leuB Resolved · high auto-curated
H37Rv Rv2995c · MTBC0 mtbc0_003182 ·
336 aa · 3373767–3374777 (-) ·
RefSeq NP_217511.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 3-isopropylmalate dehydrogenase |
|---|---|
| MTBC0 PGAP re-annotation | 3-isopropylmalate dehydrogenase |
| Revised (this work) | 3-isopropylmalate 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 |
P9WKK9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | 3-isopropylmalate dehydrogenase |
| EC (curated) |
EC 1.1.1.85
|
| Curated function | Catalyzes the oxidation of 3-carboxy-2-hydroxy-4-methylpentanoate (3-isopropylmalate) to 3-carboxy-4-methyl-2-oxopentanoate. The product decarboxylates to 4-methyl-2 oxopentanoate. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversionE Amino acid transport and metabolism
|
|---|---|
| Preferred name | leuB |
| eggNOG description | Catalyzes the oxidation of 3-carboxy-2-hydroxy-4- methylpentanoate (3-isopropylmalate) to 3-carboxy-4-methyl-2- oxopentanoate. The product decarboxylates to 4-methyl-2 oxopentanoate |
| Orthologous group | COG0473 |
| EC number |
EC 1.1.1.85
|
| KEGG orthology |
K00052
|
| KEGG pathways |
map00290, map00660, map01100, map01110, map01210, map01230
|
| KEGG modules |
M00432, M00535
|
| Gene Ontology (16) |
GO:0003674, GO:0003824, GO:0003862, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0008150, GO:0008152, GO:0016491, GO:0016614, GO:0016616 +4 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 | 0.06 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 1 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 | 8.9e-88 | 3–330 | Isocitrate/isopropylmalate dehydrogenase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: leuC (3-isopropylmalate dehydratase large subunit), high confidence from genomic context alone (score 997 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2988c leuC |
3-isopropylmalate dehydratase large subunit | 999 | 997 ctx | cooccurence:695 coexpression:857 database:900 textmining:702 |
Rv2987c leuD |
3-isopropylmalate dehydratase small subunit | 998 | 996 ctx | cooccurence:713 coexpression:857 database:900 textmining:700 |
Rv3002c ilvN |
acetolactate synthase small subunit | 995 | 985 | coexpression:768 database:900 textmining:714 |
Rv2996c serA1 |
D-3-phosphoglycerate dehydrogenase | 979 | 976 ctx | neighborhood:869 coexpression:826 |
Rv3003c ilvB1 |
acetolactate synthase large subunit IlvB | 977 | 970 ctx | cooccurence:456 coexpression:409 database:900 |
Rv3470c ilvB2 |
acetolactate synthase large subunit | 961 | 958 | coexpression:402 database:900 |
Rv1820 ilvG |
acetolactate synthase large subunit IlvG | 983 | 956 | coexpression:407 database:900 textmining:629 |
Rv1559 ilvA |
threonine dehydratase IlvA | 977 | 954 | database:900 textmining:537 |
Rv3509c ilvX |
acetohydroxyacid synthase large subunit | 960 | 948 | coexpression:409 database:900 |
Rv3001c ilvC |
ketol-acid reductoisomerase | 972 | 904 | coexpression:837 textmining:725 |
Rv0189c ilvD |
dihydroxy-acid dehydratase | 967 | 892 ctx | cooccurence:435 coexpression:791 textmining:713 |
Rv3469c mhpE |
4-hydroxy-2-oxovalerate aldolase MhpE | 789 | 767 | coexpression:694 |
Rv3710 leuA |
2-isopropylmalate synthase | 936 | 761 | coexpression:696 textmining:745 |
Rv3534c hsaF |
4-hydroxy-2-oxovalerate aldolase | 763 | 738 | coexpression:696 |
Rv1475c acn |
iron-regulated aconitate hydratase | 798 | 737 | database:446 |
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: 3-isopropylmalate dehydrogenase
- MTBC0 PGAP product: 3-isopropylmalate dehydrogenase
- Pfam (hmmscan --cut_ga): Iso_dh PF00180.26 (E=9e-88)
- (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_217511.1)
- 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
COG0473 - Curated reference: UniProt P9WKK9 (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 —
99 functional partner(s); context anchor
leuC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003182|Rv2995c|leuB MKLAIIAGDGIGPEVTAEAVKVLDAVVPGVQKTSYDLGARRFHATGEVLPDSVVAELRNHDAILLGAIGDPSVPSGVLERGLLLRLRFELDHHINLRPARLYPGVASPLSGNPGIDFVVVREGTEGPYTGNGGAIRVGTPNEVATEVSVNTAFGVRRVVADAFERARRRRKHLTLVHKTNVLTFAGGLWLRTVDEVGECYPDVEVAYQHVDAATIHMITDPGRFDVIVTDNLFGDIITDLAAAVCGGIGLAASGNIDATRANPSMFEPVHGSAPDIAGQGIADPTAAIMSVALLLSHLGEHDAAARVDRAVEAHLATRGSERLATSDVGERIAAAL