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Showing Protein N-acetyltransferase Eis (HMDBP12621)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 1 metabolite
Identification
HMDB Protein ID HMDBP12621
Secondary Accession Numbers None
Name N-acetyltransferase Eis
Synonyms
  1. Aminoglycoside N-acetyltransferase
  2. Enhanced intracellular survival protein
  3. Protein-lysine N-acetyltransferase
Gene Name EIS
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Effector that is released into the host cell and affects host immune responses; it negatively modulates inflammation, macrophage autophagy, and cell death through redox-dependent signaling (PubMed:17259625, PubMed:21187903). Acts as an acetyltransferase. Acetylates 'Lys-55' of dual-specificity protein phosphatase 16 (DUSP16)/mitogen-activated protein kinase phosphatase-7 (MKP-7), a JNK-specific phosphatase; this leads to the inhibition of JNK-dependent autophagy, phagosome maturation, and ROS (reactive oxygen species) generation for enhanced intracellular survival of M.tuberculosis (PubMed:22547814). Inhibits Con A-mediated T-cell proliferation in vitro (PubMed:17449476). Treatment of T-cells with Eis inhibits ERK1/2, JAK pathway, and subsequent production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-4 (IL-4); on the contrary, there is increased production of interferon-gamma (IFN-gamma) and interleukin-10 (IL-10), which indicates that immunity in response to Eis treatment is skewed away from a protective T(H)1 response and Eis disturbs the cross regulation of T-cells (PubMed:17449476). When expressed in M.smegmatis, enhances intracellular survival of the bacteria in host macrophages during infection (PubMed:10629183).Can also acetylate multiple amine groups of many aminoglycoside (AG) antibiotics, leading to their inactivation, and thus contributes to drug resistance (PubMed:19906990, PubMed:21628583, PubMed:24106131). Is also able to acetylate and deactivate the cyclic peptide antibiotic capreomycin, but not the other anti-tuberculous drugs isoniazid and pyrazinamide (PubMed:23233486). Acetylates kanamycin (KAN) more efficiently than amikacin (AMK), even though Eis seems to bind AMK with higher affinity (PubMed:19906990). Does not acetylate and inactivate streptomycin, apramycin and spectinomycin (PubMed:19906990, PubMed:21628583).
Pathways Not Available
Reactions Not Available
GO Classification
Biological Process
response to antibiotic
interaction with host
aminoglycoside antibiotic catabolic process
effector-mediated defense to host-produced reactive oxygen species
modulation by symbiont of host inflammatory response
modulation by symbiont of host innate immune response
modulation by symbiont of host programmed cell death
suppression by symbiont of host defense-related programmed cell death
Cellular Component
cytosol
bacterial extracellular vesicle
host cell cytoplasmic vesicle
host extracellular space
Molecular Function
identical protein binding
aminoglycoside N-acetyltransferase activity
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 402
Molecular Weight 43803.365
Theoretical pI 6.539
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P9WFK7
UniProtKB/Swiss-Prot Entry Name EIS_MYCTU
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon SV, Eiglmeier K, Gas S, Barry CE 3rd, Tekaia F, Badcock K, Basham D, Brown D, Chillingworth T, Connor R, Davies R, Devlin K, Feltwell T, Gentles S, Hamlin N, Holroyd S, Hornsby T, Jagels K, Krogh A, McLean J, Moule S, Murphy L, Oliver K, Osborne J, Quail MA, Rajandream MA, Rogers J, Rutter S, Seeger K, Skelton J, Squares R, Squares S, Sulston JE, Taylor K, Whitehead S, Barrell BG: Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature. 1998 Jun 11;393(6685):537-44. doi: 10.1038/31159. [PubMed:9634230 ]
