Rv3616c (espA)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: ESX-1 secretion-associated protein EspA
- REFSEQ: hypothetical protein
- PATRIC: ESX-1 secretion system protein (Rv3616c)
- TUBERCULIST: ESX-1 secretion-associated protein A EspA
- NCBI: ESX-1 secretion-associated protein A, EspA
- updated information (H37Rv4):
  - gene name: espA
  - function:
  - reference:
Type: Conditional
Start: 4055197
End: 4056375
Operon:

Trans-membrane region:
Role: V - Conserved hypotheticals
GO terms:
- GO:0071766 - Actinobacterium-type cell wall biogenesis (Uniprot)
- GO:0044315 - protein secretion by the type VII secretion system (Uniprot)
- GO:0009405 - pathogenesis (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005615 - extracellular space (Uniprot)
- GO:0005576 - extracellular region (Uniprot)
- GO:0005515 - protein binding (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 espA:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 1.594 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MSRAFIIDPTISAIDGLYDLLGIGIPNQGGILYSSLEYFEKALEELAAAFPGDGWLGSAADKYAGKNRNHVNFFQELADLDRQLISLIHDQANAVQTTRD
ILEGAKKGLEFVRPVAVDLTYIPVVGHALSAAFQAPFCAGAMAVVGGALAYLVVKTLINATQLLKLLAKLAELVAAAIADIISDVADIIKGTLGEVWEFI
TNALNGLKELWDKLTGWVTGLFSRGWSNLESFFAGVPGLTGATSGLSQVTGLFGAAGLSASSGLAHADSLASSASLPALAGIGGGSGFGGLPSLAQVHAA
STRQALRPRADGPVGAAAEQVGGQSQLVSAQGSQGMGGPVGMGGMHPSSGASKGTTTKKYSEGAAAGTEDAERAPVEADAGGGQKVLVRNVV

(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
Uncertain	Sodium Oleate	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.076900; 2 non-insertions in a row out of 18 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 18 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 18 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 19 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 19 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: 0.3
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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv1404 (-)

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0212c (nadR) (Direct binding)
- Rv0324 (-) (Direct binding)
- Rv0474 (-) (Direct binding)
- Rv0691c (-) (Direct binding)
- Rv1049 (-) (Direct binding)
- Rv1353c (-) (Direct binding)
- Rv1423 (whiA) (Direct binding)
- Rv1773c (-) (Direct binding)
- Rv2887 (-) (Direct binding)
- Rv3050c (-) (Direct binding)
- Rv3133c (devR) (Direct binding)
- Rv3160c (-) (Direct binding)
- Rv3173c (-) (Direct binding)
- Rv3405c (-) (Direct binding)
- Rv3574 (kstR) (Direct binding)
- Rv3862c (whiB6) (Direct binding)

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:
- Rv1404 (-)

TBCAP

Tubculosis Community Annotation Project (

Slayden et al., 2013

Rv3616c (espA)

