Rv3544c (fadE28)
Current annotations:
TBCAP: (community-based annotations - see table at bottom of page )
TBDB: hypothetical protein
REFSEQ: acyl-CoA dehydrogenase FADE28
PATRIC: Probable acyl-CoA dehydrogenase FadE28 (EC 1.3.99.-); Acyl-CoA dehydrogenase IgrB
TUBERCULIST: Probable acyl-CoA dehydrogenase FadE28
NCBI: Probable acyl-CoA dehydrogenase FadE28
updated information (H37Rv4):
gene name: chsE1/fadE28
function:
reference: Thomas (2013) PMID: 23560677
Type: Conditional
Start: 3983125
End: 3984144
Operon:
Trans-membrane region:
Role: I.A.3 - Fatty acids
GO terms:
GO:0071949 - FAD binding (Uniprot)
GO:0055114 - oxidation-reduction process (Uniprot)
GO:0050660 - flavin adenine dinucleotide binding (Uniprot)
GO:0044117 - growth of symbiont in host (Uniprot)
GO:0033539 - fatty acid beta-oxidation using acyl-CoA dehydrogenase (Uniprot)
GO:0016627 - oxidoreductase activity, acting on the CH-CH group of donors (Uniprot)
GO:0016491 - oxidoreductase activity (Uniprot)
GO:0016042 - lipid catabolic process (Uniprot)
GO:0009405 - pathogenesis (Uniprot)
GO:0009268 - response to pH (Uniprot)
GO:0008203 - cholesterol metabolic process (Uniprot)
GO:0008202 - steroid metabolic process (Uniprot)
GO:0008152 - metabolic process (Uniprot)
GO:0006707 - cholesterol catabolic process (Uniprot)
GO:0006629 - lipid metabolic process (Uniprot)
GO:0006979 - response to oxidative stress (FLUTE) (FLUTE Assigned! Y2 report, Nambi et al.)
Reaction(s) (based on iSM810 metabolic model):
Gene Expression Profile (Transcriptional Responses to Drugs; Boshoff et al, 2004)
Gene Modules extracted from cluster analysis of 249 transcriptomic datasets using ICA
Orthologs among selected mycobacteria
Protein structure:
Search for Homologs in PDB
Top 10 Homologs in PDB (as of Nov 2020): (none with >35% aa id)
Links to additional information on fadE28:
Amino Acid Sequence
MDFDPTAEQQAVADVVTSVLERDISWEALVCGGVTALPVPERLGGDGVGLFEVGALLTEVGRHGAVTPALATLGLGVVPLLELASAEQQDRFLAGVAKGG
VLTAALNEPGAALPDRPATSFVGGRLSGTKVGVGYAEQADWMLVTADNAVVVVSPTADGVRMVRTPTSNGSDEYVMTMDGVAVADCDILADVAAHRVNQL
ALAVMGAYADGLVAGALRLTADYVANRKQFGKPLSTFQTVAAQLAEVYIASRTIDLVAKSVIWRLAEDLDAGDDLGVLGYWVTSQAPPAMQICHHLHGGM
GMDVTYPMHRYYSTIKDLTRLLGGPSHRLELLGARCSLT
(
Nucleotide sequence available on
KEGG )
Additional Information
Analysis of Positive Selection in Clinical Isolates
*new*
Analysis of dN/dS (omega) in two collections of Mtb clinical isolates using GenomegaMap (Window model) (see description of methods )
Moldova: 2,057 clinical isolates
global set: 5,195 clinical isolates from 15 other countries
In the omega plots, the black line shows the mean estimate of omega (dN/dS) at each codon, and the blue lines are the bounds for the 95% credible interval (95%CI, from MCMC sampling).
A gene is under significant positive selection if the lower-bound of the 95%CI of omega (lower blue line) exceeds 1.0 at any codon.
