fadB2 Resolved · high auto-curated
H37Rv Rv0468 · MTBC0 mtbc0_000492 ·
286 aa · 562260–563120 (+) ·
RefSeq NP_214982.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 3-hydroxybutyryl-CoA dehydrogenase |
|---|---|
| MTBC0 PGAP re-annotation | 3-hydroxybutyryl-CoA dehydrogenase FadB2 |
| Revised (this work) | 3-hydroxybutyryl-CoA dehydrogenase FadB2. Pfam: 3HCDH_N (PF02737.25), 3HCDH (PF00725.28). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WNP7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | 3-hydroxybutyryl-CoA dehydrogenase |
| EC (curated) |
EC 1.1.1.157
|
| Curated function | Catalyzes the NAD-dependent oxidation of beta-hydroxybutyryl-CoA to acetoacetyl-CoA in vitro at pH 10. Also catalyzes the reverse reaction albeit in a lower pH range of 5.5-6.5. The reverse reaction is able to use NADPH as well as NADH. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
|
|---|---|
| Preferred name | fadB2 |
| eggNOG description | Dehydrogenase |
| Orthologous group | COG1250 |
| EC number |
EC 1.1.1.157
|
| KEGG orthology |
K00074
|
| KEGG pathways |
map00360, map00362, map00650, map01100, map01120
|
| Gene Ontology (72) |
GO:0003674, GO:0003824, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0006082, GO:0006629, GO:0006631 +60 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 | 0.71 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 4 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 |
|---|---|---|---|---|
3HCDH_N | PF02737.25 | 3.8e-59 | 8–187 | 3-hydroxyacyl-CoA dehydrogenase, NAD binding domain |
3HCDH | PF00725.28 | 1.1e-33 | 190–286 | 3-hydroxyacyl-CoA dehydrogenase, C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: fadA3 (beta-ketoacyl CoA thiolase FadA), high confidence from genomic context alone (score 987 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1074c fadA3 |
beta-ketoacyl CoA thiolase FadA | 987 | 987 ctx | cooccurence:510 coexpression:426 experimental:412 database:900 |
Rv1323 fadA4 |
acetyl-CoA acetyltransferase | 985 | 984 ctx | cooccurence:515 coexpression:432 experimental:412 database:900 |
Rv1070c echA8 |
enoyl-CoA hydratase EchA8 | 983 | 983 ctx | fusion:900 database:650 |
Rv3556c fadA6 |
acetyl-CoA acetyltransferase FadA | 983 | 983 ctx | cooccurence:421 coexpression:426 experimental:412 database:900 |
Rv0859 fadA |
acyltransferase | 989 | 982 ctx | cooccurence:411 coexpression:429 experimental:412 database:900 textmining:458 |
Rv3546 fadA5 |
acetyl-CoA acetyltransferase FadA | 981 | 981 ctx | cooccurence:451 coexpression:426 experimental:412 database:900 |
Rv0243 fadA2 |
acetyl-CoA acetyltransferase FadA | 973 | 972 | coexpression:425 experimental:412 database:900 |
Rv3039c echA17 |
enoyl-CoA hydratase EchA17 | 968 | 967 ctx | fusion:790 cooccurence:418 database:650 |
Rv0914c |
lipid carrier protein or keto acyl-CoA thiolase | 966 | 964 | coexpression:425 experimental:412 database:900 |
Rv3523 ltp3 |
lipid carrier protein | 966 | 964 | coexpression:424 experimental:412 database:900 |
Rv1867 hyp |
hypothetical protein | 965 | 964 | coexpression:424 experimental:412 database:900 |
Rv0467 icl1 |
isocitrate lyase | 954 | 952 ctx | neighborhood:783 coexpression:788 |
Rv0222 echA1 |
enoyl-CoA hydratase EchA1 | 952 | 951 ctx | fusion:715 database:650 |
Rv0860 fadB |
fatty oxidation protein FadB | 944 | 937 | database:900 |
Rv1715 fadB3 |
3-hydroxybutyryl-CoA dehydrogenase FadB | 922 | 922 | database:900 |
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-hydroxybutyryl-CoA dehydrogenase
- MTBC0 PGAP product: 3-hydroxybutyryl-CoA dehydrogenase FadB2
- Pfam (hmmscan --cut_ga): 3HCDH_N PF02737.25 (E=4e-59), 3HCDH PF00725.28 (E=1e-33)
- (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_214982.1)
- Domains: Pfam-A via hmmscan --cut_ga — 3HCDH_N (PF02737.25), 3HCDH (PF00725.28)
- 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
COG1250 - Curated reference: UniProt P9WNP7 (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 —
96 functional partner(s); context anchor
fadA3 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000492|Rv0468|fadB2 MSDAIQRVGVVGAGQMGSGIAEVSARAGVEVTVFEPAEALITAGRNRIVKSLERAVSAGKVTERERDRALGLLTFTTDLNDLSDRQLVIEAVVEDEAVKSEIFAELDRVVTDPDAVLASNTSSIPIMKVAAATKQPQRVLGLHFFNPVPVLPLVELVRTLVTDEAAAARTEEFASTVLGKQVVRCSDRSGFVVNALLVPYLLSAIRMVEAGFATVEDVDKAVVAGLSHPMGPLRLSDLVGLDTLKLIADKMFEEFKEPHYGPPPLLLRMVEAGQLGKKSGRGFYTY