ligA Resolved · high auto-curated
H37Rv Rv3014c · MTBC0 mtbc0_003203 ·
691 aa · 3393854–3395929 (-) ·
RefSeq NP_217530.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | DNA ligase A |
|---|---|
| MTBC0 PGAP re-annotation | NAD-dependent DNA ligase LigA |
| Revised (this work) | NAD-dependent DNA ligase LigA. Pfam: Nlig-Ia (PF22745.3), DNA_ligase_aden (PF01653.24), OB_DNA_ligase (PF03120.23), DNA_ligase_ZBD (PF03119.22), HHH_2 (PF12826.14), HHH_5 (PF14520.13), HHH (PF00633.30), BRCT (PF00533.34), PTCB-BRCT (PF12738.14). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WNV1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | DNA ligase A |
| EC (curated) |
EC 6.5.1.2
|
| Curated function | DNA ligase that catalyzes the formation of phosphodiester linkages between 5'-phosphoryl and 3'-hydroxyl groups in double-stranded DNA using NAD as a coenzyme and as the energy source for the reaction. It is essential for DNA replication and repair of damaged DNA. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
L Replication, recombination and repair
|
|---|---|
| Preferred name | ligA |
| eggNOG description | DNA ligase that catalyzes the formation of phosphodiester linkages between 5'-phosphoryl and 3'-hydroxyl groups in double-stranded DNA using NAD as a coenzyme and as the energy source for the reaction. It is essential for DNA replication and repair of damaged DNA |
| Orthologous group | COG0272 |
| EC number |
EC 6.5.1.2
|
| KEGG orthology |
K01972
|
| KEGG pathways |
map03030, map03410, map03420, map03430
|
| Gene Ontology (52) |
GO:0000287, GO:0003674, GO:0003824, GO:0003909, GO:0003911, GO:0005488, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829 +40 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 | 0.249 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 10 synonymous, 7 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 |
|---|---|---|---|---|
Nlig-Ia | PF22745.3 | 4.3e-25 | 12–72 | DNA ligase-like, N-terminal NAD+-binding domain |
DNA_ligase_aden | PF01653.24 | 1.8e-96 | 78–328 | NAD-dependent DNA ligase adenylation domain |
OB_DNA_ligase | PF03120.23 | 2.5e-31 | 331–408 | NAD-dependent DNA ligase OB-fold domain |
DNA_ligase_ZBD | PF03119.22 | 1.4e-09 | 417–444 | NAD-dependent DNA ligase C4 zinc finger domain |
HHH_2 | PF12826.14 | 7.6e-23 | 527–590 | Helix-hairpin-helix motif |
HHH_5 | PF14520.13 | 1.1e-08 | 532–577 | Helix-hairpin-helix domain |
HHH | PF00633.30 | 1.9e-05 | 551–579 | Helix-hairpin-helix motif |
BRCT | PF00533.34 | 1.4e-14 | 609–682 | BRCA1 C Terminus (BRCT) domain |
PTCB-BRCT | PF12738.14 | 6.6e-08 | 618–674 | twin BRCT domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ruvB (Holliday junction ATP-dependent DNA helicase RuvB), medium confidence from genomic context alone (score 612 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1407 fmu |
16S rRNA m5C967 methyltransferase | 913 | 908 | coexpression:893 |
Rv3062 ligB |
