fadB3 Resolved · high auto-curated
H37Rv Rv1715 · MTBC0 - ·
304 aa · 1942659–1943573 (+) ·
RefSeq YP_177829.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 3-hydroxybutyryl-CoA dehydrogenase FadB |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | 3-hydroxybutyryl-CoA dehydrogenase FadB. Pfam: 3HCDH_N (PF02737.25), NAD_binding_2 (PF03446.22), 3HCDH (PF00725.28). |
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 |
L7N688
TrEMBL · unreviewed
· Inferred from homology
|
|---|---|
| UniProt name | Probable 3-hydroxybutyryl-CoA dehydrogenase FadB3 |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
|
|---|---|
| Preferred name | fadB3 |
| eggNOG description | 3-hydroxyacyl-CoA dehydrogenase, C-terminal domain |
| Orthologous group | COG1250 |
| EC number |
EC 1.1.1.157
|
| KEGG orthology |
K00074
|
| KEGG pathways |
map00360, map00362, map00650, map01100, map01120
|
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 | 0.388 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 8 synonymous, 7 missense, 1 nonsense, 1 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 0.45% of strains (656) · clonal |
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 | 2.9e-47 | 10–174 | 3-hydroxyacyl-CoA dehydrogenase, NAD binding domain |
NAD_binding_2 | PF03446.22 | 5.6e-07 | 11–112 | NAD binding domain of 6-phosphogluconate dehydrogenase |
3HCDH | PF00725.28 | 7.8e-21 | 177–275 | 3-hydroxyacyl-CoA dehydrogenase, C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv1714 (oxidoreductase), high confidence from genomic context alone (score 987 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1714 |
oxidoreductase | 987 | 987 ctx | neighborhood:882 coexpression:862 |
Rv1716 hyp |
hypothetical protein | 984 | 985 ctx | neighborhood:881 coexpression:860 |
Rv1074c fadA3 |
beta-ketoacyl CoA thiolase FadA | 984 | 984 ctx | cooccurence:489 coexpression:426 experimental:412 database:900 |
Rv1717 hyp |
hypothetical protein | 982 | 983 ctx | neighborhood:881 coexpression:815 |
Rv1070c echA8 |
enoyl-CoA hydratase EchA8 | 983 | 982 ctx | fusion:900 database:650 |
Rv1323 fadA4 |
acetyl-CoA acetyltransferase | 982 | 981 ctx | cooccurence:495 coexpression:427 experimental:412 database:900 |
Rv3556c fadA6 |
acetyl-CoA acetyltransferase FadA | 991 | 980 | coexpression:432 experimental:412 database:900 textmining:573 |
Rv3546 fadA5 |
acetyl-CoA acetyltransferase FadA | 982 | 978 ctx | cooccurence:409 coexpression:428 experimental:412 database:900 |
Rv0859 fadA |
acyltransferase | 984 | 977 | coexpression:426 experimental:412 database:900 |
Rv0243 fadA2 |
acetyl-CoA acetyltransferase FadA | 975 | 974 | coexpression:432 experimental:412 database:900 |
Rv1718 hyp |
hypothetical protein | 973 | 972 ctx | neighborhood:808 coexpression:860 |
Rv3523 ltp3 |
lipid carrier protein | 966 | 965 | coexpression:428 experimental:412 database:900 |
Rv0914c |
lipid carrier protein or keto acyl-CoA thiolase | 966 | 964 | coexpression:426 experimental:412 database:900 |
Rv1867 hyp |
hypothetical protein | 965 | 964 | coexpression:427 experimental:412 database:900 |
Rv1719 |
transcriptional regulator | 953 | 953 ctx | neighborhood:798 coexpression:750 |
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): 3-hydroxybutyryl-CoA dehydrogenase FadB
- Pfam (hmmscan --cut_ga): 3HCDH_N PF02737.25 (E=3e-47), NAD_binding_2 PF03446.22 (E=6e-07), 3HCDH PF00725.28 (E=8e-21)
- (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_177829.1)
- Domains: Pfam-A via hmmscan --cut_ga — 3HCDH_N (PF02737.25), NAD_binding_2 (PF03446.22), 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 L7N688 (TrEMBL, unreviewed; Inferred from homology)
- 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 —
114 functional partner(s); context anchor
Rv1714 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv1715|fadB3 MLTSHGFSRAAVVGAGLMGRRIAGVLASAGLDVAITDTNAEILHAAAVEAARVAGAGRGSVAAAADLAAAIPDADLVIEAVVENLAVKQELFERLATLAPDAVLATNTSVLPIGAVTERVEDGSRVIGTHFWNPPDLIPVVEVVPSARTAPDTADRVVALLTQVGKLPVRVGRDVPGFIGNRLQHALWREAIALVAEGVCDPKTVDLVVRNTIGLRLATLGPLENADYIGLDLTLAIHDAVIPSLNHDPHPSPLLRELVAAGQLGARTGHGFLDWPAGAREATTARLAQHIAAQLQANEKGRGT