ligC Resolved · high auto-curated

H37Rv Rv3731 · MTBC0 mtbc0_003956 · 358 aa · 4205879–4206955 (+) · RefSeq NP_218248.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)DNA ligase C
MTBC0 PGAP re-annotationATP-dependent DNA ligase
Revised (this work)ATP-dependent DNA ligase. Pfam: DNA_ligase_A_M (PF01068.27), DNA_ligase_A_C (PF04679.22).

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

Curated reference (UniProt)

UniProt L0TDE1 SwissProt · reviewed · Evidence at protein level
UniProt nameDNA ligase C
EC (curated) EC 6.5.1.1
Curated functionDNA ligase that seals nicks in double-stranded DNA during DNA replication, DNA recombination and DNA repair.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
Preferred nameligC
eggNOG descriptionDNA ligase
Orthologous groupCOG1793
Gene Ontology (48) GO:0003674, GO:0003824, GO:0003909, GO:0003910, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0006139, GO:0006259, GO:0006260, GO:0006261 +36 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 0.278 · 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
DNA_ligase_A_MPF01068.27 3.4e-4411–201 ATP dependent DNA ligase domain
DNA_ligase_A_CPF04679.22 3.0e-12221–332 ATP dependent DNA ligase C terminal region

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

Closest characterised functional partner: mku (non-homologous end joining protein Ku), high confidence from genomic context alone (score 840 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3730c ligD hyp hypothetical protein 996 995 ctx neighborhood:789 fusion:895 cooccurence:773
Rv0269c hyp hypothetical protein 981 975 ctx fusion:878 cooccurence:773
Rv2116 lppK lipoprotein LppK 893 887 experimental:629 database:609
Rv0002 dnaN DNA polymerase III subunit beta 892 886 experimental:629 database:609
Rv2090 5'-3' exonuclease 858 849 experimental:429 database:569
Rv0937c mku non-homologous end joining protein Ku 983 840 ctx cooccurence:765 textmining:901
Rv1629 polA DNA polymerase I 906 840 experimental:454 database:569 textmining:439
Rv0114 gmhB D-glycero-alpha-D-manno-heptose-1,7-bisphosphate 7-phosphatase 761 737 database:597
Rv0427c xthA exodeoxyribonuclease III protein XthA 726 699 database:644
Rv1278 hyp hypothetical protein 711 680 database:611
Rv1329c dinG ATP-dependent helicase DinG 707 680 database:604
Rv1277 hyp hypothetical protein 708 677 database:611
Rv2828A hyp hypothetical protein 657 657 ctx cooccurence:657
Rv2101 helZ helicase HelZ 675 643 database:581
Rv2903c lepB signal peptidase 654 638 database:626

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 ligase C
  • MTBC0 PGAP product: ATP-dependent DNA ligase
  • Pfam (hmmscan --cut_ga): DNA_ligase_A_M PF01068.27 (E=3e-44), DNA_ligase_A_C PF04679.22 (E=3e-12)
  • (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_218248.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DNA_ligase_A_M (PF01068.27), DNA_ligase_A_C (PF04679.22)
  • 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 COG1793
  • Curated reference: UniProt L0TDE1 (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 — 73 functional partner(s); context anchor mku
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003956|Rv3731|ligC
MQLPVMPPVSPMLAKSVTAIPPDASYEPKWDGFRSICFRDGDQVELGSRNERPMTRYFPELVAAIRAELPHRCVIDGEIIIATDHGLDFEALQQRIHPAESRVRMLADRTPASFIAFDLLALGDDDYTGRPFSERRAALVDAVTGSGADADLSIHVTPATTDMATAQRWFSEFEGAGLDGVIAKPPHITYQPDKRVMFKIKHLRTADCVVAGYRVHKSGSDAIGSLLLGLYQEDGQLASVGVIGAFPMAERRRLLTELQPLVTSFDDHPWNWAAHVAGQRTPRKNEFSRWNVGKDLSFVPLRPERVVEVRYDHMEGARFRHTAQFNRWRPDRDPRSCSYAQLERPLTVSLSDIVPGLR