HLYAP_ECOLX
ID HLYAP_ECOLX Reviewed; 1024 AA.
AC P08715;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1988, sequence version 1.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Hemolysin, plasmid {ECO:0000305};
GN Name=hlyA {ECO:0000303|PubMed:7801126};
OS Escherichia coli.
OG Plasmid IncI2 pHLY152.
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=562;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Hess J., Wels W., Vogel M., Goebel W.;
RT "Nucleotide sequence of a plasmid-encoded hemolysin determinant and its
RT comparison with a corresponding chromosomal hemolysin sequence.";
RL FEMS Microbiol. Lett. 34:1-11(1986).
RN [2]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=2121650; DOI=10.1128/iai.58.11.3796-3801.1990;
RA Suttorp N., Floeer B., Schnittler H., Seeger W., Bhakdi S.;
RT "Effects of Escherichia coli hemolysin on endothelial cell function.";
RL Infect. Immun. 58:3796-3801(1990).
RN [3]
RP MYRISTOYLATION AT LYS-564 AND LYS-690.
RX PubMed=7801126; DOI=10.1126/science.7801126;
RA Stanley P., Packman L.C., Koronakis V., Hughes C.;
RT "Fatty acylation of two internal lysine residues required for the toxic
RT activity of Escherichia coli hemolysin.";
RL Science 266:1992-1996(1994).
RN [4]
RP MYRISTOYLATION AT LYS-564 AND LYS-690.
RX PubMed=8808931; DOI=10.1128/jb.178.18.5422-5430.1996;
RA Ludwig A., Garcia F., Bauer S., Jarchau T., Benz R., Hoppe J., Goebel W.;
RT "Analysis of the in vivo activation of hemolysin (HlyA) from Escherichia
RT coli.";
RL J. Bacteriol. 178:5422-5430(1996).
RN [5]
RP MYRISTOYLATION AT LYS-564 AND LYS-690.
RC PLASMID=IncI2 pHLY152;
RX PubMed=10978310; DOI=10.1074/jbc.c000544200;
RA Lim K.B., Walker C.R., Guo L., Pellett S., Shabanowitz J., Hunt D.F.,
RA Hewlett E.L., Ludwig A., Goebel W., Welch R.A., Hackett M.;
RT "Escherichia coli alpha-hemolysin (HlyA) is heterogeneously acylated in
RT vivo with 14-, 15-, and 17-carbon fatty acids.";
RL J. Biol. Chem. 275:36698-36702(2000).
RN [6]
RP SUBCELLULAR LOCATION, AND MYRISTOYLATION.
RX PubMed=12598051; DOI=10.1016/s0009-3084(02)00191-3;
RA Herlax V., Bakas L.;
RT "Acyl chains are responsible for the irreversibility in the Escherichia
RT coli alpha-hemolysin binding to membranes.";
RL Chem. Phys. Lipids 122:185-190(2003).
RN [7]
RP MYRISTOYLATION AT LYS-564 AND LYS-690, AND MUTAGENESIS OF LYS-564 AND
RP LYS-690.
RC PLASMID=IncI2 pHLY152;
RX PubMed=15065878; DOI=10.1021/bi035919k;
RA Langston K.G., Worsham L.M., Earls L., Ernst-Fonberg M.L.;
RT "Activation of hemolysin toxin: relationship between two internal protein
RT sites of acylation.";
RL Biochemistry 43:4338-4346(2004).
RN [8]
RP MYRISTOYLATION AT LYS-564 AND LYS-690.
RX PubMed=32461253; DOI=10.1074/jbc.ra120.014122;
RA Osickova A., Khaliq H., Masin J., Jurnecka D., Sukova A., Fiser R.,
RA Holubova J., Stanek O., Sebo P., Osicka R.;
RT "Acyltransferase-mediated selection of the length of the fatty acyl chain
RT and of the acylation site governs activation of bacterial RTX toxins.";
RL J. Biol. Chem. 295:9268-9280(2020).
