ilvA Resolved · high auto-curated

H37Rv Rv1559 · MTBC0 mtbc0_001667 · 429 aa · 1775392–1776681 (+) · RefSeq NP_216075.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)threonine dehydratase IlvA
MTBC0 PGAP re-annotationthreonine 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 nameL-threonine dehydratase biosynthetic IlvA
EC (curated) EC 4.3.1.19
Curated functionCatalyzes 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 nameilvA
eggNOG descriptionCatalyzes 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 groupCOG1171
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)

PfamAccessioni-EvalueResiduesDescription
PALPPF00291.32 1.3e-7530–323 Pyridoxal-phosphate dependent enzyme
Thr_dehydrat_CPF00585.25 2.0e-29336–428 C-terminal regulatory domain of Threonine dehydratase

Functional interaction network (STRING v12, guilt-by-association)

PartnerProductScoreNo text-miningChannels (≥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