gltB Family assigned · medium auto-curated

H37Rv Rv3859c · MTBC0 mtbc0_004092 · 1527 aa · 4355608–4360191 (-) · RefSeq NP_218376.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)glutamate synthase large subunit
MTBC0 PGAP re-annotationglutamate synthase large subunit
Revised (this work)Glutamate synthase large subunit. Pfam: GATase_2 (PF00310.27), Glu_syn_central (PF04898.21), Glu_synthase (PF01645.24), GXGXG (PF01493.26).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt P96218 SwissProt · reviewed · Evidence at protein level
UniProt nameGlutamate synthase [NADPH] large chain
EC (curated) EC 1.4.1.13

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
Preferred namegltB
eggNOG descriptionglutamate synthase
Orthologous groupCOG0067
EC number EC 1.4.1.13, EC 1.4.1.14, EC 1.4.7.1
KEGG orthology K00265, K00284
KEGG pathways map00250, map00630, map00910, map01100, map01110, map01120, map01130, map01230
Gene Ontology (50) GO:0003674, GO:0003824, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0006082, GO:0006520, GO:0006536, GO:0006537 +38 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 0.31 · purifying
Polymorphic sites (≥ 0.1% of strains) 14 synonymous, 13 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
GATase_2PF00310.27 1.9e-17818–439 Glutamine amidotransferases class-II
Glu_syn_centralPF04898.21 8.6e-113466–757 Glutamate synthase central domain
Glu_synthasePF01645.24 3.7e-146821–1189 Conserved region in glutamate synthase
GXGXGPF01493.26 1.5e-1011249–1498 GXGXG motif

