mesJ Resolved · high auto-curated
H37Rv Rv3625c · MTBC0 mtbc0_003842 ·
323 aa · 4087605–4088576 (-) ·
RefSeq NP_218142.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | tRNA(Ile)-lysidine synthase |
|---|---|
| MTBC0 PGAP re-annotation | tRNA lysidine(34) synthetase TilS |
| Revised (this work) | TRNA lysidine(34) synthetase TilS. Pfam: ATP_bind_3 (PF01171.27), TilS (PF09179.17). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WG53
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | tRNA(Ile)-lysidine synthase |
| EC (curated) |
EC 6.3.4.19
|
| Curated function | Ligates lysine onto the cytidine present at position 34 of the AUA codon-specific tRNA(Ile) that contains the anticodon CAU, in an ATP-dependent manner. Cytidine is converted to lysidine, thus changing the amino acid specificity of the tRNA from methionine to isoleucine. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
J Translation, ribosomal structure and biogenesis
|
|---|---|
| Preferred name | tilS |
| eggNOG description | Ligates lysine onto the cytidine present at position 34 of the AUA codon-specific tRNA(Ile) that contains the anticodon CAU, in an ATP-dependent manner. Cytidine is converted to lysidine, thus changing the amino acid specificity of the tRNA from methionine to isoleucine |
| Orthologous group | COG0037 |
| EC number |
EC 2.4.2.8, EC 6.3.4.19
|
| KEGG orthology |
K00760, K04075
|
| KEGG pathways |
map00230, map00983, map01100, map01110
|
| 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 | 2.387 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
ATP_bind_3 | PF01171.27 | 5.3e-28 | 28–193 | PP-loop domain |
TilS | PF09179.17 | 2.7e-10 | 246–300 | TilS substrate binding domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: hpt (hypoxanthine-guanine phosphoribosyltransferase), high confidence from genomic context alone (score 987 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3624c hpt |
hypoxanthine-guanine phosphoribosyltransferase | 998 | 987 ctx | neighborhood:881 fusion:855 textmining:888 |
Rv3627c dacB hyp |
hypothetical protein | 981 | 906 ctx | neighborhood:881 textmining:808 |
Rv3626c hyp |
hypothetical protein | 984 | 888 ctx | neighborhood:881 textmining:870 |
Rv0416 thiS |
sulfur carrier protein ThiS | 821 | 813 | experimental:790 |
Rv3628 ppa |
inorganic pyrophosphatase | 784 | 774 ctx | neighborhood:774 |
Rv1014c pth |
peptidyl-tRNA hydrolase | 692 | 673 | coexpression:646 |
Rv1020 mfd |
transcription-repair coupling factor | 690 | 673 | coexpression:588 |
Rv3455c truA |
tRNA pseudouridine synthase A | 649 | 536 | coexpression:414 |
Rv1165 typA |
GTP-binding translation elongation factor | 472 | 472 | coexpression:455 |
Rv2156c murX |
phospho-N-acetylmuramoyl-pentappeptidetransferase | 462 | 463 | |
Rv1409 ribG |
bifunctional riboflavin biosynthesis diaminohydroxyphosphoribosylaminopyrimidine deaminase/5-amino-6-(5-phosphoribosylamino) uracil reductas | 470 | 457 | |
Rv2118c trmI |
tRNA (adenine(58)-N(1))-methyltransferase | 527 | 456 | coexpression:418 |
Rv2793c truB |
tRNA pseudouridine synthase B | 581 | 451 | |
Rv1510 hyp |
hypothetical protein | 470 | 450 | coexpression:413 |
Rv3737 |
transmembrane protein | 449 | 450 |
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: tRNA(Ile)-lysidine synthase
- MTBC0 PGAP product: tRNA lysidine(34) synthetase TilS
- Pfam (hmmscan --cut_ga): ATP_bind_3 PF01171.27 (E=5e-28), TilS PF09179.17 (E=3e-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_218142.1)
- Domains: Pfam-A via hmmscan --cut_ga — ATP_bind_3 (PF01171.27), TilS (PF09179.17)
- 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
COG0037 - Curated reference: UniProt P9WG53 (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 —
54 functional partner(s); context anchor
hpt - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003842|Rv3625c|mesJ MDRQSAVAQLRAAAEQFARVHLDACDRWSVGLSGGPDSLALTAVAARLWPTTALIVDHGLQPGSATVAETARIQAISLGCVDARVLCVQVGAAGGREAAARSARYSALEEHRDGPVLLAHTLDDQAETVLLGLGRGSGARSIAGMRPYDPPWCRPLLGVRRSVTHAACRELGLTAWQDPHNTDRRFTRTRLRTEVLPLLEDVLGGGVAEALARTATALREDTDLIDTIAAQALPGAAVAGSRGQELSTSALTALPDAVRRRVIRGWLLAGGATGLTDRQIRGVDRLVTAWRGQGGVAVGSTLRGQRLVAGRRDGVLVLRREPV