ACTP2_ACTEQ
ID ACTP2_ACTEQ Reviewed; 214 AA.
AC P61914; P17723; Q16993; Q9TWV2; Q9TWV3;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2004, sequence version 1.
DT 03-AUG-2022, entry version 97.
DE RecName: Full=DELTA-actitoxin-Aeq1a {ECO:0000303|PubMed:22683676};
DE Short=DELTA-AITX-Aeq1a {ECO:0000303|PubMed:22683676};
DE AltName: Full=Equinatoxin II {ECO:0000303|PubMed:8645323};
DE Short=EqT II {ECO:0000303|PubMed:7912550};
DE Short=EqTII {ECO:0000303|PubMed:8645323};
DE AltName: Full=Equinatoxin-2 {ECO:0000305};
DE Flags: Precursor;
OS Actinia equina (Beadlet anemone).
OC Eukaryota; Metazoa; Cnidaria; Anthozoa; Hexacorallia; Actiniaria;
OC Actiniidae; Actinia.
OX NCBI_TaxID=6106;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8645323; DOI=10.1006/bbrc.1996.0391;
RA Anderluh G., Pungercar J., Strukelj B., Macek P., Gubensek F.;
RT "Cloning, sequencing, and expression of equinatoxin II.";
RL Biochem. Biophys. Res. Commun. 220:437-442(1996).
RN [2]
RP PROTEIN SEQUENCE OF 36-214, AND CIRCULAR DICHROISM ANALYSIS.
RX PubMed=7912550; DOI=10.1016/0005-2736(94)90119-8;
RA Belmonte G., Menestrina G., Pederzolli C., Krizaj I., Gubensek F., Turk T.,
RA Macek P.;
RT "Primary and secondary structure of a pore-forming toxin from the sea
RT anemone, Actinia equina L., and its association with lipid vesicles.";
RL Biochim. Biophys. Acta 1192:197-204(1994).
RN [3]
RP PROTEIN SEQUENCE OF 36-80; 168-197 AND 200-214.
RA Ferlan I., Jackson K.W.;
RT "Partial amino acid sequence of equinatoxin.";
RL Toxicon 21 Suppl. 3:141-144(1983).
RN [4]
RP PROTEIN SEQUENCE OF 105-118 AND 168-183.
RX PubMed=1361161; DOI=10.1248/cpb.40.2873;
RA Komatsu S., Furukawa K., Abe K., Hirano H., Ueda M.;
RT "Isolation and characterization of equinatoxins from the sea anemone
RT Actinia equina L.";
RL Chem. Pharm. Bull. 40:2873-2875(1992).
RN [5]
RP AMINO-ACID COMPOSITION, AND TOXIC DOSE.
RX PubMed=2903587; DOI=10.1016/0041-0101(88)90183-3;
RA Macek P., Lebez D.;
RT "Isolation and characterization of three lethal and hemolytic toxins from
RT the sea anemone Actinia equina L.";
RL Toxicon 26:441-451(1988).
RN [6]
RP SPHINGOMYELIN-BINDING.
RX PubMed=7679444; DOI=10.1007/bf02258530;
RA Belmonte G., Pederzolli C., Macek P., Menestrina G.;
RT "Pore formation by the sea anemone cytolysin equinatoxin II in red blood
RT cells and model lipid membranes.";
RL J. Membr. Biol. 131:11-22(1993).
RN [7]
RP MUTAGENESIS, SITE ARG-179 AND SER-195, AND DOMAINS N-TERMINAL AND TRP-RICH.
RX PubMed=10429196; DOI=10.1046/j.1432-1327.1999.00477.x;
RA Anderluh G., Barlic A., Podlesek Z., Macek P., Pungercar J., Gubensek F.,
RA Zecchini M.L., Serra M.D., Menestrina G.;
RT "Cysteine-scanning mutagenesis of an eukaryotic pore-forming toxin from sea
RT anemone: topology in lipid membranes.";
RL Eur. J. Biochem. 263:128-136(1999).
RN [8]
RP MUTAGENESIS OF TRP-80; 151-TRP-TRP-152 AND TRP-184, AND SITE INVOLVED IN
RP THE INITIAL CONTACT WITH THE MEMBRANE.
