fadD11.1 Family assigned · low auto-curated · to review
H37Rv Rv1549 · MTBC0 ·
175 aa ·
1753510–1754037 H37Rv
(+) ·
RefSeq
Genomic neighbourhood (genome browser)
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Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | Possible fatty-acid-CoA ligase FadD11.1 (fatty-acid-CoA synthetase) (fatty-acid-CoA synthase) |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Possible fatty-acid-CoA ligase FadD11.1 (fatty-acid-CoA synthetase) (fatty-acid-CoA synthase) |
| Functional category (TubercuList) | lipid metabolism |
Curation note: Added P16.5d: Mycobrowser-annotated gene absent from RefSeq NC_000962.3 (the atlas' original 3906-CDS reference). Foundation record from the Mycobrowser release + translated H37Rv sequence; heavy enrichment layers (structure, orthology, conservation, interaction) pending. P16.23 (phase135, 2026-08-17): couche tss ajoutee (leaderless=False).
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed (flagged for human review).
In the literature (TB corpus sweep)
Rv1549 (2), fadD11.1 (2).
A hit does NOT mean functional characterisation -- it may be a mention in a genome-wide table or screen (e.g. a differential-expression supplementary table), exactly the mechanism that revealed the Rv3222c/Sarkar2021 co-induction. Restricted to hits CORROBORATED by the H37Rv tag itself, the gene name, or a substantial/multi-alias hit count -- single-low-count-ortholog-only hits were excluded pending individual review (cf. Rv0027/Mb0028, a confirmed collision unrelated to Mycobacterium). Coverage limit (P52.4, measured 2026-09-30): the body-text part of this search only sees articles whose full text Europe PMC holds, about 8-13 % of the TB literature published before 2005, 21 % for 2005-2009, 40 % for 2010-2014 and 66 % since 2020, so the absence of a hit says little about older mentions.
This distinguishes a gene that is dark because nobody has looked from one that is dark despite having been studied. Source: .
CRISPRi vulnerability
Vulnerability index 0.63 (95% CI -0.23 to 1.96). A more negative index = more vulnerable to knockdown (better drug-target quality); indicative threshold VI ≤ -6 = highly vulnerable.
Quantitative CRISPRi knockdown, graded (finer than binary Tn-seq essentiality). Source: CRISPRi vulnerability index (Bosch 2021, supplementary Table S2 'mmc3.xlsx', bulk import via Europe PMC -- supersedes the per-gene pebble.rockefeller.edu scrape of phase46_crispri_vulnerability.py).
Caveat on this estimate. Bosch et al. flag this gene's vulnerability estimate as NOT certain, and here that call has a mechanical cause visible in the library itself: every guide targeting this gene is >=21 nt (str_span=0.472 on a 0-1 scale, near the genome floor), and guide repression strength saturates from 21 nt on -- so the library never sampled a partial knockdown for this gene, only the near-maximal repression plateau. The dose-response fit (and this VI) is therefore essentially unconstrained by data, not merely uncertain -- a limitation of the CRISPRi library design for the non-essential class (Bosch et al. 2021), not a defect in this specific measurement. n_guides=6 is descriptive only and does not predict this. Do not cite this VI as a standalone vulnerability claim.
Legacy record & comparison (Mycobrowser)
| Mycobrowser function | Function unknown, but involvement in lipid degradation. |
|---|
The legacy Mycobrowser record is shown for verification. Mycobrowser is no longer maintained; its EC numbers predate recent nomenclature revisions, so a class change usually reflects re-numbering, not a conflict.
Curated reference (UniProt)
| UniProt |
P9WLU5
SwissProt · reviewed
|
|---|---|
| UniProt name | Uncharacterized protein Rv1549 |
As checked on 2026-09-23, UniProt listed this protein as Uncharacterized protein Rv1549; the revised annotation above goes beyond that record. UniProt may have been recurated since: check the live entry.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
|
|---|---|
| Preferred name | fadD11.1 |
| eggNOG description | synthetase |
| Orthologous group | COG1022 |
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, 142 601 strains, snapshot of 2026-09-29)
| pN/pS | 0.696 · quasi-invariant (3 sites), pN/pS underpowered |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 2 missense, 0 nonsense, 2 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 97.85% of strains (139530) · reference-fixed |
| Which clade carries which site (attribution) |
CONVERGENCE inter-clades (sites différents) — Bovis, Caprae_La2, L1, L2, L3, L4, L5, L6, L7, L9, L_1, La4, Microti, Orygis_La3, Pinnipedii, Suricattae;
union over all sites: 180 391
strains (the count above is a maximum over sites, not a union).
|
Read the disruption percentage against its ceiling, not against 100%. The strain collection is deeply imbalanced by clade, so a loss fixed in an entire lineage still shows a small overall fraction: a gene disrupted in every L6 strain caps at 0.96% of the collection, in every M. caprae strain at 0.20%, in every M. microti strain at 0.02%. Of the 705 clades in this collection, 689 have a ceiling below 1%. A figure of "0.15% of strains" is therefore uninterpretable on its own — it can be noise or a complete, lineage-defining loss. Use the clade attribution row above, which gives the sub-clade sizes, and never read the percentage alone.
