glnA4 Family assigned · medium auto-curated

H37Rv Rv2860c · MTBC0 mtbc0_003041 · 457 aa · 3192293–3193666 (-) · RefSeq NP_217376.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)glutamine synthetase
MTBC0 PGAP re-annotationglutamine synthetase family protein
Revised (this work)Glutamine synthetase family protein. Pfam: 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 I6X5K1 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable glutamine synthetase GlnA4

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
Preferred nameglnA4
eggNOG descriptionglutamine synthetase
Orthologous groupCOG0174
EC number EC 6.3.1.2
KEGG orthology K01915
KEGG pathways map00220, map00250, map00630, map00910, map01100, map01120, map01230, map02020, map04217, map04724, map04727

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 0.999 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 6 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)

PfamAccessioni-EvalueResiduesDescription
Gln-synt_CPF00120.30 1.5e-102122–450 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).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3859c gltB glutamate synthase large subunit 985 970 ctx neighborhood:456 coexpression:499 database:900 textmining:519
Rv2857c 3-oxoacyl-ACP reductase 968 967 ctx neighborhood:881 cooccurence:732
Rv2859c glutamine amidotransferase 963 961 ctx neighborhood:881 cooccurence:459 coexpression:445
Rv2858c aldC aldehyde dehydrogenase AldC 933 930 ctx neighborhood:881 cooccurence:405
Rv3436c glmS glucosamine--fructose-6-phosphate aminotransferase 923 916 database:900
Rv3858c gltD glutamate synthase small subunit 917 913 database:900
Rv1383 carA carbamoyl-phosphate synthase small subunit 913 908 database:900
Rv1384 carB carbamoyl-phosphate synthase large subunit 913 906 database:900
Rv1187 rocA pyrroline-5-carboxylate dehydrogenase RocA 909 906 database:900
Rv3432c gadB glutamate decarboxylase GadB 910 905 database:900
Rv0252 nirB nitrite reductase large subunit NirB 929 904 database:900
Rv0808 purF amidophosphoribosyltransferase 911 904 database:900
Rv0788 purQ phosphoribosylformylglycinamidine synthase 906 902 database:900
Rv2476c gdh NAD-dependent glutamate dehydrogenase 949 901 database:900 textmining:511
Rv0253 nirD nitrite reductase small subunit NirD 906 901 database:900

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: glutamine synthetase family protein
  • Pfam (hmmscan --cut_ga): Gln-synt_C PF00120.30 (E=1e-102)
  • (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_217376.1)
  • Domains: Pfam-A via hmmscan --cut_ga — 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 I6X5K1 (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 — 62 functional partner(s); context anchor gltB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003041|Rv2860c|glnA4
MTGPGSPPLAWTELERLVAAGDVDTVIVAFTDMQGRLAGKRISGRHFVDDIATRGVECCSYLLAVDVDLNTVPGYAMASWDTGYGDMVMTPDLSTLRLIPWLPGTALVIADLVWADGSEVAVSPRSILRRQLDRLKARGLVADVATELEFIVFDQPYRQAWASGYRGLTPASDYNIDYAILASSRMEPLLRDIRLGMAGAGLRFEAVKGECNMGQQEIGFRYDEALVTCDNHAIYKNGAKEIADQHGKSLTFMAKYDEREGNSCHIHVSLRGTDGSAVFADSNGPHGMSSMFRSFVAGQLATLREFTLCYAPTINSYKRFADSSFAPTALAWGLDNRTCALRVVGHGQNIRVECRVPGGDVNQYLAVAALIAGGLYGIERGLQLPEPCVGNAYQGADVERLPVTLADAAVLFEDSALVREAFGEDVVAHYLNNARVELAAFNAAVTDWERIRGFERL