ilvD Resolved · high auto-curated
H37Rv Rv0189c · MTBC0 mtbc0_000203 ·
575 aa · 220344–222071 (-) ·
RefSeq NP_214703.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | dihydroxy-acid dehydratase |
|---|---|
| MTBC0 PGAP re-annotation | dihydroxy-acid dehydratase |
| Revised (this work) | Dihydroxy-acid dehydratase. Pfam: ILVD_EDD_N (PF00920.28), ILV_EDD_C (PF24877.2). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WKJ5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Dihydroxy-acid dehydratase |
| EC (curated) |
EC 4.2.1.9
|
| Curated function | Functions in the biosynthesis of branched-chain amino acids. Catalyzes the dehydration of (2R,3R)-2,3-dihydroxy-3-methylpentanoate (2,3-dihydroxy-3-methylvalerate) into 2-oxo-3-methylpentanoate (2-oxo-3-methylvalerate) and of (2R)-2,3-dihydroxy-3-methylbutanoate (2,3-dihydroxyisovalerate) into 2-oxo-3-methylbutanoate (2-oxoisovalerate), the penultimate precursor to L-isoleucine and L-valine, respectively. Is specific for the (R) isomer of 2,3-dihydroxy-3-methylbutanoate, with no catalytic activity against the (S) isomer. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | ilvD |
| eggNOG description | Belongs to the ILVD EDD family |
| Orthologous group | COG0129 |
| EC number |
EC 4.2.1.9
|
| KEGG orthology |
K01687
|
| KEGG pathways |
map00290, map00770, map01100, map01110, map01130, map01210, map01230
|
| KEGG modules |
M00019, M00570
|
| Gene Ontology (36) |
GO:0003674, GO:0003824, GO:0004160, GO:0005575, GO:0005623, GO:0005886, GO:0006082, GO:0006520, GO:0006807, GO:0008150, GO:0008152, GO:0008652 +24 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 | 0.713 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 8 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 |
|---|---|---|---|---|
ILVD_EDD_N | PF00920.28 | 4.1e-132 | 49–371 | Dihydroxy-acid/6-phosphogluconate dehydratase N-terminal |
ILV_EDD_C | PF24877.2 | 1.3e-68 | 383–572 | Dihydroxy-acid/6-phosphogluconate dehydratase C-terminal |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ilvC (ketol-acid reductoisomerase), high confidence from genomic context alone (score 995 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3001c ilvC |
ketol-acid reductoisomerase | 998 | 995 ctx | cooccurence:733 coexpression:791 database:900 textmining:802 |
Rv2210c ilvE |
branched-chain amino acid aminotransferase | 994 | 982 | coexpression:669 database:900 textmining:736 |
Rv3710 leuA |
2-isopropylmalate synthase | 988 | 965 | coexpression:655 database:900 textmining:695 |
Rv3003c ilvB1 |
acetolactate synthase large subunit IlvB | 967 | 955 ctx | fusion:615 cooccurence:753 coexpression:506 |
Rv2988c leuC |
3-isopropylmalate dehydratase large subunit | 967 | 933 ctx | cooccurence:546 coexpression:846 textmining:540 |
Rv0337c aspC |
aspartate aminotransferase | 927 | 921 | database:900 |
Rv2225 panB |
3-methyl-2-oxobutanoate hydroxymethyltransferase | 929 | 901 | database:900 |
Rv2987c leuD |
3-isopropylmalate dehydratase small subunit | 936 | 893 ctx | cooccurence:606 coexpression:718 textmining:427 |
Rv2995c leuB |
3-isopropylmalate dehydrogenase | 967 | 892 ctx | cooccurence:435 coexpression:791 textmining:713 |
Rv3002c ilvN |
acetolactate synthase small subunit | 960 | 892 ctx | cooccurence:583 coexpression:650 textmining:655 |
Rv3470c ilvB2 |
acetolactate synthase large subunit | 869 | 856 ctx | cooccurence:715 coexpression:499 |
Rv1559 ilvA |
threonine dehydratase IlvA | 946 | 845 ctx | cooccurence:405 coexpression:729 textmining:667 |
Rv3859c gltB |
glutamate synthase large subunit | 933 | 798 | coexpression:771 textmining:682 |
Rv0812 |
4-amino-4-deoxychorismate lyase | 815 | 791 | coexpression:668 |
Rv0190 ricR hyp |
hypothetical protein | 773 | 773 ctx | neighborhood:772 |
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: dihydroxy-acid dehydratase
- MTBC0 PGAP product: dihydroxy-acid dehydratase
- Pfam (hmmscan --cut_ga): ILVD_EDD_N PF00920.28 (E=4e-132), ILV_EDD_C PF24877.2 (E=1e-68)
- (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_214703.1)
- Domains: Pfam-A via hmmscan --cut_ga — ILVD_EDD_N (PF00920.28), ILV_EDD_C (PF24877.2)
- 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
COG0129 - Curated reference: UniProt P9WKJ5 (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 —
88 functional partner(s); context anchor
ilvC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000203|Rv0189c|ilvD MPQTTDEAASVSTVADIKPRSRDVTDGLEKAAARGMLRAVGMDDEDFAKPQIGVASSWNEITPCNLSLDRLANAVKEGVFSAGGYPLEFGTISVSDGISMGHEGMHFSLVSREVIADSVEVVMQAERLDGSVLLAGCDKSLPGMLMAAARLDLAAVFLYAGSILPGRAKLSDGSERDVTIIDAFEAVGACSRGLMSRADVDAIERAICPGEGACGGMYTANTMASAAEALGMSLPGSAAPPATDRRRDGFARRSGQAVVELLRRGITARDILTKEAFENAIAVVMAFGGSTNAVLHLLAIAHEANVALSLQDFSRIGSGVPHLADVKPFGRHVMSDVDHIGGVPVVMKALLDAGLLHGDCLTVTGHTMAENLAAITPPDPDGKVLRALANPIHPSGGITILHGSLAPEGAVVKTAGFDSDVFEGTARVFDGERAALDALEDGTITVGDAVVIRYEGPKGGPGMREMLAITGAIKGAGLGKDVLLLTDGRFSGGTTGLCVGHIAPEAVDGGPIALLRNGDRIRLDVAGRVLDVLADPAEFASRQQDFSPPPPRYTTGVLSKYVKLVSSAAVGAVCG