lysX Resolved · high auto-curated
H37Rv Rv1640c · MTBC0 - ·
1172 aa · 1848517–1852035 (-) ·
RefSeq NP_216156.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | bifunctional lysine--tRNA ligase/phosphatidylglycerol lysyltransferase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Bifunctional lysine--tRNA ligase/phosphatidylglycerol lysyltransferase. Pfam: tRNA-synt_2_TM (PF16995.11), LPG_synthase_C (PF09924.16), tRNA_anti-codon (PF01336.32), tRNA-synt_2 (PF00152.26). |
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 |
P9WFU7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Lysylphosphatidylglycerol biosynthesis bifunctional protein LysX [Includes: Lysine--tRNA ligase |
| EC (curated) |
EC 2.3.2.3, EC 6.1.1.6
|
| Curated function | Catalyzes the production of L-lysyl-tRNA(Lys)transfer and the transfer of a lysyl group from L-lysyl-tRNA(Lys) to membrane-bound phosphatidylglycerol (PG), which produces lysylphosphatidylglycerol (LPG), one of the components of the bacterial membrane with a positive net charge. LPG synthesis contributes to the resistance to cationic antimicrobial peptides (CAMPs) and likely protects M.tuberculosis against the CAMPs produced by competiting microorganisms (bacteriocins). In fact, the modification of anionic phosphatidylglycerol with positively charged L-lysine results in repulsion of the peptid. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
J Translation, ribosomal structure and biogenesis
|
|---|---|
| Preferred name | lysX |
| eggNOG description | Catalyzes the production of L-lysyl-tRNA(Lys)transfer and the transfer of a lysyl group from L-lysyl-tRNA(Lys) to membrane-bound phosphatidylglycerol (PG), which produces lysylphosphatidylglycerol (LPG), one of the components of the bacterial membrane with a positive net charge. LPG synthesis contributes to the resistance to cationic antimicrobial peptides (CAMPs) and likely protects M.tuberculosis against the CAMPs produced by competiting microorganisms (bacteriocins). In fact, the modification of anionic phosphatidylglycerol with positively charged L-lysine results in repulsion of the peptides |
| Orthologous group | COG1190 |
| EC number |
EC 6.1.1.6
|
| KEGG orthology |
K04567
|
| KEGG pathways |
map00970
|
| KEGG modules |
M00359, M00360
|
| Gene Ontology (78) |
GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0006082, GO:0006139, GO:0006399, GO:0006412, GO:0006418 +66 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 | 0.642 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 12 synonymous, 22 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_2_TM | PF16995.11 | 3.1e-81 | 76–290 | Transmembrane region of lysyl-tRNA synthetase |
LPG_synthase_C | PF09924.16 | 6.6e-98 | 309–607 | Phosphatidylglycerol lysyltransferase, C-terminal |
tRNA_anti-codon | PF01336.32 | 2.4e-12 | 726–804 | OB-fold nucleic acid binding domain |
tRNA-synt_2 | PF00152.26 | 1.5e-76 | 821–1168 | tRNA synthetases class II (D, K and N) |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3598c lysS |
lysine--tRNA ligase | 924 | 911 | database:900 |
