ID   AER4_AERHY              Reviewed;         492 AA.
AC   Q06303;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   25-MAY-2022, entry version 95.
DE   RecName: Full=Aerolysin-4;
DE   AltName: Full=Hemolysin-4;
DE   Flags: Precursor;
GN   Name=ahh4;
OS   Aeromonas hydrophila.
OC   Bacteria; Proteobacteria; Gammaproteobacteria; Aeromonadales;
OC   Aeromonadaceae; Aeromonas.
OX   NCBI_TaxID=644;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND SUBCELLULAR LOCATION.
RC   STRAIN=28SA;
RX   PubMed=1302284; DOI=10.1016/0882-4010(92)90011-c;
RA   Hirono I., Aoki T., Asao T., Kozaki S.;
RT   "Nucleotide sequences and characterization of haemolysin genes from
RT   Aeromonas hydrophila and Aeromonas sobria.";
RL   Microb. Pathog. 13:433-446(1992).
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:1302284}.
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:1302284}. Host cell
CC       membrane {ECO:0000269|PubMed:1302284}. 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}.
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; X65043; CAA46179.1; -; Genomic_DNA.
DR   PIR; I39591; I39591.
DR   AlphaFoldDB; Q06303; -.
DR   SMR; Q06303; -.
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..23
FT                   /evidence="ECO:0000255"
FT   CHAIN           24..445
FT                   /note="Aerolysin-4"
FT                   /id="PRO_0000035624"
FT   PROPEP          446..492
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000035625"
FT   REGION          68..84
FT                   /note="Interaction with host N-linked glycan"
FT                   /evidence="ECO:0000250"
FT   REGION          256..288
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          346..355
FT                   /note="Interaction with glycans from host GPI-anchor"
FT                   /evidence="ECO:0000250"
FT   SITE            155
FT                   /note="Important for oligomerization"
FT                   /evidence="ECO:0000250"
FT   SITE            374
FT                   /note="Important for heptamerization"
FT                   /evidence="ECO:0000250"
FT   SITE            390
FT                   /note="Important for heptamerization"
FT                   /evidence="ECO:0000250"
FT   DISULFID        42..98
FT                   /evidence="ECO:0000250"
FT   DISULFID        182..187
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   492 AA;  54178 MW;  C86D3C1DCEB172C4 CRC64;
     MKKLKITGLS LIISGLLMAQ AQAAEPVYPD QLRLFSLGQE VCGDKYRPVN REEAQSIKSN
     IVGMMGQWQI SGLANGWVIM GPGYNGEIKP GSASSTWCYP TNPATGEIPT LSALDIPDGD
     EVDVQWRLVH DSANFIKPTS YLAHYLGYAW VGGNHSQYVG EDMDVTRDGD GWVIRGNNDG
     GCDGYRCGDK TSIKVSNFAY NLDPDSFKHG DVTQSDRQLV KTVVGWAIND SDTPQSGYDV
     TLRYDTATNW SKTNTYGLSE KVTTKNKFKW PLVGETELSI EIAANQSWAS QNGGSTTTSL
     SQSVRPTVPA HSKIPVKIEL YKADISYPYE FKADVSYDLT LSGFLRWGGN AWYTHPDNRP
     NWNHTFVIGP YKDKASSIRY QWDKRYIPGE VKWWDWNWTI QQNGLPTMQN NLAKVLRPVR
     AGITGDFSAE SQFAGNIEIG APVPVAAASH SSRARNLSAG QGLRLEIPLD AQELSGLGFN
     NVSLSVTPAA NQ