RX PubMed=10657261; DOI=10.1042/bj3460223;
RA Malovrh P., Barlic A., Podlesek Z., Macek P., Menestrina G., Anderluh G.;
RT "Structure-function studies of tryptophan mutants of equinatoxin II, a sea
RT anemone pore-forming protein.";
RL Biochem. J. 346:223-232(2000).
RN [9]
RP TWO STEPS FOR PORE FORMATION, AND SITE INVOLVED IN THE INITIAL CONTACT WITH
RP THE MEMBRANE.
RX PubMed=12198118; DOI=10.1074/jbc.m204625200;
RA Hong Q., Gutierrez-Aguirre I., Barlic A., Malovrh P., Kristan K.,
RA Podlesek Z., Macek P., Turk D., Gonzalez-Manas J.M., Lakey J.H.,
RA Anderluh G.;
RT "Two-step membrane binding by Equinatoxin II, a pore-forming toxin from the
RT sea anemone, involves an exposed aromatic cluster and a flexible helix.";
RL J. Biol. Chem. 277:41916-41924(2002).
RN [10]
RP TOPOLOGY OF N-TERMINAL REGION IN TWO STEPS OF PORE FORMATION.
RX PubMed=12676945; DOI=10.1074/jbc.m300622200;
RA Malovrh P., Viero G., Serra M.D., Podlesek Z., Lakey J.H., Macek P.,
RA Menestrina G., Anderluh G.;
RT "A novel mechanism of pore formation: membrane penetration by the N-
RT terminal amphipathic region of equinatoxin.";
RL J. Biol. Chem. 278:22678-22685(2003).
RN [11]
RP SPHINGOMYELIN-BINDING.
RX PubMed=12668447; DOI=10.1016/s0006-3495(03)75044-9;
RA Bonev B.B., Lam Y.H., Anderluh G., Watts A., Norton R.S., Separovic F.;
RT "Effects of the eukaryotic pore-forming cytolysin Equinatoxin II on lipid
RT membranes and the role of sphingomyelin.";
RL Biophys. J. 84:2382-2392(2003).
RN [12]
RP SPHINGOMYELIN-BINDING, MUTAGENESIS OF TRP-147 AND TYR-148, SITES INVOLVED
RP IN THE INITIAL BINDING TO THE LIPID MEMBRANE, AND HYDROPHOBIC INTERACTION.
RX PubMed=18442982; DOI=10.1074/jbc.m708747200;
RA Bakrac B., Gutierrez-Aguirre I., Podlesek Z., Sonnen A.F.-P.,
RA Gilbert R.J.C., Macek P., Lakey J.H., Anderluh G.;
RT "Molecular determinants of sphingomyelin specificity of a eukaryotic pore-
RT forming toxin.";
RL J. Biol. Chem. 283:18665-18677(2008).
RN [13]
RP REVIEW.
RX PubMed=19268680; DOI=10.1016/j.toxicon.2009.02.026;
RA Kristan K.C., Viero G., Dalla Serra M., Macek P., Anderluh G.;
RT "Molecular mechanism of pore formation by actinoporins.";
RL Toxicon 54:1125-1134(2009).
RN [14]
RP NOMENCLATURE.
RX PubMed=22683676; DOI=10.1016/j.toxicon.2012.05.020;
RA Oliveira J.S., Fuentes-Silva D., King G.F.;
RT "Development of a rational nomenclature for naming peptide and protein
RT toxins from sea anemones.";
RL Toxicon 60:539-550(2012).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 40-214.
RX PubMed=11525171; DOI=10.1016/s0969-2126(01)00592-5;
RA Athanasiadis A., Anderluh G., Macek P., Turk D.;
RT "Crystal structure of the soluble form of equinatoxin II, a pore-forming
RT toxin from the sea anemone Actinia equina.";
RL Structure 9:341-346(2001).
RN [16]
RP STRUCTURE BY NMR OF 36-214.
RX PubMed=11827489; DOI=10.1006/jmbi.2001.5321;
RA Hinds M.G., Zhang W., Anderluh G., Hansen P.E., Norton R.S.;
RT "Solution structure of the eukaryotic pore-forming cytolysin equinatoxin
RT II: implications for pore formation.";
RL J. Mol. Biol. 315:1219-1229(2002).
