fadD22 Resolved · high auto-curated
H37Rv Rv2948c · MTBC0 mtbc0_003130 ·
705 aa · 3319012–3321129 (-) ·
RefSeq NP_217464.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | p-hydroxybenzoyl--AMP ligase |
|---|---|
| MTBC0 PGAP re-annotation | p-hydroxybenzoic acid--AMP ligase FadD22 |
| Revised (this work) | P-hydroxybenzoic acid--AMP ligase FadD22. Pfam: AMP-binding (PF00501.35), AMP-binding_C (PF13193.13), PP-binding (PF00550.32). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WQ61
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | p-hydroxybenzoic acid--AMP ligase FadD22 |
| EC (curated) |
EC 6.2.1.50
|
| Curated function | Catalyzes the adenylation of p-hydroxybenzoic acid (pHBA) to form p-hydroxybenzoic acid-AMP (pHBA-AMP), which is converted directly to p-hydroxybenzoyl-S-FadD22 (pHBA-S-FAdD22) thioester intermediate in a CoA-independent manner by attack of the phosphopantetheine thiol of FadD22. Usually, this intermediate primes the biosynthesis of the phenolphthiocerol (PPOL) by presenting the pHBA starter unit for elongation by Pks15/1, but M.tuberculosis lacks Pks15/1 due to a natural frameshift and thus is unable to produce PPOL. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolismQ Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | fadD22 |
| eggNOG description | Catalyzes the adenylation of p-hydroxybenzoic acid (pHBA) to form p-hydroxybenzoic acid-AMP (pHBA-AMP), which is converted directly to p-hydroxybenzoyl-S-FadD22 (pHBA-S-FAdD22) thioester intermediate in a CoA-independent manner by attack of the phosphopantetheine thiol of FadD22 |
| Orthologous group | COG0236 |
| EC number |
EC 6.2.1.50
|
| KEGG orthology |
K12424
|
| Gene Ontology (47) |
GO:0003674, GO:0003824, GO:0006066, GO:0006629, GO:0006643, GO:0006664, GO:0006725, GO:0008150, GO:0008152, GO:0008610, GO:0009058, GO:0009247 +35 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 | 0.291 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 11 synonymous, 8 missense, 1 nonsense, 1 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 0.36% of strains (526) · 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 | 1.3e-62 | 17–354 | AMP-binding enzyme |
AMP-binding_C | PF13193.13 | 4.1e-11 | 402–480 | AMP-binding enzyme C-terminal domain |
PP-binding | PF00550.32 | 8.2e-07 | 549–615 | Phosphopantetheine attachment site |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2949c (chorismate pyruvate-lyase), high confidence from genomic context alone (score 981 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2949c |
chorismate pyruvate-lyase | 987 | 981 ctx | neighborhood:739 coexpression:839 database:500 |
Rv2947c pks15 |
polyketide synthase | 980 | 973 ctx | neighborhood:774 coexpression:817 |
Rv2950c fadD29 |
long-chain-fatty-acid--AMP ligase FadD29 | 954 | 939 ctx | neighborhood:666 coexpression:791 |
Rv2946c pks1 |
polyketide synthase | 951 | 934 ctx | neighborhood:799 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 927 | 911 | coexpression:778 |
Rv2932 ppsB |
phthiocerol synthesis polyketide synthase type I PpsB | 903 | 891 | coexpression:770 |
Rv3513c fadD18 |
fatty-acid--CoA ligase FadD18 | 769 | 769 ctx | cooccurence:769 |
Rv3506 fadD17 |
long-chain-fatty-acid--CoA ligase FadD17 | 740 | 740 ctx | cooccurence:740 |
Rv2939 papA5 |
phthiocerol/phthiodiolone dimycocerosyl transferase | 760 | 730 | coexpression:730 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 816 | 719 | |
Rv0719 rplF |
50S ribosomal protein L6 | 781 | 708 | experimental:402 database:510 |
Rv2048c pks12 |
polyketide synthase | 746 | 698 | |
Rv2931 ppsA |
phthiocerol synthesis polyketide synthase type I PpsA | 752 | 688 | |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 737 | 681 | |
Rv1527c pks5 |
polyketide synthase | 706 | 681 |
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: p-hydroxybenzoyl--AMP ligase
- MTBC0 PGAP product: p-hydroxybenzoic acid--AMP ligase FadD22
- Pfam (hmmscan --cut_ga): AMP-binding PF00501.35 (E=1e-62), AMP-binding_C PF13193.13 (E=4e-11), PP-binding PF00550.32 (E=8e-07)
- (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_217464.1)
- Domains: Pfam-A via hmmscan --cut_ga — AMP-binding (PF00501.35), AMP-binding_C (PF13193.13), PP-binding (PF00550.32)
- 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
COG0236 - Curated reference: UniProt P9WQ61 (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 —
83 functional partner(s); context anchor
Rv2949c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003130|Rv2948c|fadD22 MRNGNLAGLLAEQASEAGWYDRPAFYAADVVTHGQIHDGAARLGEVLRNRGLSSGDRVLLCLPDSPDLVQLLLACLARGVMAFLANPELHRDDHALAARNTEPALVVTSDALRDRFQPSRVAEAAELMSEAARVAPGGYEPMGGDALAYATYTSGTTGPPKAAIHRHADPLTFVDAMCRKALRLTPEDTGLCSARMYFAYGLGNSVWFPLATGGSAVINSAPVTPEAAAILSARFGPSVLYGVPNFFARVIDSCSPDSFRSLRCVVSAGEALELGLAERLMEFFGGIPILDGIGSTEVGQTFVSNRVDEWRLGTLGRVLPPYEIRVVAPDGTTAGPGVEGDLWVRGPAIAKGYWNRPDSPVANEGWLDTRDRVCIDSDGWVTYRCRADDTEVIGGVNVDPREVERLIIEDEAVAEAAVVAVRESTGASTLQAFLVATSGATIDGSVMRDLHRGLLNRLSAFKVPHRFAVVDRLPRTPNGKLVRGALRKQSPTKPIWELSLTEPGSGVRAQRDDLSASNMTIAGGNDGGATLRERLVALRQERQRLVVDAVCAEAAKMLGEPDPWSVDQDLAFSELGFDSQMTVTLCKRLAAVTGLRLPETVGWDYGSISGLAQYLEAELAGGHGRLKSAGPVNSGATGLWAIEEQLNKVEELVAVIADGEKQRVADRLRALLGTIAGSEAGLGKLIQAASTPDEIFQLIDSELGK