  2. Kelkar DS, Kumar D, Kumar P, Balakrishnan L, Muthusamy B, Yadav AK, Shrivastava P, Marimuthu A, Anand S, Sundaram H, Kingsbury R, Harsha HC, Nair B, Prasad TS, Chauhan DS, Katoch K, Katoch VM, Kumar P, Chaerkady R, Ramachandran S, Dash D, Pandey A: Proteogenomic analysis of Mycobacterium tuberculosis by high resolution mass spectrometry. Mol Cell Proteomics. 2011 Dec;10(12):M111.011627. doi: 10.1074/mcp.M111.011445. Epub 2011 Oct 3. [PubMed:21969609 ]
  3. Wei J, Dahl JL, Moulder JW, Roberts EA, O'Gaora P, Young DB, Friedman RL: Identification of a Mycobacterium tuberculosis gene that enhances mycobacterial survival in macrophages. J Bacteriol. 2000 Jan;182(2):377-84. doi: 10.1128/JB.182.2.377-384.2000. [PubMed:10629183 ]
  4. Dahl JL, Wei J, Moulder JW, Laal S, Friedman RL: Subcellular localization of the Iitracellular survival-enhancing Eis protein of Mycobacterium tuberculosis. Infect Immun. 2001 Jul;69(7):4295-302. doi: 10.1128/IAI.69.7.4295-4302.2001. [PubMed:11401966 ]
  5. Lella RK, Sharma C: Eis (enhanced intracellular survival) protein of Mycobacterium tuberculosis disturbs the cross regulation of T-cells. J Biol Chem. 2007 Jun 29;282(26):18671-5. doi: 10.1074/jbc.C600280200. Epub 2007 Apr 19. [PubMed:17449476 ]
  6. Zaunbrecher MA, Sikes RD Jr, Metchock B, Shinnick TM, Posey JE: Overexpression of the chromosomally encoded aminoglycoside acetyltransferase eis confers kanamycin resistance in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):20004-9. doi: 10.1073/pnas.0907925106. Epub 2009 Nov 11. [PubMed:19906990 ]
  7. Shin DM, Jeon BY, Lee HM, Jin HS, Yuk JM, Song CH, Lee SH, Lee ZW, Cho SN, Kim JM, Friedman RL, Jo EK: Mycobacterium tuberculosis eis regulates autophagy, inflammation, and cell death through redox-dependent signaling. PLoS Pathog. 2010 Dec 16;6(12):e1001230. doi: 10.1371/journal.ppat.1001230. [PubMed:21187903 ]
  8. Houghton JL, Green KD, Pricer RE, Mayhoub AS, Garneau-Tsodikova S: Unexpected N-acetylation of capreomycin by mycobacterial Eis enzymes. J Antimicrob Chemother. 2013 Apr;68(4):800-5. doi: 10.1093/jac/dks497. Epub 2012 Dec 11. [PubMed:23233486 ]
  9. Chen W, Biswas T, Porter VR, Tsodikov OV, Garneau-Tsodikova S: Unusual regioversatility of acetyltransferase Eis, a cause of drug resistance in XDR-TB. Proc Natl Acad Sci U S A. 2011 Jun 14;108(24):9804-8. doi: 10.1073/pnas.1105379108. Epub 2011 May 31. [PubMed:21628583 ]
  10. Kim KH, An DR, Song J, Yoon JY, Kim HS, Yoon HJ, Im HN, Kim J, Kim DJ, Lee SJ, Kim KH, Lee HM, Kim HJ, Jo EK, Lee JY, Suh SW: Mycobacterium tuberculosis Eis protein initiates suppression of host immune responses by acetylation of DUSP16/MKP-7. Proc Natl Acad Sci U S A. 2012 May 15;109(20):7729-34. doi: 10.1073/pnas.1120251109. Epub 2012 Apr 30. [PubMed:22547814 ]
  11. Houghton JL, Biswas T, Chen W, Tsodikov OV, Garneau-Tsodikova S: Chemical and structural insights into the regioversatility of the aminoglycoside acetyltransferase Eis. Chembiochem. 2013 Nov 4;14(16):2127-35. doi: 10.1002/cbic.201300359. Epub 2013 Sep 17. [PubMed:24106131 ]
  12. Willby MJ, Green KD, Gajadeera CS, Hou C, Tsodikov OV, Posey JE, Garneau-Tsodikova S: Potent Inhibitors of Acetyltransferase Eis Overcome Kanamycin Resistance in Mycobacterium tuberculosis. ACS Chem Biol. 2016 Jun 17;11(6):1639-46. doi: 10.1021/acschembio.6b00110. Epub 2016 Apr 7. [PubMed:27010218 ]