ACTP2_STIHL
ID ACTP2_STIHL Reviewed; 175 AA.
AC P07845;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=DELTA-stichotoxin-She4b {ECO:0000303|PubMed:22683676};
DE Short=DELTA-SHTX-She4b {ECO:0000303|PubMed:22683676};
DE AltName: Full=Cytolysin III {ECO:0000303|PubMed:6133872};
DE AltName: Full=Sticholysin II {ECO:0000303|PubMed:11306138};
DE Short=St II {ECO:0000303|PubMed:10978735, ECO:0000303|PubMed:11478962};
DE Short=St-II {ECO:0000303|PubMed:11306138};
DE Short=StII;
DE Short=StnII {ECO:0000303|PubMed:15388326, ECO:0000303|PubMed:17573423};
DE AltName: Full=Sticholysin-2 {ECO:0000305};
DE Short=STCH2 {ECO:0000303|Ref.3};
OS Stichodactyla helianthus (Sun anemone) (Stoichactis helianthus).
OC Eukaryota; Metazoa; Cnidaria; Anthozoa; Hexacorallia; Actiniaria;
OC Stichodactylidae; Stichodactyla.
OX NCBI_TaxID=6123;
RN [1]
RP PROTEIN SEQUENCE.
RX PubMed=6133872; DOI=10.1016/s0021-9258(20)81929-2;
RA Blumenthal K.M., Kem W.R.;
RT "Primary structure of Stoichactis helianthus cytolysin III.";
RL J. Biol. Chem. 258:5574-5581(1983).
RN [2]
RP PROTEIN SEQUENCE, SEQUENCE REVISION, AND MASS SPECTROMETRY.
RX PubMed=11306138; DOI=10.1016/s0041-0101(00)00247-6;
RA Huerta V., Morera V., Guanche Y., Chinea G., Gonzalez L.J., Betancourt L.,
RA Martinez D., Alvarez C., Lanio M.E., Besada V.;
RT "Primary structure of two cytolysin isoforms from Stichodactyla helianthus
RT differing in their hemolytic activity.";
RL Toxicon 39:1253-1256(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA de los Rios V., Onaderra M., Martinez del Pozo A., Mancheno J.,
RA Gavilanes J.G.;
RT "Cloning and expression of sticholysin II from sea anemone, Stichodactyla
RT helianthus.";
RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION.
RX PubMed=10978735; DOI=10.1016/s0041-0101(00)00106-9;
RA Lanio M.E., Morera V., Alvarez C., Tejuca M., Gomez T., Pazos F.,
RA Besada V., Martinez D., Huerta V., Padron G., Chavez M.A.;
RT "Purification and characterization of two hemolysins from Stichodactyla
RT helianthus.";
RL Toxicon 39:187-194(2001).
RN [5]
RP FUNCTION.
RX PubMed=11478962; DOI=10.1016/s0041-0101(01)00127-1;
RA Martinez D., Campos A.M., Pazos F., Alvarez C., Lanio M.E., Casallanovo F.,
RA Schreier S., Salinas R.K., Vergara C., Lissi E.;
RT "Properties of St I and St II, two isotoxins isolated from Stichodactyla
RT helianthus: a comparison.";
RL Toxicon 39:1547-1560(2001).
RN [6]
RP MUTAGENESIS OF LYS-19; PHE-106 AND TYR-111.
RX PubMed=15388326; DOI=10.1016/j.febslet.2004.08.031;
RA Alegre-Cebollada J., Lacadena V., Onaderra M., Mancheno J.M.,
RA Gavilanes J.G., del Pozo A.M.;
RT "Phenotypic selection and characterization of randomly produced non-
RT haemolytic mutants of the toxic sea anemone protein sticholysin II.";
RL FEBS Lett. 575:14-18(2004).
RN [7]
RP REGION IMPORTANT FOR HEMOLYTIC ACTIVITY.
RX PubMed=16170802; DOI=10.1002/bip.20374;
RA Casallanovo F., de Oliveira F.J.F., de Souza F.C., Ros U., Martinez Y.,
RA Penton D., Tejuca M., Martinez D., Pazos F., Pertinhez T.A., Spisni A.,
RA Cilli E.M., Lanio M.E., Alvarez C., Schreier S.;
RT "Model peptides mimic the structure and function of the N-terminus of the
RT pore-forming toxin sticholysin II.";
RL Biopolymers 84:169-180(2006).
