glnA1 Resolved · high auto-curated
H37Rv Rv2220 · MTBC0 mtbc0_002357 ·
478 aa · 2513772–2515208 (+) ·
RefSeq NP_216736.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | glutamine synthetase |
|---|---|
| MTBC0 PGAP re-annotation | type I glutamate--ammonia ligase |
| Revised (this work) | Type I glutamate--ammonia ligase. Pfam: Gln-synt_N (PF03951.25), Gln-synt_C (PF00120.30). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WN39
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Glutamine synthetase |
| EC (curated) |
EC 6.3.1.2
|
| Curated function | Involved in nitrogen metabolism via ammonium assimilation. Catalyzes the ATP-dependent biosynthesis of glutamine from glutamate and ammonia. Also able to use GTP. D-glutamate is a poor substrate, and DL-glutamate shows about 50% of the standard specific activity. Also plays a key role in controlling the ammonia levels within infected host cells and so contributes to the pathogens capacity to inhibit phagosome acidification and phagosome-lysosome fusion. Involved in cell wall biosynthesis via the production of the major component poly-L-glutamine (PLG). PLG synthesis in the cell wall occurs onl. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | glnA |
| eggNOG description | glutamine synthetase |
| Orthologous group | COG0174 |
| EC number |
EC 6.3.1.2
|
| KEGG orthology |
K01915
|
| KEGG pathways |
map00220, map00250, map00630, map00910, map01100, map01120, map01230, map02020, map04217, map04724, map04727
|
| Gene Ontology (106) |
GO:0001968, GO:0003674, GO:0003824, GO:0004356, GO:0005488, GO:0005515, GO:0005575, GO:0005576, GO:0005618, GO:0005622, GO:0005623, GO:0005737 +94 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 | 0.297 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 4 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 |
|---|---|---|---|---|
Gln-synt_N | PF03951.25 | 9.6e-30 | 17–98 | Glutamine synthetase, beta-Grasp domain |
Gln-synt_C | PF00120.30 | 1.5e-135 | 106–475 | Glutamine synthetase, catalytic domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: gltB (glutamate synthase large subunit), high confidence from genomic context alone (score 970 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3859c gltB |
glutamate synthase large subunit | 989 | 970 ctx | neighborhood:456 coexpression:501 database:900 textmining:659 |
Rv3436c glmS |
glucosamine--fructose-6-phosphate aminotransferase | 931 | 917 | database:900 |
Rv3858c gltD |
glutamate synthase small subunit | 953 | 916 | database:900 textmining:467 |
Rv1383 carA |
carbamoyl-phosphate synthase small subunit | 914 | 909 | database:900 |
Rv1384 carB |
carbamoyl-phosphate synthase large subunit | 914 | 906 | database:900 |
Rv1187 rocA |
pyrroline-5-carboxylate dehydrogenase RocA | 910 | 906 | database:900 |
Rv2476c gdh |
NAD-dependent glutamate dehydrogenase | 967 | 904 | database:900 textmining:678 |
Rv3432c gadB |
glutamate decarboxylase GadB | 936 | 904 | database:900 |
Rv0808 purF |
amidophosphoribosyltransferase | 911 | 904 | database:900 |
Rv0252 nirB |
nitrite reductase large subunit NirB | 963 | 903 | database:900 textmining:642 |
Rv0788 purQ |
phosphoribosylformylglycinamidine synthase | 907 | 902 | database:900 |
Rv0253 nirD |
nitrite reductase small subunit NirD | 929 | 901 | database:900 |
Rv1878 glnA3 |
glutamine synthetase GlnA | 886 | 853 | database:800 |
Rv2222c glnA2 |
glutamine synthetase | 867 | 848 | database:800 |
Rv2860c glnA4 |
glutamine synthetase | 871 | 842 | database:800 |
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: glutamine synthetase
- MTBC0 PGAP product: type I glutamate--ammonia ligase
- Pfam (hmmscan --cut_ga): Gln-synt_N PF03951.25 (E=1e-29), Gln-synt_C PF00120.30 (E=2e-135)
- (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_216736.1)
- Domains: Pfam-A via hmmscan --cut_ga — Gln-synt_N (PF03951.25), Gln-synt_C (PF00120.30)
- 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
COG0174 - Curated reference: UniProt P9WN39 (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 —
85 functional partner(s); context anchor
gltB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002357|Rv2220|glnA1 MTEKTPDDVFKLAKDEKVEYVDVRFCDLPGIMQHFTIPASAFDKSVFDDGLAFDGSSIRGFQSIHESDMLLLPDPETARIDPFRAAKTLNINFFVHDPFTLEPYSRDPRNIARKAENYLISTGIADTAYFGAEAEFYIFDSVSFDSRANGSFYEVDAISGWWNTGAATEADGSPNRGYKVRHKGGYFPVAPNDQYVDLRDKMLTNLINSGFILEKGHHEVGSGGQAEINYQFNSLLHAADDMQLYKYIIKNTAWQNGKTVTFMPKPLFGDNGSGMHCHQSLWKDGAPLMYDETGYAGLSDTARHYIGGLLHHAPSLLAFTNPTVNSYKRLVPGYEAPINLVYSQRNRSACVRIPITGSNPKAKRLEFRSPDSSGNPYLAFSAMLMAGLDGIKNKIEPQAPVDKDLYELPPEEAASIPQTPTQLSDVIDRLEADHEYLTEGGVFTNDLIETWISFKRENEIEPVNIRPHPYEFALYYDV