ligD Resolved · high auto-curated
H37Rv Rv0938 · MTBC0 mtbc0_000996 ·
759 aa · 1049353–1051632 (+) ·
RefSeq NP_215453.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | multifunctional non-homologous end joining DNA repair protein/ATP dependent DNA ligase LigD |
|---|---|
| MTBC0 PGAP re-annotation | ATP-dependent DNA ligase |
| Revised (this work) | ATP-dependent DNA ligase. Pfam: LigD_Prim-Pol (PF21686.4), DNA_primase_S (PF01896.26), LigD_N (PF13298.13), 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 |
P9WNV3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Multifunctional non-homologous end joining DNA repair protein LigD |
| EC (curated) |
EC 6.5.1.1
|
| Curated function | With Ku forms a non-homologous end joining (NHEJ) repair enzyme which repairs DNA double-strand breaks (DSB) with reduced fidelity. Recognizes, processes and reseals DSBs, including repairs on incompatible DSB which require 3'-resection, gap filling and ligation. Anneals the 3' overhanging strands from opposing breaks to form a gapped intermediate, which then can be extended in trans by using the termini as primers for extension of the annealed break. Binds to the recessed 5'-phosphate moiety of the downstream DNA strand forming a stable synaptic complex even when the 3'-protruding ends of the. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
L Replication, recombination and repair
|
|---|---|
| Preferred name | ligD |
| eggNOG description | DNA ligase |
| Orthologous group | COG1793 |
| EC number |
EC 6.5.1.1, EC 6.5.1.6, EC 6.5.1.7
|
| KEGG orthology |
K01971, K10747
|
| KEGG pathways |
map03030, map03410, map03420, map03430, map03450
|
| Gene Ontology (104) |
GO:0000166, GO:0000287, GO:0000726, GO:0003674, GO:0003676, GO:0003677, GO:0003824, GO:0003887, GO:0003896, GO:0003899, GO:0003909, GO:0003910 +92 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 | 0.44 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 10 synonymous, 13 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
LigD_Prim-Pol | PF21686.4 | 5.9e-84 | 25–283 | LigD, primase-polymerase domain |
DNA_primase_S | PF01896.26 | 4.5e-08 | 136–257 | DNA primase small subunit |
LigD_N | PF13298.13 | 3.5e-40 | 329–433 | DNA Ligase D 3'-phosphoesterase domain |
DNA_ligase_A_M | PF01068.27 | 1.8e-28 | 461–637 | ATP dependent DNA ligase domain |
DNA_ligase_A_C | PF04679.22 | 4.2e-26 | 657–751 | ATP dependent DNA ligase C terminal region |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0939 (bifunctional 2-hydroxyhepta-2,4-diene-1,7-dioate isomerase/cyclase/dehydrase), high confidence from genomic context alone (score 972 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0939 |
bifunctional 2-hydroxyhepta-2,4-diene-1,7-dioate isomerase/cyclase/dehydrase | 973 | 972 ctx | neighborhood:882 coexpression:775 |
Rv0937c mku |
non-homologous end joining protein Ku | 997 | 954 ctx | neighborhood:628 cooccurence:774 coexpression:501 textmining:956 |
Rv2116 lppK |
lipoprotein LppK | 895 | 885 | experimental:629 database:609 |
Rv0002 dnaN |
DNA polymerase III subunit beta | 895 | 885 | experimental:629 database:609 |
Rv1629 polA |
DNA polymerase I | 949 | 850 | experimental:454 database:569 textmining:680 |
Rv2090 |
5'-3' exonuclease | 877 | 828 | experimental:429 database:569 |
Rv0114 gmhB |
D-glycero-alpha-D-manno-heptose-1,7-bisphosphate 7-phosphatase | 771 | 749 | database:597 |
Rv0427c xthA |
exodeoxyribonuclease III protein XthA | 763 | 738 | database:644 |
Rv1329c dinG |
ATP-dependent helicase DinG | 712 | 685 | database:604 |
Rv1277 hyp |
hypothetical protein | 712 | 681 | database:611 |
Rv1278 hyp |
hypothetical protein | 763 | 680 | database:611 |
Rv2101 helZ |
helicase HelZ | 685 | 654 | database:581 |
Rv2903c lepB |
signal peptidase | 664 | 648 | database:626 |
Rv3394c hyp |
hypothetical protein | 678 | 632 | database:521 |
Rv0667 rpoB |
DNA-directed RNA polymerase subunit beta | 638 | 622 | database:606 |
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: multifunctional non-homologous end joining DNA repair protein/ATP dependent DNA ligase LigD
- MTBC0 PGAP product: ATP-dependent DNA ligase
- Pfam (hmmscan --cut_ga): LigD_Prim-Pol PF21686.4 (E=6e-84), DNA_primase_S PF01896.26 (E=4e-08), LigD_N PF13298.13 (E=4e-40), DNA_ligase_A_M PF01068.27 (E=2e-28), DNA_ligase_A_C PF04679.22 (E=4e-26)
- (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_215453.1)
- Domains: Pfam-A via hmmscan --cut_ga — LigD_Prim-Pol (PF21686.4), DNA_primase_S (PF01896.26), LigD_N (PF13298.13), 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 P9WNV3 (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 —
77 functional partner(s); context anchor
Rv0939 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000996|Rv0938|ligD MGSASEQRVTLTNADKVLYPATGTTKSDIFDYYAGVAEVMLGHIAGRPATRKRWPNGVDQPAFFEKQLALSAPPWLSRATVAHRSGTTTYPIIDSATGLAWIAQQAALEVHVPQWRFVAEPGSGELNPGPATRLVFDLDPGEGVMMAQLAEVARAVRDLLADIGLVTFPVTSGSKGLHLYTPLDEPVSSRGATVLAKRVAQRLEQAMPALVTSTMTKSLRAGKVFVDWSQNSGSKTTIAPYSLRGRTHPTVAAPRTWAELDDPALRQLSYDEVLTRIARDGDLLERLDADAPVADRLTRYRRMRDASKTPEPIPTAKPVTGDGNTFVIQEHHARRPHYDFRLERDGVLVSWAVPKNLPDNTSVNHLAIHTEDHPLEYATFEGAIPSGEYGAGKVIIWDSGTYDTEKFHDDPHTGEVIVNLHGGRISGRYALIRTNGDRWLAHRLKNQKDQKVFEFDNLAPMLATHGTVAGLKASQWAFEGKWDGYRLLVEADHGAVRLRSRSGRDVTAEYPQLRALAEDLADHHVVLDGEAVVLDSSGVPSFSQMQNRGRDTRVEFWAFDLLYLDGRALLGTRYQDRRKLLETLANATSLTVPELLPGDGAQAFACSRKHGWEGVIAKRRDSRYQPGRRCASWVKDKHWNTQEVVIGGWRAGEGGRSSGVGSLLMGIPGPGGLQFAGRVGTGLSERELANLKEMLAPLHTDESPFDVPLPARDAKGITYVKPALVAEVRYSEWTPEGRLRQSSWRGLRPDKKPSEVVRE