fadD5 Resolved · high auto-curated
H37Rv Rv0166 · MTBC0 mtbc0_000179 ·
554 aa · 195341–197005 (+) ·
RefSeq NP_214680.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | fatty-acid--CoA ligase FadD5 |
|---|---|
| MTBC0 PGAP re-annotation | fatty-acid--CoA ligase FadD5 |
| Revised (this work) | Fatty-acid--CoA ligase FadD5. 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.
Curated reference (UniProt)
| UniProt |
O07411
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable fatty-acid-CoA ligase FadD5 |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolismQ Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | fadD5 |
| eggNOG description | COG0318 Acyl-CoA synthetases (AMP-forming) AMP-acid ligases II |
| 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) pseudogene candidate
| pN/pS | 0.338 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 16 synonymous, 16 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 1.67% of strains (2420) · 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 | 4.4e-88 | 32–395 | AMP-binding enzyme |
AMP-binding_C | PF13193.13 | 6.6e-18 | 445–519 | AMP-binding enzyme C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: yrbE1A (membrane protein), high confidence from genomic context alone (score 897 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0167 yrbE1A |
membrane protein | 963 | 897 ctx | neighborhood:474 coexpression:813 textmining:659 |
Rv0171 mce1C |
Mce family protein Mce1C | 890 | 891 ctx | neighborhood:481 coexpression:798 |
Rv0169 mce1A |
Mce family protein Mce1A | 976 | 886 ctx | neighborhood:459 coexpression:798 textmining:804 |
Rv0168 yrbE1B |
membrane protein | 943 | 886 ctx | neighborhood:454 coexpression:799 textmining:530 |
Rv0172 mce1D |
Mce family protein Mce1D | 883 | 863 ctx | neighborhood:460 coexpression:757 |
Rv0173 lprK |
Mce family lipoprotein LprK | 881 | 842 ctx | neighborhood:442 coexpression:729 |
Rv2947c pks15 |
polyketide synthase | 836 | 828 ctx | fusion:702 |
Rv0170 mce1B |
Mce family protein Mce1B | 842 | 824 ctx | neighborhood:460 coexpression:687 |
Rv1180 pks3 |
polyketide beta-ketoacyl synthase | 798 | 799 ctx | fusion:650 |
Rv2382c mbtC |
polyketide synthetase | 741 | 739 ctx | fusion:550 |
Rv1549 fadD11.1 |
Possible fatty-acid-CoA ligase FadD11.1 (fatty-acid-CoA synthetase) (fatty-acid-CoA synthase); Rv1549, (MTCY48.16c), len: 175 aa. Possible f | 756 | 738 | coexpression:734 |
Rv1663 pks17 |
polyketide synthase | 745 | 733 ctx | fusion:565 |
Rv0719 rplF |
50S ribosomal protein L6 | 697 | 698 | experimental:402 database:510 |
Rv2048c pks12 |
polyketide synthase | 707 | 682 | |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 707 | 682 |
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 FadD5
- MTBC0 PGAP product: fatty-acid--CoA ligase FadD5
- Pfam (hmmscan --cut_ga): AMP-binding PF00501.35 (E=4e-88), AMP-binding_C PF13193.13 (E=7e-18)
- (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_214680.1)
- 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 O07411 (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 —
92 functional partner(s); context anchor
yrbE1A - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000179|Rv0166|fadD5 MTAQLASHLTRALTLAQQQPYLARRQNWVNQLERHAMMQPDAPALRFVGNTMTWADLRRRVAALAGALSGRGVGFGDRVMILMLNRTEFVESVLAANMIGAIAVPLNFRLTPTEIAVLVEDCAAHVMLTEAALAPVAIGVRNIQPLLSVIVVAGGSSQDSVFGYEDLLNEAGDVHEPVDIPNDSPALIMYTSGTTGRPKGAVLTHANLTGQAMTALYTSGANINSDVGFVGVPLFHIAGIGNMLTGLLLGLPTVIYPLGAFDPGQLLDVLEAEKVTGIFLVPAQWQAVCTEQQARPRDLRLRVLSWGAAPAPDALLRQMSATFPETQILAAFGQTEMSPVTCMLLGEDAIAKRGSVGRVIPTVAARVVDQNMNDVPVGEVGEIVYRAPTLMSCYWNNPEATAEAFAGGWFHSGDLVRMDSDGYVWVVDRKKDMIISGGENIYCAELENVLASHPDIAEVAVIGRADEKWGEVPIAVAAVTNDDLRIEDLGEFLTDRLARYKHPKALEIVDALPRNPAGKVLKTELRLRYGACVNVERRSASAGFTERRENRQKL