Rv2689c Resolved · high auto-curated
H37Rv Rv2689c · MTBC0 mtbc0_002863 ·
405 aa · 3028260–3029477 (-) ·
RefSeq NP_217205.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | class I SAM-dependent RNA methyltransferase |
| Revised (this work) | Class I SAM-dependent RNA methyltransferase. Pfam: TRAM (PF01938.27), tRNA_U5-meth_tr (PF05958.18). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O07191
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Conserved alanine and valine and glycine rich protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
J Translation, ribosomal structure and biogenesis
|
|---|---|
| eggNOG description | Belongs to the class I-like SAM-binding methyltransferase superfamily. RNA M5U methyltransferase family |
| Orthologous group | COG0144 |
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 | 0.916 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 10 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.53% of strains (767) · clonal |
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 |
|---|---|---|---|---|
TRAM | PF01938.27 | 4.6e-06 | 16–60 | TRAM domain |
tRNA_U5-meth_tr | PF05958.18 | 2.1e-07 | 332–404 | tRNA (Uracil-5-)-methyltransferase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2690c (integral membrane protein), high confidence from genomic context alone (score 749 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2690c |
integral membrane protein | 760 | 749 ctx | neighborhood:743 |
Rv2691 ceoB |
TRK system potassium uptake protein CeoB | 686 | 686 ctx | neighborhood:684 |
Rv2692 ceoC |
TRK system potassium uptake protein CeoC | 686 | 685 ctx | neighborhood:684 |
Rv2118c trmI |
tRNA (adenine(58)-N(1))-methyltransferase | 705 | 662 | coexpression:662 |
Rv1650 pheT |
phenylalanine--tRNA ligase subunit beta | 589 | 589 ctx | cooccurence:419 |
Rv3433c nnr |
bifunctional ADP-dependent (S)-NAD(P)H-hydrate dehydratase/NAD(P)H-hydrate epimerase | 569 | 570 | |
Rv3579c rlmB |
23S rRNA (guanosine(2251)-2'-O)-methyltransferase RlmB | 584 | 547 | |
Rv2681 hyp |
hypothetical protein | 542 | 543 | coexpression:405 |
Rv1003 rsmI |
rRNA small subunit methyltransferase I | 592 | 536 ctx | cooccurence:490 |
Rv2686c |
antibiotic ABC transporter permease | 530 | 531 ctx | neighborhood:518 |
Rv2687c |
antibiotic ABC transporter permease | 523 | 524 ctx | neighborhood:518 |
Rv1407 fmu |
16S rRNA m5C967 methyltransferase | 640 | 520 | coexpression:422 |
Rv1644 tsnR |
23S rRNA methyltransferase TsnR | 529 | 487 | |
Rv1988 erm(37) |
23S rRNA (adenine(2058)-N(6))-methyltransferase Erm(37) | 534 | 474 | coexpression:400 |
Rv1630 rpsA |
30S ribosomal protein S1 | 470 | 471 | coexpression:454 |
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: hypothetical protein
- MTBC0 PGAP product: class I SAM-dependent RNA methyltransferase
- Pfam (hmmscan --cut_ga): TRAM PF01938.27 (E=5e-06), tRNA_U5-meth_tr PF05958.18 (E=2e-07)
- (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_217205.1)
- Domains: Pfam-A via hmmscan --cut_ga — TRAM (PF01938.27), tRNA_U5-meth_tr (PF05958.18)
- 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
COG0144 - Curated reference: UniProt O07191 (TrEMBL, unreviewed; 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 —
37 functional partner(s); context anchor
Rv2690c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002863|Rv2689c| MTRAGDDAVNLTLVTGAPANGGSCVAHHEGRVVFVRYALPGERVRARVTAQRGSYWHAEAFEVIDPSPDRIGSLCSIAGADGAGCCDLAFAAPEAARTLKAQVVANQLERLGRHSWQGEAQPLSDAGPTGWRIRVRLDVGADRRPGFHRYHSGELVTDLDCGQLPVGMLDGLVAADWPPEAQLYVALDDDGERHVVCSVRQGPRNRTRTVTNVVEGAYHAHQRVHRRSWRVPVTAFWQAHRDAAAVYSDLIADWAQPAPGMTAWDLYGGAGVFAAVLGEAVGESGRVLTVDTSRLASGAARAALVDLPQVEVVTGSVRRVLAVQPAGADLAVLDPPRSGAGREVVDLLAGAGVPRLIHIGCEAASFARDIGLYRGHGYAVEKIKVFDAFPLTHYVECVALLTRKV