CC -!- FUNCTION: Pore-forming protein that forms cations-selective hydrophilic
CC pores of around 1 nm and causes cardiac stimulation and hemolysis. Pore
CC formation is a multi-step process that involves specific recognition of
CC membrane sphingomyelin (but neither cholesterol nor
CC phosphatidylcholine) using aromatic rich region and adjacent
CC phosphocholine (POC) binding site, firm binding to the membrane (mainly
CC driven by hydrophobic interactions) accompanied by the transfer of the
CC N-terminal region to the lipid-water interface and finally pore
CC formation after oligomerization of monomers. Cytolytic effects include
CC red blood cells hemolysis, platelet aggregation and lysis, cytotoxic
CC and cytostatic effects on fibroblasts. Lethality in mammals has been
CC ascribed to severe vasospasm of coronary vessels, cardiac arrhythmia,
CC and inotropic effects.
CC -!- SUBUNIT: Tetramer in the presence of a lipidic interface. Monomer, in
CC soluble state.
CC -!- SUBCELLULAR LOCATION: Secreted. Nematocyst. Target cell membrane.
CC Note=Forms an alpha-helical membrane channel in the prey.
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:0000269|PubMed:10429196}.
CC -!- TOXIC DOSE: LD(50) is 35 ug/kg by intravenous injection into mice.
CC {ECO:0000269|PubMed:2903587}.
CC -!- SIMILARITY: Belongs to the actinoporin family. Sea anemone subfamily.
CC {ECO:0000305}.
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DR EMBL; U41661; AAC47005.1; -; mRNA.
DR PIR; JC4682; JC4682.
DR PDB; 1IAZ; X-ray; 1.90 A; A/B=36-214.
DR PDB; 1KD6; NMR; -; A=36-214.
DR PDB; 1TZQ; X-ray; 2.30 A; A=40-214.
DR PDBsum; 1IAZ; -.
DR PDBsum; 1KD6; -.
DR PDBsum; 1TZQ; -.
DR AlphaFoldDB; P61914; -.
DR BMRB; P61914; -.
DR SMR; P61914; -.
DR EnsemblMetazoa; EGACTEQ4350043623-RA; EGACTEQ4350043623-PA; EGACTEQ4350043623.
DR EvolutionaryTrace; P61914; -.
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: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 3D-structure; Cleavage on pair of basic residues; Cytolysis;
KW Direct protein sequencing; Hemolysis; Ion transport; Membrane; Nematocyst;
KW Secreted; Signal; Target cell membrane; Target membrane; Toxin;
KW Transmembrane; Transport.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT PROPEP 20..35
FT /evidence="ECO:0000269|PubMed:7912550, ECO:0000269|Ref.3"
FT /id="PRO_0000034830"
FT CHAIN 36..214
FT /note="DELTA-actitoxin-Aeq1a"
FT /evidence="ECO:0000269|PubMed:7912550"
FT /id="PRO_0000034831"
FT REGION 38..47
FT /note="Plays an important role in the hemolytic activity"
FT /evidence="ECO:0000250|UniProtKB:P07845"
FT REGION 46..65
FT /note="N-terminal region"
FT /evidence="ECO:0000269|PubMed:10429196"
FT REGION 140..155
FT /note="Trp-rich region, which is important for the binding
FT to lipid membrane"
FT /evidence="ECO:0000269|PubMed:10429196"
FT MOTIF 179..181
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT BINDING 89
FT /ligand="phosphocholine"
FT /ligand_id="ChEBI:CHEBI:295975"
FT /evidence="ECO:0000250|UniProtKB:P07845"