DNA ligase | 993 | 902 | database:900 textmining:932 |
Rv3015c hyp |
hypothetical protein | 748 | 748 ctx | neighborhood:740 |
Rv0041 leuS |
leucine--tRNA ligase | 774 | 706 | experimental:694 |
Rv2592c ruvB |
Holliday junction ATP-dependent DNA helicase RuvB | 823 | 612 ctx | cooccurence:612 textmining:564 |
Rv0949 uvrD1 |
ATP-dependent DNA helicase UvrD | 711 | 588 | coexpression:484 |
Rv2152c murC |
UDP-N-acetylmuramate--alanine ligase | 690 | 586 | coexpression:414 |
Rv1650 pheT |
phenylalanine--tRNA ligase subunit beta | 553 | 554 | coexpression:433 |
Rv2841c nusA |
transcription termination/antitermination protein NusA | 542 | 543 | coexpression:429 |
Rv3016 lpqA |
lipoprotein LpqA | 526 | 526 ctx | neighborhood:525 |
Rv2153c murG |
UDP-N-acetylglucosamine--N-acetylmuramyl-(pentapeptide) pyrophosphoryl-undecaprenol-N-acetylglucosamine transferase | 524 | 524 | coexpression:401 |
Rv3012c gatC |
glutamyl-tRNA(GLN) amidotransferase subunit C | 522 | 522 | coexpression:442 |
Rv3009c gatB |
aspartyl/glutamyl-tRNA(Asn/Gln) amidotransferase subunit B | 565 | 515 | coexpression:433 |
Rv3202c adnA |
ATP-dependent DNA helicase | 554 | 512 | coexpression:484 |
Rv3201c adnB |
ATP-dependent DNA helicase | 554 | 512 | coexpression:484 |
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 A
- MTBC0 PGAP product: NAD-dependent DNA ligase LigA
- Pfam (hmmscan --cut_ga): Nlig-Ia PF22745.3 (E=4e-25), DNA_ligase_aden PF01653.24 (E=2e-96), OB_DNA_ligase PF03120.23 (E=3e-31), DNA_ligase_ZBD PF03119.22 (E=1e-09), HHH_2 PF12826.14 (E=8e-23), HHH_5 PF14520.13 (E=1e-08), HHH PF00633.30 (E=2e-05), BRCT PF00533.34 (E=1e-14), PTCB-BRCT PF12738.14 (E=7e-08)
- (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_217530.1)
- Domains: Pfam-A via hmmscan --cut_ga — Nlig-Ia (PF22745.3), DNA_ligase_aden (PF01653.24), OB_DNA_ligase (PF03120.23), DNA_ligase_ZBD (PF03119.22), HHH_2 (PF12826.14), HHH_5 (PF14520.13), HHH (PF00633.30), BRCT (PF00533.34), PTCB-BRCT (PF12738.14)
- 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
COG0272 - Curated reference: UniProt P9WNV1 (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 —
85 functional partner(s); context anchor
ruvB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003203|Rv3014c|ligA MSSPDADQTAPEVLRQWQALAEEVREHQFRYYVRDAPIISDAEFDELLRRLEALEEQHPELRTPDSPTQLVGGAGFATDFEPVDHLERMLSLDNAFTADELAAWAGRIHAEVGDAAHYLCELKIDGVALSLVYREGRLTRASTRGDGRTGEDVTLNARTIADVPERLTPGDDYPVPEVLEVRGEVFFRLDDFQALNASLVEEGKAPFANPRNSAAGSLRQKDPAVTARRRLRMICHGLGHVEGFRPATLHQAYLALRAWGLPVSEHTTLATDLAGVRERIDYWGEHRHEVDHEIDGVVVKVDEVALQRRLGSTSRAPRWAIAYKYPPEEAQTKLLDIRVNVGRTGRITPFAFMTPVKVAGSTVGQATLHNASEIKRKGVLIGDTVVIRKAGDVIPEVLGPVVELRDGSEREFIMPTTCPECGSPLAPEKEGDADIRCPNARGCPGQLRERVFHVASRNGLDIEVLGYEAGVALLQAKVIADEGELFALTERDLLRTDLFRTKAGELSANGKRLLVNLDKAKAAPLWRVLVALSIRHVGPTAARALATEFGSLDAIAAASTDQLAAVEGVGPTIAAAVTEWFAVDWHREIVDKWRAAGVRMVDERDESVPRTLAGLTIVVTGSLTGFSRDDAKEAIVARGGKAAGSVSKKTNYVVAGDSPGSKYDKAVELGVPILDEDGFRRLLADGPASRT