metS Resolved · high auto-curated

H37Rv Rv1007c · MTBC0 mtbc0_001082 · 519 aa · 1132780–1134339 (-) · RefSeq NP_215523.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)methionine--tRNA ligase
MTBC0 PGAP re-annotationmethionine--tRNA ligase
Revised (this work)Methionine--tRNA ligase. Pfam: tRNA-synt_1g (PF09334.18), tRNA-synt_1 (PF00133.29), Anticodon_3 (PF19303.6).

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

Curated reference (UniProt)

UniProt P9WFU5 SwissProt · reviewed · Evidence at protein level
UniProt nameMethionine--tRNA ligase
EC (curated) EC 6.1.1.10
Curated functionCatalyzes the attachment of L-methionine to tRNA(Met). Is required not only for elongation of protein synthesis but also for the initiation of all mRNA translation through initiator tRNA(fMet) aminoacylation.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category J Translation, ribosomal structure and biogenesis
Preferred namemetG
eggNOG descriptionIs required not only for elongation of protein synthesis but also for the initiation of all mRNA translation through initiator tRNA(fMet) aminoacylation
Orthologous groupCOG0143
EC number EC 6.1.1.10
KEGG orthology K01874
KEGG pathways map00450, map00970
KEGG modules M00359, M00360
Gene Ontology (61) GO:0003674, GO:0003824, GO:0004812, GO:0004825, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005886, GO:0006082, GO:0006139, GO:0006399 +49 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 0.27 · purifying
Polymorphic sites (≥ 0.1% of strains) 6 synonymous, 4 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.11% of strains (162) · clonal

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-synt_1gPF09334.18 6.3e-64149–362 tRNA synthetases class I (M)
tRNA-synt_1PF00133.29 1.2e-13222–335 tRNA synthetases class I (I, L, M and V)
Anticodon_3PF19303.6 8.0e-10374–508 Anticodon binding domain of methionyl tRNA ligase

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

Closest characterised functional partner: tatD (deoxyribonuclease TatD), high confidence from genomic context alone (score 970 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2992c gltS glutamate--tRNA ligase 992 972 experimental:896 database:518 textmining:754
Rv0041 leuS leucine--tRNA ligase 996 970 coexpression:667 experimental:792 database:571 textmining:875
Rv1008 tatD deoxyribonuclease TatD 969 970 ctx neighborhood:783 fusion:723
Rv1292 argS arginine--tRNA ligase 962 947 experimental:814 database:571
Rv1536 ileS isoleucine--tRNA ligase 980 933 experimental:784 database:571 textmining:717
Rv2124c metH methionine synthase 921 914 database:900
Rv2845c proS proline--tRNA ligase 990 907 coexpression:425 experimental:629 database:571 textmining:900
Rv1133c metE 5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferase 905 901 database:900
Rv1406 fmt methionyl-tRNA formyltransferase 912 900 database:900
Rv1640c lysX bifunctional lysine--tRNA ligase/phosphatidylglycerol lysyltransferase 880 839 experimental:610
Rv3598c lysS lysine--tRNA ligase 874 825 experimental:610
Rv1650 pheT phenylalanine--tRNA ligase subunit beta 894 772 coexpression:739 textmining:554
Rv1009 rpfB resuscitation-promoting factor RpfB 621 621 ctx neighborhood:619
Rv2555c alaS alanine--tRNA ligase 670 569 coexpression:470
Rv2614c thrS threonine--tRNA ligase 931 566 experimental:428 textmining:849

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: methionine--tRNA ligase
  • MTBC0 PGAP product: methionine--tRNA ligase
  • Pfam (hmmscan --cut_ga): tRNA-synt_1g PF09334.18 (E=6e-64), tRNA-synt_1 PF00133.29 (E=1e-13), Anticodon_3 PF19303.6 (E=8e-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_215523.1)
  • Domains: Pfam-A via hmmscan --cut_ga — tRNA-synt_1g (PF09334.18), tRNA-synt_1 (PF00133.29), Anticodon_3 (PF19303.6)
  • 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 COG0143
  • Curated reference: UniProt P9WFU5 (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 — 71 functional partner(s); context anchor tatD
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001082|Rv1007c|metS
MKPYYVTTAIAYPNAAPHVGHAYEYIATDAIARFKRLDGYDVRFLTGTDEHGLKVAQAAAAAGVPTAALARRNSDVFQRMQEALNISFDRFIRTTDADHHEASKELWRRMSAAGDIYLDNYSGWYSVRDERFFVESETQLVDGTRLTVETGTPVTWTEEQTYFFRLSAYTDKLLAHYHANPDFIAPETRRNEVISFVSGGLDDLSISRTSFDWGVQVPEHPDHVMYVWVDALTNYLTGAGFPDTDSELFRRYWPADLHMIGKDIIRFHAVYWPAFLMSAGIELPRRIFAHGFLHNRGEKMSKSVGNIVDPVALAEALGVDQVRYFLLREVPFGQDGSYSDEAIVTRINTDLANELGNLAQRSLSMVAKNLDGRVPNPGEFADADAALLATADGLLERVRGHFDAQAMHLALEAIWLMLGDANKYFSVQQPWVLRKSESEADQARFRTTLYVTCEVVRIAALLIQPVMPESAGKILDLLGQAPNQRSFAAVGVRLTPGTALPPPTGVFPRYQPPQPPEGK