HLYE_ECOLI
ID HLYE_ECOLI Reviewed; 303 AA.
AC P77335; Q47276; Q8VU70; Q9R3G4;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Hemolysin E, chromosomal;
DE AltName: Full=Cytotoxin ClyA;
DE AltName: Full=Hemolysis-inducing protein;
DE AltName: Full=Latent pore-forming 34 kDa hemolysin;
DE AltName: Full=Silent hemolysin SheA;
GN Name=hlyE; Synonyms=clyA, hpr, sheA, ycgD; OrderedLocusNames=b1182, JW5181;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12 / XL1-Blue;
RA McNamara P.J., Iandolo J.J., Uhlich G.;
RL Submitted (MAY-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12;
RX PubMed=11902713; DOI=10.1046/j.1365-2958.1997.4391813.x;
RA del Castillo F.J., Leal S.C., Moreno F., del Castillo I.;
RT "The Escherichia coli K-12 sheA gene encodes a 34-kDa secreted
RT haemolysin.";
RL Mol. Microbiol. 25:107-115(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-13, SUBCELLULAR
RP LOCATION, AND INDUCTION.
RC STRAIN=K12;
RX PubMed=10027972; DOI=10.1046/j.1365-2958.1999.01196.x;
RA Ludwig A., Bauer S., Benz R., Bergmann B., Goebel W.;
RT "Analysis of the SlyA-controlled expression, subcellular localization and
RT pore-forming activity of a 34 kDa haemolysin (ClyA) from Escherichia coli
RT K-12.";
RL Mol. Microbiol. 31:557-567(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=3030-2;
RA Xing J., Fernandez S.V., Kapur V., Barletta R.G., Moxley R.A.;
RL Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=8905232; DOI=10.1093/dnares/3.3.137;
RA Oshima T., Aiba H., Baba T., Fujita K., Hayashi K., Honjo A., Ikemoto K.,
RA Inada T., Itoh T., Kajihara M., Kanai K., Kashimoto K., Kimura S.,
RA Kitagawa M., Makino K., Masuda S., Miki T., Mizobuchi K., Mori H.,
RA Motomura K., Nakamura Y., Nashimoto H., Nishio Y., Saito N., Sampei G.,
RA Seki Y., Tagami H., Takemoto K., Wada C., Yamamoto Y., Yano M.,
RA Horiuchi T.;
RT "A 718-kb DNA sequence of the Escherichia coli K-12 genome corresponding to
RT the 12.7-28.0 min region on the linkage map.";
RL DNA Res. 3:137-155(1996).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=CH9802;
RA Chang G.-N., Ho K.-C.;
RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-296.
RC STRAIN=K12 / XL1-Blue;
RA King C.H., Shinnick T.M.;
RL Submitted (MAR-1996) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-156.
RC STRAIN=K12 / AB1157;
RA Woodgate R.;
RL Submitted (AUG-1994) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP PROTEIN SEQUENCE OF 2-18, AND MUTAGENESIS OF 88-GLY--VAL-90;
RP 143-ASN-ALA-144; 183-ALA-GLY-184; 187-ALA-GLY-188; ASP-268 AND
RP 293-GLY-LYS-294.
RX PubMed=10383763; DOI=10.1046/j.1365-2958.1999.01435.x;
RA Oscarsson J., Mizunoe Y., Li L., Lai X.-H., Wieslander A., Uhlin B.E.;
RT "Molecular analysis of the cytolytic protein ClyA (SheA) from Escherichia
RT coli.";
RL Mol. Microbiol. 32:1226-1238(1999).
RN [12]
RP PARTIAL PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, OLIGOMERIZATION,
RP AND DISULFIDE BOND FORMATION.
RX PubMed=14532000; DOI=10.1016/s0092-8674(03)00754-2;
RA Wai S.N., Lindmark B., Soederblom T., Takade A., Westermark M.,
RA Oscarsson J., Jass J., Richter-Dahlfors A., Mizunoe Y., Uhlin B.E.;
RT "Vesicle-mediated export and assembly of pore-forming oligomers of the
RT enterobacterial clyA cytotoxin.";
RL Cell 115:25-35(2003).
RN [13]
RP MASS SPECTROMETRY, DISULFIDE BOND, AND MUTAGENESIS OF TYR-97; ASN-157;
RP TYR-165 AND ARG-261.
