Rv0244c (fadE5)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: acyl-CoA dehydrogenase fadE5
- REFSEQ: acyl-CoA dehydrogenase FADE5
- PATRIC: acyl-CoA dehydrogenase
- TUBERCULIST: Probable acyl-CoA dehydrogenase FadE5
- NCBI: Probable acyl-CoA dehydrogenase FadE5
- updated information (H37Rv4):
  - gene name: fadE5
  - function:
  - reference:
Type: Conditional
Start: 293798
End: 295633
Operon:

Trans-membrane region:
Role: I.A.3 - Fatty acids
GO terms:
- GO:0055114 - oxidation-reduction process (Uniprot)
- GO:0052572 - response to host immune response (Uniprot)
- GO:0050660 - flavin adenine dinucleotide binding (Uniprot)
- GO:0016627 - oxidoreductase activity, acting on the CH-CH group of donors (Uniprot)
- GO:0016491 - oxidoreductase activity (Uniprot)
- GO:0008152 - metabolic process (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005576 - extracellular region (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):

PDB	aa ident	species	PDB title
6KSE	99%	Mycobacterium tuberculosis	Crystal Structure of E447A Acyl-CoA Dehydrogenase FadE5 mutant from Mycobacteria tuberculosisin complex with C18CoA
6KSB	81%	Mycobacterium smegmatis	Crystal Structure of E447A M130G Acyl-CoA Dehydrogenase FadE5 mutant from Mycobacteria smegmatis in complex with C16CoA
6KRI	81%	Mycobacterium smegmatis	Crystal Structure of Acyl-CoA Dehydrogenase FadE5 from Mycobacteria smegmatis with product released
6KPT	81%	Mycobacterium smegmatis	Crystal Structure of Acyl-CoA Dehydrogenase FadE5 from Mycobacteria smegmatis
6LQ7	81%	Mycobacterium smegmatis	Crystal Structure of E447A Acyl-CoA Dehydrogenase FadE5 mutant from Mycobacteria smegmatis in complex with C17CoA
6LQ6	81%	Mycobacterium smegmatis	Crystal Structure of E447A Acyl-CoA Dehydrogenase FadE5 mutant from Mycobacteria smegmatis in complex with C20CoA
6LQ5	81%	Mycobacterium smegmatis	Crystal Structure of E447A Acyl-CoA Dehydrogenase FadE5 mutant from Mycobacteria smegmatis in complex with C16CoA
6LQ4	81%	Mycobacterium smegmatis	Crystal Structure of E447A Acyl-CoA Dehydrogenase FadE5 mutant from Mycobacteria smegmatis in complex with C14CoA
6LQ3	81%	Mycobacterium smegmatis	Crystal Structure of E447A Acyl-CoA Dehydrogenase FadE5 mutant from Mycobacteria smegmatis in complex with C12CoA
6LQ2	81%	Mycobacterium smegmatis	Crystal Structure of E447A Acyl-CoA Dehydrogenase FadE5 mutant from Mycobacteria smegmatis in complex with C10CoA

Links to additional information on fadE5:
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 0.492 (from Jeremy Rock's lab)
- BioCyc
- Systems Biology

Amino Acid Sequence

VSHYRSNVRDQVFNLFEVLGVDKALGHGEFSDVDVDTARDMLAEVSRLAEGPVAESFVEGDRNPPVFDPKTHSVMLPESFKKSVNAMLEAGWDKVGIDEA
LGGMPMPKAVVWALHEHILGANPAVWMYAGGAGFAQILYHLGTEEQKKWAVLAAERGWGSTMVLTEPDAGSDVGAARTKAVQQADGSWHIDGVKRFITSG
DSGDLFENIFHLVLARPEGAGPGTKGLSLYFVPKFLFDVETGEPGERNGVFVTNVEHKMGLKVSATCELAFGQHGVPAKGWLVGEVHNGIAQMFEVIEQA
RMMVGTKAIATLSTGYLNALQYAKSRVQGADLTQMTDKTAPRVTITHHPDVRRSLMTQKAYAEGLRALYLYTATFQDAAVAEVVHGVDAKLAVKVNDLML
PVVKGVGSEQAYAKLTESLQTLGGSGFLQDYPIEQYIRDAKIDSLYEGTTAIQAQDFFFRKIVRDKGVALAHVSGQIQEFVDSGAGNGRLKTERALLAKA
LTDVQGMAAALTGYLMAAQQDVTSLYKVGLGSVRFLMSVGDLIIGWLLQRQAAVAVAALDAGATGDERSFYEGKVAVASFFAKNFLPLLTSTREVIETLD
NDIMELDEAAF

(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	YES
omega peak height (95%CI lower bound)	2.03 (0.61)	1.89 (1.06)
codons under selection		218, 219, 220, 417, 418, 431, 432, 437, 438
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"

ESSENTIALITY

MtbTnDB - interactive tool for exploring a database of published TnSeq datasets for Mtb

TnSeqCorr - genes with correlated TnSeq profiles across ~100 conditions

Rv0244c/fadE5, gene len: 1835 bp, num TA sites: 23

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	no data	7H9	TRASH	essential if hybridization ratio<0.2
in-vivo (mice)	Sassetti 2003 PNAS	no data	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	uncertain	M9 minimal+cholesterol	Gumbel	3 replicates; Padj<0.05
differentially essential in cholesterol	Griffin 2011 PPath	YES (LFC=-3.06)	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=-1.014)	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	growth advantage	YM rich medium	HMM	7H9 supplemented with ~20 metabolites (amino acids, vitamins)
differentially essential in YM rich medium	Minato 2019 mSys	YES (LFC=3.93)	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

Binds To:
- No bindings to other targets were found.
Bound By:

Interactions based on ChIPSeq data (Minch et al. 2014)

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0023 (-) (Direct binding)
- Rv0047c (-) (Direct binding)
- Rv0678 (-) (Direct binding)
- Rv0691c (-) (Direct binding)
- Rv0818 (-) (Direct binding)
- Rv1033c (trcR) (Direct binding)
- Rv1404 (-) (Direct binding)
- Rv2034 (-) (Direct binding)
- Rv2989 (-) (Direct binding)
- Rv3597c (lsr2) (Direct binding)

Interactions based on TFOE data (Rustad et al. 2014)

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Rv0023 (-)
- Rv0081 (-)
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Rv0324 (-)
- Rv0818 (-)

Property	Value	Creator	Evidence	Comment
Interaction	RegulatedBy Rv0182c	yamir.moreno	IEP	Microarrays. mRNA levels of regulated element measured and compared between wild-type and trans-element mutation (knockout, over expression etc.) performed by using microarray (or macroarray) experiments.. JH. Lee, DE. Geiman et al. Role of stress response sigma factor SigG in Mycobacterium tuberculosis. J. Bacteriol. 2008
Interaction	RegulatedBy Rv3744	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 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 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

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