ACTPB_ACTFR
ID ACTPB_ACTFR Reviewed; 179 AA.
AC A0A515MEN7;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 29-SEP-2021, sequence version 2.
DT 03-AUG-2022, entry version 13.
DE RecName: Full=DELTA-actitoxin-Afr1c {ECO:0000305};
DE Short=DELTA-AITX-Afr1c {ECO:0000305};
DE AltName: Full=Alpha-helical pore-forming toxin {ECO:0000250|UniProtKB:B9W5G6};
DE Short=PFT {ECO:0000250|UniProtKB:B9W5G6};
DE AltName: Full=Cytolysin {ECO:0000250|UniProtKB:B9W5G6};
DE AltName: Full=Fragaceatoxin B {ECO:0000303|PubMed:31295915};
DE Short=fraB {ECO:0000303|PubMed:31295915};
OS Actinia fragacea (Strawberry anemone).
OC Eukaryota; Metazoa; Cnidaria; Anthozoa; Hexacorallia; Actiniaria;
OC Actiniidae; Actinia.
OX NCBI_TaxID=396334;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 13-179, PROTEIN SEQUENCE OF 1-20, FUNCTION,
RP MASS SPECTROMETRY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=31295915; DOI=10.3390/toxins11070401;
RA Morante K., Bellomio A., Viguera A.R., Gonzalez-Manas J.M., Tsumoto K.,
RA Caaveiro J.M.M.;
RT "The isolation of new pore-forming toxins from the sea anemone Actinia
RT fragacea provides insights into the mechanisms of actinoporin evolution.";
RL Toxins 11:0-0(2019).
CC -!- FUNCTION: Pore-forming toxin (PFT) that consists of a crown-shaped
CC octamer or nonamer that forms cation-selective hydrophilic pores of
CC about 1.5 nm (inside) and 13 nm (outside) (By similarity). It causes
CC cardiac stimulation (By similarity). Also causes hemolysis (HC(50)=0.3
CC nM) (PubMed:31295915). Interestingly, the Phe-16 is crucial for
CC hemolysis (By similarity). Pore formation is a multi-step process that
CC involves specific recognition of membrane sphingomyelin (but neither
CC cholesterol nor phosphatidylcholine) using aromatic rich region and
CC adjacent phosphocholine (POC) binding site, firm binding to the
CC membrane (mainly driven by hydrophobic interactions) accompanied by the
CC transfer of the N-terminal region to the lipid-water interface and
CC finally pore formation after oligomerization of monomers (By
CC similarity). It is probable that a dimeric form is an assembly
CC intermediate before the complete oligomerization (By similarity). The
CC formation of stable pores occurs only in vesicles composed of DOPC/SM
CC (there is no oligomerization when the PFT is treated with vesicles of
CC DOPC or SM alone) (By similarity). The transmembrane pore displays 8
CC lateral perforations, one at each subunit-subunit interface, partially
CC occupied by the acyl-chain region of a bridging lipid (By similarity).
CC Each pore contains 24 lipid molecules, firmly bound to each subunit,
CC that is, 3 lipids (L1, L2, L3, L4 and/or L5) are associated to each
CC subunit (By similarity). Lipid L1 bridges 2 subunits, whereas lipids L2
CC and L3 bind to sites at single subunit (By similarity).
CC {ECO:0000250|UniProtKB:B9W5G6, ECO:0000269|PubMed:31295915}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Temperature dependence:
CC Stable up to about 62 degrees Celsius. {ECO:0000269|PubMed:31295915};
CC -!- SUBUNIT: Octamer or nonamer in membranes. Monomer in the soluble state.
CC {ECO:0000250|UniProtKB:B9W5G6}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:31295915}.
CC Nematocyst {ECO:0000250|UniProtKB:P61914}. Target cell membrane
CC {ECO:0000250|UniProtKB:B9W5G6}. Note=Forms an alpha-helical membrane
CC channel in the prey. {ECO:0000250|UniProtKB:B9W5G6}.
CC -!- DOMAIN: The N-terminal region, before the pore is formed, is bound to
CC the lipid membrane. It partitions into the lipid-water interface and
CC stabilizes the monomeric molecule on the membrane. Finally, it
CC traverses the bilayer, thus forming the transmembrane pore.
CC {ECO:0000250|UniProtKB:P61914}.