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.
Essentiality (transposon mutagenesis)
| DeJesus 2017 call | NE · non-essential |
|---|---|
| What the call means | non-essential |
| TA sites (Himar1) |
9 in the ORF —
0 in the essential state,
0 growth-defect,
9 non-essential,
0 growth-advantage.
Saturation 1.000,
mean read count 208.333333333.
A region of the protein devoid of TA sites is invisible to this assay: nothing can be
inferred about it, in either direction.
All 9 sites lie in this ORF alone (no overlapping CDS shares any), so the call is attributable to this gene. |
| Caveat | Read with some caution: only 9 TA (Himar1) sites in the whole ORF (atlas median 13). The DeJesus 2017 call rests on fewer independent observations than for a longer gene. If this gene overlaps a neighbour (see Genomic-neighbour overlap section below), some of these 9 sites may fall inside the neighbour's ORF rather than its own, leaving even fewer truly informative sites than the raw count suggests. (P20.3) |
Genome-wide Himar1 transposon essentiality in H37Rv (DeJesus 2017). An essential call (ES/ESD/GD) is strong, independent evidence that a "hypothetical" locus encodes a functional, selectively required gene — orthogonal to intra-species conservation.
Proteomics (mass spectrometry) detected
| MS detection | detected in 5 of 16 independent MS datasets |
|---|---|
| Integrated abundance | 6.46 ppm · rank 2847/3519 (19.1th percentile) |
Detection by mass spectrometry is direct, experimental evidence that the protein product exists — orthogonal to sequence conservation and to Tn-seq essentiality, and especially decisive for a "hypothetical" locus. Read the dataset count as abundance, not as replication. Measured across this atlas (3,491 detected proteins), the number of datasets a protein appears in tracks its abundance almost monotonically: median 1.2 ppm at 1 dataset of 16, 27 ppm at 10, 392 ppm at 15, 1,325 ppm at 16 — three orders of magnitude. A high count therefore says the protein is abundant more than it says several independent experiments confirmed it. What the count does establish, at any value, is that the product exists.
Predicted localisation (DeepTMHMM + lipobox) no export signal, no TM helix
| Prediction | no signal peptide, no TM helix (DeepTMHMM class GLOB) |
|---|---|
| DeepTMHMM class | GLOB |
A verified absence of signals, which is not a compartment. No Sec/Tat signal peptide, no transmembrane helix and no lipobox were found on this sequence. The predictor reports topology and export signals; it does not measure where the protein ends up, so this page draws no cytoplasmic conclusion from it. In M. tuberculosis that reservation is not theoretical: the 12 Esx paralogues of this atlas — EsxA/ESAT-6 and EsxB/CFP-10 among them, the best-established secreted proteins of the species — carry this very call, because substrates of the type VII (ESX) secretion system leave no recognisable signal. « Secreted » and « no signal peptide » are true together here.
Transmembrane topology and signal peptide from DeepTMHMM (deep-learning reference predictor); lipoproteins from a (myco)bacterial lipobox motif. A sequence-based prediction of subcellular context.
Physico-chemical properties (computed, ProtParam)
| Length | 175 aa |
|---|---|
| Molecular weight | 19.3 kDa |
| Theoretical pI | 8.37 |
| GRAVY | -0.143 (hydrophilic) |
| Aliphatic index | 78.0 |
| Aromaticity | 0.074 |
| Instability index | 43.4 (unstable) |
Computed from the ancestral MTBC0 sequence with the ExPASy ProtParam method (Biopython). Descriptive biophysical context: a positive GRAVY flags a hydrophobic (often membrane) protein, a high instability index (>40) predicts a short in-vitro half-life, an extreme pI hints at compartment or binding partner.
Domains (Pfam, hmmscan --cut_ga)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
AMP-binding | PF00501 | n/a | – | AMP-binding |
3D structure (interactive — Mol*/pdbe-molstar)
No experimental structure is deposited for this gene: showing the AlphaFold DB predicted model (mean pLDDT 84.9, confident), coloured by per-residue confidence (dark blue = very high, orange/red = low — treat low-confidence regions as unreliable, especially termini and loops). Drag to rotate, scroll to zoom.
