Rv3543c (fadE29)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: hypothetical protein
- REFSEQ: acyl-CoA dehydrogenase FADE29
- PATRIC: Probable acyl-CoA dehydrogenase FadE29 (EC 1.3.99.-); Acyl-CoA dehydrogenase IgrC
- TUBERCULIST: Probable acyl-CoA dehydrogenase FadE29
- NCBI: Probable acyl-CoA dehydrogenase FadE29
- updated information (H37Rv4):
  - gene name: chsE2/fadE29
  - function:
  - reference: Thomas (2013) PMID: 23560677
Type: Conditional
Start: 3981977
End: 3983140
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: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)
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
6WY9	49%	Thermomonospora curvata (strain ATCC 19995 / DSM 43183 / JCM 3096 / NBRC 15933 / NCIMB 10081 / Henssen B9)	Tcur3481-Tcur3483 steroid ACAD G363A variant
4X28	45%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of the ChsE4-ChsE5 complex from Mycobacterium tuberculosis
3SWO	35%	Mycobacterium smegmatis	Crystal structure of a glutaryl-coa dehydrogenase from mycobacterium smegmatis in complex with FADH2

Links to additional information on fadE29:
- KEGG - nucleotide and amino acid sequences of gene
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 1.276 (from Jeremy Rock's lab)
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MFIDLTPEQRQLQAEIRQYFSNLISPDERTEMEKDRHGPAYRAVIRRMGRDGRLGVGWPKEFGGLGFGPIEQQIFVNEAHRADVPLPAVTLQTVGPTLQA
HGSELQKKKFLPAILAGEAHFAIGYTEPEAGTDLASLRTTAVRDGDHYIVNGQKVFTTGAHDADYIWLACRTDPNAAKHKGISILIVDTKDPGYSWTPII
LADGAHHTNATYYNDVRVPVDMLVGKENDGWRLITTQLNNERVMLGPAGRFASIYDRVHAWASVPGGNGVTPIDHDDVKRALGEIRAIWRINELLNWQVA
SAGEDINMADAAATKVFGTERVQRAGRLAEEIVGKYGNPAEPDTAELLRWLDAQTKRNLVITFGGGVNEVMREMIAASGLKVPRVPR

(Nucleotide sequence available on KEGG)

Additional Information

ESSENTIALITY

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

TnSeqCorr - genes with correlated TnSeq profiles across >100 conditions *new*

Classification	Condition	Strain	Method	Reference	Notes
Non-Essential	Sodium Oleate	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 4 non-insertions in a row out of 17 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 3 non-insertions in a row out of 17 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 4 non-insertions in a row out of 17 sites
Non-Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 3 non-insertions in a row out of 17 sites
Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 1.000000; 17 non-insertions in a row out of 17 sites
Non-Essential	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Non-Essential	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: 0.48
Non-Essential	7H09/7H10 + rich media	H37RvMA	MotifHMM	DeJesus et al. (2017)	Fully saturated (14 reps).

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

Transcription

Translation, ribosomal structure and biogenesis

Cell wall/membrane/envelope biogenesis

Replication, recombination and repair

Posttranslational modification, protein turnover, chaperones

Cell motility

Secondary metabolites biosynthesis, transport and catabolism

Inorganic ion transport and metabolism

Function unknown

General function prediction only

Intracellular trafficking, secretion, and vesicular transport

Signal transduction mechanisms

Extracellular structures

Defense mechanisms

Nuclear structure

Cytoskeleton

BioCyc Co-regulated genes based on gene expression profiling (Systems Biology, Inferelator Network)

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).

BioCyc Transcription factor binding based on ChIP-Seq (Systems Biology)

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

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv1353c (-) (Direct binding)
- Rv2034 (-) (Direct binding)
- Rv0081 (-) (Upstream of operon)
- Rv0324 (-) (Upstream of operon)
- Rv0681 (-) (Upstream of operon)
- Rv3133c (devR) (Upstream of operon)

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

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Not upregulated by other genes.
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Rv2887 (-)

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 host authors,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	FadE29	rslayden			authors,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	None
Term	EC:1.3.99.- Oxidoreductases. Acting on the CH-CH group of donors. With other acceptors. - NR	rslayden	NR		authors,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			authors,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

TB Genome Annotation Portal