EIS_MYCTO
ID EIS_MYCTO Reviewed; 402 AA.
AC P9WFK6; L0TCA0; P71727; Q9RG79;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2017, sequence version 2.
DT 03-AUG-2022, entry version 36.
DE RecName: Full=N-acetyltransferase Eis {ECO:0000255|HAMAP-Rule:MF_01812};
DE EC=2.3.1.- {ECO:0000255|HAMAP-Rule:MF_01812};
DE AltName: Full=Aminoglycoside N-acetyltransferase;
DE AltName: Full=Enhanced intracellular survival protein {ECO:0000255|HAMAP-Rule:MF_01812};
DE AltName: Full=Protein-lysine N-acetyltransferase {ECO:0000255|HAMAP-Rule:MF_01812};
GN Name=eis {ECO:0000255|HAMAP-Rule:MF_01812}; OrderedLocusNames=MT2489;
OS Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83331;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CDC 1551 / Oshkosh;
RX PubMed=12218036; DOI=10.1128/jb.184.19.5479-5490.2002;
RA Fleischmann R.D., Alland D., Eisen J.A., Carpenter L., White O.,
RA Peterson J.D., DeBoy R.T., Dodson R.J., Gwinn M.L., Haft D.H., Hickey E.K.,
RA Kolonay J.F., Nelson W.C., Umayam L.A., Ermolaeva M.D., Salzberg S.L.,
RA Delcher A., Utterback T.R., Weidman J.F., Khouri H.M., Gill J., Mikula A.,
RA Bishai W., Jacobs W.R. Jr., Venter J.C., Fraser C.M.;
RT "Whole-genome comparison of Mycobacterium tuberculosis clinical and
RT laboratory strains.";
RL J. Bacteriol. 184:5479-5490(2002).
CC -!- FUNCTION: Effector that is released into the host cell and affects host
CC immune responses; it negatively modulates inflammation, macrophage
CC autophagy, and cell death through redox-dependent signaling. Acts as an
CC acetyltransferase. Acetylates 'Lys-55' of dual-specificity protein
CC phosphatase 16 (DUSP16)/mitogen-activated protein kinase phosphatase-7
CC (MKP-7), a JNK-specific phosphatase; this leads to the inhibition of
CC JNK-dependent autophagy, phagosome maturation, and ROS (reactive oxygen
CC species) generation for enhanced intracellular survival of
CC M.tuberculosis. Inhibits Con A-mediated T-cell proliferation in vitro.
CC Treatment of T-cells with Eis inhibits ERK1/2, JAK pathway, and
CC subsequent production of tumor necrosis factor-alpha (TNF-alpha) and
CC interleukin-4 (IL-4); on the contrary, there is increased production of
CC interferon-gamma (IFN-gamma) and interleukin-10 (IL-10), which
CC indicates that immunity in response to Eis treatment is skewed away
CC from a protective T(H)1 response and Eis disturbs the cross regulation
CC of T-cells. When expressed in M.smegmatis, enhances intracellular
CC survival of the bacteria in host macrophages during infection.
CC {ECO:0000250|UniProtKB:P9WFK7}.
CC -!- FUNCTION: Can also acetylate multiple amine groups of many
CC aminoglycoside (AG) antibiotics, leading to their inactivation, and
CC thus contributes to drug resistance. Is also able to acetylate and
CC deactivate the cyclic peptide antibiotic capreomycin, but not the other
CC anti-tuberculous drugs isoniazid and pyrazinamide. Acetylates kanamycin
CC (KAN) more efficiently than amikacin (AMK), even though Eis seems to
CC bind AMK with higher affinity. Does not acetylate and inactivate
CC streptomycin, apramycin and spectinomycin.
CC {ECO:0000250|UniProtKB:P9WFK7}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + L-lysyl-[protein] = CoA + H(+) + N(6)-acetyl-L-
CC lysyl-[protein]; Xref=Rhea:RHEA:45948, Rhea:RHEA-COMP:9752,
CC Rhea:RHEA-COMP:10731, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:61930;
CC Evidence={ECO:0000250|UniProtKB:P9WFK7};
CC -!- ACTIVITY REGULATION: Is potently inhibited by several small-molecule
CC that share an isothiazole S,S-dioxide heterocyclic core. Some of these
CC inhibitors, when used in combination with KAN against resistant
CC M.tuberculosis, efficiently overcome Eis-mediated KAN resistance by
CC restoring the antibacterial activity of KAN.
CC {ECO:0000250|UniProtKB:P9WFK7}.
CC -!- SUBUNIT: Homohexamer; trimer of dimers. {ECO:0000250|UniProtKB:P9WFK7}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P9WFK7}. Host
CC cytoplasmic vesicle, host phagosome {ECO:0000250|UniProtKB:P9WFK7}.