CC -!- FUNCTION: Bacterial hemolysins are exotoxins that attack blood cell
CC membranes and cause cell rupture by forming a pore.
CC {ECO:0000269|PubMed:2121650}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P09983}. Host
CC cell membrane {ECO:0000305|PubMed:12598051,
CC ECO:0000305|PubMed:2121650}; Multi-pass membrane protein
CC {ECO:0000305|PubMed:2121650}.
CC -!- DOMAIN: The Gly-rich region is probably involved in binding calcium,
CC which is required for target cell-binding or cytolytic activity.
CC -!- DOMAIN: The three transmembrane domains are involved in pore formation
CC by the cytotoxin. {ECO:0000305|PubMed:2121650}.
CC -!- PTM: Myristoylated by HlyC; the toxin only becomes active when modified
CC (PubMed:7801126, PubMed:8808931, PubMed:10978310, PubMed:32461253).
CC Mainly myristoylated, while a minor fraction is acylated with
CC pentadecanoyl (C15:0; 26%) and heptadecanoyl (C17:0; 6%) fatty acyl
CC groups (PubMed:10978310). Fatty acylation is involved in binding to
CC host membranes and promotes the irreversible insertion of Hemolysin
CC into the host cell membrane (PubMed:12598051). Can be activated by both
CC myristoylation and palmitoylation, but HlyC catalyzes lysine
CC myristoylation (PubMed:32461253). {ECO:0000269|PubMed:10978310,
CC ECO:0000269|PubMed:12598051, ECO:0000269|PubMed:32461253,
CC ECO:0000269|PubMed:7801126, ECO:0000269|PubMed:8808931}.
CC -!- MISCELLANEOUS: The hemolysin of E.coli is produced predominantly by
CC strains causing extraintestinal infections, such as those of the
CC urinary tract. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the RTX prokaryotic toxin (TC 1.C.11) family.
CC {ECO:0000305}.
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DR EMBL; M14107; AAA98233.1; -; Genomic_DNA.
DR PIR; S10056; S10056.
DR SASBDB; P08715; -.
DR PRIDE; P08715; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
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:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0015267; F:channel activity; IDA:UniProtKB.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0044179; P:hemolysis in another organism; IDA:UniProtKB.
DR Gene3D; 2.150.10.10; -; 3.
DR InterPro; IPR018511; Hemolysin-typ_Ca-bd_CS.
DR InterPro; IPR001343; Hemolysn_Ca-bd.
DR InterPro; IPR013550; RTX_C.
DR InterPro; IPR018504; RTX_N.
DR InterPro; IPR003995; RTX_toxin_determinant-A.
DR InterPro; IPR011049; Serralysin-like_metalloprot_C.
DR Pfam; PF00353; HemolysinCabind; 4.
DR Pfam; PF02382; RTX; 1.
DR Pfam; PF08339; RTX_C; 1.
DR PRINTS; PR01488; RTXTOXINA.
DR SUPFAM; SSF51120; SSF51120; 1.
DR PROSITE; PS00330; HEMOLYSIN_CALCIUM; 4.
PE 1: Evidence at protein level;
KW Calcium; Cytolysis; Hemolysis; Host cell membrane; Host membrane;
KW Lipoprotein; Membrane; Myristate; Plasmid; Repeat; Secreted; Toxin;
KW Transmembrane; Transmembrane helix; Virulence.
