gltD Family assigned · medium auto-curated

H37Rv Rv3858c · MTBC0 mtbc0_004091 · 488 aa · 4354149–4355615 (-) · RefSeq NP_218375.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)glutamate synthase small subunit
MTBC0 PGAP re-annotationglutamate synthase subunit beta
Revised (this work)Glutamate synthase subunit beta. Pfam: Fer4_20 (PF14691.12), Pyr_redox_2 (PF07992.21), FAD_binding_3 (PF01494.26), Pyr_redox (PF00070.34), FAD_oxidored (PF12831.14), DAO (PF01266.31), FAD_binding_2 (PF00890.31), NAD_binding_8 (PF13450.13), Amino_oxidase (PF01593.31).

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

Curated reference (UniProt)

UniProt P9WN19 SwissProt · reviewed · Evidence at protein level
UniProt nameGlutamate synthase [NADPH] small chain
EC (curated) EC 1.4.1.13

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
Preferred namegltD
eggNOG descriptionglutamate synthase
Orthologous groupCOG0493
EC number EC 1.4.1.13, EC 1.4.1.14
KEGG orthology K00266
KEGG pathways map00250, map00910, map01100, map01110, map01120, map01130, map01230
Gene Ontology (13) GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0008150, GO:0016020, GO:0040007, GO:0044424, GO:0044444, GO:0044464 +1 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 0.335 · purifying
Polymorphic sites (≥ 0.1% of strains) 6 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
Fer4_20PF14691.12 4.9e-2525–132 Dihydroprymidine dehydrogenase domain II, 4Fe-4S cluster
Pyr_redox_2PF07992.21 4.1e-26146–459 Pyridine nucleotide-disulphide oxidoreductase
FAD_binding_3PF01494.26 3.5e-05146–177 FAD binding domain
Pyr_redoxPF00070.34 1.4e-05147–180 Pyridine nucleotide-disulphide oxidoreductase
FAD_oxidoredPF12831.14 2.4e-07147–183 FAD dependent oxidoreductase
DAOPF01266.31 1.2e-06147–180 FAD dependent oxidoreductase
FAD_binding_2PF00890.31 1.2e-05147–181 FAD binding domain
NAD_binding_8PF13450.13 1.8e-10149–183 NAD(P)-binding Rossmann-like domain
Amino_oxidasePF01593.31 3.7e-09155–184 Flavin containing amine oxidoreductase

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

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

PartnerProductScoreNo text-miningChannels (≥400)
Rv3859c gltB glutamate synthase large subunit 999 1000 ctx neighborhood:881 fusion:900 cooccurence:774 coexpression:999 experimental:999 database:900 textmining:711
Rv1937 oxygenase 992 989 experimental:973 database:568
Rv2220 glnA1 glutamine synthetase 953 916 database:900 textmining:467
Rv2860c glnA4 glutamine synthetase 917 913 database:900
Rv2222c glnA2 glutamine synthetase 917 913 database:900
Rv1878 glnA3 glutamine synthetase GlnA 916 913 database:900
Rv1187 rocA pyrroline-5-carboxylate dehydrogenase RocA 915 911 database:900
Rv1384 carB carbamoyl-phosphate synthase large subunit 930 907 database:900
Rv0808 purF amidophosphoribosyltransferase 913 905 database:900
Rv2476c gdh NAD-dependent glutamate dehydrogenase 910 905 database:900
Rv3436c glmS glucosamine--fructose-6-phosphate aminotransferase 916 904 database:900
Rv1383 carA carbamoyl-phosphate synthase small subunit 907 904 database:900
Rv0788 purQ phosphoribosylformylglycinamidine synthase 900 901 database:900
Rv3432c gadB glutamate decarboxylase GadB 900 900 database:900
Rv2455c korA 2-oxoglutarate oxidoreductase subunit KorA 851 829 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: glutamate synthase small subunit
  • MTBC0 PGAP product: glutamate synthase subunit beta
  • Pfam (hmmscan --cut_ga): Fer4_20 PF14691.12 (E=5e-25), Pyr_redox_2 PF07992.21 (E=4e-26), FAD_binding_3 PF01494.26 (E=3e-05), Pyr_redox PF00070.34 (E=1e-05), FAD_oxidored PF12831.14 (E=2e-07), DAO PF01266.31 (E=1e-06), FAD_binding_2 PF00890.31 (E=1e-05), NAD_binding_8 PF13450.13 (E=2e-10), Amino_oxidase PF01593.31 (E=4e-09)
  • (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_218375.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Fer4_20 (PF14691.12), Pyr_redox_2 (PF07992.21), FAD_binding_3 (PF01494.26), Pyr_redox (PF00070.34), FAD_oxidored (PF12831.14), DAO (PF01266.31), FAD_binding_2 (PF00890.31), NAD_binding_8 (PF13450.13), Amino_oxidase (PF01593.31)
  • 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 COG0493
  • Curated reference: UniProt P9WN19 (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 — 86 functional partner(s); context anchor gltB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_004091|Rv3858c|gltD
MADPGGFLKYTHRKLPKRRPVPLRLRDWREVYEEFDNESLRQQATRCMDCGIPFCHNGCPLGNLIPEWNDLVRRGRWRDAIERLHATNNFPDFTGRLCPAPCEPACVLGINQDPVTIKQIELEIIDKAFDEGWVQPRPPRKLTGQTVAVVGSGPAGLAAAQQLTRAGHTVTVFEREDRIGGLLRYGIPEFKMEKRHLDRRLDQMRSEGTEFRPGVNVGVDISAEKLRADFDAVVLAGGATAWRELPIPGRELEGVHQAMEFLPWANRVQEGDDVLDEDGQPPITAKGKKVVIIGGGDTGADCLGTVHRQGAIAVHQFEIMPRPPDARAESTPWPTYPLMYRVSAAHEEGGERVFSVNTEAFVGTDGRVSALRAHEVTMLDGKFVKVEGSDFELEADLVLLAMGFVGPERAGLLTDLGVKFTERGNVARGDDFDTSVPGVFVAGDMGRGQSLIVWAIAEGRAAAAAVDRYLMGSSALPAPVKPTAAPLQ