016020, 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 0.28 · purifying
Polymorphic sites (≥ 0.1% of strains) 6 synonymous, 5 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
Zn_ribbon_DnaGPF01807.26 2.0e-346–100 CHC2 zinc finger
DNAG_NPF08275.18 2.1e-36127–255 DNA primase catalytic core, N-terminal domain
Toprim_4PF13662.13 1.3e-12263–333 Toprim domain
ToprimPF01751.29 5.7e-08264–332 Toprim domain
Toprim_2PF13155.13 7.9e-11265–355 Toprim-like
DnaB_bindPF10410.15 1.9e-19376–429 DnaB-helicase binding domain of primase
DnaG_DnaB_bindPF08278.17 2.3e-34487–614 DNA primase DnaG DnaB-binding

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

Closest characterised functional partner: dgt (deoxyguanosine triphosphate triphosphohydrolase), high confidence from genomic context alone (score 899 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0058 dnaB replicative DNA helicase 995 983 experimental:916 database:540 textmining:735
Rv2344c dgt deoxyguanosine triphosphate triphosphohydrolase 938 899 ctx neighborhood:881 textmining:411
Rv1713 engA GTPase Der 873 866 coexpression:863
Rv1340 rphA ribonuclease PH 852 824 experimental:821
Rv2703 sigA RNA polymerase sigma factor SigA 833 811 ctx cooccurence:426 coexpression:646
Rv2710 sigB RNA polymerase sigma factor SigB 817 793 coexpression:644
Rv1406 fmt methionyl-tRNA formyltransferase 750 739 ctx cooccurence:555 coexpression:405
Rv1547 dnaE1 DNA polymerase III subunit alpha 864 694 ctx cooccurence:610 textmining:576
Rv2345 transmembrane protein 676 676 ctx neighborhood:673
Rv1650 pheT phenylalanine--tRNA ligase subunit beta 753 647 ctx cooccurence:563
Rv3201c adnB ATP-dependent DNA helicase 653 622
Rv3644c DNA polymerase 661 616 ctx cooccurence:595
Rv1629 polA DNA polymerase I 897 611 textmining:748
Rv0002 dnaN DNA polymerase III subunit beta 680 603 ctx cooccurence:590
Rv2906c trmD tRNA (guanine-N1)-methyltransferase 596 570 ctx cooccurence:497

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 primase
  • MTBC0 PGAP product: DNA primase
  • Pfam (hmmscan --cut_ga): Zn_ribbon_DnaG PF01807.26 (E=2e-34), DNAG_N PF08275.18 (E=2e-36), Toprim_4 PF13662.13 (E=1e-12), Toprim PF01751.29 (E=6e-08), Toprim_2 PF13155.13 (E=8e-11), DnaB_bind PF10410.15 (E=2e-19), DnaG_DnaB_bind PF08278.17 (E=2e-34)
  • (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_216859.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Zn_ribbon_DnaG (PF01807.26), DNAG_N (PF08275.18), Toprim_4 (PF13662.13), Toprim (PF01751.29), Toprim_2 (PF13155.13), DnaB_bind (PF10410.15), DnaG_DnaB_bind (PF08278.17)
  • 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 COG0358
  • Curated reference: UniProt P9WNW1 (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 — 126 functional partner(s); context anchor dgt
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002495|Rv2343c|dnaG
MSGRISDRDIAAIREGARIEDVVGDYVQLRRAGADSLKGLCPFHNEKSPSFHVRPNHGHFHCFGCGEGGDVYAFIQKIEHVSFVEAVELLADRIGHTISYTGAATSVQRDRGSRSRLLAANAAAAAFYAQALQSDEAAPARQYLTERSFDAAAARKFGCGFAPSGWDSLTKHLQRKGFEFEELEAAGLSRQGRHGPMDRFHRRLLWPIRTSAGEVVGFGARRLFDDDAMEAKYVNTPETLLYKKSSVMFGIDLAKRDIAKGHQAVVVEGYTDVMAMHLAGVTTAVASCGTAFGGEHLAMLRRLMMDDSFFRGELIYVFDGDEAGRAAALKAFDGEQKLAGQSFVAVAPDGMDPCDLRLKCGDAALRDLVARRTPLFEFAIRAAIAEMDLDSAEGRVAALRRCVPMVGQIKDPTLRDEYARQLAGWVGWADVAQVIGRVRGEAKRTKHPRLGRLGSTTIARAAQRPTAGPPTELAVRPDPRDPTLWPQREALKSALQYPALAGPVFDALTVEGFTHPEYAAVRAAIDTAGGTSAGLSGAQWLDMVRQQTTSTVTSALISELGVEAIQVDDDKLPRYIAGVLARLQEVWLGRQIAEVKSKLQRMSPIEQGDEYHALFGDLVAMEAYRRSLLEQASGDDLTA