gnd2 Resolved · high auto-curated
H37Rv Rv1122 · MTBC0 mtbc0_001205 ·
340 aa · 1253569–1254591 (+) ·
RefSeq NP_215638.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 6-phosphogluconate dehydrogenase (decarboxylating) |
|---|---|
| MTBC0 PGAP re-annotation | decarboxylating 6-phosphogluconate dehydrogenase |
| Revised (this work) | Decarboxylating 6-phosphogluconate dehydrogenase. Pfam: NAD_binding_2 (PF03446.22), F420_oxidored (PF03807.24), TrkA_N (PF02254.25), 6PGD (PF00393.25). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O06574
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable 6-phosphogluconate dehydrogenase,decarboxylating Gnd2 |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
G Carbohydrate transport and metabolism
|
|---|---|
| Preferred name | gnd2 |
| eggNOG description | 6-phosphogluconate dehydrogenase |
| Orthologous group | COG1023 |
| EC number |
EC 1.1.1.343, EC 1.1.1.44
|
| KEGG orthology |
K00033
|
| KEGG pathways |
map00030, map00480, map01100, map01110, map01120, map01130, map01200
|
| KEGG modules |
M00004, M00006
|
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 | 2.01 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
NAD_binding_2 | PF03446.22 | 4.4e-37 | 2–155 | NAD binding domain of 6-phosphogluconate dehydrogenase |
F420_oxidored | PF03807.24 | 2.5e-05 | 3–94 | NADP oxidoreductase coenzyme F420-dependent |
TrkA_N | PF02254.25 | 1.3e-04 | 6–44 | TrkA-N domain |
6PGD | PF00393.25 | 2.3e-09 | 186–214 | 6-phosphogluconate dehydrogenase, C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: zwf1 (glucose-6-phosphate 1-dehydrogenase), high confidence from genomic context alone (score 980 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1121 zwf1 |
glucose-6-phosphate 1-dehydrogenase | 984 | 980 ctx | neighborhood:851 fusion:454 cooccurence:754 |
Rv1445c devB |
6-phosphogluconolactonase | 964 | 962 ctx | cooccurence:577 database:900 |
Rv1844c gnd1 |
6-phosphogluconate dehydrogenase | 916 | 916 | database:900 |
Rv1447c zwf2 |
glucose-6-phosphate 1-dehydrogenase | 935 | 910 ctx | fusion:643 cooccurence:718 |
Rv2465c rpiB |
ribose-5-phosphate isomerase B | 914 | 908 | database:900 |
Rv1408 rpe |
ribulose-phosphate 3-epimerase | 909 | 902 | database:900 |
Rv1119c hyp |
hypothetical protein | 520 | 521 ctx | neighborhood:519 |
Rv1120c hyp |
hypothetical protein | 519 | 519 ctx | neighborhood:519 |
Rv0004 hyp |
hypothetical protein | 708 | 463 ctx | neighborhood:458 textmining:479 |
Rv0003 recF |
DNA replication/repair protein RecF | 590 | 461 ctx | neighborhood:458 |
Rv1448c tal |
transaldolase | 515 | 438 | |
Rv1118c hyp |
hypothetical protein | 411 | 412 ctx | neighborhood:408 |
Rv0729 xylB |
D-xylulose kinase XylB | 448 | 374 | |
Rv3673c |
membrane-anchored thioredoxin-like protein | 662 | 55 | textmining:658 |
Rv0542c menE |
2-succinylbenzoic acid--CoA ligase | 661 | 54 | textmining:657 |
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: 6-phosphogluconate dehydrogenase (decarboxylating)
- MTBC0 PGAP product: decarboxylating 6-phosphogluconate dehydrogenase
- Pfam (hmmscan --cut_ga): NAD_binding_2 PF03446.22 (E=4e-37), F420_oxidored PF03807.24 (E=3e-05), TrkA_N PF02254.25 (E=1e-04), 6PGD PF00393.25 (E=2e-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_215638.1)
- Domains: Pfam-A via hmmscan --cut_ga — NAD_binding_2 (PF03446.22), F420_oxidored (PF03807.24), TrkA_N (PF02254.25), 6PGD (PF00393.25)
- 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
COG1023 - Curated reference: UniProt O06574 (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 —
26 functional partner(s); context anchor
zwf1 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001205|Rv1122|gnd2 MQLGMIGLGRMGANIVRRLAKGGHDCVVYDHDPDAVKAMAGEDRTTGVASLRELSQRLSAPRVVWVMVPAGNITTAVIEELANTLEAGDIVIDGGNTYYRDDLRHEKLLFKKGIHLLDCGTSGGVWGRERGYCLMIGGDGDAFARAEPIFATVAPGVAAAPRTPGRDGEVAPSEQGYLHCGPCGSGHFVKMVHNGIEYGMMASLAEGLNILRNADVGTRVQHGDAETAPLPNPECYQYDFDIPEVAEVWRRGSVIGSWLLDLTAIALRESPDLAEFSGRVSDSGEGRWTAIAAIDEGVPAPVLTTALQSRFASRDLDDFANKALSAMRKQFGGHAEKPAN