Moldova (2,057) global set (5,195)
under significant positive selection? NO NO
omega peak height (95%CI lower bound) 1.31 (0.13) 0.99 (0.42)
codons under selection
omega plots
genetic variants* link link
statistics at each codon link link
* example format for variants: "D27 (GAC): D27H (CAC,11)" means "Asp27 (native codon GAC) mutated to His (codon CAC) in 11 isolates"
MtbTnDB - interactive tool for exploring a database of published TnSeq datasets for Mtb
TnSeqCorr - genes with correlated TnSeq profiles across ~100 conditions
Rv3544c/fadE28,
gene len: 1019 bp, num TA sites: 16
condition dataset call medium method notes
in-vitro DeJesus 2017 mBio non-essential 7H9 HMM fully saturated, 14 TnSeq libraries combined
in-vitro Sassetti 2003 Mol Micro non-essential 7H9 TRASH essential if hybridization ratio<0.2
in-vivo (mice) Sassetti 2003 PNAS essential BL6 mice TRASH essential if hybridization ratio<0.4, min over 4 timepoints (1-8 weeks)
in-vitro (glycerol) Griffin 2011 PPath non-essential M9 minimal+glycerol Gumbel 2 replicates; Padj<0.05
in-vitro (cholesterol) Griffin 2011 PPath non-essential M9 minimal+cholesterol Gumbel 3 replicates; Padj<0.05
differentially essential in cholesterol Griffin 2011 PPath YES (LFC=-6.66) cholesterol vs glycerol resampling-SR YES if Padj<0.05, else not significant; LFC<0 means less insertions/more essential in cholesterol
in-vitro Smith 2022 eLife growth defect 7H9 HMM 6 replicates (raw data in Subramaniam 2017, PMID 31752678)
in-vivo (mice) Smith 2022 eLife growth defect BL6 mice HMM 6 replicates (raw data in Subramaniam 2017, PMID 31752678)
differentially essential in mice Smith 2022 eLife YES (LFC=-3.441) in-vivo vs in-vitro ZINB YES if Padj<0.05, else not significant; LFC<0 means less insertions/more essential in mice
in-vitro (minimal) Minato 2019 mSys non-essential minimal medium HMM
in-vitro (YM rich medium) Minato 2019 mSys non-essential YM rich medium HMM 7H9 supplemented with ~20 metabolites (amino acids, vitamins)
differentially essential in YM rich medium Minato 2019 mSys NO (LFC=-1.52) YM rich vs minimal medium resampling
TnSeq Data No data currently available.
No TnSeq data currently available for this Target.
RNASeq Data No data currently available.
No RNA-Seq data currently available for this Target.
Metabolomic Profiles No data currently available.
No Metabolomic data currently available for this Target.
Proteomic Data No data currently available.
No Proteomic data currently available for this Target.
Regulatory Relationships from Systems Biology
BioCyc
Gene interactions based on ChIPSeq and Transcription Factor Over-Expression (TFOE) (Systems Biology )
NOTE:
Green edges represent the connected genes being classified as differentially essential as a result of the middle gene being knocked out. These interactions are inferred based on RNASeq.
Interactions based on ChIPSeq data
RNA processing and modification
Energy production and conversion
Chromatin structure and dynamics
Amino acid transport and metabolism
Cell cycle control, cell division, chromosome partitioning
Carbohydrate transport and metabolism
Nucleotide transport and metabolism
Lipid transport and metabolism
Coenzyme transport and metabolism
Translation, ribosomal structure and biogenesis
Cell wall/membrane/envelope biogenesis
Replication, recombination and repair
Posttranslational modification, protein turnover, chaperones
Secondary metabolites biosynthesis, transport and catabolism
Inorganic ion transport and metabolism
General function prediction only
Intracellular trafficking, secretion, and vesicular transport
Signal transduction mechanisms
Differentially expressed as result of RNASeq in glycerol environment (Only top 20 genes shown sorted by log fold change with p_adj 0.05).
Conditionally essential as result of TNSeq (Only top 20 genes shown sorted by log fold change with p_adj 0.05).
Binds To:
No bindings to other targets were found.
Bound By:
No bindings from other targets were found.
Binds To:
No bindings to other targets were found.
Bound By:
Upregulates:
Does not upregulate other genes.
Upregulated by:
Not upregulated by other genes.
Downregulates:
Does not downregulate other genes.
Downregulated by:
Not downregulated by other genes.
