ilvB1 Family assigned · medium auto-curated

H37Rv Rv3003c · MTBC0 - · 618 aa · 3361130–3362986 (-) · RefSeq YP_177917.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)acetolactate synthase large subunit IlvB
MTBC0 PGAP re-annotation
Revised (this work)Acetolactate synthase large subunit IlvB. 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.

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt P9WG41 SwissProt · reviewed · Evidence at protein level
UniProt nameAcetolactate synthase large subunit IlvB1
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. Also involved in condensing pyruvate and 2-ketobutyrate to form 2-aceto-2-hydroxybutyrate.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category H Coenzyme transport and metabolism
Preferred nameilvB
eggNOG descriptionAcetolactate synthase, large subunit
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 (55) GO:0000287, GO:0003674, GO:0003824, GO:0003984, GO:0005488, GO:0005575, GO:0005618, GO:0005623, GO:0006082, GO:0006520, GO:0006549, GO:0006573 +43 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 0.779 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 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
TPP_enzyme_NPF02776.24 5.5e-4039–153 Thiamine pyrophosphate enzyme, N-terminal TPP binding domain
TPP_enzyme_MPF00205.29 7.9e-54228–363 Thiamine pyrophosphate enzyme, central domain
TPP_enzyme_CPF02775.27 3.4e-52426–579 Thiamine pyrophosphate enzyme, C-terminal TPP binding domain

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

Closest characterised functional partner: ilvN (acetolactate synthase small subunit), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3002c ilvN acetolactate synthase small subunit 999 1000 ctx neighborhood:882 cooccurence:769 coexpression:919 experimental:704 database:900 textmining:907
Rv3001c ilvC ketol-acid reductoisomerase 999 997 ctx neighborhood:732 cooccurence:766 coexpression:618 database:900 textmining:813
Rv2995c leuB 3-isopropylmalate dehydrogenase 977 970 ctx cooccurence:456 coexpression:409 database:900
Rv1559 ilvA threonine dehydratase IlvA 972 958 database:900
Rv0189c ilvD dihydroxy-acid dehydratase 967 955 ctx fusion:615 cooccurence:753 coexpression:506
Rv3470c ilvB2 acetolactate synthase large subunit 949 928 database:900
Rv1820 ilvG acetolactate synthase large subunit IlvG 949 926 database:900
Rv3710 leuA 2-isopropylmalate synthase 980 922 database:872 textmining:755
Rv2455c korA 2-oxoglutarate oxidoreductase subunit KorA 935 914 database:900
Rv3509c ilvX acetohydroxyacid synthase large subunit 943 911 database:900
Rv2454c korB 2-oxoglutarate oxidoreductase subunit KorB 910 905 database:900
Rv1872c lldD2 L-lactate dehydrogenase 904 899 database:893
Rv0694 mftD mycofactocin system heme/flavin oxidoreductase MftD 904 899 database:893
Rv2332 mez malate oxidoreductase 854 844 database:800
Rv1617 pykA pyruvate kinase 846 834 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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): acetolactate synthase large subunit IlvB
  • Pfam (hmmscan --cut_ga): TPP_enzyme_N PF02776.24 (E=6e-40), TPP_enzyme_M PF00205.29 (E=8e-54), TPP_enzyme_C PF02775.27 (E=3e-52)
  • (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 YP_177917.1)
  • 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 P9WG41 (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 — 166 functional partner(s); context anchor ilvN
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3003c|ilvB1
MSAPTKPHSPTFKPEPHSAANEPKHPAARPKHVALQQLTGAQAVIRSLEELGVDVIFGIPGGAVLPVYDPLFDSKKLRHVLVRHEQGAGHAASGYAHVTGRVGVCMATSGPGATNLVTPLADAQMDSIPVVAITGQVGRGLIGTDAFQEADISGITMPITKHNFLVRSGDDIPRVLAEAFHIAASGRPGAVLVDIPKDVLQGQCTFSWPPRMELPGYKPNTKPHSRQVREAAKLIAAARKPVLYVGGGVIRGEATEQLRELAELTGIPVVTTLMARGAFPDSHRQNLGMPGMHGTVAAVAALQRSDLLIALGTRFDDRVTGKLDSFAPEAKVIHADIDPAEIGKNRHADVPIVGDVKAVITELIAMLRHHHIPGTIEMADWWAYLNGVRKTYPLSYGPQSDGSLSPEYVIEKLGEIAGPDAVFVAGVGQHQMWAAQFIRYEKPRSWLNSGGLGTMGFAIPAAMGAKIALPGTEVWAIDGDGCFQMTNQELATCAVEGIPVKVALINNGNLGMVRQWQSLFYAERYSQTDLATHSHRIPDFVKLAEALGCVGLRCEREEDVVDVINQARAINDCPVVIDFIVGADAQVWPMVAAGTSNDEIQAARGIRPLFDDITEGHA