RX PubMed=11006277; DOI=10.1074/jbc.m005420200;
RA Atkins A., Wyborn N.R., Wallace A.J., Stillman T.J., Black L.K.,
RA Fielding A.B., Hisakado M., Artymiuk P.J., Green J.;
RT "Structure-function relationships of a novel bacterial toxin, hemolysin E.
RT The role of alpha G.";
RL J. Biol. Chem. 275:41150-41155(2000).
RN [14]
RP INDUCTION.
RX PubMed=11053378; DOI=10.1128/jb.182.22.6347-6357.2000;
RA Westermark M., Oscarsson J., Mizunoe Y., Urbonaviciene J., Uhlin B.E.;
RT "Silencing and activation of ClyA cytotoxin expression in Escherichia
RT coli.";
RL J. Bacteriol. 182:6347-6357(2000).
RN [15]
RP INDUCTION.
RX PubMed=12057949; DOI=10.1128/jb.184.13.3549-3559.2002;
RA Spory A., Bosserhoff A., von Rhein C., Goebel W., Ludwig A.;
RT "Differential regulation of multiple proteins of Escherichia coli and
RT Salmonella enterica serovar Typhimurium by the transcriptional regulator
RT SlyA.";
RL J. Bacteriol. 184:3549-3559(2002).
RN [16]
RP MUTANT PMWK16 DEL.
RX PubMed=12949101; DOI=10.1128/jb.185.18.5491-5499.2003;
RA Wai S.N., Westermark M., Oscarsson J., Jass J., Maier E., Benz R.,
RA Uhlin B.E.;
RT "Characterization of dominantly negative mutant ClyA cytotoxin proteins in
RT Escherichia coli.";
RL J. Bacteriol. 185:5491-5499(2003).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
RX PubMed=10660049; DOI=10.1016/s0092-8674(00)81564-0;
RA Wallace A.J., Stillman T.J., Atkins A., Jamieson S.J., Bullough P.A.,
RA Green J., Artymiuk P.J.;
RT "E. coli hemolysin E (HlyE, ClyA, SheA): X-ray crystal structure of the
RT toxin and observation of membrane pores by electron microscopy.";
RL Cell 100:265-276(2000).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (3.29 ANGSTROMS), PORE FORMATION, MEMBRANE TOPOLOGY,
RP AND SUBUNIT.
RX PubMed=19421192; DOI=10.1038/nature08026;
RA Mueller M., Grauschopf U., Maier T., Glockshuber R., Ban N.;
RT "The structure of a cytolytic alpha-helical toxin pore reveals its assembly
RT mechanism.";
RL Nature 459:726-730(2009).
CC -!- FUNCTION: Toxin, which has some hemolytic activity towards mammalian
CC cells. Acts by forming a pore-like structure upon contact with
CC mammalian cells. {ECO:0000269|PubMed:14532000}.
CC -!- SUBUNIT: Monomer and oligomer. In periplasm, it is present as a
CC monomer, while in outer membrane vesicles, it oligomerizes to form a
CC pore structure that is active. The pore is formed by a dodecamer.
CC {ECO:0000269|PubMed:19421192}.
CC -!- INTERACTION:
CC P77335; P77335: hlyE; NbExp=6; IntAct=EBI-8516553, EBI-8516553;
CC -!- SUBCELLULAR LOCATION: Secreted. Periplasm. Host cell membrane
CC {ECO:0000305}; Single-pass membrane protein {ECO:0000305}.
CC Note=Exported from the cell by outer membrane vesicles. Also found in
CC the periplasmic space.
CC -!- INDUCTION: During anaerobic growth. Weakly or not expressed in most
CC strains. It is activated by SlyA, while it is silenced by H-NS. Its
CC expression is also regulated by CRP and FNR.
CC {ECO:0000269|PubMed:10027972, ECO:0000269|PubMed:11053378,
CC ECO:0000269|PubMed:12057949}.
CC -!- PTM: In periplasm, it forms a disulfide bond between Cys-87 and Cys-
CC 285, which prevents the oligomerization. In outer membrane vesicles,
CC the redox status prevents formation of the disulfide bond, leading to
CC oligomerization and pore formation.