Property Value Creator Evidence PMID Comment
Interaction Regulatory Rv3574 priyadarshinipriyanka2001 IEP Co-expression (Functional linkage)SL. Kendall,P. Burgess,R. Balhana,M. Withers,A. Ten Bokum,JS. Lott,C. Gao,I. Uhia Castro,NG. Stoker Cholesterol utilisation in mycobacteria is controlled by two TetR-type transcriptional regulators; kstR and kstR2. Microbiology (Reading, England) 2010
Interaction Regulatory Rv3574 priyadarshinipriyanka2001 IEP Co-expression (Functional linkage)SL. Kendall, M. Withers et al. A highly conserved transcriptional repressor controls a large regulon involved in lipid degradation in Mycobacterium smegmatis and Mycobacterium tuberculosis. Mol. Microbiol. 2007
Interaction RegulatedBy Rv3416 yamir.moreno IDA One hybrid reporter system. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. .M. Guo, H. Feng et al. Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res. 2009
Interaction RegulatedBy Rv2034 yamir.moreno IDA One hybrid reporter system. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. .M. Guo, H. Feng et al. Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res. 2009
Interaction RegulatedBy Rv2017 yamir.moreno IDA One hybrid reporter system. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. .M. Guo, H. Feng et al. Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res. 2009
Interaction RegulatedBy Rv1956 yamir.moreno IDA One hybrid reporter system. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. .M. Guo, H. Feng et al. Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res. 2009
Interaction RegulatedBy Rv0818 yamir.moreno IDA One hybrid reporter system. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. .M. Guo, H. Feng et al. Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res. 2009
Interaction RegulatedBy Rv0445c yamir.moreno IDA One hybrid reporter system. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. .M. Guo, H. Feng et al. Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res. 2009
Interaction RegulatedBy Rv3574 yamir.moreno ISO M.smegmatis orthology based inference. Orthologous pair regulator-target found in M.smegmatis.SL. Kendall, M. Withers et al. A highly conserved transcriptional repressor controls a large regulon involved in lipid degradation in Mycobacterium smegmatis and Mycobacterium tuberculosis. Mol. Microbiol. 2007
Interaction RegulatedBy Rv3574 yamir.moreno TAS Literature previously reported link (from Balazsi et al. 2008). Traceable author statement to experimental support.G. Balzsi, AP. Heath et al. The temporal response of the Mycobacterium tuberculosis gene regulatory network during growth arrest. Mol. Syst. Biol. 2008
Citation Pathway profiling in Mycobacterium tuberculosis: elucidation of cholesterol-derived catabolite and enzymes that catalyze its metabolism. authors,ST. Thomas,BC. VanderVen,DR. Sherman,DG. Russell,NS. Sampson J. Biol. Chem. 2011 nsampson 22045806 Assay of protein purified to homogeneity from a heterlogous host
Term EC:1.3.99.- Oxidoreductases. Acting on the CH-CH group of donors. With other acceptors. - NR nsampson NR Assay of protein purified to homogeneity from a heterlogous hostauthors,ST. Thomas,BC. VanderVen,DR. Sherman,DG. Russell,NS. Sampson Pathway profiling in Mycobacterium tuberculosis: elucidation of cholesterol-derived catabolite and enzymes that catalyze its metabolism. J. Biol. Chem. 2011
Symbol FadE28 rslayden enzyme is a heterodimer, digit four of EC number not yet assignedauthors,ST. Thomas,BC. VanderVen,DR. Sherman,DG. Russell,NS. Sampson Pathway profiling in Mycobacterium tuberculosis: elucidation of cholesterol-derived catabolite and enzymes that catalyze its metabolism. J. Biol. Chem. 2011
Citation Pathway profiling in Mycobacterium tuberculosis: elucidation of cholesterol-derived catabolite and enzymes that catalyze its metabolism. authors,ST. Thomas,BC. VanderVen,DR. Sherman,DG. Russell,NS. Sampson J. Biol. Chem. 2011 rslayden 22045806 enzyme is a heterodimer, digit four of EC number not yet assigned
Term EC:1.3.99.- Oxidoreductases. Acting on the CH-CH group of donors. With other acceptors. - NR rslayden NR enzyme is a heterodimer, digit four of EC number not yet assignedauthors,ST. Thomas,BC. VanderVen,DR. Sherman,DG. Russell,NS. Sampson Pathway profiling in Mycobacterium tuberculosis: elucidation of cholesterol-derived catabolite and enzymes that catalyze its metabolism. J. Biol. Chem. 2011
Other product:2 rslayden enzyme is a heterodimer, digit four of EC number not yet assignedauthors,ST. Thomas,BC. VanderVen,DR. Sherman,DG. Russell,NS. Sampson Pathway profiling in Mycobacterium tuberculosis: elucidation of cholesterol-derived catabolite and enzymes that catalyze its metabolism. J. Biol. Chem. 2011