Rv2241 (aceE)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: pyruvate dehydrogenase E1 component
- REFSEQ: pyruvate dehydrogenase subunit E1
- PATRIC: Pyruvate dehydrogenase E1 component (EC 1.2.4.1)
- TUBERCULIST: Pyruvate dehydrogenase E1 component AceE (pyruvate decarboxylase) (pyruvate dehydrogenase) (pyruvic dehydrogenase)
- NCBI: Pyruvate dehydrogenase E1 component AceE (pyruvate decarboxylase) (pyruvate dehydrogenase) (pyruvic dehydrogenase)
- updated information (H37Rv4):
  - gene name: aceE
  - function:
  - reference:
Type: Not Target
Start: 2512539
End: 2515244
Operon:

Trans-membrane region:
Role: I.B.2 - Pyruvate dehydrogenase
GO terms:
- GO:0055114 - oxidation-reduction process (Uniprot)
- GO:0045254 - pyruvate dehydrogenase complex (Uniprot)
- GO:0016491 - oxidoreductase activity (Uniprot)
- GO:0008152 - metabolic process (Uniprot)
- GO:0006096 - glycolytic process (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005618 - cell wall (Uniprot)
- GO:0005576 - extracellular region (Uniprot)
- GO:0005515 - protein binding (Uniprot)
- GO:0004739 - pyruvate dehydrogenase (acetyl-transferring) activity (Uniprot)
- GO:0003824 - catalytic activity (Uniprot)
- GO:0000287 - magnesium ion binding (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- PYR[c] + LIPO[c] + 0.001 THI[c] -> CO2[c] + ADLIPO[c]
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
4QOY	52%	Escherichia coli	Novel binding motif and new flexibility revealed by structural analysis of a pyruvate dehydrogenase-dihydrolipoyl acetyltransferase sub-complex from the escherichia coli pyruvate dehydrogenase multi-enzyme complex
2IEA	52%	Escherichia coli	E. coli pyruvate dehydrogenase
2G67	52%	Escherichia coli	E. Coli Pyruvate Dehydrogenase E1 Component (Apoenzyme)
2G28	52%	Escherichia coli	E. Coli Pyruvate Dehydrogenase H407A variant Phosphonolactylthiamin Diphosphate Complex
2G25	52%	Escherichia coli	E. Coli Pyruvate Dehydrogenase Phosphonolactylthiamin Diphosphate Complex
1RP7	52%	Escherichia coli	E. COLI PYRUVATE DEHYDROGENASE INHIBITOR COMPLEX
1L8A	52%	Escherichia coli	E. COLI PYRUVATE DEHYDROGENASE
3LQ4	52%	Escherichia coli	E. coli pyruvate dehydrogenase complex E1 E235A mutant with high TDP concentration
3LQ2	52%	Escherichia coli	E. coli pyruvate dehydrogenase complex E1 E235A mutant with low TDP concentration
3LPL	52%	Escherichia coli	E. coli pyruvate dehydrogenase complex E1 component E571A mutant

Links to additional information on aceE:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -1.054 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

VASYLPDIDPEETSEWLESFDTLLQRCGPSRARYLMLRLLERAGEQRVAIPALTSTDYVNTIPTELEPWFPGDEDVERRYRAWIRWNAAIMVHRAQRPGV
GVGGHISTYASSAALYEVGFNHFFRGKSHPGGGDQVFIQGHASPGIYARAFLEGRLTAEQLDGFRQEHSHVGGGLPSYPHPRLMPDFWEFPTVSMGLGPL
NAIYQARFNHYLHDRGIKDTSDQHVWCFLGDGEMDEPESRGLAHVGALEGLDNLTFVINCNLQRLDGPVRGNGKIIQELESFFRGAGWNVIKVVWGREWD
ALLHADRDGALVNLMNTTPDGDYQTYKANDGGYVRDHFFGRDPRTKALVENMSDQDIWNLKRGGHDYRKVYAAYRAAVDHKGQPTVILAKTIKGYALGKH
FEGRNATHQMKKLTLEDLKEFRDTQRIPVSDAQLEENPYLPPYYHPGLNAPEIRYMLDRRRALGGFVPERRTKSKALTLPGRDIYAPLKKGSGHQEVATT
MATVRTFKEVLRDKQIGPRIVPIIPDEARTFGMDSWFPSLKIYNRNGQLYTAVDADLMLAYKESEVGQILHEGINEAGSVGSFIAAGTSYATHNEPMIPI
YIFYSMFGFQRTGDSFWAAADQMARGFVLGATAGRTTLTGEGLQHADGHSLLLAATNPAVVAYDPAFAYEIAYIVESGLARMCGENPENIFFYITVYNEP
YVQPPEPENFDPEGVLRGIYRYHAATEQRTNKAQILASGVAMPAALRAAQMLAAEWDVAADVWSVTSWGELNRDGVAIETEKLRHPDRPAGVPYVTRALE
NARGPVIAVSDWMRAVPEQIRPWVPGTYLTLGTDGFGFSDTRPAARRYFNTDAESQVVAVLEALAGDGEIDPSVPVAAARQYRIDDVAAAPEQTTDPGPG
A

(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
Essential	Sodium Oleate	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.999350; 19 non-insertions in a row out of 57 sites
Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 1.000000; 57 non-insertions in a row out of 57 sites
Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 1.000000; 53 non-insertions in a row out of 57 sites
Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 1.000000; 57 non-insertions in a row out of 58 sites
Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 1.000000; 57 non-insertions in a row out of 58 sites
Growth-Defect	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Growth-Defect	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: 0.96
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:
- No bindings to other targets were found.

