Rv2416c (eis)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: enhanced intracellular survival protein
- REFSEQ: hypothetical protein
- PATRIC: Enhanced intracellular survival protein
- TUBERCULIST: Enhanced intracellular survival protein Eis GCN5-related N-acetyltransferase
- NCBI: Enhanced intracellular survival protein Eis,GCN5-related N-acetyltransferase
- updated information (H37Rv4):
  - gene name: eis
  - function: aminoglycoside acetyltransferase; confers kanamycin resistance
  - reference: Zaunbrecher (2009) PMID 19906990
Type: Conditional
Start: 2714124
End: 2715332
Operon:

Trans-membrane region:
Role: V - Conserved hypotheticals
GO terms:
- GO:0097691 - bacterial extracellular vesicle (Uniprot)
- GO:0052167 - modulation by symbiont of host innate immune response (Uniprot)
- GO:0052164 - modulation by symbiont of defense-related host reactive oxygen species production (Uniprot)
- GO:0052040 - modulation by symbiont of host programmed cell death (Uniprot)
- GO:0052035 - positive regulation by symbiont of host inflammatory response (Uniprot)
- GO:0046677 - response to antibiotic (Uniprot)
- GO:0044161 - host cell cytoplasmic vesicle (Uniprot)
- GO:0044121 - growth of symbiont in host organelle (Uniprot)
- GO:0044119 - growth of symbiont in host cell (Uniprot)
- GO:0043655 - extracellular space of host (Uniprot)
- GO:0042802 - identical protein binding (Uniprot)
- GO:0034069 - aminoglycoside N-acetyltransferase activity (Uniprot)
- GO:0030649 - aminoglycoside antibiotic catabolic process (Uniprot)
- GO:0016746 - transferase activity, transferring acyl groups (Uniprot)
- GO:0016740 - transferase activity (Uniprot)
- GO:0008080 - N-acetyltransferase activity (Uniprot)
- GO:0005576 - extracellular region (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: 3r1k, 3uy5, 3ryo, 3sxo
Search for Homologs in PDB

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

PDB	aa ident	species	PDB title
3UY5	100%	Mycobacterium tuberculosis	crystal structure of Eis from Mycobacterium tuberculosis
3SXO	100%	Mycobacterium tuberculosis	Mycobacterium tuberculosis Eis protein initiates modulation of host immune responses by acetylation of DUSP16/MKP-7
3RYO	100%	Mycobacterium tuberculosis	Crystal Structure of Enhanced Intracellular Survival (Eis) Protein from Mycobacterium tuberculosis with Acetyl CoA
6B0U	99%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of acetyltransferase Eis from Mycobacterium tuberculosis in complex with a Lys-containing peptide
3R1K	99%	Mycobacterium tuberculosis	Crystal structure of acetyltransferase Eis from Mycobacterium tuberculosis H37Rv in complex with CoA and an acetamide moiety
6VV3	99%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of Eis from Mycobacterium tuberculosis in complex with inhibitor SGT1358
6VV2	99%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of Eis from Mycobacterium tuberculosis in complex with inhibitor SGT1348
6VV1	99%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of Eis from Mycobacterium tuberculosis in complex with inhibitor SGT384
6VV0	99%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of Eis from Mycobacterium tuberculosis in complex with inhibitor SGT1354
6VUZ	99%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of Eis from Mycobacterium tuberculosis in complex with inhibitor SGT353

Links to additional information on eis:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -0.233 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

VTVTLCSPTEDDWPGMFLLAAASFTDFIGPESATAWRTLVPTDGAVVVRDGAGPGSEVVGMALYMDLRLTVPGEVVLPTAGLSFVAVAPTHRRRGLLRAM
CAELHRRIADSGYPVAALHASEGGIYGRFGYGPATTLHELTVDRRFARFHADAPGGGLGGSSVRLVRPTEHRGEFEAIYERWRQQVPGGLLRPQVLWDEL
LAECKAAPGGDRESFALLHPDGYALYRVDRTDLKLARVSELRAVTADAHCALWRALIGLDSMERISIITHPQDPLPHLLTDTRLARTTWRQDGLWLRIMN
VPAALEARGYAHEVGEFSTVLEVSDGGRFALKIGDGRARCTPTDAAAEIEMDRDVLGSLYLGAHRASTLAAANRLRTKDSQLLRRLDAAFASDVPVQTAF
EF

(Nucleotide sequence available on KEGG)

Additional Information

kanamycin resistance - Zaunbrecher (2009), http://www.ncbi.nlm.nih.gov/pubmed/19906990
link to autophagy - Shin (2010), http://www.ncbi.nlm.nih.gov/pubmed/21187903

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; 6 non-insertions in a row out of 28 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 6 non-insertions in a row out of 28 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 6 non-insertions in a row out of 28 sites
Non-Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 4 non-insertions in a row out of 28 sites
Non-Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 4 non-insertions in a row out of 28 sites
No-Data	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Too-Short	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: -1
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:

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0047c (-) (Direct binding)

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

Upregulates:
- Does not upregulate other genes.
Upregulated by:
Downregulates:
- Does not downregulate other genes.
Downregulated by:

Property	Value	Creator	Evidence	PMID	Comment
Citation	Activation of the eis gene in a W-Beijing strain of Mycobacterium tuberculosis correlates with increased SigA levels and enhanced intracellular growth. S. Wu, PF. Barnes et al. Microbiology (Reading, Engl.) 2009	hibeeluck	IEP	19332828	co expression(functional linkage)
Interaction	Regulatory Rv2703	hibeeluck	IEP		co expression(functional linkage) S. Wu, PF. Barnes et al. Activation of the eis gene in a W-Beijing strain of Mycobacterium tuberculosis correlates with increased SigA levels and enhanced intracellular growth. Microbiology (Reading, Engl.) 2009
Citation	Overexpression of the chromosomally encoded aminoglycoside acetyltransferase eis confers kanamycin resistance in Mycobacterium tuberculosis. MA. Zaunbrecher, RD. Sikes et al. Proc. Natl. Acad. Sci. U.S.A. 2009	hibeeluck	IEP	19906990	co expression(functional linkage)
Interaction	Regulatory Rv2703	hibeeluck	IEP		co expression(functional linkage) MA. Zaunbrecher, RD. Sikes et al. Overexpression of the chromosomally encoded aminoglycoside acetyltransferase eis confers kanamycin resistance in Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. U.S.A. 2009

TB Genome Annotation Portal