Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | NAD-dependent glutamate dehydrogenase |
|---|
| MTBC0 PGAP re-annotation | NAD-glutamate dehydrogenase |
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| Revised (this work) | NAD-glutamate dehydrogenase. Pfam: GDH_ACT1 (PF21075.4), GDH_HM1 (PF21073.3), GDH_ACT2 (PF21076.4), GDH_HM2 (PF21079.3), GDH_ACT3 (PF21077.4), GDH_HM3 (PF21078.3), Bac_GDH_CD (PF05088.19), GDH_C (PF21074.3). |
|---|
Auto-curated: this verdict and function were generated by rules from
PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53203
SwissProt · reviewed
· Evidence at protein level
|
|---|
| UniProt name | NAD-specific glutamate dehydrogenase |
|---|
| EC (curated) |
EC 1.4.1.2
|
|---|
| Curated function | Catalyzes the reversible conversion of L-glutamate to 2-oxoglutarate. |
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|
| Preferred name | gdh |
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| eggNOG description | Dehydrogenase |
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| Orthologous group | COG2902 |
|---|
| EC number |
EC 1.4.1.2
|
|---|
| KEGG orthology |
K15371
|
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| KEGG pathways |
map00220, map00250, map00430, map00910, map01100
|
|---|
| Gene Ontology (13) |
GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0016020, GO:0030312, 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 |
0.422 · purifying
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
14 synonymous, 17 missense, 0 nonsense, 0 frameshift
|
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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 |
|---|
GDH_ACT1 | PF21075.4 |
1.2e-10 | 64–176 |
Glutamate dehydrogenase, ACT1 domain |
GDH_HM1 | PF21073.3 |
1.2e-08 | 328–383 |
Glutamate dehydrogenase, helical motif 1 |
GDH_ACT2 | PF21076.4 |
1.3e-21 | 391–490 |
Glutamate dehydrogenase, ACT2 domain |
GDH_HM2 | PF21079.3 |
2.2e-04 | 512–538 |
Glutamate dehydrogenase, helical motif 2 |
GDH_ACT3 | PF21077.4 |
2.0e-13 | 550–608 |
Glutamate dehydrogenase, ACT3 domain |
GDH_HM3 | PF21078.3 |
4.4e-28 | 641–706 |
Glutamate dehydrogenase, helical motif 3 |
Bac_GDH_CD | PF05088.19 |
4.8e-252 | 724–1230 |
Bacterial NAD-glutamate dehydrogenase, catalytic domain |
GDH_C | PF21074.3 |
1.2e-105 | 1278–1612 |
Glutamate dehydrogenase, C-terminal |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv2475c hyp |
hypothetical protein |
968 |
968 ctx |
neighborhood:881 coexpression:744 |
Rv1187 rocA |
pyrroline-5-carboxylate dehydrogenase RocA |
909 |
907 |
database:900 |
Rv1827 garA |
glycogen accumulation regulator GarA |
945 |
906 |
experimental:905 textmining:446 |
Rv0337c aspC |
aspartate aminotransferase |
943 |
905 |
database:900 textmining:437 |
Rv3858c gltD |
glutamate synthase small subunit |
910 |
905 |
database:900 |
Rv2220 glnA1 |
glutamine synthetase |
967 |
904 |
database:900 textmining:678 |
Rv0788 purQ |
phosphoribosylformylglycinamidine synthase |
904 |
904 |
database:900 |
Rv0252 nirB |
nitrite reductase large subunit NirB |
903 |
903 |
database:900 |
Rv3859c gltB |
glutamate synthase large subunit |
975 |
