NLEF_ECO57
ID NLEF_ECO57 Reviewed; 189 AA.
AC Q8XAL7; Q7AEM9;
DT 01-MAY-2013, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 89.
DE RecName: Full=Effector protein NleF;
DE AltName: Full=Non-LEE-encoded type III effector F;
GN Name=nleF; OrderedLocusNames=Z6020.1, ECs1815;
OS Escherichia coli O157:H7.
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83334;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=O157:H7 / EDL933 / ATCC 700927 / EHEC;
RX PubMed=11206551; DOI=10.1038/35054089;
RA Perna N.T., Plunkett G. III, Burland V., Mau B., Glasner J.D., Rose D.J.,
RA Mayhew G.F., Evans P.S., Gregor J., Kirkpatrick H.A., Posfai G.,
RA Hackett J., Klink S., Boutin A., Shao Y., Miller L., Grotbeck E.J.,
RA Davis N.W., Lim A., Dimalanta E.T., Potamousis K., Apodaca J.,
RA Anantharaman T.S., Lin J., Yen G., Schwartz D.C., Welch R.A.,
RA Blattner F.R.;
RT "Genome sequence of enterohaemorrhagic Escherichia coli O157:H7.";
RL Nature 409:529-533(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=O157:H7 / Sakai / RIMD 0509952 / EHEC;
RX PubMed=11258796; DOI=10.1093/dnares/8.1.11;
RA Hayashi T., Makino K., Ohnishi M., Kurokawa K., Ishii K., Yokoyama K.,
RA Han C.-G., Ohtsubo E., Nakayama K., Murata T., Tanaka M., Tobe T., Iida T.,
RA Takami H., Honda T., Sasakawa C., Ogasawara N., Yasunaga T., Kuhara S.,
RA Shiba T., Hattori M., Shinagawa H.;
RT "Complete genome sequence of enterohemorrhagic Escherichia coli O157:H7 and
RT genomic comparison with a laboratory strain K-12.";
RL DNA Res. 8:11-22(2001).
RN [3]
RP SUBCELLULAR LOCATION, AND FUNCTION.
RC STRAIN=O157:H7 / EDL933 / ATCC 700927 / EHEC;
RX PubMed=18279332; DOI=10.1111/j.1574-6968.2008.01088.x;
RA Echtenkamp F., Deng W., Wickham M.E., Vazquez A., Puente J.L.,
RA Thanabalasuriar A., Gruenheid S., Finlay B.B., Hardwidge P.R.;
RT "Characterization of the NleF effector protein from attaching and effacing
RT bacterial pathogens.";
RL FEMS Microbiol. Lett. 281:98-107(2008).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (3.49 ANGSTROMS) IN COMPLEX WITH HUMAN CASP9,
RP INTERACTION WITH HUMAN CASP4; CASP8 AND CASP9, FUNCTION, SUBUNIT, AND
RP MUTAGENESIS OF 168-LEU--GLY-189 AND GLY-189.
RC STRAIN=O157:H7 / Sakai / RIMD 0509952 / EHEC;
RX PubMed=23516580; DOI=10.1371/journal.pone.0058937;
RA Blasche S., Mortl M., Steuber H., Siszler G., Nisa S., Schwarz F.,
RA Lavrik I., Gronewold T.M., Maskos K., Donnenberg M.S., Ullmann D., Uetz P.,
RA Kogl M.;
RT "The E. coli effector protein NleF is a caspase inhibitor.";
RL PLoS ONE 8:E58937-E58937(2013).
CC -!- FUNCTION: Effector protein that alters host cell physiology and
CC promotes bacterial survival in host tissues. Inhibits the catalytic
CC activity of human CASP4, CASP8 and CASP9, and thereby inhibits
CC apoptosis of infected host cells. {ECO:0000269|PubMed:18279332,
CC ECO:0000269|PubMed:23516580}.
CC -!- SUBUNIT: Monomer. Interacts (via C-terminus) with human CASP4, CASP8
CC and CASP9. {ECO:0000269|PubMed:23516580}.
CC -!- INTERACTION:
CC Q8XAL7; P55211: CASP9; Xeno; NbExp=6; IntAct=EBI-10039292, EBI-516799;
CC Q8XAL7; P49755: TMED10; Xeno; NbExp=6; IntAct=EBI-10039292, EBI-998422;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:18279332}. Host
CC cytoplasm {ECO:0000269|PubMed:18279332}. Note=Injected into host cells
CC via a type III secretion system.
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; AE005174; AAK16936.1; -; Genomic_DNA.
DR EMBL; BA000007; BAB35238.1; -; Genomic_DNA.
DR PIR; G90855; G90855.
DR RefSeq; NP_309842.1; NC_002695.1.