CC -!- MASS SPECTROMETRY: Mass=19672; Mass_error=3; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:31295915};
CC -!- MISCELLANEOUS: This protein has been found to bind carbohydrates, since
CC it shows a substantial delay in elution profile in size-exclusion
CC chromatography. The carbohydrate pocket ovelaps with the lipid-binding
CC module of actinoporins. {ECO:0000250|UniProtKB:B9W5G6}.
CC -!- SIMILARITY: Belongs to the actinoporin family. Sea anemone subfamily.
CC {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; MK936900; QDM54907.1; -; mRNA.
DR SMR; A0A515MEN7; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0042151; C:nematocyst; IEA:UniProtKB-SubCell.
DR GO; GO:0046930; C:pore complex; IEA:InterPro.
DR GO; GO:0015267; F:channel activity; IEA:InterPro.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0006812; P:cation transport; IEA:InterPro.
DR GO; GO:0044179; P:hemolysis in another organism; IEA:UniProtKB-KW.
DR GO; GO:0046931; P:pore complex assembly; IEA:InterPro.
DR Gene3D; 2.60.270.20; -; 1.
DR InterPro; IPR009104; Anemon_actinoporin-like.
DR InterPro; IPR015926; Cytolysin/lectin.
DR Pfam; PF06369; Anemone_cytotox; 1.
DR SUPFAM; SSF63724; SSF63724; 1.
PE 1: Evidence at protein level;
KW Cytolysis; Direct protein sequencing; Hemolysis; Ion transport;
KW Lipid-binding; Membrane; Nematocyst; Secreted; Target cell membrane;
KW Target membrane; Toxin; Transmembrane; Transport.
FT CHAIN 1..179
FT /note="DELTA-actitoxin-Afr1c"
FT /evidence="ECO:0000305|PubMed:31295915"
FT /id="PRO_0000453823"
FT REGION 1..29
FT /note="N-terminal alpha-helix that contributes to the pore"
FT /evidence="ECO:0000250|UniProtKB:B9W5G6"
FT REGION 105..120
FT /note="Trp-rich region, which is important for the binding
FT to lipid membrane"
FT /evidence="ECO:0000250|UniProtKB:P61914"
FT MOTIF 144..146
FT /note="Cell attachment site"
FT /evidence="ECO:0000250|UniProtKB:P61914, ECO:0000255"
FT BINDING 31
FT /ligand="an N-(acyl)-sphingosylphosphocholine"
FT /ligand_id="ChEBI:CHEBI:64583"
FT /ligand_label="1"
FT /ligand_note="bridging lipid L1"
FT /note="in subunit A; in oligomeric forms only"
FT /evidence="ECO:0000250|UniProtKB:B9W5G6"
FT BINDING 51
FT /ligand="N-acetyl-D-glucosamine 6-sulfate"
FT /ligand_id="ChEBI:CHEBI:84775"
FT /evidence="ECO:0000250|UniProtKB:B9W5G6"
FT BINDING 53
FT /ligand="an N-(acyl)-sphingosylphosphocholine"
FT /ligand_id="ChEBI:CHEBI:64583"
FT /ligand_label="2"
FT /ligand_note="lipid L2"
FT /note="in monomeric and oligomeric forms"
FT /evidence="ECO:0000250|UniProtKB:B9W5G6"
FT BINDING 53
FT /ligand="N-acetyl-D-glucosamine 6-sulfate"
FT /ligand_id="ChEBI:CHEBI:84775"
FT /evidence="ECO:0000250|UniProtKB:B9W5G6"
FT BINDING 54
FT /ligand="an N-(acyl)-sphingosylphosphocholine"
FT /ligand_id="ChEBI:CHEBI:64583"
FT /ligand_label="2"
FT /ligand_note="lipid L2"
FT /note="in monomeric and oligomeric forms"
FT /evidence="ECO:0000250|UniProtKB:B9W5G6"
FT BINDING 79
FT /ligand="an N-(acyl)-sphingosylphosphocholine"
FT /ligand_id="ChEBI:CHEBI:64583"
FT /ligand_label="1"
FT /ligand_note="bridging lipid L1"
FT /note="in subunit B; in oligomeric forms only"
FT /evidence="ECO:0000250|UniProtKB:B9W5G6"