Structural search (AlphaFold DB model, Foldseek vs PDB — genome-wide) pLDDT 84.9
| PDB hit | prob | TM (aln) | TM (query) | TM (target) | Seq. id. | Cov. q / t | E-value | Description |
|---|---|---|---|---|---|---|---|---|
3t5c-assembly2_B |
1.00 | 0.86 | 0.65 | 0.30 | 25% | 71% / 33% | 1.1e-09 sig | 3t5c-assembly2_B Crystal structure of N-terminal domain of FACL13 from Mycobacterium tuberculosis in different space group C2 |
3r44-assembly1_A |
1.00 | 0.86 | 0.65 | 0.24 | 25% | 71% / 26% | 1.7e-09 sig | 3r44-assembly1_A Mycobacterium tuberculosis fatty acyl CoA synthetase |
4wv3-assembly1_A |
1.00 | 0.84 | 0.68 | 0.24 | 24% | 77% / 27% | 1.2e-09 sig | 4wv3-assembly1_A Crystal structure of the anthranilate CoA ligase AuaEII in complex with anthranoyl-AMP |
3a9u-assembly1_A |
1.00 | 0.91 | 0.68 | 0.24 | 23% | 74% / 25% | 5.2e-09 sig | 3a9u-assembly1_A Crystal structures and enzymatic mechanisms of a Populus tomentosa 4-coumarate--CoA ligase |
5u95-assembly3_C |
1.00 | 0.89 | 0.66 | 0.23 | 23% | 71% / 24% | 4.9e-09 sig | 5u95-assembly3_C Structure of the open conformation of 4-coumarate-CoA ligase from Nicotiana tabacum |
Foldseek search of the AlphaFold DB model (mean pLDDT 84.9, gated at 70) against the PDB — a genome-wide extension of the ESMFold dark-gene search that also covers proteins beyond the single-sequence length limit. Confident structural neighbours (E < 0.01) shown.
Additional regulons (curated, outside the TFOE-derived TRN)
crp |
binding site only -- direction not determined (low confidence · CRP regulon (Kahramanoglou et al. 2014))
ChIP-seq : site de fixation CRP (1 des 191 sites de Kahramanoglou et al. 2014) ; aucun changement d'expression rapporte pour ce gene chez le mutant delta-crp Caveat: Site de fixation CRP mesure par ChIP-seq (Kahramanoglou et al. 2014), SANS changement d'expression mesure pour ce gene chez le mutant delta-crp : le sens de la regulation n'est PAS determine. Ecrire « site de fixation CRP en amont », jamais « regule par CRP ». L'article ne distingue pas « non differentiellement exprime » de « sous le seuil », donc l'absence de ce gene de la table d'expression n'est pas une preuve de non-regulation. |
|---|
Curated from primary literature not covered by the ISB signed TRN (Minch 2015 / Rustad 2014): Zur regulon (Maciag et al. 2007, PMID 17098899), SigG regulon (Gaudion et al. 2013, PMID 23871545), LexA/SOS regulon (Smollett et al. 2012, PMID 22528497) — added P16.25 (2026-08-18); CRP regulon (Kahramanoglou et al. 2014, PMID 24957601) — added P16.25b (2026-09-27). Confidence and caveats are per-edge and carried from the source paper — read them before citing a specific gene as "regulated by" its listed TF. An entry reading "binding site only — direction not determined" is not a regulation claim: it records a measured ChIP-seq binding site for which the source reports no expression change, and the absence of such a change is not evidence of absent regulation.
Functional interaction network (STRING v12, guilt-by-association)
Explore full network →Node colour = verdict, dashed = still uncharacterised; edge colour = evidence (green experimental, orange genomic-context, grey co-expression), width ∝ score. Click a partner to open its page; "Explore full network" to walk the graph.
Closest characterised functional partner: fadD11 (fatty-acid--CoA ligase FadD11), high confidence (score 999, all STRING channels except text-mining; the partner is chosen on its genomic-context evidence).