RN [8]
RP PORE FORMATION, AND ALPHA-HELICAL STRUCTURE.
RX PubMed=17573423; DOI=10.1529/biophysj.106.102566;
RA Alegre-Cebollada J., Martinez del Pozo A., Gavilanes J.G., Goormaghtigh E.;
RT "Infrared spectroscopy study on the conformational changes leading to pore
RT formation of the toxin sticholysin II.";
RL Biophys. J. 93:3191-3201(2007).
RN [9]
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 [10]
RP SUBUNIT, AND TISSUE SPECIFICITY.
RX PubMed=16432881; DOI=10.1002/jez.a.256;
RA Basulto A., Perez V.M., Noa Y., Varela C., Otero A.J., Pico M.C.;
RT "Immunohistochemical targeting of sea anemone cytolysins on tentacles,
RT mesenteric filaments and isolated nematocysts of Stichodactyla
RT helianthus.";
RL J. Exp. Zool. A Comp. Exp. Biol. 305:253-258(2006).
RN [11]
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 [12] {ECO:0000312|PDB:1GWY, ECO:0000312|PDB:1O71, ECO:0000312|PDB:1O72}
RP X-RAY CRYSTALLOGRAPHY (1.71 ANGSTROMS), PHOSPHOCHOLINE-BINDING SITES, AND
RP SUBUNIT.
RX PubMed=14604522; DOI=10.1016/j.str.2003.09.019;
RA Mancheno J.M., Martin-Benito J., Martinez-Ripoll M., Gavilanes J.G.,
RA Hermoso J.A.;
RT "Crystal and electron microscopy structures of sticholysin II actinoporin
RT reveal insights into the mechanism of membrane pore formation.";
RL Structure 11:1319-1328(2003).
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. {ECO:0000269|PubMed:10978735,
CC ECO:0000269|PubMed:11478962}.
CC -!- SUBUNIT: Tetramer in the presence of a lipidic interface
CC (PubMed:14604522). Monomer, in soluble state (PubMed:14604522).
CC {ECO:0000269|PubMed:14604522}.
CC -!- INTERACTION:
CC P07845; P07845: -; NbExp=2; IntAct=EBI-9084009, EBI-9084009;
CC -!- SUBCELLULAR LOCATION: Secreted. Nematocyst
CC {ECO:0000269|PubMed:16432881}. Target cell membrane. Note=Forms an
CC alpha-helical membrane channel in the prey.
CC -!- TISSUE SPECIFICITY: Expressed in tentacles and mesenteric filaments.
CC {ECO:0000269|PubMed:16432881}.
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=19293; Mass_error=2; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:11306138};
CC -!- SIMILARITY: Belongs to the actinoporin family. Sea anemone subfamily.
CC {ECO:0000305}.
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DR EMBL; AJ005038; CAC20912.1; -; mRNA.
DR PDB; 1GWY; X-ray; 1.71 A; A/B=1-175.
DR PDB; 1O71; X-ray; 2.26 A; A/B=1-175.
DR PDB; 1O72; X-ray; 2.41 A; A/B=1-175.
DR PDB; 2L2B; NMR; -; A=1-175.
DR PDB; 2L38; NMR; -; A=1-175.
DR PDBsum; 1GWY; -.
DR PDBsum; 1O71; -.
DR PDBsum; 1O72; -.
DR PDBsum; 2L2B; -.
DR PDBsum; 2L38; -.
DR AlphaFoldDB; P07845; -.
DR BMRB; P07845; -.
DR SMR; P07845; -.
DR MINT; P07845; -.
DR EvolutionaryTrace; P07845; -.
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:0042802; F:identical protein binding; IPI:IntAct.
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; Cytolysis; Direct protein sequencing; Hemolysis;
KW Ion transport; Membrane; Nematocyst; Secreted; Target cell membrane;
KW Target membrane; Toxin; Transmembrane; Transport.
