ligD Resolved · high auto-curated

H37Rv Rv3730c · MTBC0 mtbc0_003955 · 346 aa · 4204801–4205841 (-) · RefSeq NP_218247.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationnon-homologous end-joining DNA ligase
Revised (this work)Non-homologous end-joining DNA ligase. Pfam: LigD_Prim-Pol (PF21686.4), DNA_primase_S (PF01896.26).

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

Curated reference (UniProt)

UniProt O69697 TrEMBL · unreviewed · Evidence at protein level
UniProt nameDNA ligase D polymerase domain-containing protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
Preferred nameligD
eggNOG descriptionDNA primase
Orthologous groupCOG3285

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 0.552 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 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
LigD_Prim-PolPF21686.4 5.5e-8833–287 LigD, primase-polymerase domain
DNA_primase_SPF01896.26 4.1e-10138–260 DNA primase small subunit

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

Closest characterised functional partner: ligC (DNA ligase C), high confidence from genomic context alone (score 995 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3731 ligC DNA ligase C 996 995 ctx neighborhood:789 fusion:895 cooccurence:773
Rv0937c mku non-homologous end joining protein Ku 927 864 ctx cooccurence:773 coexpression:404 textmining:489
Rv3062 ligB DNA ligase 739 647 ctx cooccurence:633
Rv2828A hyp hypothetical protein 456 456 ctx cooccurence:455
Rv3296 lhr ATP-dependent helicase 439 439 ctx cooccurence:434
Rv3732 hyp hypothetical protein 421 420 ctx neighborhood:415
Rv3014c ligA DNA ligase A 413 44 textmining:412
Rv2737c recA recombinase A 407 44 textmining:406

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: hypothetical protein
  • MTBC0 PGAP product: non-homologous end-joining DNA ligase
  • Pfam (hmmscan --cut_ga): LigD_Prim-Pol PF21686.4 (E=5e-88), DNA_primase_S PF01896.26 (E=4e-10)
  • (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_218247.1)
  • Domains: Pfam-A via hmmscan --cut_ga — LigD_Prim-Pol (PF21686.4), DNA_primase_S (PF01896.26)
  • 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 COG3285
  • Curated reference: UniProt O69697 (TrEMBL, unreviewed; 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 — 8 functional partner(s); context anchor ligC
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003955|Rv3730c|ligD
MAAAAEELDVDGIAVRLTSPDRMYFPKLGSHGTKRRLVEYYFAVAGGPMLTALRDRPTHLQRFPDGVDGEQIYQKRIPRHRPDYLQTCRVTFPSGRMADALKVTHPAAIVWAAQMGTITLHPWQVRCPDTEHPDELRIDLDPQPGTGFVEARTVAVDVLRSVLDDLGLVGYPKTSGGRGIHVFLRIATDWDFVEVRRAGIALAREVERRAPDAVTTSWWKEERGARIFIDFNQNARDRTMASAYSVRPTPIATVSMPLTWEELAGADPDDYTMTTVPELVKIRDDPWAGMDDVAQSIAPLLDLAAADEERGLGDMPYPPNYPKMPGEPKRVQPSRDTDLKGGNTSK