DR RefSeq; WP_000938103.1; NZ_SWKA01000005.1.
DR PDB; 3V3K; X-ray; 3.49 A; B/D/F/H/J/L/N/P=25-189.
DR PDBsum; 3V3K; -.
DR AlphaFoldDB; Q8XAL7; -.
DR SMR; Q8XAL7; -.
DR IntAct; Q8XAL7; 11.
DR MINT; Q8XAL7; -.
DR EnsemblBacteria; AAK16936; AAK16936; Z6020.
DR EnsemblBacteria; BAB35238; BAB35238; ECs_1815.
DR GeneID; 912903; -.
DR KEGG; ece:Z6020; -.
DR KEGG; ecs:ECs_1815; -.
DR PATRIC; fig|83334.175.peg.4904; -.
DR HOGENOM; CLU_1432549_0_0_6; -.
DR OMA; AMISIYS; -.
DR Proteomes; UP000000558; Chromosome.
DR Proteomes; UP000002519; Chromosome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0030414; F:peptidase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0010466; P:negative regulation of peptidase activity; IEA:UniProtKB-KW.
DR Gene3D; 1.20.1260.90; -; 1.
DR InterPro; IPR031829; NleF.
DR InterPro; IPR038334; NleF_sf.
DR Pfam; PF16809; NleF_casp_inhib; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Host cytoplasm; Protease inhibitor; Reference proteome;
KW Secreted.
FT CHAIN 1..189
FT /note="Effector protein NleF"
FT /id="PRO_0000422160"
FT REGION 186..189
FT /note="Interaction with host caspases"
FT MUTAGEN 186..189
FT /note="Missing: Abolishes caspase-binding and inhibition of
FT host cell apoptosis."
FT MUTAGEN 186
FT /note="L->A: Abolishes interaction with CASP4 and CASP8.
FT Strongly reduces CASP9 binding. Reduces inhibition of host
FT cell apoptosis."
FT MUTAGEN 187
FT /note="Q->A: Abolishes caspase-binding. Reduces inhibition
FT of host cell apoptosis."
FT MUTAGEN 188
FT /note="C->A: Strongly reduces interaction with CASP4 and
FT abolishes interaction with CASP8. Reduces interaction with
FT CASP9. Reduces inhibition of host cell apoptosis."
FT MUTAGEN 189
FT /note="G->A: Abolishes interaction with CASP4 and CASP8.
FT Strongly reduces CASP9 binding. Reduces inhibition of host
FT cell apoptosis."
FT /evidence="ECO:0000269|PubMed:23516580"
FT MUTAGEN 189
FT /note="G->GA: Abolishes caspase-binding and inhibition of
FT host cell apoptosis."
FT /evidence="ECO:0000269|PubMed:23516580"
FT MUTAGEN 189
FT /note="Missing: Abolishes interaction with CASP4 and CASP8.
FT Strongly reduces CASP9 binding. Reduces inhibition of host
FT cell apoptosis."
FT /evidence="ECO:0000269|PubMed:23516580"
FT HELIX 34..36
FT /evidence="ECO:0007829|PDB:3V3K"
FT HELIX 40..55
FT /evidence="ECO:0007829|PDB:3V3K"
FT TURN 59..62
FT /evidence="ECO:0007829|PDB:3V3K"
FT HELIX 63..83
FT /evidence="ECO:0007829|PDB:3V3K"
FT STRAND 84..88
FT /evidence="ECO:0007829|PDB:3V3K"
FT STRAND 95..98
FT /evidence="ECO:0007829|PDB:3V3K"
FT HELIX 104..127
FT /evidence="ECO:0007829|PDB:3V3K"
FT STRAND 129..131
FT /evidence="ECO:0007829|PDB:3V3K"
FT HELIX 137..141
FT /evidence="ECO:0007829|PDB:3V3K"
FT HELIX 149..161
FT /evidence="ECO:0007829|PDB:3V3K"
FT TURN 179..182
FT /evidence="ECO:0007829|PDB:3V3K"
FT STRAND 184..188
FT /evidence="ECO:0007829|PDB:3V3K"
SQ SEQUENCE 189 AA; 21388 MW; EE5461D5021DAE54 CRC64;
MLPTSGSSAN LYSWMYVSGR GNPSTPESVS ELNHNHFLSP ELQDKLDVMV SIYSCARNNN
ELEEIFQELS AFVSGLMDKR NSVFEVRNEN TDEVVGALRA GMTIEDRDSY IRDLFFLHSL
KVKIEESRQG KEDSKCKVYN LLCPHHSSEL YGDLRAMKCL VEGCSDDFNP FDIIRVPDLT
YNKGSLQCG
