fadD9 Resolved · high auto-curated
H37Rv Rv2590 · MTBC0 mtbc0_002757 ·
1168 aa · 2941415–2944921 (+) ·
RefSeq NP_217106.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | fatty-acid--CoA ligase FadD9 |
|---|---|
| MTBC0 PGAP re-annotation | carboxylic acid reductase |
| Revised (this work) | Carboxylic acid reductase. Pfam: AMP-binding (PF00501.35), PP-binding (PF00550.32), Epimerase (PF01370.28), NAD_binding_4 (PF07993.19). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
Q50631
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Carboxylic acid reductase |
| EC (curated) |
EC 1.2.1.-, EC 6.2.1.-
|
| Curated function | Catalyzes the ATP- and NADPH-dependent reduction of carboxylic acids to the corresponding aldehydes (By similarity). In vitro, also catalyzes the activation of medium/long-chain fatty acids as acyl-adenylates (acyl-AMP). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolismQ Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | fadD9 |
| eggNOG description | Thioester reductase domain |
| Orthologous group | COG1022 |
| KEGG orthology |
K12421
|
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 | 0.689 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 7 synonymous, 14 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.21% of strains (301) · 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 | 8.1e-55 | 82–465 | AMP-binding enzyme |
PP-binding | PF00550.32 | 8.6e-12 | 650–716 | Phosphopantetheine attachment site |
Epimerase | PF01370.28 | 5.1e-09 | 771–975 | NAD dependent epimerase/dehydratase family |
NAD_binding_4 | PF07993.19 | 2.6e-61 | 773–1035 | Male sterility protein |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: pks13 (polyketide synthase), high confidence from genomic context alone (score 916 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3800c pks13 |
polyketide synthase | 957 | 916 ctx | neighborhood:544 coexpression:811 textmining:519 |
Rv2383c mbtB |
phenyloxazoline synthase | 966 | 897 ctx | neighborhood:544 coexpression:755 textmining:691 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 950 | 795 ctx | neighborhood:544 coexpression:510 textmining:767 |
Rv2946c pks1 |
polyketide synthase | 942 | 785 ctx | neighborhood:544 coexpression:424 textmining:745 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 936 | 761 ctx | neighborhood:544 coexpression:429 textmining:745 |
Rv2048c pks12 |
polyketide synthase | 936 | 761 ctx | neighborhood:544 coexpression:429 textmining:745 |
Rv1527c pks5 |
polyketide synthase | 936 | 760 ctx | neighborhood:544 coexpression:426 textmining:745 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 936 | 760 ctx | neighborhood:544 coexpression:427 textmining:745 |
Rv1181 pks4 |
polyketide beta-ketoacyl synthase | 916 | 754 ctx | neighborhood:532 coexpression:437 textmining:675 |
Rv1661 pks7 |
polyketide synthase | 905 | 750 ctx | neighborhood:532 coexpression:426 textmining:637 |
Rv2932 ppsB |
phthiocerol synthesis polyketide synthase type I PpsB | 902 | 745 ctx | neighborhood:544 coexpression:425 textmining:635 |
Rv1389 gmk |
guanylate kinase | 664 | 644 | database:591 |
Rv2931 ppsA |
phthiocerol synthesis polyketide synthase type I PpsA | 756 | 606 | coexpression:426 textmining:407 |
Rv2589 gabT |
4-aminobutyrate aminotransferase | 643 | 606 ctx | neighborhood:604 |
Rv0405 pks6 |
membrane bound polyketide synthase | 755 | 604 | coexpression:424 textmining:407 |
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: fatty-acid--CoA ligase FadD9
- MTBC0 PGAP product: carboxylic acid reductase
- Pfam (hmmscan --cut_ga): AMP-binding PF00501.35 (E=8e-55), PP-binding PF00550.32 (E=9e-12), Epimerase PF01370.28 (E=5e-09), NAD_binding_4 PF07993.19 (E=3e-61)
- (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_217106.1)
- Domains: Pfam-A via hmmscan --cut_ga — AMP-binding (PF00501.35), PP-binding (PF00550.32), Epimerase (PF01370.28), NAD_binding_4 (PF07993.19)
- 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
COG1022 - Curated reference: UniProt Q50631 (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 —
90 functional partner(s); context anchor
pks13 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002757|Rv2590|fadD9 MSINDQRLTRRVEDLYASDAQFAAASPNEAITQAIDQPGVALPQLIRMVMEGYADRPALGQRALRFVTDPDSGRTMVELLPRFETITYRELWARAGTLATALSAEPAIRPGDRVCVLGFNSVDYTTIDIALIRLGAVSVPLQTSAPVTGLRPIVTETEPTMIATSIDNLGDAVEVLAGHAPARLVVFDYHGKVDTHREAVEAARARLAGSVTIDTLAELIERGRALPATPIADSADDALALLIYTSGSTGAPKGAMYRESQVMSFWRKSSGWFEPSGYPSITLNFMPMSHVGGRQVLYGTLSNGGTAYFVAKSDLSTLFEDLALVRPTELCFVPRIWDMVFAEFHSEVDRRLVDGADRAALEAQVKAELRENVLGGRFVMALTGSAPISAEMTAWVESLLADVHLVEGYGSTEAGMVLNDGMVRRPAVIDYKLVDVPELGYFGTDQPYPRGELLVKTQTMFPGYYQRPDVTAEVFDPDGFYRTGDIMAKVGPDQFVYLDRRNNVLKLSQGEFIAVSKLEAVFGDSPLVRQIFIYGNSARAYPLAVVVPSGDALSRHGIENLKPVISESLQEVARAAGLQSYEIPRDFIIETTPFTLENGLLTGIRKLARPQLKKFYGERLERLYTELADSQSNELRELRQSGPDAPVLPTLCRAAAALLGSTAADVRPDAHFADLGGDSLSALSLANLLHEIFGVDVPVGVIVSPASDLRALADHIEAARTGVRRPSFASIHGRSATEVHASDLTLDKFIDAATLAAAPNLPAPSAQVRTVLLTGATGFLGRYLALEWLDRMDLVNGKLICLVRARSDEEAQARLDATFDSGDPYLVRHYRELGAGRLEVLAGDKGEADLGLDRVTWQRLADTVDLIVDPAALVNHVLPYSQLFGPNAAGTAELLRLALTGKRKPYIYTSTIAVGEQIPPEAFTEDADIRAISPTRRIDDSYANGYANSKWAGEVLLREAHEQCGLPVTVFRCDMILADTSYTGQLNLPDMFTRLMLSLAATGIAPGSFYELDAHGNRQRAHYDGLPVEFVAEAICTLGTHSPDRFVTYHVMNPYDDGIGLDEFVDWLNSPTSGSGCTIQRIADYGEWLQRFETSLRALPDRQRHASLLPLLHNYREPAKPICGSIAPTDQFRAAVQEAKIGPDKDIPHLTAAIIAKYISNLRLLGLL