FT BINDING 85
FT /ligand="an N-(acyl)-sphingosylphosphocholine"
FT /ligand_id="ChEBI:CHEBI:64583"
FT /ligand_label="2"
FT /ligand_note="lipid L2"
FT /note="in monomeric and oligomeric forms"
FT /evidence="ECO:0000250|UniProtKB:B9W5G6"
FT BINDING 113
FT /ligand="an N-(acyl)-sphingosylphosphocholine"
FT /ligand_id="ChEBI:CHEBI:64583"
FT /ligand_label="2"
FT /ligand_note="lipid L2"
FT /note="in monomeric and oligomeric forms"
FT /evidence="ECO:0000250|UniProtKB:B9W5G6"
FT BINDING 114
FT /ligand="an N-(acyl)-sphingosylphosphocholine"
FT /ligand_id="ChEBI:CHEBI:64583"
FT /ligand_label="5"
FT /ligand_note="lipid L5"
FT /note="in monomeric and oligomeric forms"
FT /evidence="ECO:0000250|UniProtKB:B9W5G6"
FT BINDING 116
FT /ligand="an N-(acyl)-sphingosylphosphocholine"
FT /ligand_id="ChEBI:CHEBI:64583"
FT /ligand_label="3"
FT /ligand_note="lipid L3"
FT /note="in monomeric and oligomeric forms"
FT /evidence="ECO:0000250|UniProtKB:B9W5G6"
FT BINDING 133
FT /ligand="an N-(acyl)-sphingosylphosphocholine"
FT /ligand_id="ChEBI:CHEBI:64583"
FT /ligand_label="4"
FT /ligand_note="lipid L4"
FT /note="in monomeric and oligomeric forms"
FT /evidence="ECO:0000250|UniProtKB:B9W5G6"
FT BINDING 137
FT /ligand="an N-(acyl)-sphingosylphosphocholine"
FT /ligand_id="ChEBI:CHEBI:64583"
FT /ligand_label="3"
FT /ligand_note="lipid L3"
FT /note="in monomeric and oligomeric forms"
FT /evidence="ECO:0000250|UniProtKB:B9W5G6"
FT BINDING 138
FT /ligand="an N-(acyl)-sphingosylphosphocholine"
FT /ligand_id="ChEBI:CHEBI:64583"
FT /ligand_label="4"
FT /ligand_note="lipid L4"
FT /note="in monomeric and oligomeric forms"
FT /evidence="ECO:0000250|UniProtKB:B9W5G6"
FT BINDING 138
FT /ligand="N-acetyl-D-glucosamine 6-sulfate"
FT /ligand_id="ChEBI:CHEBI:84775"
FT /evidence="ECO:0000250|UniProtKB:B9W5G6"
FT BINDING 144
FT /ligand="an N-(acyl)-sphingosylphosphocholine"
FT /ligand_id="ChEBI:CHEBI:64583"
FT /ligand_label="5"
FT /ligand_note="lipid L5"
FT /note="in monomeric and oligomeric forms"
FT /evidence="ECO:0000250|UniProtKB:B9W5G6"
FT BINDING 168
FT /ligand="an N-(acyl)-sphingosylphosphocholine"
FT /ligand_id="ChEBI:CHEBI:64583"
FT /ligand_label="1"
FT /ligand_note="bridging lipid L1"
FT /note="in subunit A; in oligomeric forms only"
FT /evidence="ECO:0000250|UniProtKB:B9W5G6"
FT SITE 16
FT /note="Part of the hydrophobic cavity (in subunit A) that
FT receives Val-60 from the adjacent subunit (B); essential in
FT hemolysis, since it is critical for pore formation in
FT cholesterol-rich membrane cells (such as red blood cells)"
FT /evidence="ECO:0000250|UniProtKB:B9W5G6"
FT SITE 149
FT /note="Part of the hydrophobic cavity (in subunit A) that
FT receives Val-60 from the adjacent subunit (B)"
FT /evidence="ECO:0000250|UniProtKB:B9W5G6"
FT SITE 163
FT /note="Part of the hydrophobic cavity (in subunit A) that
FT receives Val-60 from the adjacent subunit (B)"
FT /evidence="ECO:0000250|UniProtKB:B9W5G6"
SQ SEQUENCE 179 AA; 19672 MW; BA2341AA9D3E5FF5 CRC64;
SAEVAGAIID GASLTFDVLQ TVLKALGDVS RKIAVGIDNE PGMTWTAMNT YFRSGTSDVI
LPHTVPHSKA LLYDGQKNRG PVTTGVVGVI AYAMSDGNTL AVLFSIPFDY NLYSNWWNVK
VYKGHRRADQ AMYEELYYDF SPFRGDNGWH TKSIGYGLKG RGFMNSSGKA ILQIHVNKV