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: gltD (glutamate synthase small subunit), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3858c gltD glutamate synthase small subunit 999 1000 ctx neighborhood:881 fusion:900 cooccurence:774 coexpression:999 experimental:999 database:900 textmining:711
Rv3106 fprA NADPH-ferredoxin reductase FprA 999 1000 ctx neighborhood:455 coexpression:999 experimental:999 textmining:519
Rv1175c fadH NADPH dependent 2,4-dienoyl-CoA reductase FadH 999 1000 ctx neighborhood:544 coexpression:999 experimental:999 textmining:670
Rv0886 fprB ferredoxin/ferredoxin--NADP reductase 999 1000 ctx neighborhood:544 coexpression:999 experimental:999 textmining:621
Rv1384 carB carbamoyl-phosphate synthase large subunit 991 971 ctx neighborhood:544 coexpression:407 database:900 textmining:730
Rv2220 glnA1 glutamine synthetase 989 970 ctx neighborhood:456 coexpression:501 database:900 textmining:659
Rv2860c glnA4 glutamine synthetase 985 970 ctx neighborhood:456 coexpression:499 database:900 textmining:519
Rv1878 glnA3 glutamine synthetase GlnA 985 970 ctx neighborhood:456 coexpression:497 database:900 textmining:519
Rv2222c glnA2 glutamine synthetase 985 970 ctx neighborhood:456 coexpression:500 database:900 textmining:519
Rv3575c LacI family transcriptional regulator 976 963 experimental:963
Rv3436c glmS glucosamine--fructose-6-phosphate aminotransferase 981 958 ctx neighborhood:544 database:900 textmining:589
Rv0808 purF amidophosphoribosyltransferase 965 953 ctx neighborhood:544 database:900
Rv1383 carA carbamoyl-phosphate synthase small subunit 954 953 ctx neighborhood:544 database:900
Rv1187 rocA pyrroline-5-carboxylate dehydrogenase RocA 940 917 database:900
Rv0788 purQ phosphoribosylformylglycinamidine synthase 903 904 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: glutamate synthase large subunit
  • MTBC0 PGAP product: glutamate synthase large subunit
  • Pfam (hmmscan --cut_ga): GATase_2 PF00310.27 (E=2e-178), Glu_syn_central PF04898.21 (E=9e-113), Glu_synthase PF01645.24 (E=4e-146), GXGXG PF01493.26 (E=2e-101)
  • (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_218376.1)
  • Domains: Pfam-A via hmmscan --cut_ga — GATase_2 (PF00310.27), Glu_syn_central (PF04898.21), Glu_synthase (PF01645.24), GXGXG (PF01493.26)
  • 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 COG0067
  • Curated reference: UniProt P96218 (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 — 449 functional partner(s); context anchor gltD
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_004092|Rv3859c|gltB
MTPKRVGLYNPAFEHDSCGVAMVVDMHGRRSRDIVDKAITALLNLEHRGAQGAEPRSGDGAGILIQVPDEFLREAVDFELPAPGSYATGIAFLPQSSKDAAAACAAVQKIAEAEGLQVLGWRSVPTDDSSLGALSRDAMPTFRQVFLAGASGMALERRCYVVRKRAEHELGTKGPGQDGPGRETVYFPSLSGQTLVYKGMLTTPQLKAFYLDLQDERLTSALGIVHSRFSTNTFPSWPLAHPFRRIAHNGEINTVTGNENWMRAREALIKTDIFGSAADVEKLFPICTPGASDTARFDEVLELLHLGGRSLAHAVLMMIPEAWERHESMDPARRAFYQYHASLMEPWDGPASMTFTDGTVVGAVLDRNGLRPSRIWVTDDGLVVMASEAGVLDLHPSTVVRRMRLQPGRMFLVDTAQGRIVSDEEIKADLAAEHPYQEWLDNGLVPLDELPEGKDVRMPHHRIVMRQLAFGYTYEELNLLVAPMARLGAEPIGSMGTDTPVAVLSQRPRMLYDYFHQLFAQVTNPPLDAIREEVVTSLQGTTGGERDLLNPDENSCHQIVLPQPILRNHELAKLVSLDPNDKVNGRPHGLRSKVIRCLYRVSEGGAGLAAALEEVRGAAAAAIADGARIIILSDRESDEEMAPIPSLLAVAGVHHHLVRERTRTQVGLVVESGDAREVHHMAALVGFGAAAINPYLVFESIEDMLDRGVIEGIDRTAALNNYIKAAGKGVLKVMSKMGISTLASYTGAQLFQAVGISEQVLDEYFTGLTCPTGGITLDDIAADVAARHRLAYLDRPDERAHRELEVGGEYQWRREGEYHLFNPETVFKLQHSTRTGQYKIFKEYTRLVDDQSERMASLRGLLKFRTGVRPPVPLDEVEPASEIVKRFSTGAMSYGSISAEAHETLAIAMNRLGARSNCGEGGEDVKRFDRDPNGDWRRSAIKQVASARFGVTSHYLTNCTDLQIKMAQGAKPGEGGQLPGHKVYPWVAEVRHSTPGVGLISPPPHHDIYSIEDLAQLIHDLKNANPSARVHVKLVSENGVGTVAAGVSKAHADVVLISGHDGGTGATPLTSMKHAGAPWELGLAETQQTLLLNGLRDRIVVQVDGQLKTGRDVMIATLLGAEEFGFATAPLVVAGCIMMRVCHLDTCPVGVATQNPLLRERFTGKPEFVENFFMFIAEEVREYLAQLGFRTVNEAVGQAGALDTTLARAHWKAHKLDLAPVLHEPESAFMNQDLYCSSRQDHGLDKALDQQLIVMSREALDSGKPVRFSTTIGNVNRTVGTMLGHELTKAYGGQGLPDGTIDITFDGSAGNSFGAFVPKGITLRVYGDANDYVGKGLSGGRIVVRPSDDAPQDYVAEDNIIGGNVILFGATSGEVYLRGVVGERFAVRNSGAHAVVEGVGDHGCEYMTGGRVVILGRTGRNFAAGMSGGVAYVYDPDGELPANLNSEMVELETLDEDDADWLHGTIQVHVDATDSAVGQRILSDWSGQQRHFVKVMPRDYKRVLQAIALAERDGVDVDKAIMAAAHG