Property	Value	Creator	Evidence	PMID	Comment
Interaction	Transcription Rv3849	shahanup86	IEP		Co-expression (Functional linkage) S. Raghavan, P. Manzanillo et al. Secreted transcription factor controls Mycobacterium tuberculosis virulence. Nature 2008
Interaction	Transcription Rv3849	shahanup86	IEP		Co-expression (Functional linkage) authors,R. Simeone,D. Bottai,R. Brosch ESX/type VII secretion systems and their role in host-pathogen interaction. Curr. Opin. Microbiol. 2009
Interaction	PhysicalInteraction Rv3614c	darhngu	IMP		Co-expression (Functional Linkage) authors,SM. Fortune,A. Jaeger,DA. Sarracino,MR. Chase,CM. Sassetti,DR. Sherman,BR. Bloom,EJ. Rubin Mutually dependent secretion of proteins required for mycobacterial virulence. Proc. Natl. Acad. Sci. U.S.A. 2005
Interaction	PhysicalInteraction Rv3849	darhngu	IMP		Co-expression (Functional Linkage) authors,SM. Fortune,A. Jaeger,DA. Sarracino,MR. Chase,CM. Sassetti,DR. Sherman,BR. Bloom,EJ. Rubin Mutually dependent secretion of proteins required for mycobacterial virulence. Proc. Natl. Acad. Sci. U.S.A. 2005
Citation	Secreted transcription factor controls Mycobacterium tuberculosis virulence. S. Raghavan, P. Manzanillo et al. Nature 2008	darhngu	IMP	18685700	Co-expression (Functional Linkage)
Interaction	PhysicalInteraction Rv3615c	darhngu	IMP		Co-expression (Functional Linkage) S. Raghavan, P. Manzanillo et al. Secreted transcription factor controls Mycobacterium tuberculosis virulence. Nature 2008
Interaction	PhysicalInteraction Rv3614c	darhngu	IMP		Co-expression (Functional Linkage) S. Raghavan, P. Manzanillo et al. Secreted transcription factor controls Mycobacterium tuberculosis virulence. Nature 2008
Interaction	PhysicalInteraction Rv3849	darhngu	IMP		Co-expression (Functional Linkage) S. Raghavan, P. Manzanillo et al. Secreted transcription factor controls Mycobacterium tuberculosis virulence. Nature 2008
Interaction	PhysicalInteraction Rv3615c	darhngu	IMP		Co-expression (Functional Linkage) B. Sidders, C. Pirson et al. Screening of highly expressed mycobacterial genes identifies Rv3615c as a useful differential diagnostic antigen for the Mycobacterium tuberculosis complex. Infect. Immun. 2008
Interaction	PhysicalInteraction Rv3615c	darhngu	IMP		Co-expression (Functional Linkage) authors,SM. Fortune,A. Jaeger,DA. Sarracino,MR. Chase,CM. Sassetti,DR. Sherman,BR. Bloom,EJ. Rubin Mutually dependent secretion of proteins required for mycobacterial virulence. Proc. Natl. Acad. Sci. U.S.A. 2005
Citation	Mutually dependent secretion of proteins required for mycobacterial virulence. authors,SM. Fortune,A. Jaeger,DA. Sarracino,MR. Chase,CM. Sassetti,DR. Sherman,BR. Bloom,EJ. Rubin Proc. Natl. Acad. Sci. U.S.A. 2005	darhngu	IMP	16030141	Co-expression (Functional Linkage)
Interaction	PhysicalInteraction Rv3615c	darhngu	IMP		Co-expression (Functional Linkage) authors,SM. Fortune,A. Jaeger,DA. Sarracino,MR. Chase,CM. Sassetti,DR. Sherman,BR. Bloom,EJ. Rubin Mutually dependent secretion of proteins required for mycobacterial virulence. Proc. Natl. Acad. Sci. U.S.A. 2005
Interaction	PhysicalInteraction Rv3614c	darhngu	IMP		Co-expression (Functional Linkage) authors,SM. Fortune,A. Jaeger,DA. Sarracino,MR. Chase,CM. Sassetti,DR. Sherman,BR. Bloom,EJ. Rubin Mutually dependent secretion of proteins required for mycobacterial virulence. Proc. Natl. Acad. Sci. U.S.A. 2005
Interaction	PhysicalInteraction Rv3614c	darhngu	IMP		Co-expression (Functional Linkage) S. Raghavan, P. Manzanillo et al. Secreted transcription factor controls Mycobacterium tuberculosis virulence. Nature 2008
Interaction	RegulatedBy Rv3911	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.. S. Raman, X. Puyang et al. Mycobacterium tuberculosis SigM positively regulates Esx secreted protein and nonribosomal peptide synthetase genes and down regulates virulence-associated surface lipid synthesis. J. Bacteriol. 2006
Interaction	RegulatedBy Rv0757	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.. SB. Walters, E. Dubnau et al. The Mycobacterium tuberculosis PhoPR two-component system regulates genes essential for virulence and complex lipid biosynthesis. Mol. Microbiol. 2006
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
Interaction	RegulatedBy Rv3849	yamir.moreno	IDA		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.. qRT-PCR. mRNA expression levels of regulated element measured and compared between wild-type and trans-element mutation (knockout, over expression etc.) performed by using qRT-PCR technique. Electrophoretic mobility shift assays EMSA. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. . S. Raghavan, P. Manzanillo et al. Secreted transcription factor controls Mycobacterium tuberculosis virulence. Nature 2008
Interaction	RegulatedBy Rv3849	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.. qRT-PCR. mRNA expression levels of regulated element measured and compared between wild-type and trans-element mutation (knockout, over expression etc.) performed by using qRT-PCR technique. Electrophoretic mobility shift assays EMSA. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. . S. Raghavan, P. Manzanillo et al. Secreted transcription factor controls Mycobacterium tuberculosis virulence. Nature 2008
Interaction	RegulatedBy Rv3849	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.. qRT-PCR. mRNA expression levels of regulated element measured and compared between wild-type and trans-element mutation (knockout, over expression etc.) performed by using qRT-PCR technique. Electrophoretic mobility shift assays EMSA. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. . S. Raghavan, P. Manzanillo et al. Secreted transcription factor controls Mycobacterium tuberculosis virulence. Nature 2008

Property

Value

Creator

Evidence

PMID

Comment

Interaction

Transcription Rv3849

shahanup86

IEP

Co-expression (Functional linkage)
S. Raghavan, P. Manzanillo et al. Secreted transcription factor controls Mycobacterium tuberculosis virulence. Nature 2008

