tlyA Resolved · high auto-curated
H37Rv Rv1694 · MTBC0 mtbc0_001802 ·
268 aa · 1929955–1930761 (+) ·
RefSeq NP_216210.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 16S/23S rRNA (cytidine-2'-O)-methyltransferase TlyA |
|---|---|
| MTBC0 PGAP re-annotation | 16S/23S rRNA (cytidine-2'-O)-methyltransferase TlyA |
| Revised (this work) | 16S/23S rRNA (cytidine-2'-O)-methyltransferase TlyA. Pfam: S4 (PF01479.31), FtsJ (PF01728.26). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WJ63
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | 16S/23S rRNA |
| EC (curated) |
EC 2.1.1.226, EC 2.1.1.227
|
| Curated function | Acts as a host evasion factor, that significantly contributes to the pathogenesis of M.tuberculosis by modulating adaptive immune responses by inhibiting host-protective Th1 and Th17 cytokine responses as well as autophagy. Catalyzes the 2'-O-methylation at nucleotides C1409 in 16S rRNA and C1920 in 23S rRNA. Is likely involved in ribosomal biogenesis. Also exhibits hemolytic activity in vitro, by binding with and oligomerizing into host cell membranes. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
J Translation, ribosomal structure and biogenesis
|
|---|---|
| Preferred name | tlyA |
| eggNOG description | Hemolysin TlyA |
| Orthologous group | COG1189 |
| EC number |
EC 2.1.1.226, EC 2.1.1.227
|
| KEGG orthology |
K06442
|
| Gene Ontology (65) |
GO:0000154, GO:0001510, GO:0001897, GO:0001906, GO:0001907, GO:0003674, GO:0003824, GO:0006139, GO:0006364, GO:0006396, GO:0006725, GO:0006807 +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 | 0.588 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 3 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 |
|---|---|---|---|---|
S4 | PF01479.31 | 3.1e-07 | 6–47 | S4 domain |
FtsJ | PF01728.26 | 1.4e-45 | 62–244 | FtsJ-like methyltransferase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ppnK (inorganic polyphosphate/ATP-NAD kinase), high confidence from genomic context alone (score 938 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1695 ppnK |
inorganic polyphosphate/ATP-NAD kinase | 986 | 938 ctx | neighborhood:882 coexpression:494 textmining:790 |
Rv1696 recN |
DNA repair protein RecN | 917 | 895 ctx | neighborhood:867 |
Rv1691 hyp |
hypothetical protein | 946 | 886 ctx | neighborhood:882 textmining:548 |
Rv1693 hyp |
hypothetical protein | 945 | 883 ctx | neighborhood:882 textmining:548 |
Rv1692 |
phosphatase | 944 | 882 ctx | neighborhood:882 textmining:548 |
Rv1697 steA hyp |
hypothetical protein | 768 | 768 ctx | neighborhood:766 |
Rv1698 mctB |
copper transporter MctB | 750 | 750 ctx | neighborhood:748 |
Rv1690 lprJ |
lipoprotein LprJ | 732 | 733 ctx | neighborhood:732 |
Rv1700 |
NUDIX hydrolase | 657 | 657 ctx | neighborhood:648 |
Rv0668 rpoC |
DNA-directed RNA polymerase subunit beta' | 784 | 651 | coexpression:647 textmining:407 |
Rv1701 xerD |
tyrosine recombinase XerD | 646 | 646 ctx | neighborhood:625 |
Rv1699 pyrG |
CTP synthase | 670 | 629 ctx | neighborhood:627 |
Rv2682c dxs1 |
1-deoxy-D-xylulose 5-phosphate synthase | 469 | 469 | coexpression:439 |
Rv3379c dxs2 |
1-deoxy-D-xylulose-5-phosphate synthase | 455 | 455 | coexpression:424 |
Rv1007c metS |
methionine--tRNA ligase | 440 | 441 ctx | cooccurence:409 |
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: 16S/23S rRNA (cytidine-2'-O)-methyltransferase TlyA
- MTBC0 PGAP product: 16S/23S rRNA (cytidine-2'-O)-methyltransferase TlyA
- Pfam (hmmscan --cut_ga): S4 PF01479.31 (E=3e-07), FtsJ PF01728.26 (E=1e-45)
- (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_216210.1)
- Domains: Pfam-A via hmmscan --cut_ga — S4 (PF01479.31), FtsJ (PF01728.26)
- 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
COG1189 - Curated reference: UniProt P9WJ63 (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 —
61 functional partner(s); context anchor
ppnK - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001802|Rv1694|tlyA MARRARVDAELVRRGLARSRQQAAELIGAGKVRIDGLPAVKPATAVSDTTALTVVTDSERAWVSRGAHKLVGALEAFAIAVAGRRCLDAGASTGGFTEVLLDRGAAHVVAADVGYGQLAWSLRNDPRVVVLERTNARGLTPEAIGGRVDLVVADLSFISLATVLPALVGCASRDADIVPLVKPQFEVGKGQVGPGGVVHDPQLRARSVLAVARRAQELGWHSVGVKASPLPGPSGNVEYFLWLRTQTDRALSAKGLEDAVHRAISEGP