leuC Family assigned · medium auto-curated
H37Rv Rv2988c · MTBC0 mtbc0_003173 ·
473 aa · 3365963–3367384 (-) ·
RefSeq NP_217504.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 3-isopropylmalate dehydratase large subunit |
|---|---|
| MTBC0 PGAP re-annotation | 3-isopropylmalate dehydratase large subunit |
| Revised (this work) | 3-isopropylmalate dehydratase large subunit. Pfam: Aconitase (PF00330.26). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WQF5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | 3-isopropylmalate dehydratase large subunit |
| EC (curated) |
EC 4.2.1.33
|
| Curated function | Catalyzes the isomerization between 2-isopropylmalate and 3-isopropylmalate, via the formation of 2-isopropylmaleate. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | leuC |
| eggNOG description | Catalyzes the isomerization between 2-isopropylmalate and 3-isopropylmalate, via the formation of 2-isopropylmaleate |
| Orthologous group | COG0065 |
| EC number |
EC 4.2.1.33, EC 4.2.1.35
|
| KEGG orthology |
K01703
|
| KEGG pathways |
map00290, map00660, map00966, map01100, map01110, map01210, map01230
|
| KEGG modules |
M00432, M00535
|
| Gene Ontology (6) |
GO:0005575, GO:0005618, GO:0005623, GO:0030312, GO:0044464, GO:0071944
|
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 | 0.23 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 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 |
|---|---|---|---|---|
Aconitase | PF00330.26 | 5.8e-177 | 13–464 | Aconitase family (aconitate hydratase) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: leuD (3-isopropylmalate dehydratase small subunit), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2987c leuD |
3-isopropylmalate dehydratase small subunit | 999 | 1000 ctx | neighborhood:849 fusion:899 cooccurence:774 coexpression:976 experimental:511 database:900 textmining:948 |
Rv2995c leuB |
3-isopropylmalate dehydrogenase | 999 | 997 ctx | cooccurence:695 coexpression:857 database:900 textmining:702 |
Rv3710 leuA |
2-isopropylmalate synthase | 990 | 976 | coexpression:696 database:900 textmining:615 |
Rv2989 |
transcriptional regulator | 983 | 969 ctx | neighborhood:785 coexpression:860 textmining:499 |
Rv0189c ilvD |
dihydroxy-acid dehydratase | 967 | 933 ctx | cooccurence:546 coexpression:846 textmining:540 |
Rv3001c ilvC |
ketol-acid reductoisomerase | 958 | 903 | coexpression:852 textmining:588 |
Rv3002c ilvN |
acetolactate synthase small subunit | 867 | 828 | coexpression:777 |
Rv2454c korB |
2-oxoglutarate oxidoreductase subunit KorB | 817 | 811 | database:800 |
Rv2455c korA |
2-oxoglutarate oxidoreductase subunit KorA | 820 | 810 | database:800 |
Rv2332 mez |
malate oxidoreductase | 816 | 807 | database:800 |
Rv1617 pykA |
pyruvate kinase | 822 | 806 | database:800 |
Rv1127c ppdK |
pyruvate, phosphate dikinase PpdK | 806 | 806 | database:800 |
Rv1872c lldD2 |
L-lactate dehydrogenase | 803 | 802 | database:800 |
Rv2241 aceE |
pyruvate dehydrogenase E1 component | 813 | 801 | database:800 |
Rv0694 mftD |
mycofactocin system heme/flavin oxidoreductase MftD | 801 | 801 | 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: 3-isopropylmalate dehydratase large subunit
- MTBC0 PGAP product: 3-isopropylmalate dehydratase large subunit
- Pfam (hmmscan --cut_ga): Aconitase PF00330.26 (E=6e-177)
- (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_217504.1)
- Domains: Pfam-A via hmmscan --cut_ga — Aconitase (PF00330.26)
- 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
COG0065 - Curated reference: UniProt P9WQF5 (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 —
55 functional partner(s); context anchor
leuD - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003173|Rv2988c|leuC MALQTGEPRTLAEKIWDDHIVVSGGGCAPDLIYIDLHLVHEVTSPQAFDGLRLAGRRVRRPELTLATEDHNVPTVDIDQPIADPVSRTQVETLRRNCAEFGIRLHSMGDIEQGIVHVVGPQLGLTQPGMTIVCGDSHTSTHGAFGALAMGIGTSEVEHVLATQTLPLRPFKTMAVNVDGRLPDGVSAKDIILALIAKIGTGGGQGHVIEYRGSAIESLSMEGRMTICNMSIEAGARAGMVAPDETTYAFLRGRPHAPTGAQWDTALVYWQRLRTDVGAVFDTEVYLDAASLSPFVTWGTNPGQGVPLAAAVPDPQLMTDDAERQAAEKALAYMDLRPGTAMRDIAVDAVFVGSCTNGRIEDLRVVAEVLRGRKVADGVRMLIVPGSMRVRAQAEAEGLGEIFTDAGAQWRQAGCSMCLGMNPDQLASGERCAATSNRNFEGRQGAGGRTHLVSPAVAAATAVRGTLSSPADLN