mtn Resolved · high auto-curated
H37Rv Rv0091 · MTBC0 mtbc0_000101 ·
255 aa · 99847–100614 (+) ·
RefSeq NP_214605.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase |
|---|---|
| MTBC0 PGAP re-annotation | 5'-methylthioadenosine/adenosylhomocysteine nucleosidase |
| Revised (this work) | 5'-methylthioadenosine/adenosylhomocysteine nucleosidase. Pfam: PNP_UDP_1 (PF01048.27). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WJM3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase |
| EC (curated) |
EC 3.2.2.9
|
| Curated function | Catalyzes the irreversible cleavage of the glycosidic bond in both 5'-methylthioadenosine (MTA) and S-adenosylhomocysteine (SAH/AdoHcy) to adenine and the corresponding thioribose, 5'-methylthioribose and S-ribosylhomocysteine, respectively. Also cleaves 5'-deoxyadenosine, a toxic by-product of radical S-adenosylmethionine (SAM) enzymes, into 5-deoxyribose and adenine. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | mtnN |
| eggNOG description | Catalyzes the irreversible cleavage of the glycosidic bond in both 5'-methylthioadenosine (MTA) and S- adenosylhomocysteine (SAH AdoHcy) to adenine and the corresponding thioribose, 5'-methylthioribose and S-ribosylhomocysteine, respectively |
| Orthologous group | COG0775 |
| EC number |
EC 3.2.2.9
|
| KEGG orthology |
K01243
|
| KEGG pathways |
map00270, map01100, map01230
|
| KEGG modules |
M00034, M00609
|
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 | 0.242 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 2 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.89% of strains (1287) · 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 |
|---|---|---|---|---|
PNP_UDP_1 | PF01048.27 | 9.6e-47 | 4–249 | Phosphorylase superfamily |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ctpA (cation transporter ATPase A), medium confidence from genomic context alone (score 541 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3248c sahH |
adenosylhomocysteinase | 909 | 904 | database:900 |
Rv0535 pnp |
5'-methylthioadenosine phosphorylase | 992 | 903 | database:900 textmining:929 |
Rv2601 speE |
spermidine synthase | 979 | 900 | database:900 textmining:804 |
Rv0092 ctpA |
cation transporter ATPase A | 559 | 541 ctx | neighborhood:525 |
Rv3859c gltB |
glutamate synthase large subunit | 490 | 490 ctx | neighborhood:488 |
Rv2148c hyp |
hypothetical protein | 480 | 480 ctx | fusion:460 |
Rv2524c fas |
fatty acid synthase | 451 | 441 | |
Rv0018c pstP |
phosphoserine/threonine phosphatase PstP | 422 | 423 | coexpression:422 |
Rv3025c iscS |
cysteine desulfurase | 451 | 416 | |
Rv2584c apt |
adenine phosphoribosyltransferase | 419 | 369 | |
Rv2438c nadE |
glutamine-dependent NAD(+) synthetase | 457 | 236 | |
Rv1603 hisA |
1-(5-phosphoribosyl)-5-((5-phosphoribosylamino)methylideneamino)imidazole-4-carboxamide isomerase | 470 | 103 | textmining:434 |
Rv1568 bioA |
adenosylmethionine--8-amino-7-oxononanoate aminotransferase BioA | 426 | 91 | |
Rv1589 bioB |
biotin synthetase | 769 | 86 | textmining:759 |
Rv2855 mtr |
mycothione reductase | 460 | 85 | textmining:435 |
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: 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase
- MTBC0 PGAP product: 5'-methylthioadenosine/adenosylhomocysteine nucleosidase
- Pfam (hmmscan --cut_ga): PNP_UDP_1 PF01048.27 (E=1e-46)
- (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_214605.1)
- Domains: Pfam-A via hmmscan --cut_ga — PNP_UDP_1 (PF01048.27)
- 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
COG0775 - Curated reference: UniProt P9WJM3 (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 —
28 functional partner(s); context anchor
ctpA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000101|Rv0091|mtn MAVTVGVICAIPQELAYLRGVLVDAKRQQVAQILFDSGQLDAHRVVLAAAGMGKVNTGLTATLLADRFGCRTIVFTGVAGGLDPELCIGDIVIADRVVQHDFGLLTDERLRPYQPGHIPFIEPTERLGYPVDPAVIDRVKHRLDGFTLAPLSTAAGGGGRQPRIYYGTILTGDQYLHCERTRNRLHHELGGMAVEMEGGAVAQICASFDIPWLVIRALSDLAGADSGVDFNRFVGEVAASSARVLLRLLPVLTAC