FT BINDING 122
FT /ligand="phosphocholine"
FT /ligand_id="ChEBI:CHEBI:295975"
FT /evidence="ECO:0000250|UniProtKB:P07845"
FT BINDING 140
FT /ligand="phosphocholine"
FT /ligand_id="ChEBI:CHEBI:295975"
FT /evidence="ECO:0000250|UniProtKB:P07845"
FT BINDING 142
FT /ligand="phosphocholine"
FT /ligand_id="ChEBI:CHEBI:295975"
FT /evidence="ECO:0000250|UniProtKB:P07845"
FT BINDING 168
FT /ligand="phosphocholine"
FT /ligand_id="ChEBI:CHEBI:295975"
FT /evidence="ECO:0000250|UniProtKB:P07845"
FT BINDING 172
FT /ligand="phosphocholine"
FT /ligand_id="ChEBI:CHEBI:295975"
FT /evidence="ECO:0000250|UniProtKB:P07845"
FT BINDING 173
FT /ligand="phosphocholine"
FT /ligand_id="ChEBI:CHEBI:295975"
FT /evidence="ECO:0000250|UniProtKB:P07845"
FT SITE 147
FT /note="Important in the initial contact with the lipid
FT membrane"
FT /evidence="ECO:0000269|PubMed:18442982"
FT SITE 148
FT /note="Important in the initial contact with the lipid
FT membrane"
FT /evidence="ECO:0000269|PubMed:18442982"
FT SITE 179
FT /note="Interacts with the lipid membrane"
FT /evidence="ECO:0000269|PubMed:18442982"
FT SITE 195
FT /note="Interacts with the lipid membrane"
FT /evidence="ECO:0000269|PubMed:18442982"
FT VARIANT 116
FT /note="P -> D"
FT MUTAGEN 80
FT /note="W->F: Expressed only 7% of the wild-type hemolytic
FT activity."
FT /evidence="ECO:0000269|PubMed:10657261"
FT MUTAGEN 147
FT /note="W->A: Inhibition of direct binding of
FT sphingomyelin."
FT /evidence="ECO:0000269|PubMed:18442982"
FT MUTAGEN 148
FT /note="Y->A: Inhibition of direct binding of
FT sphingomyelin."
FT /evidence="ECO:0000269|PubMed:18442982"
FT MUTAGEN 151..152
FT /note="WW->FF: Expressed only 31% of the wild-type
FT hemolytic activity."
FT /evidence="ECO:0000269|PubMed:10657261"
FT MUTAGEN 184
FT /note="W->F: Expressed only 2% of the wild-type hemolytic
FT activity."
FT /evidence="ECO:0000269|PubMed:10657261"
FT STRAND 43..45
FT /evidence="ECO:0007829|PDB:1IAZ"
FT HELIX 46..48
FT /evidence="ECO:0007829|PDB:1IAZ"
FT HELIX 51..60
FT /evidence="ECO:0007829|PDB:1IAZ"
FT STRAND 65..78
FT /evidence="ECO:0007829|PDB:1IAZ"
FT STRAND 80..89
FT /evidence="ECO:0007829|PDB:1IAZ"
FT STRAND 98..100
FT /evidence="ECO:0007829|PDB:1IAZ"
FT STRAND 104..111
FT /evidence="ECO:0007829|PDB:1IAZ"
FT STRAND 114..116
FT /evidence="ECO:0007829|PDB:1IAZ"
FT STRAND 121..129
FT /evidence="ECO:0007829|PDB:1IAZ"
FT STRAND 134..141
FT /evidence="ECO:0007829|PDB:1IAZ"
FT TURN 145..147
FT /evidence="ECO:0007829|PDB:1IAZ"
FT STRAND 151..159
FT /evidence="ECO:0007829|PDB:1IAZ"
FT HELIX 165..173
FT /evidence="ECO:0007829|PDB:1IAZ"
FT STRAND 181..190
FT /evidence="ECO:0007829|PDB:1IAZ"
FT STRAND 193..199
FT /evidence="ECO:0007829|PDB:1IAZ"
FT STRAND 201..213
FT /evidence="ECO:0007829|PDB:1IAZ"
SQ SEQUENCE 214 AA; 23796 MW; 182AD60801E41DF4 CRC64;
MSRLIIVFIV VTMICSATAL PSKKIIDEDE EDEKRSADVA GAVIDGASLS FDILKTVLEA
LGNVKRKIAV GVDNESGKTW TALNTYFRSG TSDIVLPHKV PHGKALLYNG QKDRGPVATG
AVGVLAYLMS DGNTLAVLFS VPYDYNWYSN WWNVRIYKGK RRADQRMYEE LYYNLSPFRG
DNGWHTRNLG YGLKSRGFMN SSGHAILEIH VSKA
