ID   AERA_AERSA              Reviewed;         489 AA.
AC   Q08676;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   25-MAY-2022, entry version 90.
DE   RecName: Full=Aerolysin;
DE   AltName: Full=Hemolysin-3;
DE   Flags: Precursor;
GN   Name=ash3;
OS   Aeromonas salmonicida.
OC   Bacteria; Proteobacteria; Gammaproteobacteria; Aeromonadales;
OC   Aeromonadaceae; Aeromonas.
OX   NCBI_TaxID=645;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND SUBCELLULAR LOCATION.
RC   STRAIN=17-2;
RX   PubMed=8309354; DOI=10.1006/mpat.1993.1077;
RA   Hirono I., Aoki T.;
RT   "Cloning and characterization of three hemolysin genes from Aeromonas
RT   salmonicida.";
RL   Microb. Pathog. 15:269-282(1993).
CC   -!- FUNCTION: Secreted, cytolytic toxin that forms pores in host membranes
CC       after proteolytic removal of a C-terminal propeptide, leading to
CC       destruction of the membrane permeability barrier and cell death. The
CC       pores are formed by transmembrane beta-strands and are approximately 3
CC       nm in diameter. {ECO:0000269|PubMed:8309354}.
CC   -!- SUBUNIT: Homodimer in solution; homoheptamer in the host membrane.
CC       After binding to GPI-anchored proteins in target membranes and
CC       proteolytic removal of the C-terminal propeptide, the protein assembles
CC       into a heptameric pre-pore complex. A further conformation change leads
CC       to insertion into the host membrane (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:8309354}. Host cell
CC       membrane {ECO:0000269|PubMed:8309354}. Note=Secreted as a soluble
CC       precursor.
CC   -!- DOMAIN: The C-terminal propeptide is required for normal protein
CC       folding and secretion; it maintains the aerolysin precursor in its
CC       soluble form and prevents premature heptamerization and pore formation.
CC       {ECO:0000250}.
CC   -!- PTM: Proteolytic cleavage and subsequent release of the propeptide
CC       trigger a major conformation change, leading to the formation of a
CC       heptameric pre-pore that then inserts into the host membrane.
CC       {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the aerolysin family. {ECO:0000305}.
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DR   EMBL; X65048; CAA46184.1; -; Genomic_DNA.
DR   PIR; I39672; I39672.
DR   AlphaFoldDB; Q08676; -.
DR   SMR; Q08676; -.
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:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   GO; GO:0044179; P:hemolysis in another organism; IEA:UniProtKB-KW.
DR   Gene3D; 3.10.40.10; -; 1.
DR   InterPro; IPR005831; Aerolysin/haemolysin_CS.
DR   InterPro; IPR005830; Aerolysn.
DR   InterPro; IPR005138; APT_dom.
DR   InterPro; IPR037015; APT_N_sf.
DR   InterPro; IPR016187; CTDL_fold.
DR   Pfam; PF01117; Aerolysin; 1.
DR   Pfam; PF03440; APT; 1.
DR   PRINTS; PR00754; AEROLYSIN.
DR   SMART; SM00999; Aerolysin; 1.
DR   SUPFAM; SSF56436; SSF56436; 1.
DR   PROSITE; PS00274; AEROLYSIN; 1.
PE   3: Inferred from homology;
KW   Cytolysis; Disulfide bond; Hemolysis; Host cell membrane; Host membrane;
KW   Membrane; Secreted; Signal; Toxin; Transmembrane;
KW   Transmembrane beta strand; Virulence.
FT   SIGNAL          1..24
FT                   /evidence="ECO:0000255"
FT   CHAIN           25..444
FT                   /note="Aerolysin"
FT                   /id="PRO_0000035628"
FT   PROPEP          445..489
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000035629"
FT   REGION          70..86
FT                   /note="Interaction with host N-linked glycan"
FT                   /evidence="ECO:0000250"
FT   REGION          257..289
FT                   /note="Part of the transmembrane beta-barrel after
FT                   proteolytic activation of the toxin and insertion into the
FT                   host membrane"
FT                   /evidence="ECO:0000250"
FT   REGION          347..356
FT                   /note="Interaction with glycans from host GPI-anchor"
FT                   /evidence="ECO:0000250"
FT   SITE            157
FT                   /note="Important for oligomerization"
FT                   /evidence="ECO:0000250"
FT   SITE            391
FT                   /note="Important for heptamerization"
FT                   /evidence="ECO:0000250"
FT   DISULFID        44..100
FT                   /evidence="ECO:0000250"
FT   DISULFID        184..189
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   489 AA;  54189 MW;  81D92EEDBD2F3171 CRC64;
     MMNRIITANL ANLASSLMLA QVLGWHEPVY PDQVKWAGLG TGVCASGYRP LTRDEAMSIK
     GNLVSRMGQW QITGLADRWV IMGPGYNGEI KQGTAGETWC YPNSPVSGEI PTLSDWNIPA
     GDEVDVQWRL VHDNDYFIKP VSYLAHYLGY AWVGGNHSPY VGEDMDVTRV GDGWLIKGNN
     DGGCSGYRCG EKSSIKVSNF SYTLEPDSFS HGQVTESGKQ LVKTITANAT NYTDLPQQVV
     VTLKYDKATN WSKTDTYSLS EKVTTKNKFQ WPLVGETELA IEIAASQSWA SQKGGSTTET
     VSVEARPTVP PHSSLPVRVA LYKSNISYPY EFKAEVNYDL TMKGFLRWGG NAWYTHPDNR
     PTWEHTFRLG PFRGQGEQHP LPVDKRYIPG EVKWWDWNWT ISEYGLSTMQ NNLGRVLRPI
     RSAVTGDFYA ESQFAGDIEI GQPQTRSAKA AQLRSASAEE VALTSVDLDS EALANEGFGN
     VSLTIVPVQ