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:
- Not downregulated by other genes.

Property	Value	Creator	Evidence	PMID	Comment
Citation	Mycobacterium tuberculosis appears to lack alpha-ketoglutarate dehydrogenase and encodes pyruvate dehydrogenase in widely separated genes. J. Tian, R. Bryk et al. Mol. Microbiol. 2005	njamshidi	IDA	16045627	previous annotations with sequence based annotations of pdhA, pdhB, pdhC (Rv2497c, Rv2496c,Rv2495c) were found to be incorrect and removed - this is the appropriate annotation for PDH according to PMID: 16045627.
Term	TBRXN:PDH pyruvate dehydrogenase - IDA	njamshidi	IDA	16045627	previous annotations with sequence based annotations of pdhA, pdhB, pdhC (Rv2497c, Rv2496c,Rv2495c) were found to be incorrect and removed - this is the appropriate annotation for PDH according to PMID: 16045627. J. Tian, R. Bryk et al. Mycobacterium tuberculosis appears to lack alpha-ketoglutarate dehydrogenase and encodes pyruvate dehydrogenase in widely separated genes. Mol. Microbiol. 2005
Citation	Mycobacterium tuberculosis appears to lack alpha-ketoglutarate dehydrogenase and encodes pyruvate dehydrogenase in widely separated genes. J. Tian, R. Bryk et al. Mol. Microbiol. 2005	njamshidi	ISS	16045627	previous annotations with sequence based annotations of pdhA, pdhB, pdhC (Rv2497c, Rv2496c,Rv2495c) were found to be incorrect and removed - this is the appropriate annotation for PDH according to PMID: 16045627.
Term	TBRXN:PDH pyruvate dehydrogenase - ISS	njamshidi	ISS	16045627	previous annotations with sequence based annotations of pdhA, pdhB, pdhC (Rv2497c, Rv2496c,Rv2495c) were found to be incorrect and removed - this is the appropriate annotation for PDH according to PMID: 16045627. J. Tian, R. Bryk et al. Mycobacterium tuberculosis appears to lack alpha-ketoglutarate dehydrogenase and encodes pyruvate dehydrogenase in widely separated genes. Mol. Microbiol. 2005
Interaction	Signaling Rv1571	razeeth.new	IEP		Co-expression AH. Li, WL. Lam et al. Bacterial artificial chromosome fingerprint arrays for the differentiation of transcriptomic differences in mycobacteria. J. Microbiol. Methods 2008
Interaction	Signaling Rv1571	razeeth.new	IEP		Co-expression AH. Li, WL. Lam et al. Characterization of genes differentially expressed within macrophages by virulent and attenuated Mycobacterium tuberculosis identifies candidate genes involved in intracellular growth. Microbiology (Reading, Engl.) 2008
Interaction	RegulatedBy Rv1221	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.. R. Manganelli, MI. Voskuil et al. The Mycobacterium tuberculosis ECF sigma factor sigmaE: role in global gene expression and survival in macrophages. Mol. Microbiol. 2001
Citation	Variant tricarboxylic acid cycle in Mycobacterium tuberculosis: identification of alpha-ketoglutarate decarboxylase. J. Tian, R. Bryk et al. Proc. Natl. Acad. Sci. U.S.A. 2005	jjmcfadden		16027371	Inferred from direct assay
Term	EC:1.2.4.1 Pyruvate dehydrogenase (acetyl-transferring). - NR	jjmcfadden	NR		Inferred from direct assay J. Tian, R. Bryk et al. Variant tricarboxylic acid cycle in Mycobacterium tuberculosis: identification of alpha-ketoglutarate decarboxylase. Proc. Natl. Acad. Sci. U.S.A. 2005
Citation	Central carbon metabolism in Mycobacterium tuberculosis: an unexpected frontier. authors,KY. Rhee,LP. de Carvalho,R. Bryk,S. Ehrt,J. Marrero,SW. Park,D. Schnappinger,A. Venugopal,C. Nathan Trends Microbiol. 2011	extern:JZUCKER		21561773	Traceable author statement to experimental support
Term	EC:1.2.4.1 Pyruvate dehydrogenase (acetyl-transferring). - NR	extern:JZUCKER	NR		Traceable author statement to experimental support authors,KY. Rhee,LP. de Carvalho,R. Bryk,S. Ehrt,J. Marrero,SW. Park,D. Schnappinger,A. Venugopal,C. Nathan Central carbon metabolism in Mycobacterium tuberculosis: an unexpected frontier. Trends Microbiol. 2011
Citation	Mycobacterium tuberculosis appears to lack alpha-ketoglutarate dehydrogenase and encodes pyruvate dehydrogenase in widely separated genes. J. Tian, R. Bryk et al. Mol. Microbiol. 2005	extern:JZUCKER		16045627	Inferred from mutant phenotype
Term	EC:1.2.4.1 Pyruvate dehydrogenase (acetyl-transferring). - NR	extern:JZUCKER	NR		Inferred from mutant phenotype J. Tian, R. Bryk et al. Mycobacterium tuberculosis appears to lack alpha-ketoglutarate dehydrogenase and encodes pyruvate dehydrogenase in widely separated genes. Mol. Microbiol. 2005

TB Genome Annotation Portal