Rv2992c gltS |
glutamate--tRNA ligase | 910 | 877 | coexpression:648 experimental:488 |
Rv1536 ileS |
isoleucine--tRNA ligase | 962 | 849 | coexpression:581 experimental:448 textmining:763 |
Rv1007c metS |
methionine--tRNA ligase | 880 | 839 | experimental:610 |
Rv3396c guaA |
GMP synthase | 906 | 837 | coexpression:815 textmining:452 |
Rv1292 argS |
arginine--tRNA ligase | 859 | 811 | coexpression:450 experimental:462 |
Rv2845c proS |
proline--tRNA ligase | 883 | 806 | coexpression:411 experimental:473 textmining:421 |
Rv0041 leuS |
leucine--tRNA ligase | 894 | 794 | experimental:469 textmining:510 |
Rv1307 atpH |
ATP synthase subunit b/delta | 756 | 756 | coexpression:739 |
Rv3458c rpsD |
30S ribosomal protein S4 | 750 | 751 | coexpression:657 |
Rv3105c prfB |
peptide chain release factor PrfB | 866 | 745 | coexpression:689 textmining:500 |
Rv0120c fusA2 |
elongation factor G | 749 | 715 | coexpression:646 |
Rv0701 rplC |
50S ribosomal protein L3 | 721 | 710 | coexpression:647 |
Rv1309 atpG |
ATP synthase subunit gamma | 735 | 706 | coexpression:689 |
Rv0684 fusA1 |
elongation factor G | 739 | 704 | coexpression:644 |
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): bifunctional lysine--tRNA ligase/phosphatidylglycerol lysyltransferase
- Pfam (hmmscan --cut_ga): tRNA-synt_2_TM PF16995.11 (E=3e-81), LPG_synthase_C PF09924.16 (E=7e-98), tRNA_anti-codon PF01336.32 (E=2e-12), tRNA-synt_2 PF00152.26 (E=2e-76)
- (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_216156.1)
- Domains: Pfam-A via hmmscan --cut_ga — tRNA-synt_2_TM (PF16995.11), LPG_synthase_C (PF09924.16), tRNA_anti-codon (PF01336.32), tRNA-synt_2 (PF00152.26)
- 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
COG1190 - Curated reference: UniProt P9WFU7 (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 — 150 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv1640c|lysX MGLHLTVPGLRRDGRGVQSNSHDTSSKTTADISRCPQHTDAGLQRAATPGISRLLGISSRSVTLTKPRSATRGNSRYHWVPAAAGWTVGVIATLSLLASVSPLIRWIIKVPREFINDYLFNFPDTNFAWSFVLALLAAALTARKRIAWLVLLANMVLAAVVNAAEIAAGGNTAAESFGENLGFAVHVVAIVVLVLGYREFWAKVRRGALFRAAAVWLAGAVVGIVASWGLVELFPGSLAPDERLGYAANRVVGFALADPDLFTGRPHVFLNAIFGLFGAFALIGAAIVLFLSQRADNALTGEDESAIRGLLDLYGKDDSLGYFATRRDKSVVFASSGRACITYRVEVGVCLASGDPVGDHRAWPQAVDAWLRLCQTYGWAPGVMGASSQGAQTYREAGLTALELGDEAILRPADFKLSGPEMRGVRQAVTRARRAGLTVRIRRHRDIAEDEMAQTITRADSWRDTETERGFSMALGRLGDPADSDCLLVEAIDPHNQVLAMLSLVPWGTTGVSLDLMRRSPQSPNGTIELMVSELALHAESLGITRISLNFAVFRAAFEQGAQLGAGPVARLWRGLLVFFSRWWQLETLYRSNMKYQPEWVPRYACYEDARVIPRVGVASVIAEGFLVLPFSRRNRVHTGHHPAVPERLAATGLLHHDGSAPDVSGLRQVGLTNGDGVERRLPEQVRVRFDKLEKLRSSGIDAFPVGRPPSHTVAQALAADHQASVSVSGRIMRIRNYGGVLFAQLRDWSGEMQVLLDNSRLDQGCAADFNAATDLGDLVEMTGHMGASKTGTPSLIVSGWRLIGKCLRPLPNKWKGLLDPEARVRTRYLDLAVNAESRALITARSSVLRAVRETLFAKGFVEVETPILQQLHGGATARPFVTHINTYSMDLFLRIAPELYLKRLCVGGVERVFELGRAFRNEGVDFSHNPEFTLLEAYQAHADYLEWIDGCRELIQNAAQAANGAPIAMRPRTDKGSDGTRHHLEPVDISGIWPVRTVHDAISEALGERIDADTGLTTLRKLCDAAGVPYRTQWDAGAVVLELYEHLVECRTEQPTFYIDFPTSVSPLTRPHRSKRGVAERWDLVAWGIELGTAYSELTDPVEQRRRLQEQSLLAAGGDPEAMELDEDFLQAMEYAMPPTGGLGMGIDRVVMLITGRSIRETLPFPLAKPH