glnE Resolved · high auto-curated
H37Rv Rv2221c · MTBC0 mtbc0_002358 ·
994 aa · 2515526–2518510 (-) ·
RefSeq NP_216737.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | [glutamate--ammonia-ligase |
|---|---|
| MTBC0 PGAP re-annotation | bifunctional [glutamine synthetase] adenylyltransferase/[glutamine synthetase]-adenylyl-L-tyrosine phosphorylase |
| Revised (this work) | Bifunctional [glutamine synthetase] adenylyltransferase/[glutamine synthetase]-adenylyl-L-tyrosine phosphorylase. Pfam: GlnD_UR_UTase (PF08335.17), GlnE (PF03710.22). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WN27
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Bifunctional glutamine synthetase adenylyltransferase/adenylyl-removing enzyme |
| EC (curated) |
EC 2.7.7.42, EC 2.7.7.89
|
| Curated function | Involved in the regulation of glutamine synthetase GlnA, a key enzyme in the process to assimilate ammonia. When cellular nitrogen levels are high, the C-terminal adenylyl transferase (AT) inactivates GlnA by covalent transfer of an adenylyl group from ATP to specific tyrosine residue of GlnA, thus reducing its activity. Conversely, when nitrogen levels are low, the N-terminal adenylyl removase (AR) activates GlnA by removing the adenylyl group by phosphorolysis, increasing its activity. The regulatory region of GlnE binds the signal transduction protein PII (GlnB) which indicates the nitrogen. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | glnE |
| eggNOG description | Involved in the regulation of glutamine synthetase GlnA, a key enzyme in the process to assimilate ammonia. When cellular nitrogen levels are high, the C-terminal adenylyl transferase (AT) inactivates GlnA by covalent transfer of an adenylyl group from ATP to specific tyrosine residue of GlnA, thus reducing its activity. Conversely, when nitrogen levels are low, the N-terminal adenylyl removase (AR) activates GlnA by removing the adenylyl group by phosphorolysis, increasing its activity. The regulatory region of GlnE binds the signal transduction protein PII (GlnB) which indicates the nitrogen status of the cell |
| Orthologous group | COG1391 |
| EC number |
EC 2.7.7.42, EC 2.7.7.89
|
| KEGG orthology |
K00982
|
| Gene Ontology (38) |
GO:0000820, GO:0003674, GO:0003824, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0006521, GO:0008150 +26 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 | 0.274 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 12 synonymous, 9 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 |
|---|---|---|---|---|
GlnD_UR_UTase | PF08335.17 | 1.7e-27 | 337–483 | GlnD PII-uridylyltransferase |
GlnE | PF03710.22 | 1.3e-74 | 589–828 | Glutamate-ammonia ligase adenylyltransferase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: glnA2 (glutamine synthetase), high confidence from genomic context alone (score 818 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2222c glnA2 |
glutamine synthetase | 975 | 818 ctx | neighborhood:815 textmining:869 |
Rv2223c caeB |
carboxylesterase B | 747 | 737 ctx | neighborhood:734 |
Rv2050 rbpA |
RNA polymerase-binding protein RbpA | 708 | 709 ctx | cooccurence:706 |
Rv2224c caeA |
carboxylesterase A | 707 | 693 ctx | neighborhood:693 |
Rv2681 hyp |
hypothetical protein | 691 | 691 ctx | cooccurence:690 |
Rv2220 glnA1 |
glutamine synthetase | 973 | 639 ctx | cooccurence:617 textmining:930 |
Rv1830 |
HTH-type transcriptional regulator | 639 | 639 ctx | cooccurence:637 |
Rv2699c hyp |
hypothetical protein | 627 | 628 ctx | cooccurence:624 |
Rv2219 |
transmembrane protein | 594 | 594 ctx | cooccurence:575 |
Rv2413c hyp |
hypothetical protein | 590 | 590 ctx | cooccurence:588 |
Rv3859c gltB |
glutamate synthase large subunit | 763 | 548 ctx | neighborhood:544 textmining:498 |
Rv0807 hyp |
hypothetical protein | 541 | 541 ctx | cooccurence:470 |
Rv1440 secG |
protein-export membrane protein SecG | 536 | 537 ctx | cooccurence:534 |
Rv2696c hyp |
hypothetical protein | 533 | 534 ctx | cooccurence:512 |
Rv2680 hyp |
hypothetical protein | 518 | 518 ctx | cooccurence:515 |
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: [glutamate--ammonia-ligase
- MTBC0 PGAP product: bifunctional [glutamine synthetase] adenylyltransferase/[glutamine synthetase]-adenylyl-L-tyrosine phosphorylase
- Pfam (hmmscan --cut_ga): GlnD_UR_UTase PF08335.17 (E=2e-27), GlnE PF03710.22 (E=1e-74)
- (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_216737.1)
- Domains: Pfam-A via hmmscan --cut_ga — GlnD_UR_UTase (PF08335.17), GlnE (PF03710.22)
- 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
COG1391 - Curated reference: UniProt P9WN27 (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 —
39 functional partner(s); context anchor
glnA2 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002358|Rv2221c|glnE MVVTKLATQRPKLPSVGRLGLVDPPAGERLAQLGWDRHEDQAHVDLLWSLSRAPDADAALRALIRLSENPDTGWDELNAALLRERSLRGRLFSVLGSSLALGDHLVAHPQSWKLLRGKVTLPSHDQLQRSFVECVEESEGMPGSLVHRLRTQYRDYVLMLAALDLAATVEDEPVLPFTVVAARLADAADAALAAALRVAEASVCGEHPPPRLAVIAMGKCGARELNYVSDVDVIFVAERSDPRNARVASEMMRVASAAFFEVDAALRPEGRNGELVRTLESHIAYYQRWAKTWEFQALLKARPVVGDAELGERYLTALMPMVWRACEREDFVVEVQAMRRRVEQLVPADVRGRELKLGSGGLRDVEFAVQLLQLVHARSDESLRVASTVDALAALGEGGYIGREDAANMTASYEFLRLLEHRLQLQRLKRTHLLPDPEDEEAVRWLARAAHIRPDGRNDAAGVLREELKKQNVRVSKLHTKLFYQPLLESIGPTGLEIAHGMTLEAAGRRLAALGYEGPQTALKHMSALVNQSGRRGRVQSVLLPRLLDWMSYAPDPDGGLLAYRRLSEALATESWYLATLRDKPAVAKRLMHVLGTSAYVPDLLMRAPRVIQQYEDGPAGPKLLETEPAAVARALIASASRYPDPERAIAGARTLRRRELARIGSADLLGLLEVTEVCRALTSVWVAVLQAALDVMIRASLPDDDRAPAAIAVIGMGRLGGAELGYGSDADVMFVCEPATGVDDARAVKWSTSIAERVRALLGTPSVDPPLELDANLRPEGRNGPLVRTLGSYAAYYEQWAQPWEIQALLRAHAVAGDAELGQRFLRMVDKTRYPPDGVSADSVREIRRIKARIESERLPRGADPNTHTKLGRGGLADIEWTVQLLQLQHAHQVPALHNTSTLQSLDVIAAADLVPAADVELLRQAWLTATRARNALVLVRGKPTDQLPGPGRQLNAVAVAAGWRNDDGGEFLDNYLRVTRRAKAVVRKVFGS