ilvG Resolved · high auto-curated

H37Rv Rv1820 · MTBC0 mtbc0_001934 · 547 aa · 2082887–2084530 (+) · RefSeq NP_216336.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)acetolactate synthase large subunit IlvG
MTBC0 PGAP re-annotationacetolactate synthase
Revised (this work)Acetolactate synthase. Pfam: TPP_enzyme_N (PF02776.24), TPP_enzyme_M (PF00205.29), TPP_enzyme_C (PF02775.27).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt P9WG39 SwissProt · reviewed · Evidence at protein level
UniProt nameAcetolactate synthase large subunit IlvG
EC (curated) EC 2.2.1.6
Curated functionCatalyzes the conversion of 2 pyruvate molecules into acetolactate in the first common step of the biosynthetic pathway of the branched-amino acids such as leucine, isoleucine, and valine.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
H Coenzyme transport and metabolism
Preferred nameilvG
eggNOG descriptionBelongs to the TPP enzyme family
Orthologous groupCOG0028
EC number EC 2.2.1.6
KEGG orthology K01652
KEGG pathways map00290, map00650, map00660, map00770, map01100, map01110, map01130, map01210, map01230
KEGG modules M00019, M00570
Gene Ontology (48) GO:0000287, GO:0003674, GO:0003824, GO:0003984, GO:0005488, GO:0006082, GO:0006520, GO:0006549, GO:0006573, GO:0006807, GO:0008150, GO:0008152 +36 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 0.181 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 2 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)

PfamAccessioni-EvalueResiduesDescription
TPP_enzyme_NPF02776.24 9.2e-3611–125 Thiamine pyrophosphate enzyme, N-terminal TPP binding domain
TPP_enzyme_MPF00205.29 1.1e-20199–326 Thiamine pyrophosphate enzyme, central domain
TPP_enzyme_CPF02775.27 7.2e-31385–532 Thiamine pyrophosphate enzyme, C-terminal TPP binding domain

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

Closest characterised functional partner: ilvC (ketol-acid reductoisomerase), high confidence from genomic context alone (score 975 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3002c ilvN acetolactate synthase small subunit 998 993 coexpression:650 experimental:704 database:900 textmining:740
Rv3001c ilvC ketol-acid reductoisomerase 991 975 ctx cooccurence:463 coexpression:540 database:900 textmining:670
Rv2995c leuB 3-isopropylmalate dehydrogenase 983 956 coexpression:407 database:900 textmining:629
Rv1559 ilvA threonine dehydratase IlvA 973 945 database:900 textmining:531
Rv3470c ilvB2 acetolactate synthase large subunit 950 927 database:900
Rv3003c ilvB1 acetolactate synthase large subunit IlvB 949 926 database:900
Rv3710 leuA 2-isopropylmalate synthase 969 920 database:872 textmining:640
Rv2455c korA 2-oxoglutarate oxidoreductase subunit KorA 935 914 database:900
Rv2454c korB 2-oxoglutarate oxidoreductase subunit KorB 911 905 database:900
Rv3509c ilvX acetohydroxyacid synthase large subunit 937 901 database:900
Rv1872c lldD2 L-lactate dehydrogenase 904 899 database:893
Rv0694 mftD mycofactocin system heme/flavin oxidoreductase MftD 903 898 database:893
Rv2332 mez malate oxidoreductase 854 844 database:800
Rv1617 pykA pyruvate kinase 844 832 database:800
Rv2496c bkdB 3-methyl-2-oxobutanoate dehydrogenase subunit beta 840 818 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: acetolactate synthase large subunit IlvG
  • MTBC0 PGAP product: acetolactate synthase
  • Pfam (hmmscan --cut_ga): TPP_enzyme_N PF02776.24 (E=9e-36), TPP_enzyme_M PF00205.29 (E=1e-20), TPP_enzyme_C PF02775.27 (E=7e-31)
  • (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_216336.1)
  • Domains: Pfam-A via hmmscan --cut_ga — TPP_enzyme_N (PF02776.24), TPP_enzyme_M (PF00205.29), TPP_enzyme_C (PF02775.27)
  • 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 COG0028
  • Curated reference: UniProt P9WG39 (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 — 171 functional partner(s); context anchor ilvC
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001934|Rv1820|ilvG
MSTDTAPAQTMHAGRLIARRLKASGIDTVFTLSGGHLFSIYDGCREEGIRLIDTRHEQTAAFAAEGWSKVTRVPGVAALTAGPGITNGMSAMAAAQQNQSPLVVLGGRAPALRWGMGSLQEIDHVPFVAPVARFAATAQSAENAGLLVDQALQAAVSAPSGVAFVDFPMDHAFSMSSDNGRPGALTELPAGPTPAGDALDRAAGLLSTAQRPVIMAGTNVWWGHAEAALLRLVEERHIPVLMNGMARGVVPADHRLAFSRARSKALGEADVALIVGVPMDFRLGFGGVFGSTTQLIVADRVEPAREHPRPVAAGLYGDLTATLSALAGSGGTDHQGWIEELATAETMARDLEKAELVDDRIPLHPMRVYAELAALLERDALVVIDAGDFGSYAGRMIDSYLPGCWLDSGPFGCLGSGPGYALAAKLARPQRQVVLLQGDGAFGFSGMEWDTLVRHNVAVVSVIGNNGIWGLEKHPMEALYGYSVVAELRPGTRYDEVVRALGGHGELVSVPAELRPALERAFASGLPAVVNVLTDPSVAYPRRSNLA