leuS Resolved · high auto-curated
H37Rv Rv0041 · MTBC0 mtbc0_000046 ·
969 aa · 43661–46570 (+) ·
RefSeq NP_214555.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | leucine--tRNA ligase |
|---|---|
| MTBC0 PGAP re-annotation | leucine--tRNA ligase |
| Revised (this work) | Leucine--tRNA ligase. Pfam: tRNA-synt_1 (PF00133.29), tRNA-synt_1g (PF09334.18), tRNA-synt_1_2 (PF13603.13), Anticodon_1 (PF08264.20). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WFV1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Leucine--tRNA ligase |
| EC (curated) |
EC 6.1.1.4
|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
J Translation, ribosomal structure and biogenesis
|
|---|---|
| Preferred name | leuS |
| eggNOG description | Belongs to the class-I aminoacyl-tRNA synthetase family |
| Orthologous group | COG0495 |
| EC number |
EC 6.1.1.4
|
| KEGG orthology |
K01869
|
| KEGG pathways |
map00970
|
| KEGG modules |
M00359, M00360
|
| Gene Ontology (65) |
GO:0003674, GO:0003824, GO:0004812, GO:0004823, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0006082 +53 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 | 0.355 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 13 synonymous, 14 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 |
|---|---|---|---|---|
tRNA-synt_1 | PF00133.29 | 2.8e-05 | 73–141 | tRNA synthetases class I (I, L, M and V) |
tRNA-synt_1g | PF09334.18 | 5.2e-12 | 75–182 | tRNA synthetases class I (M) |
tRNA-synt_1_2 | PF13603.13 | 4.9e-54 | 305–504 | Leucyl-tRNA synthetase, editing domain |
Anticodon_1 | PF08264.20 | 3.1e-15 | 818–933 | Anticodon-binding domain of tRNA ligase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0039c (transmembrane protein), high confidence from genomic context alone (score 702 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1007c metS |
methionine--tRNA ligase | 996 | 970 | coexpression:667 experimental:792 database:571 textmining:875 |
Rv1650 pheT |
phenylalanine--tRNA ligase subunit beta | 994 | 970 | coexpression:965 textmining:825 |
Rv1536 ileS |
isoleucine--tRNA ligase | 997 | 960 | coexpression:661 experimental:598 database:597 textmining:930 |
Rv2992c gltS |
glutamate--tRNA ligase | 989 | 958 | coexpression:421 experimental:851 database:546 textmining:770 |
Rv1292 argS |
arginine--tRNA ligase | 994 | 919 | coexpression:411 experimental:675 database:597 textmining:940 |
Rv1354c hyp |
hypothetical protein | 900 | 897 | experimental:875 |
Rv2845c proS |
proline--tRNA ligase | 930 | 868 | coexpression:415 experimental:467 database:597 textmining:494 |
Rv2448c valS |
valine--tRNA ligase | 973 | 819 | coexpression:749 textmining:861 |
Rv1640c lysX |
bifunctional lysine--tRNA ligase/phosphatidylglycerol lysyltransferase | 894 | 794 | experimental:469 textmining:510 |
Rv3598c lysS |
lysine--tRNA ligase | 915 | 790 | coexpression:401 experimental:469 textmining:616 |
Rv0040c mtc28 hyp |
hypothetical protein | 731 | 732 ctx | neighborhood:730 |
Rv2555c alaS |
alanine--tRNA ligase | 877 | 730 | coexpression:650 textmining:567 |
Rv3014c ligA |
DNA ligase A | 774 | 706 | experimental:694 |
Rv0039c |
transmembrane protein | 701 | 702 ctx | neighborhood:700 |
Rv0702 rplD |
50S ribosomal protein L4 | 779 | 681 | coexpression:418 |
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: leucine--tRNA ligase
- MTBC0 PGAP product: leucine--tRNA ligase
- Pfam (hmmscan --cut_ga): tRNA-synt_1 PF00133.29 (E=3e-05), tRNA-synt_1g PF09334.18 (E=5e-12), tRNA-synt_1_2 PF13603.13 (E=5e-54), Anticodon_1 PF08264.20 (E=3e-15)
- (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_214555.1)
- Domains: Pfam-A via hmmscan --cut_ga — tRNA-synt_1 (PF00133.29), tRNA-synt_1g (PF09334.18), tRNA-synt_1_2 (PF13603.13), Anticodon_1 (PF08264.20)
- 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
COG0495 - Curated reference: UniProt P9WFV1 (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 —
130 functional partner(s); context anchor
Rv0039c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000046|Rv0041|leuS MTESPTAGPGGVPRADDADSDVPRYRYTAELAARLERTWQENWARLGTFNVPNPVGSLAPPDGAAVPDDKLFVQDMFPYPSGEGLHVGHPLGYIATDVYARYFRMVGRNVLHALGFDAFGLPAEQYAVQTGTHPRTRTEANVVNFRRQLGRLGFGHDSRRSFSTTDVDFYRWTQWIFLQIYNAWFDTTANKARPISELVAEFESGARCLDGGRDWAKLTAGERADVIDEYRLVYRADSLVNWCPGLGTVLANEEVTADGRSDRGNFPVFRKRLRQWMMRITAYADRLLDDLDVLDWPEQVKTMQRNWIGRSTGAVALFSARAASDDGFEVDIEVFTTRPDTLFGATYLVLAPEHDLVDELVAASWPAGVNPLWTYGGGTPGEAIAAYRRAIAAKSDLERQESREKTGVFLGSYAINPANGEPVPIFIADYVLAGYGTGAIMAVPGHDQRDWDFARAFGLPIVEVIAGGNISESAYTGDGILVNSDYLNGMSVPAAKRAIVDRLESAGRGRARIEFKLRDWLFARQRYWGEPFPIVYDSDGRPHALDEAALPVELPDVPDYSPVLFDPDDADSEPSPPLAKATEWVHVDLDLGDGLKPYSRDTNVMPQWAGSSWYELRYTDPHNSERFCAKENEAYWMGPRPAEHGPDDPGGVDLYVGGAEHAVLHLLYSRFWHKVLYDLGHVSSREPYRRLVNQGYIQAYAYTDARGSYVPAEQVIERGDRFVYPGPDGEVEVFQEFGKIGKSLKNSVSPDEICDAYGADTLRVYEMSMGPLEASRPWATKDVVGAYRFLQRVWRLVVDEHTGETRVADGVELDIDTLRALHRTIVGVSEDFAALRNNTATAKLIEYTNHLTKKHRDAVPRAAVEPLVQMLAPLAPHIAEELWLRLGNTTSLAHGPFPKADAAYLVDETVEYPVQVNGKVRGRVVVAADTDEETLKAAVLTDEKVQAFLAGATPRKVIVVAGRLVNLVI