ileS Resolved · high auto-curated

H37Rv Rv1536 · MTBC0 mtbc0_001643 · 1041 aa · 1746328–1749453 (+) · RefSeq NP_216052.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)isoleucine--tRNA ligase
MTBC0 PGAP re-annotationisoleucine--tRNA ligase
Revised (this work)Isoleucine--tRNA ligase. Pfam: tRNA-synt_1 (PF00133.29), tRNA-synt_1g (PF09334.18), Anticodon_1 (PF08264.20), DUF5915 (PF19302.5).

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

Curated reference (UniProt)

UniProt P9WFV3 SwissProt · reviewed · Evidence at protein level
UniProt nameIsoleucine--tRNA ligase
EC (curated) EC 6.1.1.5
Curated functionCatalyzes the attachment of isoleucine to tRNA(Ile). As IleRS can inadvertently accommodate and process structurally similar amino acids such as valine, to avoid such errors it has two additional distinct tRNA(Ile)-dependent editing activities. One activity is designated as 'pretransfer' editing and involves the hydrolysis of activated Val-AMP. The other activity is designated 'posttransfer' editing and involves deacylation of mischarged Val-tRNA(Ile) (By similarity)..; FUNCTION: Confers high-level resistance to the antibiotic mupirocin (pseudomonic acid A), an Ile-analog that competitively in.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category J Translation, ribosomal structure and biogenesis
Preferred nameileS
eggNOG descriptionamino acids such as valine, to avoid such errors it has two additional distinct tRNA(Ile)-dependent editing activities. One activity is designated as 'pretransfer' editing and involves the hydrolysis of activated Val-AMP. The other activity is designated 'posttransfer' editing and involves deacylation of mischarged Val-tRNA(Ile)
Orthologous groupCOG0060
EC number EC 6.1.1.5
KEGG orthology K01870
KEGG pathways map00970
KEGG modules M00359, M00360
Gene Ontology (62) GO:0003674, GO:0003824, GO:0004812, GO:0004822, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005886, GO:0006082, GO:0006139 +50 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 0.351 · purifying
Polymorphic sites (≥ 0.1% of strains) 14 synonymous, 15 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-synt_1PF00133.29 1.0e-12423–653 tRNA synthetases class I (I, L, M and V)
tRNA-synt_1gPF09334.18 3.7e-0653–116 tRNA synthetases class I (M)
Anticodon_1PF08264.20 4.1e-25701–841 Anticodon-binding domain of tRNA ligase
DUF5915PF19302.5 3.4e-23857–1026 Domain of unknown function (DUF5915)

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

Closest characterised functional partner: gltB (glutamate synthase large subunit), medium confidence from genomic context alone (score 660 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2845c proS proline--tRNA ligase 993 987 coexpression:763 experimental:875 database:597 textmining:513
Rv2992c gltS glutamate--tRNA ligase 991 973 coexpression:432 experimental:898 database:546 textmining:700
Rv0041 leuS leucine--tRNA ligase 997 960 coexpression:661 experimental:598 database:597 textmining:930
Rv1292 argS arginine--tRNA ligase 993 958 coexpression:513 experimental:788 database:597 textmining:851
Rv1650 pheT phenylalanine--tRNA ligase subunit beta 980 958 coexpression:916 textmining:554
Rv1007c metS methionine--tRNA ligase 980 933 experimental:784 database:571 textmining:717
Rv1640c lysX bifunctional lysine--tRNA ligase/phosphatidylglycerol lysyltransferase 962 849 coexpression:581 experimental:448 textmining:763
Rv3598c lysS lysine--tRNA ligase 937 848 coexpression:579 experimental:448 textmining:603
Rv2448c valS valine--tRNA ligase 908 828 coexpression:775 textmining:492
Rv2555c alaS alanine--tRNA ligase 821 767 coexpression:646
Rv2357c glyS glycine--tRNA ligase 890 698 textmining:653
Rv3859c gltB glutamate synthase large subunit 661 660 ctx neighborhood:544
Rv2572c aspS aspartate--tRNA ligase 908 649 coexpression:648 textmining:751
Rv1689 tyrS tyrosine--tRNA ligase 934 634 coexpression:544 textmining:829
Rv2614c thrS threonine--tRNA ligase 939 600 textmining:856

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: isoleucine--tRNA ligase
  • MTBC0 PGAP product: isoleucine--tRNA ligase
  • Pfam (hmmscan --cut_ga): tRNA-synt_1 PF00133.29 (E=1e-124), tRNA-synt_1g PF09334.18 (E=4e-06), Anticodon_1 PF08264.20 (E=4e-25), DUF5915 PF19302.5 (E=3e-23)
  • (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_216052.1)
  • Domains: Pfam-A via hmmscan --cut_ga — tRNA-synt_1 (PF00133.29), tRNA-synt_1g (PF09334.18), Anticodon_1 (PF08264.20), DUF5915 (PF19302.5)
  • 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 COG0060
  • Curated reference: UniProt P9WFV3 (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 — 102 functional partner(s); context anchor gltB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001643|Rv1536|ileS
MTDNAYPKLAGGAPDLPALELEVLDYWSRDDTFRASIARRDGAPEYVFYDGPPFANGLPHYGHLLTGYVKDIVPRYRTMRGYKVERRFGWDTHGLPAELEVERQLGITDKSQIEAMGIAAFNDACRASVLRYTDEWQAYVTRQARWVDFDNDYKTLDLAYMESVIWAFKQLWDKGLAYEGYRVLPYCWRDETPLSNHELRMDDDVYQSRQDPAVTVGFKVVGGQPDNGLDGAYLLVWTTTPWTLPSNLAVAVSPDITYVQVQAGDRRFVLAEARLAAYARELGEEPVVLGTYRGAELLGTRYLPPFAYFMDWPNAFQVLAGDFVTTDDGTGIVHMAPAYGEDDMVVAEAVGIAPVTPVDSKGRFDVTVADYQGQHVFDANAQIVRDLKTQSGPAAVNGPVLIRHETYEHPYPHCWRCRNPLIYRSVSSWFVRVTDFRDRMVELNQQITWYPEHVKDGQFGKWLQGARDWSISRNRYWGTPIPVWKSDDPAYPRIDVYGSLDELERDFGVRPANLHRPYIDELTRPNPDDPTGRSTMRRIPDVLDVWFDSGSMPYAQVHYPFENLDWFQGHYPGDFIVEYIGQTRGWFYTLHVLATALFDRPAFKTCVAHGIVLGFDGQKMSKSLRNYPDVTEVFDRDGSDAMRWFLMASPILRGGNLIVTEQGIRDGVRQVLLPLWNTYSFLALYAPKVGTWRVDSVHVLDRYILAKLAVLRDDLSESMEVYDIPGACEHLRQFTEALTNWYVRRSRSRFWAEDADAIDTLHTVLEVTTRLAAPLLPLITEIIWRGLTRERSVHLTDWPAPDLLPSDADLVAAMDQVRDVCSAASSLRKAKKLRVRLPLPKLIVAVENPQLLRPFVDLIGDELNVKQVELTDAIDTYGRFELTVNARVAGPRLGKDVQAAIKAVKAGDGVINPDGTLLAGPAVLTPDEYNSRLVAADPESTAALPDGAGLVVLDGTVTAELEAEGWAKDRIRELQELRKSTGLDVSDRIRVVMSVPAEREDWARTHRDLIAGEILATDFEFADLADGVAIGDGVRVSIEKT