CC -!- MASS SPECTROMETRY: Mass=34940; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:11006277};
CC -!- SIMILARITY: Belongs to the hemolysin E family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB07048.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAA67204.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; U57430; AAB07048.1; ALT_INIT; Genomic_DNA.
DR EMBL; X98615; CAA67204.1; ALT_INIT; Genomic_DNA.
DR EMBL; AJ001829; CAA05035.1; -; Genomic_DNA.
DR EMBL; U73842; AAD04731.1; -; Genomic_DNA.
DR EMBL; U00096; AAC74266.2; -; Genomic_DNA.
DR EMBL; AP009048; BAA36016.2; -; Genomic_DNA.
DR EMBL; AF240780; AAL55667.1; -; Genomic_DNA.
DR EMBL; U22466; AAA92081.1; -; Genomic_DNA.
DR EMBL; U13610; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; C64864; C64864.
DR RefSeq; NP_415700.4; NC_000913.3.
DR RefSeq; WP_001336523.1; NZ_SSZK01000010.1.
DR PDB; 1QOY; X-ray; 2.00 A; A=1-303.
DR PDB; 2WCD; X-ray; 3.29 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X=2-303.
DR PDB; 4PHO; X-ray; 2.12 A; A/B/C=2-303.
DR PDB; 4PHQ; X-ray; 1.94 A; A/B/C/D=6-303.
DR PDB; 6MRT; EM; 2.80 A; A/B/C/D/E/F/G/H/I/J/K/L=1-303.
DR PDB; 6MRU; EM; 3.20 A; A/B/C/D/E/F/G/H/I/J/K/L/M=1-303.
DR PDB; 6MRW; EM; 4.30 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N=1-303.
DR PDBsum; 1QOY; -.
DR PDBsum; 2WCD; -.
DR PDBsum; 4PHO; -.
DR PDBsum; 4PHQ; -.
DR PDBsum; 6MRT; -.
DR PDBsum; 6MRU; -.
DR PDBsum; 6MRW; -.
DR AlphaFoldDB; P77335; -.
DR SMR; P77335; -.
DR BioGRID; 4260100; 4.
DR DIP; DIP-9915N; -.
DR MINT; P77335; -.
DR STRING; 511145.b1182; -.
DR TCDB; 1.C.10.1.1; the pore-forming haemolysin e (hlye) family.
DR jPOST; P77335; -.
DR PaxDb; P77335; -.
DR PRIDE; P77335; -.
DR EnsemblBacteria; AAC74266; AAC74266; b1182.
DR EnsemblBacteria; BAA36016; BAA36016; BAA36016.
DR GeneID; 945745; -.
DR KEGG; ecj:JW5181; -.
DR KEGG; eco:b1182; -.
DR PATRIC; fig|1411691.4.peg.1105; -.
DR EchoBASE; EB3032; -.
DR eggNOG; ENOG502ZB9A; Bacteria.
DR HOGENOM; CLU_080941_0_0_6; -.
DR InParanoid; P77335; -.
DR OMA; LTICHAD; -.
DR BioCyc; EcoCyc:G6619-MON; -.
DR EvolutionaryTrace; P77335; -.
DR PRO; PR:P77335; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005576; C:extracellular region; IMP:EcoCyc.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0042597; C:periplasmic space; IMP:EcoCyc.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0001897; P:cytolysis by symbiont of host cells; IDA:EcoCyc.
DR GO; GO:0044179; P:hemolysis in another organism; IDA:EcoCyc.
DR GO; GO:0044532; P:modulation of apoptotic process in another organism; IDA:EcoliWiki.
DR InterPro; IPR027018; Hemolysin_E.
DR Pfam; PF06109; HlyE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytolysis; Direct protein sequencing; Disulfide bond;
KW Hemolysis; Host cell membrane; Host membrane; Membrane; Periplasm;
KW Reference proteome; Secreted; Toxin; Transmembrane; Transmembrane helix;
KW Virulence.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:10027972,
FT ECO:0000269|PubMed:10383763"
FT CHAIN 2..303
FT /note="Hemolysin E, chromosomal"
FT /id="PRO_0000083996"
FT TRANSMEM 183..203
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DISULFID 87..285
FT /note="In monomeric form"
FT /evidence="ECO:0000269|PubMed:11006277,
FT ECO:0000269|PubMed:14532000"
FT VARIANT 175
FT /note="K -> R (in strain: CH9802)"
FT VARIANT 201
FT /note="G -> A (in strain: CH9802)"
FT MUTAGEN 88..90
FT /note="GVA->DVD: Abolishes cytotoxic activity."
