Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | threonine dehydratase IlvA |
| MTBC0 PGAP re-annotation | threonine ammonia-lyase |
| Revised (this work) | Threonine ammonia-lyase. Pfam: PALP (PF00291.32), Thr_dehydrat_C (PF00585.25). |
Auto-curated: this verdict and function were generated by rules from
PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WG95
SwissProt · reviewed
· Evidence at protein level
|
| UniProt name | L-threonine dehydratase biosynthetic IlvA |
| EC (curated) |
EC 4.3.1.19
|
| Curated function | Catalyzes the anaerobic formation of alpha-ketobutyrate and ammonia from threonine in a two-step reaction. The first step involved a dehydration of threonine and a production of enamine intermediates (aminocrotonate), which tautomerizes to its imine form (iminobutyrate). Both intermediates are unstable and short-lived. The second step is the nonenzymatic hydrolysis of the enamine/imine intermediates to form 2-ketobutyrate and free ammonia. In the low water environment of the cell, the second step is accelerated by RidA (By similarity). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
| Preferred name | ilvA |
| eggNOG description | Catalyzes the anaerobic formation of alpha-ketobutyrate and ammonia from threonine in a two-step reaction. The first step involved a dehydration of threonine and a production of enamine intermediates (aminocrotonate), which tautomerizes to its imine form (iminobutyrate). Both intermediates are unstable and short- lived. The second step is the nonenzymatic hydrolysis of the enamine imine intermediates to form 2-ketobutyrate and free ammonia. In the low water environment of the cell, the second step is accelerated by RidA |
| Orthologous group | COG1171 |
| EC number |
EC 4.3.1.19
|
| KEGG orthology |
K01754
|
| KEGG pathways |
map00260, map00290, map01100, map01110, map01130, map01200, map01230
|
| KEGG modules |
M00570
|
| Gene Ontology (22) |
GO:0005575, GO:0005623, GO:0005886, GO:0006082, GO:0006520, GO:0006566, GO:0006807, GO:0008150, GO:0008152, GO:0009066, GO:0009987, GO:0016020 +10 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 |
2.556 · diversifying/relaxed
|
| Polymorphic sites (≥ 0.1% of strains) |
1 synonymous, 7 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 |
PALP | PF00291.32 |
1.3e-75 | 30–323 |
Pyridoxal-phosphate dependent enzyme |
Thr_dehydrat_C | PF00585.25 |
2.0e-29 | 336–428 |
C-terminal regulatory domain of Threonine dehydratase |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
Rv3002c ilvN |
acetolactate synthase small subunit |
991 |
972 |
coexpression:676 database:900 textmining:707 |
Rv3003c ilvB1 |
acetolactate synthase large subunit IlvB |
972 |
958 |
database:900 |
Rv2995c leuB |
3-isopropylmalate dehydrogenase |
977 |
954 |
database:900 textmining:537 |
Rv1295 thrC |
threonine synthase |
967 |
953 |
coexpression:525 database:900 |
Rv3470c ilvB2 |
acetolactate synthase large subunit |
953 |
949 |
database:900 |
Rv1820 ilvG |
acetolactate synthase large subunit IlvG |
973 |
945 |
database:900 textmining:531 |
Rv3509c ilvX |
acetohydroxyacid synthase large subunit |
957 |
935 |
database:900 |
Rv1612 trpB |
tryptophan synthase subunit beta |
949 |
934 |
database:900 |
Rv1613 trpA |
tryptophan synthase subunit alpha |
934 |
924 |
database:900 |
Rv0069c sdaA |
L-serine dehydratase |
960 |
922 |
database:900 textmining:518 |
Rv1077 cbs |
cystathionine beta-synthase |
925 |
914 |
database:900 |
Rv3042c serB2 |
phosphoserine phosphatase SerB |
915 |
907 |
database:900 |
Rv1093 glyA1 |
serine hydroxymethyltransferase |
949 |
906 |
database:900 textmining:489 |
Rv0436c pssA |
CDP-diacylglycerol--serine O-phosphatidyltransferase |
904 |
905 |
database:900 |
Rv0070c glyA2 |
serine hydroxymethyltransferase |
937 |
901 |
database:900 |
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: threonine dehydratase IlvA
- MTBC0 PGAP product: threonine ammonia-lyase
- Pfam (hmmscan --cut_ga): PALP PF00291.32 (E=1e-75), Thr_dehydrat_C PF00585.25 (E=2e-29)
- (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_216075.1)
- Domains: Pfam-A via hmmscan --cut_ga — PALP (PF00291.32), Thr_dehydrat_C (PF00585.25)
- 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
COG1171
- Curated reference: UniProt
P9WG95
(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 —
66 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001667|Rv1559|ilvA
MSAELSQSPSSSPLFSLSGADIDRAAKRIAPVVTPTPLQPSDRLSAITGATVYLKREDLQTVRSYKLRGAYNLLVQLSDEELAAGVVCSSAGNHAQGFAYACRCLGVHGRVYVPAKTPKQKRDRIRYHGGEFIDLIVGGSTYDLAAAAALEDVERTGATLVPPFDDLRTIAGQGTIAVEVLGQLEDEPDLVVVPVGGGGCIAGITTYLAERTTNTAVLGVEPAGAAAMMAALAAGEPVTLDHVDQFVDGAAVNRAGTLTYAALAAAGDMVSLTTVDEGAVCTAMLDLYQNEGIIAEPAGALSVAGLLEADIEPGSTVVCLISGGNNDVSRYGEVLERSLVHLGLKHYFLVDFPQEPGALRRFLDDVLGPNDDITLFEYVKRNNRETGEALVGIELGSAADLDGLLARMRATDIHVEALEPGSPAYRYLL
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