metK Resolved · high auto-curated
H37Rv Rv1392 · MTBC0 - ·
403 aa · 1566825–1568036 (+) ·
RefSeq NP_215908.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | S-adenosylmethionine synthetase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | S-adenosylmethionine synthetase. Pfam: S-AdoMet_synt_N (PF00438.26), S-AdoMet_synt_M (PF02772.22), S-AdoMet_synt_C (PF02773.22). |
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 |
P9WGV1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | S-adenosylmethionine synthase |
| EC (curated) |
EC 2.5.1.6
|
| Curated function | Catalyzes the formation of S-adenosylmethionine (AdoMet) from methionine and ATP. The overall synthetic reaction is composed of two sequential steps, AdoMet formation and the subsequent tripolyphosphate hydrolysis which occurs prior to release of AdoMet from the enzyme. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | metK |
| eggNOG description | Catalyzes the formation of S-adenosylmethionine (AdoMet) from methionine and ATP. The overall synthetic reaction is composed of two sequential steps, AdoMet formation and the subsequent tripolyphosphate hydrolysis which occurs prior to release of AdoMet from the enzyme |
| Orthologous group | COG0192 |
| EC number |
EC 2.5.1.6
|
| KEGG orthology |
K00789
|
| KEGG pathways |
map00270, map01100, map01110, map01230
|
| KEGG modules |
M00034, M00035, M00368, M00609
|
| Gene Ontology (24) |
GO:0003674, GO:0003824, GO:0004478, GO:0005488, GO:0005515, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886 +12 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 | 0.524 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 8 synonymous, 12 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.27% of strains (397) · 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 |
|---|---|---|---|---|
S-AdoMet_synt_N | PF00438.26 | 1.1e-37 | 7–106 | S-adenosylmethionine synthetase, N-terminal domain |
S-AdoMet_synt_M | PF02772.22 | 2.6e-45 | 130–251 | S-adenosylmethionine synthetase, central domain |
S-AdoMet_synt_C | PF02773.22 | 2.8e-65 | 253–392 | S-adenosylmethionine synthetase, C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: gmk (guanylate kinase), high confidence from genomic context alone (score 899 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1416 ribH |
6,7-dimethyl-8-ribityllumazine synthase | 991 | 991 | coexpression:987 |
Rv1133c metE |
5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferase | 981 | 970 | coexpression:662 database:900 textmining:410 |
Rv0985c mscL |
large-conductance ion mechanosensitive channel | 945 | 945 | coexpression:945 |
Rv2124c metH |
methionine synthase | 968 | 932 | database:900 textmining:554 |
Rv2458 mmuM |
homocysteine S-methyltransferase MmuM | 923 | 900 | database:900 |
Rv1389 gmk |
guanylate kinase | 918 | 899 ctx | neighborhood:699 cooccurence:672 |
Rv1408 rpe |
ribulose-phosphate 3-epimerase | 797 | 776 ctx | cooccurence:683 |
Rv1417 |
membrane protein | 785 | 775 | database:584 |
Rv3248c sahH |
adenosylhomocysteinase | 919 | 758 | coexpression:705 textmining:680 |
Rv3396c guaA |
GMP synthase | 795 | 756 | coexpression:583 |
Rv1391 dfp |
bifunctional phosphopantothenoylcysteine decarboxylase/phosphopantothenate--cysteine ligase | 773 | 751 ctx | neighborhood:593 |
Rv1390 rpoZ |
DNA-directed RNA polymerase subunit omega | 751 | 751 ctx | neighborhood:748 |
Rv0501 galE2 |
UDP-glucose 4-epimerase GalE | 744 | 731 | database:584 |
Rv0112 gca |
GDP-mannose 4,6-dehydratase | 741 | 728 | database:584 |
Rv2047c hyp |
hypothetical protein | 777 | 727 | database:584 |
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): S-adenosylmethionine synthetase
- Pfam (hmmscan --cut_ga): S-AdoMet_synt_N PF00438.26 (E=1e-37), S-AdoMet_synt_M PF02772.22 (E=3e-45), S-AdoMet_synt_C PF02773.22 (E=3e-65)
- (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_215908.1)
- Domains: Pfam-A via hmmscan --cut_ga — S-AdoMet_synt_N (PF00438.26), S-AdoMet_synt_M (PF02772.22), S-AdoMet_synt_C (PF02773.22)
- 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
COG0192 - Curated reference: UniProt P9WGV1 (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 —
120 functional partner(s); context anchor
gmk - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv1392|metK MSEKGRLFTSESVTEGHPDKICDAISDSVLDALLAADPRSRVAVETLVTTGQVHVVGEVTTSAKEAFADITNTVRARILEIGYDSSDKGFDGATCGVNIGIGAQSPDIAQGVDTAHEARVEGAADPLDSQGAGDQGLMFGYAINATPELMPLPIALAHRLSRRLTEVRKNGVLPYLRPDGKTQVTIAYEDNVPVRLDTVVISTQHAADIDLEKTLDPDIREKVLNTVLDDLAHETLDASTVRVLVNPTGKFVLGGPMGDAGLTGRKIIVDTYGGWARHGGGAFSGKDPSKVDRSAAYAMRWVAKNVVAAGLAERVEVQVAYAIGKAAPVGLFVETFGTETEDPVKIEKAIGEVFDLRPGAIIRDLNLLRPIYAPTAAYGHFGRTDVELPWEQLDKVDDLKRAI