NLEE_ECO27
ID NLEE_ECO27 Reviewed; 224 AA.
AC B7UI22;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2009, sequence version 1.
DT 03-AUG-2022, entry version 48.
DE RecName: Full=Cysteine S-methyltransferase NleE {ECO:0000305};
DE EC=2.1.1.- {ECO:0000269|PubMed:22158122, ECO:0000269|PubMed:25412445};
DE AltName: Full=Effector protein NleE {ECO:0000303|PubMed:17984206};
DE AltName: Full=Non-LEE-encoded type III effector E {ECO:0000303|PubMed:17984206};
GN Name=nleE {ECO:0000303|PubMed:17984206}; OrderedLocusNames=E2348C_3232;
OS Escherichia coli O127:H6 (strain E2348/69 / EPEC).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=574521;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=E2348/69 / EPEC;
RX PubMed=18952797; DOI=10.1128/jb.01238-08;
RA Iguchi A., Thomson N.R., Ogura Y., Saunders D., Ooka T., Henderson I.R.,
RA Harris D., Asadulghani M., Kurokawa K., Dean P., Kenny B., Quail M.A.,
RA Thurston S., Dougan G., Hayashi T., Parkhill J., Frankel G.;
RT "Complete genome sequence and comparative genome analysis of
RT enteropathogenic Escherichia coli O127:H6 strain E2348/69.";
RL J. Bacteriol. 191:347-354(2009).
RN [2]
RP SUBCELLULAR LOCATION.
RC STRAIN=E2348/69 / EPEC;
RX PubMed=17984206; DOI=10.1128/iai.00684-07;
RA Zurawski D.V., Mumy K.L., Badea L., Prentice J.A., Hartland E.L.,
RA McCormick B.A., Maurelli A.T.;
RT "The NleE/OspZ family of effector proteins is required for
RT polymorphonuclear transepithelial migration, a characteristic shared by
RT enteropathogenic Escherichia coli and Shigella flexneri infections.";
RL Infect. Immun. 76:369-379(2008).
RN [3]
RP FUNCTION, AND MUTAGENESIS OF 209-ILE--LYS-214.
RC STRAIN=E2348/69 / EPEC;
RX PubMed=20126447; DOI=10.1371/journal.ppat.1000743;
RA Nadler C., Baruch K., Kobi S., Mills E., Haviv G., Farago M., Alkalay I.,
RA Bartfeld S., Meyer T.F., Ben-Neriah Y., Rosenshine I.;
RT "The type III secretion effector NleE inhibits NF-kappaB activation.";
RL PLoS Pathog. 6:e1000743-e1000743(2010).
RN [4]
RP FUNCTION.
RC STRAIN=E2348/69 / EPEC;
RX PubMed=20485572; DOI=10.1371/journal.ppat.1000898;
RA Newton H.J., Pearson J.S., Badea L., Kelly M., Lucas M., Holloway G.,
RA Wagstaff K.M., Dunstone M.A., Sloan J., Whisstock J.C., Kaper J.B.,
RA Robins-Browne R.M., Jans D.A., Frankel G., Phillips A.D., Coulson B.S.,
RA Hartland E.L.;
RT "The type III effectors NleE and NleB from enteropathogenic E. coli and
RT OspZ from Shigella block nuclear translocation of NF-kappaB p65.";
RL PLoS Pathog. 6:e1000898-e1000898(2010).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ARG-107; 209-ILE--LYS-214
RP AND TYR-212.
RC STRAIN=E2348/69 / EPEC;
RX PubMed=22158122; DOI=10.1038/nature10690;
RA Zhang L., Ding X., Cui J., Xu H., Chen J., Gong Y.N., Hu L., Zhou Y.,
RA Ge J., Lu Q., Liu L., Chen S., Shao F.;
RT "Cysteine methylation disrupts ubiquitin-chain sensing in NF-kappaB
RT activation.";
RL Nature 481:204-208(2011).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ARG-107; GLU-191 AND
RP TYR-212.
RC STRAIN=E2348/69 / EPEC;
RX PubMed=25412445; DOI=10.1371/journal.ppat.1004522;
RA Yao Q., Zhang L., Wan X., Chen J., Hu L., Ding X., Li L., Karar J.,
RA Peng H., Chen S., Huang N., Rauscher F.J. III, Shao F.;
RT "Structure and specificity of the bacterial cysteine methyltransferase
RT effector NleE suggests a novel substrate in human DNA repair pathway.";
RL PLoS Pathog. 10:e1004522-e1004522(2014).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF 49-GLY--ARG-52 AND
RP 209-ILE--LYS-214.
RC STRAIN=E2348/69 / EPEC;
RX PubMed=27445336; DOI=10.1074/jbc.m116.734079;
RA Zhang Y., Muehlen S., Oates C.V., Pearson J.S., Hartland E.L.;
RT "Identification of a distinct substrate-binding domain in the bacterial
RT cysteine methyltransferase effectors NleE and OspZ.";
RL J. Biol. Chem. 291:20149-20162(2016).