FT /evidence="ECO:0000269|PubMed:10383763"
FT MUTAGEN 97
FT /note="Y->H: Strongly reduces cytotoxic activity."
FT /evidence="ECO:0000269|PubMed:11006277"
FT MUTAGEN 143..144
FT /note="NA->DD: Abolishes cytotoxic activity."
FT /evidence="ECO:0000269|PubMed:10383763"
FT MUTAGEN 157
FT /note="N->H: Strongly reduces cytotoxic activity."
FT /evidence="ECO:0000269|PubMed:11006277"
FT MUTAGEN 165
FT /note="Y->C: Strongly reduces cytotoxic activity."
FT /evidence="ECO:0000269|PubMed:11006277"
FT MUTAGEN 183..186
FT /note="Missing: In PMWK16; retained in cytosol. Loss of
FT function."
FT MUTAGEN 183..184
FT /note="AG->DD: Abolishes cytotoxic activity."
FT /evidence="ECO:0000269|PubMed:10383763"
FT MUTAGEN 187..188
FT /note="AG->DD: Abolishes cytotoxic activity."
FT /evidence="ECO:0000269|PubMed:10383763"
FT MUTAGEN 261
FT /note="R->K: Strongly reduces cytotoxic activity."
FT /evidence="ECO:0000269|PubMed:11006277"
FT MUTAGEN 268
FT /note="D->A: Strongly reduces cytotoxic activity."
FT /evidence="ECO:0000269|PubMed:10383763"
FT MUTAGEN 293..294
FT /note="GK->DA: Strongly reduces cytotoxic activity."
FT /evidence="ECO:0000269|PubMed:10383763"
FT HELIX 7..28
FT /evidence="ECO:0007829|PDB:4PHQ"
FT HELIX 31..34
FT /evidence="ECO:0007829|PDB:4PHQ"
FT HELIX 37..46
FT /evidence="ECO:0007829|PDB:4PHQ"
FT TURN 47..50
FT /evidence="ECO:0007829|PDB:4PHQ"
FT HELIX 51..53
FT /evidence="ECO:0007829|PDB:4PHQ"
FT HELIX 56..99
FT /evidence="ECO:0007829|PDB:4PHQ"
FT TURN 100..103
FT /evidence="ECO:0007829|PDB:4PHQ"
FT HELIX 106..159
FT /evidence="ECO:0007829|PDB:4PHQ"
FT HELIX 164..179
FT /evidence="ECO:0007829|PDB:4PHQ"
FT STRAND 182..187
FT /evidence="ECO:0007829|PDB:4PHQ"
FT HELIX 189..191
FT /evidence="ECO:0007829|PDB:4PHQ"
FT STRAND 193..195
FT /evidence="ECO:0007829|PDB:4PHQ"
FT HELIX 196..199
FT /evidence="ECO:0007829|PDB:4PHQ"
FT HELIX 207..258
FT /evidence="ECO:0007829|PDB:4PHQ"
FT HELIX 268..291
FT /evidence="ECO:0007829|PDB:4PHQ"
SQ SEQUENCE 303 AA; 33759 MW; 9BE348DA095668A5 CRC64;
MTEIVADKTV EVVKNAIETA DGALDLYNKY LDQVIPWQTF DETIKELSRF KQEYSQAASV
LVGDIKTLLM DSQDKYFEAT QTVYEWCGVA TQLLAAYILL FDEYNEKKAS AQKDILIKVL
DDGITKLNEA QKSLLVSSQS FNNASGKLLA LDSQLTNDFS EKSSYFQSQV DKIRKEAYAG
AAAGVVAGPF GLIISYSIAA GVVEGKLIPE LKNKLKSVQN FFTTLSNTVK QANKDIDAAK
LKLTTEIAAI GEIKTETETT RFYVDYDDLM LSLLKEAAKK MINTCNEYQK RHGKKTLFEV
PEV
