ilvB2 Family assigned · medium auto-curated
H37Rv Rv3470c · MTBC0 mtbc0_003687 ·
552 aa · 3913084–3914742 (-) ·
RefSeq NP_217987.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | acetolactate synthase large subunit |
|---|---|
| MTBC0 PGAP re-annotation | thiamine pyrophosphate-binding protein |
| Revised (this work) | Thiamine pyrophosphate-binding protein. 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 |
O06335
SwissProt · reviewed
· Evidence at transcript level
|
|---|---|
| UniProt name | Putative acetolactate synthase large subunit IlvB2 |
| EC (curated) |
EC 2.2.1.6
|
| Curated function | Catalyzes 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. |
UniProt still lists this protein as Putative acetolactate synthase large subunit IlvB2; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | ilvB2 |
| eggNOG description | Acetolactate synthase, large subunit |
| Orthologous group | COG0028 |
| EC number |
EC 2.2.1.6, EC 4.1.1.7
|
| KEGG orthology |
K01576, K01652
|
| KEGG pathways |
map00290, map00627, map00650, map00660, map00770, map01100, map01110, map01120, map01130, map01210, map01230
|
| KEGG modules |
M00019, M00570
|
| Gene Ontology (29) |
GO:0006082, GO:0006520, GO:0006549, GO:0006573, GO:0006807, GO:0008150, GO:0008152, GO:0008652, GO:0009058, GO:0009081, GO:0009082, GO:0009097 +17 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 | 0.743 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 6 missense, 0 nonsense, 4 frameshift |
| Disruption | 4 distinct premature-stop/frameshift site(s); most common in 0.56% of strains (810) · convergent |
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 |
|---|---|---|---|---|
TPP_enzyme_N | PF02776.24 | 1.0e-30 | 1–114 | Thiamine pyrophosphate enzyme, N-terminal TPP binding domain |
TPP_enzyme_M | PF00205.29 | 2.4e-27 | 198–336 | Thiamine pyrophosphate enzyme, central domain |
TPP_enzyme_C | PF02775.27 | 1.9e-31 | 391–537 | 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 997 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3002c ilvN |
acetolactate synthase small subunit | 997 | 997 ctx | cooccurence:731 coexpression:648 experimental:704 database:900 |
Rv3001c ilvC |
ketol-acid reductoisomerase | 988 | 987 ctx | cooccurence:735 coexpression:537 database:900 |
Rv2995c leuB |
3-isopropylmalate dehydrogenase | 961 | 958 | coexpression:402 database:900 |
Rv1559 ilvA |
threonine dehydratase IlvA | 953 | 949 | database:900 |
Rv3003c ilvB1 |
acetolactate synthase large subunit IlvB | 949 | 928 | database:900 |
Rv1820 ilvG |
acetolactate synthase large subunit IlvG | 950 | 927 | database:900 |
Rv3509c ilvX |
acetohydroxyacid synthase large subunit | 990 | 926 | database:900 textmining:870 |
Rv3710 leuA |
2-isopropylmalate synthase | 924 | 917 | database:872 |
Rv2455c korA |
2-oxoglutarate oxidoreductase subunit KorA | 935 | 914 | database:900 |
Rv3469c mhpE |
4-hydroxy-2-oxovalerate aldolase MhpE | 986 | 906 ctx | neighborhood:677 coexpression:439 textmining:860 |
Rv2454c korB |
2-oxoglutarate oxidoreductase subunit KorB | 910 | 905 | database:900 |
Rv0694 mftD |
mycofactocin system heme/flavin oxidoreductase MftD | 911 | 899 | database:893 |
Rv1872c lldD2 |
L-lactate dehydrogenase | 911 | 898 | database:893 |
Rv3471c hyp |
hypothetical protein | 883 | 883 ctx | neighborhood:881 |
Rv0189c ilvD |
dihydroxy-acid dehydratase | 869 | 856 ctx | cooccurence:715 coexpression:499 |
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
- MTBC0 PGAP product: thiamine pyrophosphate-binding protein
- Pfam (hmmscan --cut_ga): TPP_enzyme_N PF02776.24 (E=1e-30), TPP_enzyme_M PF00205.29 (E=2e-27), TPP_enzyme_C PF02775.27 (E=2e-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_217987.1)
- 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 O06335 (SwissProt, reviewed; Evidence at transcript 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 —
172 functional partner(s); context anchor
ilvN - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003687|Rv3470c|ilvB2 MTVGDHLVARMRAAGISVVCGLPTSRLDSLLVRLSRDAGFQIVLARHEGGAGYLADGFARASGKSAAVFVAGPGATNVISAVANASVNQVPMLILTGEVAVGEFGLHSQQDTSDDGLGLGATFRRFCRCSVSIESIANARSKIDSAFRALASIPRGPVHIALPRDLVDERLPAHQLGTAAAGLGGLRTLAPCGPDVADEVIGRLDRSRAPMLVLGNGCRLDGIGEQIVAFCEKAGLPFATTPNGRGIVAETHPLSLGVLGIFGDGRADEYLFDTPCDLLIAVGVSFGGLVTRSFSPRWRGLKADVVHVDPDPSAVGRFVATSLGITTSGRAFVNALNCGRPPRFCRRVGVRPPAPAALPGTPQARGESIHPLELMHELDRELAPNATICADVGTCISWTFRGIPVRRPGRFFATVDFSPMGCGIAGAIGVALARPEEHVICIAGDGAFLMHGTEISTAVAHGIRVTWAVLNDGQMSASAGPVSGRMDPSPVARIGANDLAAMARALGAEGIRVDTRCELRAGVQKALAATGPCVLDIAIDPEINKPDIGLGR