CC -!- FUNCTION: Cysteine methyltransferase effector that inhibits host cell
CC NF-kappa-B activation by preventing nuclear translocation of host
CC protein RELA/p65 (PubMed:20126447, PubMed:20485572, PubMed:22158122,
CC PubMed:25412445, PubMed:27445336). Acts by mediating cysteine
CC methylation of host proteins TAB2 and TAB3: methylation of a conserved
CC cysteine residue of the RanBP2-type zinc finger (NZF) of TAB2 and TAB3
CC disrupts zinc-binding, thereby inactivating the ubiquitin chain-binding
CC activity of TAB2 and TAB3, leading to NF-kappa-B inactivation
CC (PubMed:22158122, PubMed:25412445, PubMed:27445336). Also mediates
CC cysteine methylation of host protein ZRANB3, inactivating its ability
CC to bind ubiquitin chains (PubMed:25412445).
CC {ECO:0000269|PubMed:20126447, ECO:0000269|PubMed:20485572,
CC ECO:0000269|PubMed:22158122, ECO:0000269|PubMed:25412445,
CC ECO:0000269|PubMed:27445336}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-cysteinyl-[protein] + S-adenosyl-L-methionine = H(+) + S-
CC adenosyl-L-homocysteine + S-methyl-L-cysteinyl-[protein];
CC Xref=Rhea:RHEA:66544, Rhea:RHEA-COMP:10131, Rhea:RHEA-COMP:10132,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29950, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:82612;
CC Evidence={ECO:0000269|PubMed:22158122, ECO:0000269|PubMed:25412445,
CC ECO:0000269|PubMed:27445336};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66545;
CC Evidence={ECO:0000269|PubMed:22158122, ECO:0000269|PubMed:25412445,
CC ECO:0000269|PubMed:27445336};
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q7DBA6}.
CC -!- INTERACTION:
CC B7UI22; Q9NYJ8: TAB2; Xeno; NbExp=5; IntAct=EBI-15957770, EBI-358708;
CC B7UI22; Q8N5C8-1: TAB3; Xeno; NbExp=7; IntAct=EBI-15957770, EBI-15957777;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:17984206}. Host
CC nucleus {ECO:0000269|PubMed:17984206}. Note=Secreted via the type III
CC secretion system (TTSS) (PubMed:17984206). Localizes in the nucleus of
CC the infected cells (PubMed:17984206). {ECO:0000269|PubMed:17984206}.
CC -!- SIMILARITY: Belongs to the NleE/OspZ family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; FM180568; CAS10780.1; -; Genomic_DNA.
DR RefSeq; WP_000609744.1; NC_011601.1.
DR AlphaFoldDB; B7UI22; -.
DR SMR; B7UI22; -.
DR DIP; DIP-60470N; -.
DR IntAct; B7UI22; 3.
DR EnsemblBacteria; CAS10780; CAS10780; E2348C_3232.
DR KEGG; ecg:E2348C_3232; -.
DR HOGENOM; CLU_1347196_0_0_6; -.
DR OMA; TANTEYI; -.
DR Proteomes; UP000008205; Chromosome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IDA:UniProtKB.
DR GO; GO:0106363; F:protein-cysteine methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0090729; F:toxin activity; IDA:UniProtKB.
DR GO; GO:0085034; P:suppression by symbiont of host I-kappaB kinase/NF-kappaB cascade; IDA:UniProtKB.
PE 1: Evidence at protein level;
KW Host nucleus; Methyltransferase; S-adenosyl-L-methionine; Secreted; Toxin;
KW Transferase; Virulence.
FT CHAIN 1..224
FT /note="Cysteine S-methyltransferase NleE"
FT /id="PRO_0000452524"
FT REGION 49..52
FT /note="Interaction with host proteins TAB2, TAB3 and
FT ZRANB3"
FT /evidence="ECO:0000269|PubMed:27445336"
FT BINDING 92
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q7DBA6"
FT BINDING 98
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q7DBA6"
FT BINDING 107
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q7DBA6"
FT BINDING 111
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q7DBA6"
FT BINDING 204
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q7DBA6"
FT BINDING 208
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q7DBA6"
FT MUTAGEN 49..52
FT /note="GITR->AAAA: Abolished interaction with host proteins
FT TAB2, TAB3 and ZRANB3."
FT /evidence="ECO:0000269|PubMed:27445336"
FT MUTAGEN 107
FT /note="R->A: Abolished cysteine methyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:22158122,
FT ECO:0000269|PubMed:25412445"
FT MUTAGEN 191
FT /note="E->A: Abolished cysteine methyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:25412445"
FT MUTAGEN 209..214
FT /note="Missing: Abolished cysteine methyltransferase
FT activity and ability to inhibit host cell NF-kappa-B
FT activation. Does not affect interaction with host protein
FT TAB3."
FT /evidence="ECO:0000269|PubMed:20126447,
FT ECO:0000269|PubMed:22158122, ECO:0000269|PubMed:27445336"
FT MUTAGEN 212
FT /note="Y->A,D: Abolished cysteine methyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:22158122,
FT ECO:0000269|PubMed:25412445"
SQ SEQUENCE 224 AA; 26057 MW; CA13FD0DAC7F6E7B CRC64;
MINPVTNTQG VSPINTKYAE HVVKNIYPKI KHDYFNESPN IYDKKYISGI TRGVAELKQE
EFVNEKARRF SYMKTMYSVC PEAFEPISRN EASTPEGSWL TVISGKRPMG QFSVDSLYNP
DLHALCELPD ICCKIFPKEN NDFLYIVVVY RNDSPLGEQR ANRFIELYNI KRDIMQELNY
ELPELKAVKS EMIIAREMGE IFSYMPGEID SYMKYINNKL SKIE
