Rv2498c (citE)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: citrate lyase subunit beta-like protein
- REFSEQ: citrate (Pro-3S)-lyase beta subunit
- PATRIC: Hydroxymethylglutaryl-CoA lyase (EC 4.1.3.4)
- TUBERCULIST: Probable citrate (pro-3S)-lyase (beta subunit) CitE (citrase) (citratase) (citritase) (citridesmolase) (citrase aldolase)
- NCBI: Probable citrate (pro-3S)-lyase (beta subunit) CitE (citrase) (citratase) (citritase) (citridesmolase) (citrase aldolase)
- updated information (H37Rv4):
  - gene name: citE
  - function:
  - reference:
Type: Conditional
Start: 2812355
End: 2813176
Operon:

Trans-membrane region:
Role: I.B.3 - TCA cycle
GO terms:
- GO:0046872 - metal ion binding (Uniprot)
- GO:0016829 - lyase activity (Uniprot)
- GO:0006107 - oxaloacetate metabolic process (Uniprot)
- GO:0003824 - catalytic activity (Uniprot)
- GO:0000287 - magnesium ion binding (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: 1u5v, 1u5h, 1z6k
Search for Homologs in PDB

Top 10 Homologs in PDB (as of Nov 2020):

PDB	aa ident	species	PDB title
6CJ4	100%	Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh)	CRYSTAL STRUCTURE OF PROTEIN CITE FROM MYCOBACTERIUM TUBERCULOSIS IN COMPLEX WITH MAGNESIUM AND ACETOACETATE
6CJ3	100%	Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh)	CRYSTAL STRUCTURE OF PROTEIN CITE FROM MYCOBACTERIUM TUBERCULOSIS IN COMPLEX WITH MAGNESIUM AND PYRUVATE
6CHU	100%	Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh)	CRYSTAL STRUCTURE OF PROTEIN CITE FROM MYCOBACTERIUM TUBERCULOSIS IN COMPLEX WITH MAGNESIUM AND ACETATE
6AS5	100%	Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh)	CRYSTAL STRUCTURE OF PROTEIN CitE FROM MYCOBACTERIUM TUBERCULOSIS IN COMPLEX WITH MAGNESIUM, ACETOACETATE AND COENZYME A
6ARB	100%	Mycobacterium tuberculosis CDC1551	CRYSTAL STRUCTURE OF PROTEIN CitE FROM MYCOBACTERIUM TUBERCULOSIS IN COMPLEX WITH MAGNESIUM, PYRUVATE AND COENZYME A
6AQ4	100%	Mycobacterium tuberculosis	CRYSTAL STRUCTURE OF PROTEIN CiTE FROM MYCOBACTERIUM TUBERCULOSIS IN COMPLEX WITH MAGNESIUM, PYRUVATE AND CITRAMALYL-COA
1Z6K	100%	Mycobacterium tuberculosis	Citrate lyase beta subunit complexed with oxaloacetate and magnesium from M. tuberculosis
1U5H	98%	Mycobacterium tuberculosis	Structure of Citrate Lyase beta subunit from Mycobacterium tuberculosis
1U5V	97%	Mycobacterium tuberculosis	Structure of CitE complexed with triphosphate group of ATP form Mycobacterium tuberculosis
3QLL	36%	Yersinia pestis	Crystal Structure of RipC from Yersinia pestis

Links to additional information on citE:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 0.745 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MNLRAAGPGWLFCPADRPERFAKAAAAADVVILDLEDGVAEAQKPAARNALRDTPLDPERTVVRINAGGTADQARDLEALAGTAYTTVMLPKAESAAQVI
ELAPRDVIALVETARGAVCAAEIAAADPTVGMMWGAEDLIATLGGSSSRRADGAYRDVARHVRSTILLAASAFGRLALDAVHLDILDVEGLQEEARDAAA
VGFDVTVCIHPSQIPVVRKAYRPSHEKLAWARRVLAASRSERGAFAFEGQMVDSPVLTHAETMLRRAGEATSE

(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; 2 non-insertions in a row out of 9 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 9 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 2 non-insertions in a row out of 9 sites
Non-Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 2 non-insertions in a row out of 9 sites
Non-Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 2 non-insertions in a row out of 9 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: 0.85
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:
- Rv1816 (-) (Upstream of operon)
- Rv2250c (-) (Upstream of operon)
- Rv2506 (-) (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:
- Not downregulated by other genes.

