fadD4 Resolved · high auto-curated
H37Rv Rv0214 · MTBC0 - ·
537 aa · 256064–257677 (+) ·
RefSeq NP_214728.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | fatty-acid--CoA ligase FadD4 |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Fatty-acid--CoA ligase FadD4. Pfam: AMP-binding (PF00501.35), AMP-binding_C (PF13193.13). |
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 |
P96396
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable fatty-acid-CoA ligase FadD4 |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolismQ Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | fadD4 |
| eggNOG description | Activates fatty acids by binding to coenzyme A |
| Orthologous group | COG0318 |
| EC number |
EC 6.2.1.3
|
| KEGG orthology |
K00666, K01897
|
| KEGG pathways |
map00061, map00071, map01100, map01212, map02024, map03320, map04146, map04216, map04714, map04920
|
| KEGG modules |
M00086
|
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 | 0.475 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 6 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.31% of strains (444) · 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 |
|---|---|---|---|---|
AMP-binding | PF00501.35 | 7.7e-66 | 42–389 | AMP-binding enzyme |
AMP-binding_C | PF13193.13 | 3.8e-17 | 447–525 | AMP-binding enzyme C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: pckA (phosphoenolpyruvate carboxykinase), medium confidence from genomic context alone (score 654 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1550 fadD11 |
fatty-acid--CoA ligase FadD11 | 924 | 922 | database:900 |
Rv2187 fadD15 |
long-chain-fatty-acid--CoA ligase FadD15 | 924 | 922 | database:900 |
Rv2524c fas |
fatty acid synthase | 924 | 915 | database:900 |
Rv3097c lipY |
triacylglycerol lipase Lip | 852 | 834 | database:800 |
Rv0719 rplF |
50S ribosomal protein L6 | 695 | 695 | experimental:402 database:510 |
Rv1527c pks5 |
polyketide synthase | 706 | 681 | |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 705 | 680 | |
Rv2048c pks12 |
polyketide synthase | 705 | 680 | |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 704 | 679 | |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 704 | 679 | |
Rv0211 pckA |
phosphoenolpyruvate carboxykinase | 654 | 654 ctx | neighborhood:544 |
Rv3800c pks13 |
polyketide synthase | 668 | 635 | |
Rv2946c pks1 |
polyketide synthase | 664 | 632 | |
Rv1345 mbtM |
long-chain-fatty-acid--ACP ligase MbtM | 631 | 631 ctx | cooccurence:631 |
Rv2932 ppsB |
phthiocerol synthesis polyketide synthase type I PpsB | 629 | 608 |
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): fatty-acid--CoA ligase FadD4
- Pfam (hmmscan --cut_ga): AMP-binding PF00501.35 (E=8e-66), AMP-binding_C PF13193.13 (E=4e-17)
- (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_214728.1)
- Domains: Pfam-A via hmmscan --cut_ga — AMP-binding (PF00501.35), AMP-binding_C (PF13193.13)
- 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
COG0318 - Curated reference: UniProt P96396 (TrEMBL, unreviewed; 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 —
85 functional partner(s); context anchor
pckA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0214|fadD4 MPRGELYKRFRLVMGGIAPCGSGRRAATYPRRMQIRPYIGADKPAVILYPSGTVISFDELEARANRLAHWFRQAGLREDDVVAILMENNEHVHAVMWAARRSGLYYVPINTHLTASEAAYIVDNSGAKAIVGSAALRETCHGLAEHLPGGLPDLLMLAGGGLVGWMTYPECVADQPDTPIEDEREGDLLQYSSGTTGRPKGIKRELPHVSPDAAPGMMPALLDFWMDADSVYLSPAPMYHTAPSVWTMSALAAGVTTVVMEKFDAEGALDAIQRYRVTHAQFVPAMFVRMLKLPEAVRNSYDMSSLRRVIHAAAPCPVQIKEQMIHWWGPIIDEYYASSEASGSTLITAEDWLTHPGSVGKPIQGGVHIVGADGSELPPNQPGEIYFEGGYPFEYLNDPAKTAASRNKHGWVTVGDVGYLDDDGYLFLTGRRHHMIISGGVNIYPQEAENLLVAHPKVLDAAVFGVPDDEMGQRVMAAVQTVDSADANDQFAGELLAWLRDRLSHFKCPRSIAFEPQLPRTDTGKLYKSGLVEKYSV