Showing the 15 strongest of this gene's 53 partners at medium confidence (5 at high confidence). The table is an extract, not a neighbourhood: across the proteome the real median degree is 34 while the served median is 15, so no hub, degree distribution or centrality may be read on this table. None of the 53 partners rests on an interaction measured in M. tuberculosis itself.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1550 fadD11 |
fatty-acid--CoA ligase FadD11 | 999 | 999 ctx | neighborhood:781 fusion:900 cooccurence:745 coexpression:838 |
Rv2485c lipQ |
carboxylesterase LipQ | 884 | 839 | coexpression:838 |
Rv1551 plsB1 |
acyltransferase PlsB | 843 | 835 ctx | neighborhood:771 |
Rv0458 |
aldehyde dehydrogenase | 772 | 764 | coexpression:742 |
Rv0166 fadD5 paralog |
fatty-acid--CoA ligase FadD5 | 756 | 738 | coexpression:734 |
Rv1389 gmk curated |
guanylate kinase | 642 | 643 | database:591 |
Rv2390c |
hypothetical protein | 552 | 550 | |
Rv1548c PPE21 |
PPE family protein PPE21 | 522 | 522 ctx | neighborhood:519 |
Rv0009 ppiA curated |
iron-regulated peptidyl-prolyl cis-trans isomerase PpiA | 499 | 497 | database:428 |
Rv2582 ppiB curated |
peptidyl-prolyl cis-trans isomerase B | 495 | 496 | database:428 |
Rv0178 |
Mce associated membrane protein | 581 | 489 | |
Rv1363c |
membrane protein | 491 | 489 | |
Rv1972 |
Mce associated membrane protein | 491 | 489 | |
Rv3492c |
Mce associated protein | 491 | 489 | |
Rv1362c |
membrane protein | 490 | 488 |
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.
Where the experimental evidence comes from, and why it matters here. STRING's experimental channel fuses interactions measured in M. tuberculosis with interactions measured in another organism and transferred to this pair by orthology. The two are not equivalent for this atlas, whose standing rule is that better studied elsewhere is not a function established in M. tuberculosis. Measured on the served network: of the 38 229 partner pairs shown across the atlas, 13 483 partner rows carry a non-zero experimental channel, and only 106 pairs rest on an interaction measured in M. tuberculosis itself — 0.3 % of the network. Those 106 are long-established complexes (ESX-1/ESAT-6, RNA polymerase with CarD and RbpA, the Pup–Mpa proteasome, gyrase, Emb, GarA with PknB and PknG, the Rel modules); no still-uncharacterised gene is among them. The reason is not a gap in this atlas but in the literature: there is almost no experimental interactome of this bacterium, IntAct holding 134 curated protein pairs for a ~4 000-gene proteome. A exp (transferred) badge is therefore a lead, never a measurement, and an absence of badge is not evidence that the pair does not interact.
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 )
- Domains: Pfam-A via hmmscan --cut_ga — AMP-binding (PF00501)
- 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 P9WLU5 (SwissProt, reviewed)
- Intra-MTBC selection: pN/pS and disruption from SPDI variants of 142 601 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
- Genome-wide structure: AlphaFold DB model (Jumper et al. 2021, doi:10.1038/s41586-021-03819-2; Varadi et al. 2024, doi:10.1093/nar/gkad1011) searched vs PDB with Foldseek (mean pLDDT 84.9)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
53 functional partner(s); context anchor
fadD11 - Essentiality: genome-wide transposon mutagenesis in H37Rv — DeJesus et al. 2017 (mBio, doi:10.1128/mBio.02133-16, CC BY)
- Proteomics: integrated mass-spectrometry abundance from PaxDb 5.0 (Huang et al. 2023, doi:10.1016/j.mcpro.2023.100640), taxon 83332 — weighted average of 16 datasets, incl. Schubert et al. 2013 (doi:10.1016/j.chom.2013.04.008) and Albrethsen et al. 2013 (doi:10.1074/mcp.M112.018846)
- Functional category: TubercuList scheme (Cole et al. 1998, doi:10.1038/31159), via Mycobrowser (Kapopoulou et al. 2011, doi:10.1016/j.tube.2010.09.006)
- Physico-chemical properties: ExPASy ProtParam method via Biopython (Gasteiger et al. 2005), computed from the MTBC0 sequence
- Predicted localisation: DeepTMHMM (Hallgren et al. 2022, doi:10.1101/2022.04.08.487609) for transmembrane topology and signal peptide
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>|Rv1549|fadD11.1 VVAAPCFRVLRLWTYAHRCDLGHTDPLSRRTEMTTTERPTTMCEAFQRTAVMDPDAVALRTPGGNQTMTWRDYAAQVRRVAAGLAGLGVRRGDTVSLMMANRIEFYPLDVGAQHVGATSFSVYNTLPAEQLTYVFDNAGTKVVICEQQYVDRVRASGVPIEHIVCVDGAPPARSR
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