Property	Value	Creator	Evidence	PMID	Comment
Citation	Ancient genes in contemporary persistent microbial pathogens. authors,V. Srinivasan,HJ. Morowitz Biol. Bull. 2006	njamshidi	ISS	16501059\|12486050	Reversible form added, suggestions in the literature indicate possibility of rev TCA - also Tuberculist associates EC 4.1.3.6 (rev cit lyase) with this locus. PMID: 16501059, 12486050
Term	EC:4.1.3.6 Citrate (pro-3S)-lyase. - ISS	njamshidi	ISS	16501059\|12486050	Reversible form added, suggestions in the literature indicate possibility of rev TCA - also Tuberculist associates EC 4.1.3.6 (rev cit lyase) with this locus. PMID: 16501059, 12486050 authors,V. Srinivasan,HJ. Morowitz Ancient genes in contemporary persistent microbial pathogens. Biol. Bull. 2006
Term	TBRXN:CITLr Citrate lyase (reversible) - ISS	njamshidi	ISS	16501059\|12486050	Reversible form added, suggestions in the literature indicate possibility of rev TCA - also Tuberculist associates EC 4.1.3.6 (rev cit lyase) with this locus. PMID: 16501059, 12486050 authors,V. Srinivasan,HJ. Morowitz Ancient genes in contemporary persistent microbial pathogens. Biol. Bull. 2006
Citation	Growth of mycobacteria on carbon monoxide and methanol. authors,SW. Park,EH. Hwang,H. Park,JA. Kim,J. Heo,KH. Lee,T. Song,E. Kim,YT. Ro,SW. Kim,YM. Kim J. Bacteriol. 2003	njamshidi	ISS	16501059\|12486050	Reversible form added, suggestions in the literature indicate possibility of rev TCA - also Tuberculist associates EC 4.1.3.6 (rev cit lyase) with this locus. PMID: 16501059, 12486050
Term	EC:4.1.3.6 Citrate (pro-3S)-lyase. - ISS	njamshidi	ISS	16501059\|12486050	Reversible form added, suggestions in the literature indicate possibility of rev TCA - also Tuberculist associates EC 4.1.3.6 (rev cit lyase) with this locus. PMID: 16501059, 12486050 authors,SW. Park,EH. Hwang,H. Park,JA. Kim,J. Heo,KH. Lee,T. Song,E. Kim,YT. Ro,SW. Kim,YM. Kim Growth of mycobacteria on carbon monoxide and methanol. J. Bacteriol. 2003
Term	TBRXN:CITLr Citrate lyase (reversible) - ISS	njamshidi	ISS	16501059\|12486050	Reversible form added, suggestions in the literature indicate possibility of rev TCA - also Tuberculist associates EC 4.1.3.6 (rev cit lyase) with this locus. PMID: 16501059, 12486050 authors,SW. Park,EH. Hwang,H. Park,JA. Kim,J. Heo,KH. Lee,T. Song,E. Kim,YT. Ro,SW. Kim,YM. Kim Growth of mycobacteria on carbon monoxide and methanol. J. Bacteriol. 2003
Interaction	PhysicalInteraction Rv2499c	shahanup86	RCA		Operon (Functional Linkage) CW. Goulding, PM. Bowers et al. The structure and computational analysis of Mycobacterium tuberculosis protein CitE suggest a novel enzymatic function. J. Mol. Biol. 2007
Interaction	PhysicalInteraction Rv2500c	shahanup86	RCA		Operon (Functional Linkage) CW. Goulding, PM. Bowers et al. The structure and computational analysis of Mycobacterium tuberculosis protein CitE suggest a novel enzymatic function. J. Mol. Biol. 2007

TB Genome Annotation Portal