valS Resolved · high auto-curated
H37Rv Rv2448c · MTBC0 - ·
876 aa · 2747595–2750225 (-) ·
RefSeq NP_216964.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | valine--tRNA ligase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Valine--tRNA ligase. Pfam: tRNA-synt_1 (PF00133.29), tRNA-synt_1_2 (PF13603.13), tRNA-synt_1g (PF09334.18), Anticodon_1 (PF08264.20), Val_tRNA-synt_C (PF10458.15). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
P9WFS9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Valine--tRNA ligase |
| EC (curated) |
EC 6.1.1.9
|
| Curated function | Catalyzes the attachment of valine to tRNA(Val). As ValRS can inadvertently accommodate and process structurally similar amino acids such as threonine, to avoid such errors, it has a 'posttransfer' editing activity that hydrolyzes mischarged Thr-tRNA(Val) in a tRNA-dependent manner. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
J Translation, ribosomal structure and biogenesis
|
|---|---|
| Preferred name | valS |
| eggNOG description | amino acids such as threonine, to avoid such errors, it has a posttransfer editing activity that hydrolyzes mischarged Thr-tRNA(Val) in a tRNA-dependent manner |
| Orthologous group | COG0525 |
| EC number |
EC 6.1.1.9
|
| KEGG orthology |
K01873
|
| KEGG pathways |
map00970
|
| KEGG modules |
M00359, M00360
|
| Gene Ontology (65) |
GO:0003674, GO:0003824, GO:0004812, GO:0004832, 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 | 0.229 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 10 synonymous, 7 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 | 7.0e-93 | 15–426 | tRNA synthetases class I (I, L, M and V) |
tRNA-synt_1_2 | PF13603.13 | 4.7e-06 | 242–300 | Leucyl-tRNA synthetase, editing domain |
tRNA-synt_1g | PF09334.18 | 1.4e-06 | 517–579 | tRNA synthetases class I (M) |
Anticodon_1 | PF08264.20 | 5.7e-36 | 611–750 | Anticodon-binding domain of tRNA ligase |
Val_tRNA-synt_C | PF10458.15 | 1.1e-16 | 811–876 | Valyl tRNA synthetase tRNA binding arm |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: folC (folylpolyglutamate synthase FolC), high confidence from genomic context alone (score 935 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2447c folC |
folylpolyglutamate synthase FolC | 959 | 935 ctx | neighborhood:881 coexpression:475 textmining:406 |
Rv2446c |
integral membrane protein | 940 | 904 ctx | neighborhood:881 textmining:406 |
Rv1536 ileS |
isoleucine--tRNA ligase | 908 | 828 | coexpression:775 textmining:492 |
Rv2445c ndkA |
nucleoside diphosphate kinase | 845 | 825 ctx | neighborhood:822 |
Rv0041 leuS |
leucine--tRNA ligase | 973 | 819 | coexpression:749 textmining:861 |
Rv3396c guaA |
GMP synthase | 905 | 803 | coexpression:788 textmining:542 |
Rv2555c alaS |
alanine--tRNA ligase | 832 | 781 | coexpression:738 |
Rv2572c aspS |
aspartate--tRNA ligase | 810 | 752 | coexpression:732 |
Rv2614c thrS |
threonine--tRNA ligase | 976 | 731 | coexpression:656 textmining:915 |
Rv3834c serS |
serine--tRNA ligase | 835 | 730 | coexpression:651 textmining:416 |
Rv2580c hisS |
histidine--tRNA ligase | 967 | 678 | coexpression:426 textmining:903 |
Rv1594 nadA |
quinolinate synthetase A | 667 | 667 ctx | fusion:652 |
Rv1630 rpsA |
30S ribosomal protein S1 | 720 | 660 | coexpression:654 |
Rv0667 rpoB |
DNA-directed RNA polymerase subunit beta | 736 | 655 | coexpression:649 |
Rv1292 argS |
arginine--tRNA ligase | 979 | 651 | coexpression:624 textmining:944 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): valine--tRNA ligase
- Pfam (hmmscan --cut_ga): tRNA-synt_1 PF00133.29 (E=7e-93), tRNA-synt_1_2 PF13603.13 (E=5e-06), tRNA-synt_1g PF09334.18 (E=1e-06), Anticodon_1 PF08264.20 (E=6e-36), Val_tRNA-synt_C PF10458.15 (E=1e-16)
- (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_216964.1)
- Domains: Pfam-A via hmmscan --cut_ga — tRNA-synt_1 (PF00133.29), tRNA-synt_1_2 (PF13603.13), tRNA-synt_1g (PF09334.18), Anticodon_1 (PF08264.20), Val_tRNA-synt_C (PF10458.15)
- 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
COG0525 - Curated reference: UniProt P9WFS9 (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 —
103 functional partner(s); context anchor
folC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2448c|valS MLPKSWDPAAMESAIYQKWLDAGYFTADPTSTKPAYSIVLPPPNVTGSLHMGHALEHTMMDALTRRKRMQGYEVLWQPGTDHAGIATQSVVEQQLAVDGKTKEDLGRELFVDKVWDWKRESGGAIGGQMRRLGDGVDWSRDRFTMDEGLSRAVRTIFKRLYDAGLIYRAERLVNWSPVLQTAISDLEVNYRDVEGELVSFRYGSLDDSQPHIVVATTRVETMLGDTAIAVHPDDERYRHLVGTSLAHPFVDRELAIVADEHVDPEFGTGAVKVTPAHDPNDFEIGVRHQLPMPSILDTKGRIVDTGTRFDGMDRFEARVAVRQALAAQGRVVEEKRPYLHSVGHSERSGEPIEPRLSLQWWVRVESLAKAAGDAVRNGDTVIHPASMEPRWFSWVDDMHDWCISRQLWWGHRIPIWYGPDGEQVCVGPDETPPQGWEQDPDVLDTWFSSALWPFSTLGWPDKTAELEKFYPTSVLVTGYDILFFWVARMMMFGTFVGDDAAITLDGRRGPQVPFTDVFLHGLIRDESGRKMSKSKGNVIDPLDWVEMFGADALRFTLARGASPGGDLAVSEDAVRASRNFGTKLFNATRYALLNGAAPAPLPSPNELTDADRWILGRLEEVRAEVDSAFDGYEFSRACESLYHFAWDEFCDWYLELAKTQLAQGLTHTTAVLAAGLDTLLRLLHPVIPFLTEALWLALTGRESLVSADWPEPSGISVDLVAAQRINDMQKLVTEVRRFRSDQGLADRQKVPARMHGVRDSDLSNQVAAVTSLAWLTEPGPDFEPSVSLEVRLGPEMNRTVVVELDTSGTIDVAAERRRLEKELAGAQKELASTAAKLANADFLAKAPDAVIAKIRDRQRVAQQETERITTRLAALQ