Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | isocitrate dehydrogenase |
|---|
| MTBC0 PGAP re-annotation | NADP-dependent isocitrate dehydrogenase |
|---|
| Revised (this work) | NADP-dependent isocitrate dehydrogenase. Pfam: Iso_dh (PF00180.26). |
|---|
Auto-curated: this verdict and function were generated by rules from
PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WKL1
SwissProt · reviewed
· Evidence at protein level
|
|---|
| UniProt name | Isocitrate dehydrogenase [NADP] 1 |
|---|
| EC (curated) |
EC 1.1.1.42
|
|---|
| Curated function | Catalyzes the oxidative decarboxylation of isocitrate to 2-oxoglutarate and carbon dioxide with the concomitant reduction of NADP(+). Cannot use NAD(+). |
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|
| Preferred name | icd |
|---|
| eggNOG description | Belongs to the isocitrate and isopropylmalate dehydrogenases family |
|---|
| Orthologous group | COG0538 |
|---|
| EC number |
EC 1.1.1.42
|
|---|
| KEGG orthology |
K00031
|
|---|
| KEGG pathways |
map00020, map00480, map00720, map01100, map01110, map01120, map01130, map01200, map01210, map01230, map04146
|
|---|
| KEGG modules |
M00009, M00010, M00173, M00740
|
|---|
| Gene Ontology (47) |
GO:0000287, GO:0003674, GO:0003824, GO:0004448, GO:0004450, GO:0005488, GO:0005575, GO:0005623, GO:0005886, GO:0005975, GO:0006081, GO:0006082 +35 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 |
0.3 · purifying
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
4 synonymous, 4 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 |
|---|
Iso_dh | PF00180.26 |
7.3e-65 | 12–398 |
Isocitrate/isopropylmalate dehydrogenase |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv1475c acn |
iron-regulated aconitate hydratase |
988 |
983 |
coexpression:806 database:900 |
Rv1248c kgd |
multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase |
959 |
910 |
coexpression:908 textmining:573 |
Rv0066c icd2 |
isocitrate dehydrogenase |
938 |
908 |
database:900 |
Rv2455c korA |
2-oxoglutarate oxidoreductase subunit KorA |
959 |
906 |
database:900 textmining:589 |
Rv2454c korB |
2-oxoglutarate oxidoreductase subunit KorB |
931 |
900 |
database:900 |
Rv1240 mdh |
malate dehydrogenase |
931 |
895 |
coexpression:794 experimental:428 |
Rv1832 gcvB |
glycine dehydrogenase |
855 |
840 |
coexpression:840 |
Rv0337c aspC |
aspartate aminotransferase |
852 |
839 |
database:800 |
Rv3859c gltB |
glutamate synthase large subunit |
960 |
823 |
database:800 textmining:787 |
Rv0951 sucC |
succinyl-CoA ligase subunit beta |
884 |
823 |
coexpression:808 |
Rv0777 purB |
adenylosuccinate lyase PurB |
824 |
817 |
database:800 |
Rv0234c gabD1 |
succinate-semialdehyde dehydrogenase |
825 |
815 |
database:800 |
Rv1731 gabD2 |
succinate-semialdehyde dehydrogenase |
824 |
814 |
database:800 |
Rv2476c gdh |
NAD-dependent glutamate dehydrogenase |
834 |
805 |
database:800 |
Rv1595 nadB |
L-aspartate oxidase |
822 |
802 |
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: isocitrate dehydrogenase
- MTBC0 PGAP product: NADP-dependent isocitrate dehydrogenase
- Pfam (hmmscan --cut_ga): Iso_dh PF00180.26 (E=7e-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_217856.1)
- Domains: Pfam-A via hmmscan --cut_ga — Iso_dh (PF00180.26)
- 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
COG0538
- Curated reference: UniProt
P9WKL1
(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 —
208 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003551|Rv3339c|icd1
MSNAPKIKVSGPVVELDGDEMTRVIWKLIKDMLILPYLDIRLDYYDLGIEHRDATDDQVTIDAAYAIKKHGVGVKCATITPDEARVEEFNLKKMWLSPNGTIRNILGGTIFREPIVISNVPRLVPGWTKPIVIGRHAFGDQYRATNFKVDQPGTVTLTFTPADGSAPIVHEMVSIPEDGGVVLGMYNFKESIRDFARASFSYGLNAKWPVYLSTKNTILKAYDGMFKDEFERVYEEEFKAQFEAAGLTYEHRLIDDMVAACLKWEGGYVWACKNYDGDVQSDTVAQGYGSLGLMTSVLMTADGKTVEAEAAHGTVTRHYRQYQAGKPTSTNPIASIFAWTRGLQHRGKLDGTPEVIDFAHKLESVVIATVESGKMTKDLAILIGPEQDWLNSEEFLDAIADNLEKELAN
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