HLYAC_ECOLX
ID HLYAC_ECOLX Reviewed; 1023 AA.
AC P09983;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=Hemolysin, chromosomal {ECO:0000305};
GN Name=hlyA {ECO:0000303|PubMed:3894051};
OS Escherichia coli.
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=562;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=J96 / Serotype O4;
RX PubMed=3891743; DOI=10.1128/jb.163.1.94-105.1985;
RA Felmlee T., Pellett S., Welch R.A.;
RT "Nucleotide sequence of an Escherichia coli chromosomal hemolysin.";
RL J. Bacteriol. 163:94-105(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-44, FUNCTION, AND SUBCELLULAR
RP LOCATION.
RC STRAIN=2001;
RX PubMed=3894051; DOI=10.1016/0014-5793(85)81272-2;
RA Nicaud J.-M., Mackman N., Gray L., Holland I.B.;
RT "Characterisation of HlyC and mechanism of activation and secretion of
RT haemolysin from E. coli 2001.";
RL FEBS Lett. 187:339-344(1985).
RN [3]
RP PROTEIN SEQUENCE OF 544-573 AND 682-693, AND MYRISTOYLATION AT LYS-563 AND
RP LYS-689.
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 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 [5]
RP SUBCELLULAR LOCATION, AND ACYLATION.
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 [6]
RP MYRISTOYLATION AT LYS-563 AND LYS-689.
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, ECO:0000269|PubMed:3891743,
CC ECO:0000269|PubMed:3894051}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:3894051}. Host cell
CC membrane {ECO:0000305|PubMed:12598051, ECO:0000305|PubMed:2121650};
CC Multi-pass membrane protein {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:12598051). Mainly myristoylated, while a minor
CC fraction is acylated with pentadecanoyl (C15:0; 26%) and heptadecanoyl
CC (C17:0; 6%) fatty acyl groups (By similarity). Fatty acylation is
CC involved in binding to host membranes and promotes the irreversible
CC insertion of Hemolysin into the host cell membrane (PubMed:12598051).
CC Can be activated by both myristoylation and palmitoylation, but HlyC
CC catalyzes lysine myristoylation (PubMed:32461253).
CC {ECO:0000250|UniProtKB:P08715, ECO:0000269|PubMed:12598051,
CC ECO:0000269|PubMed:32461253, ECO:0000269|PubMed:7801126}.
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; M10133; AAA23975.1; -; Genomic_DNA.
DR EMBL; X02768; CAA26546.1; -; Genomic_DNA.
DR PIR; A24433; LEECA.
DR PIR; S10056; S10056.
DR AlphaFoldDB; P09983; -.
DR SMR; P09983; -.
DR DIP; DIP-16932N; -.
DR TCDB; 1.C.11.1.3; the pore-forming rtx toxin (rtx-toxin) family.
DR PHI-base; PHI:7837; -.
DR GO; GO:0005615; C:extracellular space; IMP:CAFA.
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 GO; GO:1901998; P:toxin transport; IMP:CAFA.
DR DisProt; DP00389; -.
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; 2.
DR PROSITE; PS00330; HEMOLYSIN_CALCIUM; 4.
PE 1: Evidence at protein level;
KW Calcium; Cytolysis; Direct protein sequencing; Hemolysis;
KW Host cell membrane; Host membrane; Lipoprotein; Membrane; Myristate;
KW Repeat; Secreted; Toxin; Transmembrane; Transmembrane helix; Virulence.
FT CHAIN 1..1023
FT /note="Hemolysin, chromosomal"
FT /id="PRO_0000196215"
FT TRANSMEM 237..259
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 267..326
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 364..410
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REPEAT 731..748
FT /note="Hemolysin-type calcium-binding 1"
FT REPEAT 749..766
FT /note="Hemolysin-type calcium-binding 2"
FT REPEAT 767..784
FT /note="Hemolysin-type calcium-binding 3"
FT REPEAT 785..802
FT /note="Hemolysin-type calcium-binding 4"
FT REPEAT 815..832
FT /note="Hemolysin-type calcium-binding 5"
FT REPEAT 833..850
FT /note="Hemolysin-type calcium-binding 6"
FT REGION 747..780
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 563
FT /note="N6-myristoyl lysine"
FT /evidence="ECO:0000269|PubMed:32461253,
FT ECO:0000305|PubMed:7801126"
FT LIPID 689
FT /note="N6-myristoyl lysine"
FT /evidence="ECO:0000269|PubMed:32461253,
FT ECO:0000305|PubMed:7801126"
FT VARIANT 6
FT /note="A -> T (in strain: 2001)"
SQ SEQUENCE 1023 AA; 109867 MW; 196D5C0A9A28B54D CRC64;
MPTITAAQIK STLQSAKQSA ANKLHSAGQS TKDALKKAAE QTRNAGNRLI LLIPKDYKGQ
GSSLNDLVRT ADELGIEVQY DEKNGTAITK QVFGTAEKLI GLTERGVTIF APQLDKLLQK
YQKAGNKLGG SAENIGDNLG KAGSVLSTFQ NFLGTALSSM KIDELIKKQK SGGNVSSSEL
AKASIELINQ LVDTAASLNN VNSFSQQLNK LGSVLSNTKH LNGVGNKLQN LPNLDNIGAG
LDTVSGILSA ISASFILSNA DADTGTKAAA GVELTTKVLG NVGKGISQYI IAQRAAQGLS
TSAAAAGLIA SVVTLAISPL SFLSIADKFK RANKIEEYSQ RFKKLGYDGD SLLAAFHKET
GAIDASLTRI STVLASVSSG ISAAATTSLV GAPVSALVGA VTGIISGILE ASKQAMFEHV
ASKMADVIAE WEKKHGKNYF ENGYDARHAA FLEDNFKILS QYNKEYSVER SVLITQQHWD
TLIGELAGVT RNGDKTLSGK SYIDYYEEGK RLEKKPDEFQ KQVFDPLKGN IDLSDSKSST
LLKFVTPLLT PGEEIRERRQ SGKYEYITEL LVKGVDKWTV KGVQDKGSVY DYSNLIQHAS
VGNNQYREIR IESHLGDGDD KVFLSAGSAN IYAGKGHDVV YYDKTDTGYL TIDGTKATEA
GNYTVTRVLG GDVKVLQEVV KEQEVSVGKR TEKTQYRSYE FTHINGKNLT ETDNLYSVEE
LIGTTRADKF FGSKFADIFH GADGDDHIEG NDGNDRLYGD KGNDTLSGGN GDDQLYGGDG
NDKLIGGAGN NYLNGGDGDD ELQVQGNSLA KNVLSGGKGN DKLYGSEGAD LLDGGEGNDL
LKGGYGNDIY RYLSGYGHHI IDDDGGKDDK LSLADIDFRD VAFRREGNDL IMYKAEGNVL
SIGHKNGITF KNWFEKESGD ISNHQIEQIF DKDGRVITPD SLKKALEYQQ SNNKASYVYG
NDALAYGSQG NLNPLINEIS KIISAAGNFD VKEERAAASL LQLSGNASDF SYGRNSITLT
ASA
