mmsB Resolved · high auto-curated
H37Rv Rv0751c · MTBC0 mtbc0_000798 ·
294 aa · 846772–847656 (-) ·
RefSeq NP_215265.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 3-hydroxyisobutyrate dehydrogenase |
|---|---|
| MTBC0 PGAP re-annotation | 3-hydroxyisobutyrate dehydrogenase |
| Revised (this work) | 3-hydroxyisobutyrate dehydrogenase. Pfam: NAD_binding_2 (PF03446.22), F420_oxidored (PF03807.24), 2-Hacid_dh_C (PF02826.26), NAD_binding_11 (PF14833.12). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WNY5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable 3-hydroxyisobutyrate dehydrogenase |
| EC (curated) |
EC 1.1.1.31
|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
|
|---|---|
| Preferred name | mmsB |
| eggNOG description | Belongs to the 3-hydroxyisobutyrate dehydrogenase family |
| Orthologous group | COG2084 |
| EC number |
EC 1.1.1.31
|
| KEGG orthology |
K00020
|
| KEGG pathways |
map00280, map01100
|
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 | 1.08 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 6 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 |
|---|---|---|---|---|
NAD_binding_2 | PF03446.22 | 2.3e-45 | 3–159 | NAD binding domain of 6-phosphogluconate dehydrogenase |
F420_oxidored | PF03807.24 | 2.7e-07 | 3–69 | NADP oxidoreductase coenzyme F420-dependent |
2-Hacid_dh_C | PF02826.26 | 1.2e-05 | 3–104 | D-isomer specific 2-hydroxyacid dehydrogenase, NAD binding domain |
NAD_binding_11 | PF14833.12 | 1.6e-32 | 162–287 | NAD-binding of NADP-dependent 3-hydroxyisobutyrate dehydrogenase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mmsA (methylmalonate-semialdehyde dehydrogenase), high confidence from genomic context alone (score 998 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0753c mmsA |
methylmalonate-semialdehyde dehydrogenase | 998 | 998 ctx | neighborhood:875 cooccurence:426 coexpression:753 database:900 |
Rv0752c fadE9 |
acyl-CoA dehydrogenase FadE9 | 988 | 989 ctx | neighborhood:879 cooccurence:516 coexpression:821 |
Rv1071c echA9 |
enoyl-CoA hydratase EchA9 | 965 | 963 ctx | fusion:898 cooccurence:474 |
Rv0860 fadB |
fatty oxidation protein FadB | 946 | 921 | database:900 |
Rv0147 |
aldehyde dehydrogenase | 916 | 912 | database:900 |
Rv0768 aldA |
aldehyde dehydrogenase AldA | 916 | 912 | database:900 |
Rv3293 pcd |
piperideine-6-carboxylic acid dehydrogenase | 915 | 912 | database:900 |
Rv0223c |
aldehyde dehydrogenase | 915 | 912 | database:900 |
Rv2589 gabT |
4-aminobutyrate aminotransferase | 900 | 901 | database:900 |
Rv2501c accA1 |
acetyl/propionyl-CoA carboxylase subuit alpha | 837 | 834 | database:800 |
Rv0973c accA2 |
acetyl/propionyl-CoA carboxylase subuit alpha | 836 | 832 | database:800 |
Rv3285 accA3 |
bifunctional protein acetyl-/propionyl-CoA carboxylase subunit alpha AccA | 835 | 832 | database:800 |
Rv3667 acs |
acetyl-CoAsynthetase | 824 | 817 | database:800 |
Rv3280 accD5 |
propionyl-CoA carboxylase subunit beta | 807 | 807 | database:800 |
Rv2247 accD6 |
acetyl-/propionyl-CoA carboxylase subunit beta | 807 | 807 | 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: 3-hydroxyisobutyrate dehydrogenase
- MTBC0 PGAP product: 3-hydroxyisobutyrate dehydrogenase
- Pfam (hmmscan --cut_ga): NAD_binding_2 PF03446.22 (E=2e-45), F420_oxidored PF03807.24 (E=3e-07), 2-Hacid_dh_C PF02826.26 (E=1e-05), NAD_binding_11 PF14833.12 (E=2e-32)
- (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_215265.1)
- Domains: Pfam-A via hmmscan --cut_ga — NAD_binding_2 (PF03446.22), F420_oxidored (PF03807.24), 2-Hacid_dh_C (PF02826.26), NAD_binding_11 (PF14833.12)
- 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
COG2084 - Curated reference: UniProt P9WNY5 (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 —
25 functional partner(s); context anchor
mmsA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000798|Rv0751c|mmsB MTTIAFLGLGNMGAPMSANLVGAGHVVRGFDPAPTAASGAAAHGVAVFRSAPEAVAEADVVITMLPTGEVVRRCYTDVLAAARPATLFIDSSTISVTDAREVHALAESHGMLQLDAPVSGGVKGAAAATLAFMVGGDESTLRRARPVLEPMAGKIIHCGAAGAGQAAKVCNNMVLAVQQIAIAEAFVLAEKLGLSAQSLFDVITGATGNCWAVHTNCPVPGPVPTSPANNDFKPGFSTALMNKDLGLAMDAVAATGATAPLGSHAADIYAKFAADHADLDFSAVIHTLRARADA