FT CHAIN 1..1024
FT /note="Hemolysin, plasmid"
FT /id="PRO_0000196214"
FT TRANSMEM 238..260
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 268..327
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 365..411
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REPEAT 732..749
FT /note="Hemolysin-type calcium-binding 1"
FT REPEAT 750..767
FT /note="Hemolysin-type calcium-binding 2"
FT REPEAT 768..785
FT /note="Hemolysin-type calcium-binding 3"
FT REPEAT 786..803
FT /note="Hemolysin-type calcium-binding 4"
FT REPEAT 816..833
FT /note="Hemolysin-type calcium-binding 5"
FT REPEAT 834..851
FT /note="Hemolysin-type calcium-binding 6"
FT REGION 20..39
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 564
FT /note="N6-myristoyl lysine"
FT /evidence="ECO:0000269|PubMed:10978310,
FT ECO:0000269|PubMed:32461253, ECO:0000305|PubMed:15065878,
FT ECO:0000305|PubMed:7801126, ECO:0000305|PubMed:8808931"
FT LIPID 690
FT /note="N6-myristoyl lysine"
FT /evidence="ECO:0000269|PubMed:10978310,
FT ECO:0000269|PubMed:32461253, ECO:0000305|PubMed:15065878,
FT ECO:0000305|PubMed:7801126, ECO:0000305|PubMed:8808931"
FT MUTAGEN 564
FT /note="K->R,A,C: Abolished acylation by HlyC and subsequent
FT activation; when associated with A-690 or R-690."
FT /evidence="ECO:0000269|PubMed:15065878"
FT MUTAGEN 690
FT /note="K->R,A,C: Abolished acylation by HlyC and subsequent
FT activation; when associated with A-564 or R-564."
FT /evidence="ECO:0000269|PubMed:15065878"
SQ SEQUENCE 1024 AA; 110203 MW; 83944917F76C945B CRC64;
MTTITTAQIK STLQSAKQSA ANKLHSAGQS TKDALKKAAE QTRNAGNRLI LLIPKDYKGQ
GSSLNDLVRT ADELGIEVQY DEKNGTAITK QVFGTAEKLI GLTERGVTIF APQLDKLLQK
YQKAGNILGG GAENIGDNLG KAGGILSTFQ NFLGTALSSM KIDELIKKQK SGGNVSSSEL
AKASIELINQ LVDTVASLNN NVNSFSQQLN TLGSVLSNTK HLNGVGNKLQ NLPNLDNIGA
GLDTVSGILS AISASFILSN ADADTRTKAA AGVELTTKVL GNVGKGISQY IIAQRAAQGL
STSAAAAGLI ASAVTLAISP LSFLSIADKF KRANKIEEYS QRFKKLGYDG DSLLAAFHKE
TGAIDASLTT ISTVLASVSS GISAAATTSL VGAPVSALVG AVTGIISGIL EASKQAMFEH
VASKMADVIA EWEKKHGKNY FENGYDARHA AFLEDNFKIL SQYNKEYSVE RSVLITQQHW
DTLIGELAGV TRNGDKTLSG KSYIDYYEEG KRLEKKXDEF QKQVFDPLKG NIDLSDSKSS
TLLKFVTPLL TPGEEIRERR QSGKYEYITE LLVKGVDKWT VKGVQDKGAV YDYSNLIQHA
SVGNNQYREI RIESHLGDGD DKVFLSAGSA NIYAGKGHDV VYYDKTDTGY LTIDGTKATE
AGNYTVTRVL GGDVKVLQEV VKEQEVSVGK RTEKTQYRSY EFTHINGKNL TETDNLYSVE
ELIGTTRADK FFGSKFTDIF HGADGDDLIE GNDGNDRLYG DKGNDTLSGG NGDDQLYGGD
GNDKLIGVAG NNYLNGGDGD DEFQVQGNSL AKNVLFGGKG NDKLYGSEGA DLLDGGEGDD
LLKGGYGNDI YRYLSGYGHH IIDDDGGKED KLSLADIDFR DVAFKREGND LIMYKGEGNV
LSIGHKNGIT FRNWFEKESG DISNHEIEQI FDKSGRIITP DSLKKALEYQ QRNNKASYVY
GNDALAYGSQ GDLNPLINEI SKIISAAGSF DVKEERTAAS LLQLSGNASD FSYGRNSITL
TTSA
