panB Resolved · high auto-curated
H37Rv Rv2225 · MTBC0 mtbc0_002363 ·
281 aa · 2523899–2524744 (+) ·
RefSeq NP_216741.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 3-methyl-2-oxobutanoate hydroxymethyltransferase |
|---|---|
| MTBC0 PGAP re-annotation | 3-methyl-2-oxobutanoate hydroxymethyltransferase |
| Revised (this work) | 3-methyl-2-oxobutanoate hydroxymethyltransferase. Pfam: Pantoate_transf (PF02548.22). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WIL7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | 3-methyl-2-oxobutanoate hydroxymethyltransferase |
| EC (curated) |
EC 2.1.2.11
|
| Curated function | Catalyzes the reversible reaction in which hydroxymethyl group from 5,10-methylenetetrahydrofolate is transferred onto alpha-ketoisovalerate to form ketopantoate. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | panB |
| eggNOG description | Catalyzes the reversible reaction in which hydroxymethyl group from 5,10-methylenetetrahydrofolate is transferred onto alpha-ketoisovalerate to form ketopantoate |
| Orthologous group | COG0413 |
| EC number |
EC 2.1.2.11
|
| KEGG orthology |
K00606
|
| KEGG pathways |
map00770, map01100, map01110
|
| KEGG modules |
M00119
|
| Gene Ontology (54) |
GO:0000287, GO:0003674, GO:0003824, GO:0003864, GO:0005488, GO:0005575, GO:0005623, GO:0005886, GO:0006082, GO:0006575, GO:0006732, GO:0006766 +42 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 | 1.031 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 3 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 |
|---|---|---|---|---|
Pantoate_transf | PF02548.22 | 1.2e-107 | 20–276 | Ketopantoate hydroxymethyltransferase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: panC (pantothenate synthetase), high confidence from genomic context alone (score 995 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3602c panC |
pantothenate synthetase | 999 | 995 ctx | fusion:811 cooccurence:774 coexpression:859 textmining:917 |
Rv3601c panD |
aspartate 1-decarboxylase | 981 | 944 ctx | cooccurence:581 coexpression:852 textmining:691 |
Rv2573 |
2-dehydropantoate 2-reductase | 930 | 908 | database:900 |
Rv2210c ilvE |
branched-chain amino acid aminotransferase | 916 | 904 | database:900 |
Rv0189c ilvD |
dihydroxy-acid dehydratase | 929 | 901 | database:900 |
Rv2226 hyp |
hypothetical protein | 730 | 730 ctx | neighborhood:726 |
Rv3603c hyp |
hypothetical protein | 783 | 547 ctx | cooccurence:484 textmining:541 |
Rv1832 gcvB |
glycine dehydrogenase | 591 | 426 | coexpression:407 |
Rv2438c nadE |
glutamine-dependent NAD(+) synthetase | 429 | 410 | |
Rv3396c guaA |
GMP synthase | 710 | 392 | textmining:543 |
Rv1415 ribA2 |
bifunctional riboflavin biosynthesis GTP cyclohydrolase II/3,4-dihydroxy-2-butanone 4-phosphate synthase | 421 | 337 | |
Rv1940 ribA1 |
riboflavin biosynthesis protein RibA | 421 | 337 | |
Rv1391 dfp |
bifunctional phosphopantothenoylcysteine decarboxylase/phosphopantothenate--cysteine ligase | 671 | 304 | textmining:547 |
Rv3279c birA |
bifunctional biotin operon repressor/biotin--[acetyl-CoA-carboxylase | 419 | 224 | |
Rv1409 ribG |
bifunctional riboflavin biosynthesis diaminohydroxyphosphoribosylaminopyrimidine deaminase/5-amino-6-(5-phosphoribosylamino) uracil reductas | 433 | 215 |
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: 3-methyl-2-oxobutanoate hydroxymethyltransferase
- MTBC0 PGAP product: 3-methyl-2-oxobutanoate hydroxymethyltransferase
- Pfam (hmmscan --cut_ga): Pantoate_transf PF02548.22 (E=1e-107)
- (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_216741.1)
- Domains: Pfam-A via hmmscan --cut_ga — Pantoate_transf (PF02548.22)
- 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
COG0413 - Curated reference: UniProt P9WIL7 (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 —
35 functional partner(s); context anchor
panC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002363|Rv2225|panB MSEQTIYGANTPGGSGPRTKIRTHHLQRWKADGHKWAMLTAYDYSTARIFDEAGIPVLLVGDSAANVVYGYDTTVPISIDELIPLVRGVVRGAPHALVVADLPFGSYEAGPTAALAAATRFLKDGGAHAVKLEGGERVAEQIACLTAAGIPVMAHIGFTPQSVNTLGGFRVQGRGDAAEQTIADAIAVAEAGAFAVVMEMVPAELATQITGKLTIPTVGIGAGPNCDGQVLVWQDMAGFSGAKTARFVKRYADVGGELRRAAMQYAQEVAGGVFPADEHSF