glnA3 Family assigned · medium auto-curated

H37Rv Rv1878 · MTBC0 mtbc0_001992 · 450 aa · 2146061–2147413 (+) · RefSeq NP_216394.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)glutamine synthetase GlnA
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 O07752 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable glutamine synthetase GlnA3

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
Preferred nameglnA3
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 0.177 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 2 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 9.2e-65112–432 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)
Rv1879 hyp hypothetical protein 998 995 ctx neighborhood:881 fusion:862 cooccurence:697 textmining:654
Rv3859c gltB glutamate synthase large subunit 985 970 ctx neighborhood:456 coexpression:497 database:900 textmining:519
Rv3436c glmS glucosamine--fructose-6-phosphate aminotransferase 923 916 database:900
Rv3858c gltD glutamate synthase small subunit 916 913 database:900
Rv1383 carA carbamoyl-phosphate synthase small subunit 914 909 database:900
Rv1384 carB carbamoyl-phosphate synthase large subunit 914 906 database:900
Rv3432c gadB glutamate decarboxylase GadB 911 906 database:900
Rv1187 rocA pyrroline-5-carboxylate dehydrogenase RocA 909 906 database:900
Rv0252 nirB nitrite reductase large subunit NirB 933 904 database:900
Rv0808 purF amidophosphoribosyltransferase 911 904 database:900
Rv0253 nirD nitrite reductase small subunit NirD 907 902 database:900
Rv0788 purQ phosphoribosylformylglycinamidine synthase 906 901 database:900
Rv2476c gdh NAD-dependent glutamate dehydrogenase 938 900 database:900 textmining:409
Rv2222c glnA2 glutamine synthetase 869 858 database:800
Rv2220 glnA1 glutamine synthetase 886 853 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 GlnA
  • MTBC0 PGAP product: glutamine synthetase family protein
  • Pfam (hmmscan --cut_ga): Gln-synt_C PF00120.30 (E=9e-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_216394.1)
  • 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 O07752 (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 — 63 functional partner(s); context anchor gltB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001992|Rv1878|glnA3
MTATPLAAAAIAQLEAEGVDTVIGTVVNPAGLTQAKTVPIRRTNTFANPGLGASPVWHTFCIDQCSIAFTADISVVGDQRLRIDLSALRIIGDGLAWAPAGFFEQDGTPVPACSRGTLSRIEAALADAGIDAVIGHEVEFLLVDADGQRLPSTLWAQYGVAGVLEHEAFVRDVNAAATAAGIAIEQFHPEYGANQFEISLAPQPPVAAADQLVLTRLIIGRTARRHGLRVSLSPAPFAGSIGSGAHQHFSLTMSEGMLFSGGTGAAGMTSAGEAAVAGVLRGLPDAQGILCGSIVSGLRMRPGNWAGIYACWGTENREAAVRFVKGGAGSAYGGNVEVKVVDPSANPYLASAAILGLALDGMKTKAVLPSETTVDPTQLSDVDRDRAGILRLAADQADAIAVLDSSKLLRCILGDPVVDAVVAVRQLEHERYGDLDPAQLADKFRMAWSV