902 |
database:900 textmining:756 |
Rv2860c glnA4 |
glutamine synthetase |
949 |
901 |
database:900 textmining:511 |
Rv2222c glnA2 |
glutamine synthetase |
941 |
901 |
database:900 textmining:431 |
Rv1653 argJ |
bifunctional glutamate N-acetyltransferase/amino-acid acetyltransferase |
901 |
901 |
database:900 |
Rv0428c |
GCN5-like N-acetyltransferase |
900 |
901 |
database:900 |
Rv3432c gadB |
glutamate decarboxylase GadB |
952 |
900 |
database:900 textmining:541 |
Rv1878 glnA3 |
glutamine synthetase GlnA |
938 |
900 |
database:900 textmining:409 |
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: NAD-dependent glutamate dehydrogenase
- MTBC0 PGAP product: NAD-glutamate dehydrogenase
- Pfam (hmmscan --cut_ga): GDH_ACT1 PF21075.4 (E=1e-10), GDH_HM1 PF21073.3 (E=1e-08), GDH_ACT2 PF21076.4 (E=1e-21), GDH_HM2 PF21079.3 (E=2e-04), GDH_ACT3 PF21077.4 (E=2e-13), GDH_HM3 PF21078.3 (E=4e-28), Bac_GDH_CD PF05088.19 (E=5e-252), GDH_C PF21074.3 (E=1e-105)
- (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_216992.1)
- Domains: Pfam-A via hmmscan --cut_ga — GDH_ACT1 (PF21075.4), GDH_HM1 (PF21073.3), GDH_ACT2 (PF21076.4), GDH_HM2 (PF21079.3), GDH_ACT3 (PF21077.4), GDH_HM3 (PF21078.3), Bac_GDH_CD (PF05088.19), GDH_C (PF21074.3)
- 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
COG2902
- Curated reference: UniProt
O53203
(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 —
62 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002638|Rv2476c|gdh
MTIDPGAKQDVEAWTTFTASADIPDWISKAYIDSYRGPRDDSSEATKAAEASWLPASLLTPAMLGAHYRLGRHRAAGESCVAVYRADDPAGFGPALQVVAEHGGMLMDSVTVLLHRLGIAYAAILTPVFDVHRSPTGELLRIEPKAEGTSPHLGEAWMHVALSPAVDHKGLAEVERLLPKVLADVQRVATDATALIATLSELAGEVESNAGGRFSAPDRQDVGELLRWLGDGNFLLLGYQRCRVADGMVYGEGSSGMGVLRGRTGSRPRLTDDDKLLVLAQARVGSYLRYGAYPYAIAVREYVDGSVVEHRFVGLFSVAAMNADVLEIPTISRRVREALAMAESDPSHPGQLLLDVIQTVPRPELFTLSAQRLLTMARAVVDLGSQRQALLFLRADRLQYFVSCLVYMPRDRYTTAVRMQFEDILVREFGGTRLEFTARVSESPWALMHFMVRLPEVGVAGEGAAAPPVDVSEANRIRIQGLLTEAARTWADRLIGAAAAAGSVGQADAMHYAAAFSEAYKQAVTPADAIGDIAVITELTDDSVKLVFSERDEQGVAQLTWFLGGRTASLSQLLPMLQSMGVVVLEERPFSVTRPDGLPVWIYQFKISPHPTIPLAPTVAERAATAHRFAEAVTAIWHGRVEIDRFNELVMRAGLTWQQVVLLRAYAKYLRQAGFPYSQSYIESVLNEHPATVRSLVDLFEALFVPVPSGSASNRDAQAAAAAVAADIDALVSLDTDRILRAFASLVQATLRTNYFVTRQGSARCRDVLALKLNAQLIDELPLPRPRYEIFVYSPRVEGVHLRFGPVARGGLRWSDRRDDFRTEILGLVKAQAVKNAVIVPVGAKGGFVVKRPPLPTGDPAADRDATRAEGVACYQLFISGLLDVTDNVDHATASVNPPPEVVRRDGDDAYLVVAADKGTATFSDIANDVAKSYGFWLGDAFASGGSVGYDHKAMGITARGAWEAVKRHFREIGIDTQTQDFTVVGIGDMSGDVFGNGMLLSKHIRLIAAFDHRHIFLDPNPDAAVSWAERRRMFELPRSSWGDYDRSLISEGGGVYSREQKAIPLSAQVRAVLGIDGSVDGGAAEMAPPNLIRAILRAPVDLLFNGGIGTYIKAESESDADVGDRANDPVRVNANQVRAKVIGEGGNLGVTALGRVEFDLSGGRINTDALDNSAGVDCSDHEVNIKILIDSLVSAGTVKADERTQLLESMTDEVAQLVLADNEDQNDLMGTSRANAASLLPVHAMQIKYLVAERGVNRELEALPSEKEIARRSEAGIGLTSPELATLMAHVKLGLKEEVLATELPDQDVFASRLPRYFPTALRERFTPEIRSHQLRREIVTTMLINDLVDTAGITYAFRIAEDVGVTPIDAVRTYVATDAIFGVGHIWRRIRAANLPIALSDRLTLDTRRLIDRAGRWLLNYRPQPLAVGAEINRFAAMVKALTPRMSEWLRGDDKAIVEKTAAEFASQGVPEDLAYRVSTGLYRYSLLDIIDIADIADIDAAEVADTYFALMDRLGTDGLLTAVSQLPRHDRWHSLARLAIRDDIYGALRSLCFDVLAVGEPGESSEQKIAEWEHLSASRVARARRTLDDIRASGQKDLATLSVAARQIRRMTRTSGRGISG
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