Rv3614c (espD)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: ESX-1 secretion-associated protein EspD
- REFSEQ: hypothetical protein
- PATRIC: ESX-1 secretion system protein (Rv3614c)
- TUBERCULIST: ESX-1 secretion-associated protein EspD
- NCBI: ESX-1 secretion-associated protein EspD
- updated information (H37Rv4):
  - gene name: espD
  - function:
  - reference:
Type: Conditional
Start: 4054142
End: 4054696
Operon:

Trans-membrane region:
Role: V - Conserved hypotheticals
GO terms:
- GO:0044315 - protein secretion by the type VII secretion system (Uniprot)
- GO:0009405 - pathogenesis (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005618 - cell wall (Uniprot)
- GO:0005576 - extracellular region (Uniprot)
- GO:0005515 - protein 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:
Search for Homologs in PDB
Top 10 Homologs in PDB (as of Nov 2020): (none with >35% aa id)
Links to additional information on espD:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 0.159 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

VDLPGNDFDSNDFDAVDLWGADGAEGWTADPIIGVGSAATPDTGPDLDNAHGQAETDTEQEIALFTVTNPPRTVSVSTLMDGRIDHVELSARVAWMSESQ
LASEILVIADLARQKAQSAQYAFILDRMSQQVDADEHRVALLRKTVGETWGLPSPEEAAAAEAEVFATRYSDDCPAPDDESDPW

(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; 1 non-insertions in a row out of 8 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 8 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 8 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 8 sites
Non-Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 3 non-insertions in a row out of 8 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: 0.76
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:
- Rv0880 (-) (Direct binding)
- Rv0967 (csoR) (Direct binding)
- Rv2009 (vapB15) (Direct binding)
- Rv3849 (espR) (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:
- Not downregulated by other genes.

Property	Value	Creator	Evidence	PMID	Comment
Interaction	PhysicalInteraction Rv3882c	shahanup86	IPI		Yeast two-hybrid (Physical interaction) JA. MacGurn, S. Raghavan et al. A non-RD1 gene cluster is required for Snm secretion in Mycobacterium tuberculosis. Mol. Microbiol. 2005
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 Rv3616c	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 Rv3616c	darhngu	IMP		Co-expression (Functional Linkage) S. Raghavan, P. Manzanillo et al. Secreted transcription factor controls Mycobacterium tuberculosis virulence. Nature 2008
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 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
Interaction	PhysicalInteraction Rv3616c	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 Rv3849	darhngu	IMP		Co-expression (Functional Linkage) S. Raghavan, P. Manzanillo et al. Secreted transcription factor controls Mycobacterium tuberculosis virulence. Nature 2008
Interaction	PhysicalInteraction Rv3616c	darhngu	IMP		Co-expression (Functional Linkage) S. Raghavan, P. Manzanillo et al. Secreted transcription factor controls Mycobacterium tuberculosis virulence. Nature 2008
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	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. 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. S. Raghavan, P. Manzanillo et al. Secreted transcription factor controls Mycobacterium tuberculosis virulence. Nature 2008

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