CC Extracellular vesicle, bacterial extracellular vesicle
CC {ECO:0000250|UniProtKB:P9WFK7}. Host extracellular space
CC {ECO:0000250|UniProtKB:P9WFK7}. Note=Eis is present in the macrophage
CC cytoplasm from 4 to 96 hours post-infection.
CC {ECO:0000250|UniProtKB:P9WFK7}.
CC -!- DOMAIN: The Eis monomer consists of three regions that are assembled
CC into a heart-shaped molecule. This shape is formed by an unusual fusion
CC of two general control non-derepressible 5 (GCN5)-related N-
CC acetyltransferase (GNAT) regions and a C-terminal region. The N-
CC acetyltransferase domain of Eis is responsible for its modulation of
CC ROS generation and pro-inflammatory responses in macrophages.
CC {ECO:0000250|UniProtKB:P9WFK7}.
CC -!- MISCELLANEOUS: Increased expression of eis due to point mutations in
CC the promoter region of eis is responsible for resistance to the second-
CC line injectable drug kanamycin in a number of M.tuberculosis clinical
CC isolates, through acetylation of its amino groups, which leads to
CC inactivation of the drug. {ECO:0000250|UniProtKB:P9WFK7}.
CC -!- SIMILARITY: Belongs to the acetyltransferase Eis family.
CC {ECO:0000255|HAMAP-Rule:MF_01812}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK46786.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AE000516; AAK46786.1; ALT_INIT; Genomic_DNA.
DR PIR; C70685; C70685.
DR AlphaFoldDB; P9WFK6; -.
DR SMR; P9WFK6; -.
DR EnsemblBacteria; AAK46786; AAK46786; MT2489.
DR KEGG; mtc:MT2489; -.
DR HOGENOM; CLU_050659_0_0_11; -.
DR Proteomes; UP000001020; Chromosome.
DR GO; GO:0097691; C:bacterial extracellular vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0044161; C:host cell cytoplasmic vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0043655; C:host extracellular space; IEA:UniProtKB-SubCell.
DR GO; GO:0008080; F:N-acetyltransferase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR Gene3D; 3.30.1050.10; -; 1.
DR HAMAP; MF_01812; Eis; 1.
DR InterPro; IPR041380; Acetyltransf_17.
DR InterPro; IPR016181; Acyl_CoA_acyltransferase.
DR InterPro; IPR025559; Eis_dom.
DR InterPro; IPR000182; GNAT_dom.
DR InterPro; IPR022902; NAcTrfase_Eis.
DR InterPro; IPR036527; SCP2_sterol-bd_dom_sf.
DR Pfam; PF17668; Acetyltransf_17; 1.
DR Pfam; PF13530; SCP2_2; 1.
DR SUPFAM; SSF55718; SSF55718; 1.
DR SUPFAM; SSF55729; SSF55729; 1.
DR PROSITE; PS51186; GNAT; 1.
PE 3: Inferred from homology;
KW Acyltransferase; Antibiotic resistance; Host cytoplasmic vesicle; Secreted;
KW Transferase.
FT CHAIN 1..402
FT /note="N-acetyltransferase Eis"
FT /id="PRO_0000428522"
FT DOMAIN 3..154
FT /note="N-acetyltransferase"
FT ACT_SITE 126
FT /note="Proton donor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01812"
FT ACT_SITE 402
FT /note="Proton acceptor; via carboxylate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01812"
FT BINDING 85..87
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01812"
FT BINDING 93..98
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01812"
FT BINDING 121..122
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01812"
SQ SEQUENCE 402 AA; 43804 MW; EF06F75C00F05333 CRC64;
MTVTLCSPTE DDWPGMFLLA AASFTDFIGP ESATAWRTLV PTDGAVVVRD GAGPGSEVVG
MALYMDLRLT VPGEVVLPTA GLSFVAVAPT HRRRGLLRAM CAELHRRIAD SGYPVAALHA
SEGGIYGRFG YGPATTLHEL TVDRRFARFH ADAPGGGLGG SSVRLVRPTE HRGEFEAIYE
RWRQQVPGGL LRPQVLWDEL LAECKAAPGG DRESFALLHP DGYALYRVDR TDLKLARVSE
LRAVTADAHC ALWRALIGLD SMERISIITH PQDPLPHLLT DTRLARTTWR QDGLWLRIMN
VPAALEARGY AHEVGEFSTV LEVSDGGRFA LKIGDGRARC TPTDAAAEIE MDRDVLGSLY
LGAHRASTLA AANRLRTKDS QLLRRLDAAF ASDVPVQTAF EF