FT CHAIN 1..175
FT /note="DELTA-stichotoxin-She4b"
FT /evidence="ECO:0000269|PubMed:11306138,
FT ECO:0000269|PubMed:6133872"
FT /id="PRO_0000221538"
FT REGION 1..10
FT /note="Plays an important role in the hemolytic activity"
FT /evidence="ECO:0000269|PubMed:16170802"
FT REGION 9..28
FT /note="N-terminal region"
FT /evidence="ECO:0000250|UniProtKB:P61914"
FT REGION 103..118
FT /note="Trp-rich region, which is important for the binding
FT to lipid membrane"
FT /evidence="ECO:0000250|UniProtKB:P61914"
FT BINDING 52
FT /ligand="phosphocholine"
FT /ligand_id="ChEBI:CHEBI:295975"
FT /evidence="ECO:0000269|PubMed:14604522"
FT BINDING 85
FT /ligand="phosphocholine"
FT /ligand_id="ChEBI:CHEBI:295975"
FT /evidence="ECO:0000269|PubMed:14604522"
FT BINDING 103
FT /ligand="phosphocholine"
FT /ligand_id="ChEBI:CHEBI:295975"
FT /evidence="ECO:0000269|PubMed:14604522"
FT BINDING 105
FT /ligand="phosphocholine"
FT /ligand_id="ChEBI:CHEBI:295975"
FT /evidence="ECO:0000269|PubMed:14604522"
FT BINDING 131
FT /ligand="phosphocholine"
FT /ligand_id="ChEBI:CHEBI:295975"
FT /evidence="ECO:0000269|PubMed:14604522"
FT BINDING 135
FT /ligand="phosphocholine"
FT /ligand_id="ChEBI:CHEBI:295975"
FT /evidence="ECO:0000269|PubMed:14604522"
FT BINDING 136
FT /ligand="phosphocholine"
FT /ligand_id="ChEBI:CHEBI:295975"
FT /evidence="ECO:0000269|PubMed:14604522"
FT SITE 110
FT /note="Important in the initial contact with the lipid
FT membrane"
FT /evidence="ECO:0000250|UniProtKB:P61914"
FT SITE 111
FT /note="Important in the initial contact with the lipid
FT membrane"
FT /evidence="ECO:0000250|UniProtKB:P61914"
FT SITE 141
FT /note="Interacts with the lipid membrane"
FT /evidence="ECO:0000250"
FT MUTAGEN 19
FT /note="K->E: Reduction of hemolytic activity."
FT /evidence="ECO:0000269|PubMed:15388326"
FT MUTAGEN 106
FT /note="F->L: Reduction of hemolytic activity."
FT /evidence="ECO:0000269|PubMed:15388326"
FT MUTAGEN 111
FT /note="Y->N: Reduction of hemolytic activity."
FT /evidence="ECO:0000269|PubMed:15388326"
FT STRAND 6..8
FT /evidence="ECO:0007829|PDB:1GWY"
FT HELIX 9..11
FT /evidence="ECO:0007829|PDB:1GWY"
FT HELIX 14..23
FT /evidence="ECO:0007829|PDB:1GWY"
FT STRAND 28..41
FT /evidence="ECO:0007829|PDB:1GWY"
FT STRAND 43..54
FT /evidence="ECO:0007829|PDB:1GWY"
FT STRAND 61..63
FT /evidence="ECO:0007829|PDB:1GWY"
FT STRAND 67..74
FT /evidence="ECO:0007829|PDB:1GWY"
FT STRAND 77..79
FT /evidence="ECO:0007829|PDB:1GWY"
FT STRAND 81..83
FT /evidence="ECO:0007829|PDB:2L38"
FT STRAND 84..92
FT /evidence="ECO:0007829|PDB:1GWY"
FT STRAND 95..104
FT /evidence="ECO:0007829|PDB:1GWY"
FT TURN 108..110
FT /evidence="ECO:0007829|PDB:1O71"
FT STRAND 114..122
FT /evidence="ECO:0007829|PDB:1GWY"
FT HELIX 128..135
FT /evidence="ECO:0007829|PDB:1GWY"
FT STRAND 146..152
FT /evidence="ECO:0007829|PDB:1GWY"
FT STRAND 155..161
FT /evidence="ECO:0007829|PDB:1GWY"
FT STRAND 163..174
FT /evidence="ECO:0007829|PDB:1GWY"
SQ SEQUENCE 175 AA; 19283 MW; B50566B02D351B1D CRC64;
ALAGTIIAGA SLTFQVLDKV LEELGKVSRK IAVGIDNESG GTWTALNAYF RSGTTDVILP
EFVPNTKALL YSGRKDTGPV ATGAVAAFAY YMSSGNTLGV MFSVPFDYNW YSNWWDVKIY
SGKRRADQGM YEDLYYGNPY RGDNGWHEKN LGYGLRMKGI MTSAGEAKMQ IKISR
