lysS Resolved · high auto-curated

H37Rv Rv3598c · MTBC0 mtbc0_003817 · 505 aa · 4065127–4066644 (-) · RefSeq NP_218115.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)lysine--tRNA ligase
MTBC0 PGAP re-annotationlysine--tRNA ligase
Revised (this work)Lysine--tRNA ligase. Pfam: tRNA_anti-codon (PF01336.32), tRNA-synt_2 (PF00152.26).

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

Curated reference (UniProt)

UniProt P9WFU9 SwissProt · reviewed · Evidence at protein level
UniProt nameLysine--tRNA ligase 1
EC (curated) EC 6.1.1.6

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category J Translation, ribosomal structure and biogenesis
Preferred namelysS
eggNOG descriptionBelongs to the class-II aminoacyl-tRNA synthetase family
Orthologous groupCOG1190
EC number EC 6.1.1.6
KEGG orthology K04567
KEGG pathways map00970
KEGG modules M00359, M00360
Gene Ontology (2) GO:0008150, GO:0040007

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 0.336 · purifying
Polymorphic sites (≥ 0.1% of strains) 6 synonymous, 6 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
tRNA_anti-codonPF01336.32 1.9e-1264–140 OB-fold nucleic acid binding domain
tRNA-synt_2PF00152.26 5.8e-80156–499 tRNA synthetases class II (D, K and N)

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

Closest characterised functional partner: coaX (type III pantothenate kinase), high confidence from genomic context alone (score 800 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1640c lysX bifunctional lysine--tRNA ligase/phosphatidylglycerol lysyltransferase 924 911 database:900
Rv2992c gltS glutamate--tRNA ligase 930 903 coexpression:653 experimental:488
Rv1536 ileS isoleucine--tRNA ligase 937 848 coexpression:579 experimental:448 textmining:603
Rv3396c guaA GMP synthase 901 838 coexpression:818 textmining:418
Rv1292 argS arginine--tRNA ligase 887 835 coexpression:452 experimental:462
Rv1007c metS methionine--tRNA ligase 874 825 experimental:610
Rv2845c proS proline--tRNA ligase 889 803 coexpression:416 experimental:473 textmining:462
Rv3600c coaX type III pantothenate kinase 958 800 ctx neighborhood:773 textmining:803
Rv3603c hyp hypothetical protein 957 791 ctx neighborhood:773 textmining:803
Rv0041 leuS leucine--tRNA ligase 915 790 coexpression:401 experimental:469 textmining:616
Rv3602c panC pantothenate synthetase 881 787 ctx neighborhood:773 textmining:465
Rv3601c panD aspartate 1-decarboxylase 824 774 ctx neighborhood:773
Rv1307 atpH ATP synthase subunit b/delta 744 745 coexpression:741
Rv3105c prfB peptide chain release factor PrfB 890 739 coexpression:688 textmining:595
Rv1017c prsA ribose-phosphate pyrophosphokinase 766 737 coexpression:650

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: lysine--tRNA ligase
  • MTBC0 PGAP product: lysine--tRNA ligase
  • Pfam (hmmscan --cut_ga): tRNA_anti-codon PF01336.32 (E=2e-12), tRNA-synt_2 PF00152.26 (E=6e-80)
  • (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_218115.1)
  • Domains: Pfam-A via hmmscan --cut_ga — tRNA_anti-codon (PF01336.32), tRNA-synt_2 (PF00152.26)
  • 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 COG1190
  • Curated reference: UniProt P9WFU9 (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 — 150 functional partner(s); context anchor coaX
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003817|Rv3598c|lysS
MSAADTAEDLPEQFRIRRDKRARLLAQGRDPYPVAVPRTHTLAEVRAAHPDLPIDTATEDIVGVAGRVIFARNSGKLCFATLQDGDGTQLQVMISLDKVGQAALDAWKADVDLGDIVYVHGAVISSRRGELSVLADCWRIAAKSLRPLPVAHKEMSEESRVRQRYVDLIVRPEARAVARLRIAVVRAIRTALQRRGFLEVETPVLQTLAGGAAARPFATHSNALDIDLYLRIAPELFLKRCIVGGFDKVFELNRVFRNEGADSTHSPEFSMLETYQTYGTYDDSAVVTRELIQEVADEAIGTRQLPLPDGSVYDIDGEWATIQMYPSLSVALGEEITPQTTVDRLRGIADSLGLEKDPAIHDNRGFGHGKLIEELWERTVGKSLSAPTFVKDFPVQTTPLTRQHRSIPGVTEKWDLYLRGIELATGYSELSDPVVQRERFADQARAAAAGDDEAMVLDEDFLAALEYGMPPCTGTGMGIDRLLMSLTGLSIRETVLFPIVRPHSN