Interaction

Transcription Rv3849

shahanup86

IEP

Co-expression (Functional linkage)
authors,R. Simeone,D. Bottai,R. Brosch ESX/type VII secretion systems and their role in host-pathogen interaction. Curr. Opin. Microbiol. 2009

Interaction

PhysicalInteraction Rv3614c

darhngu

IMP

Co-expression (Functional Linkage)
authors,SM. Fortune,A. Jaeger,DA. Sarracino,MR. Chase,CM. Sassetti,DR. Sherman,BR. Bloom,EJ. Rubin Mutually dependent secretion of proteins required for mycobacterial virulence. Proc. Natl. Acad. Sci. U.S.A. 2005

Interaction

PhysicalInteraction Rv3849

darhngu

IMP

Citation

Secreted transcription factor controls Mycobacterium tuberculosis virulence. S. Raghavan, P. Manzanillo et al. Nature 2008

darhngu

IMP

18685700

Co-expression (Functional Linkage)

Interaction

PhysicalInteraction Rv3615c

darhngu

IMP

Co-expression (Functional Linkage)
S. Raghavan, P. Manzanillo et al. Secreted transcription factor controls Mycobacterium tuberculosis virulence. Nature 2008

Interaction

PhysicalInteraction Rv3614c

darhngu

IMP

Co-expression (Functional Linkage)
S. Raghavan, P. Manzanillo et al. Secreted transcription factor controls Mycobacterium tuberculosis virulence. Nature 2008

Interaction

PhysicalInteraction Rv3849

darhngu

IMP

Co-expression (Functional Linkage)
S. Raghavan, P. Manzanillo et al. Secreted transcription factor controls Mycobacterium tuberculosis virulence. Nature 2008

Interaction

PhysicalInteraction Rv3615c

darhngu

IMP

Co-expression (Functional Linkage)
B. Sidders, C. Pirson et al. Screening of highly expressed mycobacterial genes identifies Rv3615c as a useful differential diagnostic antigen for the Mycobacterium tuberculosis complex. Infect. Immun. 2008

Interaction

PhysicalInteraction Rv3615c

darhngu

IMP

Citation

Mutually dependent secretion of proteins required for mycobacterial virulence. authors,SM. Fortune,A. Jaeger,DA. Sarracino,MR. Chase,CM. Sassetti,DR. Sherman,BR. Bloom,EJ. Rubin Proc. Natl. Acad. Sci. U.S.A. 2005

darhngu

IMP

16030141

Co-expression (Functional Linkage)

Interaction

PhysicalInteraction Rv3615c

darhngu

IMP

Interaction

PhysicalInteraction Rv3614c

darhngu

IMP

Interaction

PhysicalInteraction Rv3614c

darhngu

IMP

Co-expression (Functional Linkage)
S. Raghavan, P. Manzanillo et al. Secreted transcription factor controls Mycobacterium tuberculosis virulence. Nature 2008

Interaction

RegulatedBy Rv3911

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..
S. Raman, X. Puyang et al. Mycobacterium tuberculosis SigM positively regulates Esx secreted protein and nonribosomal peptide synthetase genes and down regulates virulence-associated surface lipid synthesis. J. Bacteriol. 2006

Interaction

RegulatedBy Rv0757

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..
SB. Walters, E. Dubnau et al. The Mycobacterium tuberculosis PhoPR two-component system regulates genes essential for virulence and complex lipid biosynthesis. Mol. Microbiol. 2006

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

Interaction

RegulatedBy Rv3849

yamir.moreno

IDA

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.. qRT-PCR. mRNA expression levels of regulated element measured and compared between wild-type and trans-element mutation (knockout, over expression etc.) performed by using qRT-PCR technique. Electrophoretic mobility shift assays EMSA. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. .
S. Raghavan, P. Manzanillo et al. Secreted transcription factor controls Mycobacterium tuberculosis virulence. Nature 2008

Interaction

RegulatedBy Rv3849

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.. qRT-PCR. mRNA expression levels of regulated element measured and compared between wild-type and trans-element mutation (knockout, over expression etc.) performed by using qRT-PCR technique. Electrophoretic mobility shift assays EMSA. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. .
S. Raghavan, P. Manzanillo et al. Secreted transcription factor controls Mycobacterium tuberculosis virulence. Nature 2008

Interaction

RegulatedBy Rv3849

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.. qRT-PCR. mRNA expression levels of regulated element measured and compared between wild-type and trans-element mutation (knockout, over expression etc.) performed by using qRT-PCR technique. Electrophoretic mobility shift assays EMSA. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. .
S. Raghavan, P. Manzanillo et al. Secreted transcription factor controls Mycobacterium tuberculosis virulence. Nature 2008

Comments