ACTP1_STIHL
ID ACTP1_STIHL Reviewed; 176 AA.
AC P81662; Q9N601;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1999, sequence version 1.
DT 03-AUG-2022, entry version 105.
DE RecName: Full=DELTA-stichotoxin-She4a {ECO:0000303|PubMed:22683676};
DE Short=DELTA-SHTX-She4a {ECO:0000303|PubMed:22683676};
DE AltName: Full=Cytolysin sticholysin I {ECO:0000303|PubMed:11306138};
DE Short=St I {ECO:0000303|PubMed:10978735};
DE Short=St-I {ECO:0000303|PubMed:11306138};
DE AltName: Full=Sticholysin I {ECO:0000303|PubMed:19636934};
DE Short=Stn I {ECO:0000303|PubMed:19636934};
DE AltName: Full=Sticholysin-1 {ECO:0000305};
DE Short=STCH {ECO:0000303|Ref.2};
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, 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 [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 9-176.
RA de los Rios V., Onaderra M., Martinez del Pozo A., Mancheno J.M.,
RA Gavilanes J.G.;
RT "Cloning and expression of sticholysins from sea aemone, Stichodactyla
RT helianthus.";
RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
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 [4]
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 [5]
RP MUTAGENESIS OF GLU-16.
RX PubMed=17067649; DOI=10.1016/j.toxicon.2006.09.004;
RA Pazos F., Valle A., Martinez D., Ramirez A., Calderon L., Pupo A.,
RA Tejuca M., Morera V., Campos J., Fando R., Dyszy F., Schreier S.,
RA Horjales E., Alvarez C., Lanio M.E., Lissi E.;
RT "Structural and functional characterization of a recombinant sticholysin I
RT (rSt I) from the sea anemone Stichodactyla helianthus.";
RL Toxicon 48:1083-1094(2006).
RN [6]
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 [7]
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 [8]
RP STRUCTURE BY NMR.
RX PubMed=19636934; DOI=10.1007/s12104-008-9127-3;
RA Castrillo I., Alegre-Cebollada J., del Pozo A.M., Gavilanes J.G.,
RA Santoro J., Bruix M.;
RT "1H, 13C, and 15N NMR assignments of the actinoporin Sticholysin I.";
RL Biomol. NMR. Assign. 3:5-7(2009).
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. Monomer, in
CC soluble state. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted. Nematocyst. Target cell membrane
CC {ECO:0000250}. Note=Forms an alpha-helical membrane channel in the
CC prey. {ECO:0000250}.
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=19392; Mass_error=2; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:11306138};
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; AJ009931; CAC00651.2; -; Genomic_DNA.
DR PDB; 2KS4; NMR; -; A=1-176.
DR PDBsum; 2KS4; -.
DR AlphaFoldDB; P81662; -.
DR BMRB; P81662; -.
DR SMR; P81662; -.
DR TCDB; 1.C.38.1.2; the pore-forming equinatoxin (equinatoxin) family.
DR EvolutionaryTrace; P81662; -.
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; Cytolysis; Direct protein sequencing; Hemolysis;
KW Ion transport; Membrane; Nematocyst; Secreted; Target cell membrane;
KW Target membrane; Toxin; Transmembrane; Transport.
FT CHAIN 1..176
FT /note="DELTA-stichotoxin-She4a"
FT /evidence="ECO:0000269|PubMed:11306138"
FT /id="PRO_0000221537"
FT REGION 2..11
FT /note="Plays an important role in the hemolytic activity"
FT /evidence="ECO:0000250|UniProtKB:P07845"
FT REGION 10..29
FT /note="N-terminal region"
FT /evidence="ECO:0000250|UniProtKB:P61914"
FT REGION 104..119
FT /note="Trp-rich region, which is important for the binding
FT to lipid membrane"
FT /evidence="ECO:0000250|UniProtKB:P61914"
FT MOTIF 142..144
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT BINDING 53
FT /ligand="phosphocholine"
FT /ligand_id="ChEBI:CHEBI:295975"
FT /evidence="ECO:0000250|UniProtKB:P07845"
FT BINDING 86
FT /ligand="phosphocholine"
FT /ligand_id="ChEBI:CHEBI:295975"
FT /evidence="ECO:0000250|UniProtKB:P07845"
FT BINDING 104
FT /ligand="phosphocholine"
FT /ligand_id="ChEBI:CHEBI:295975"
FT /evidence="ECO:0000250|UniProtKB:P07845"
FT BINDING 106
FT /ligand="phosphocholine"
FT /ligand_id="ChEBI:CHEBI:295975"
FT /evidence="ECO:0000250|UniProtKB:P07845"
FT BINDING 132
FT /ligand="phosphocholine"
FT /ligand_id="ChEBI:CHEBI:295975"
FT /evidence="ECO:0000250|UniProtKB:P07845"
FT BINDING 136
FT /ligand="phosphocholine"
FT /ligand_id="ChEBI:CHEBI:295975"
FT /evidence="ECO:0000250|UniProtKB:P07845"
FT BINDING 137
FT /ligand="phosphocholine"
FT /ligand_id="ChEBI:CHEBI:295975"
FT /evidence="ECO:0000250|UniProtKB:P07845"
FT SITE 111
FT /note="Important in the initial contact with the lipid
FT membrane"
FT /evidence="ECO:0000250|UniProtKB:P61914"
FT SITE 112
FT /note="Important in the initial contact with the lipid
FT membrane"
FT /evidence="ECO:0000250|UniProtKB:P61914"
FT SITE 142
FT /note="Interacts with the lipid membrane"
FT /evidence="ECO:0000250"
FT MUTAGEN 16
FT /note="E->Q: Shows larger hemolytic activity in human red
FT blood cells, but no change in capacity to form pore."
FT /evidence="ECO:0000269|PubMed:17067649"
FT TURN 10..12
FT /evidence="ECO:0007829|PDB:2KS4"
FT HELIX 15..24
FT /evidence="ECO:0007829|PDB:2KS4"
FT STRAND 28..38
FT /evidence="ECO:0007829|PDB:2KS4"
FT STRAND 40..42
FT /evidence="ECO:0007829|PDB:2KS4"
FT STRAND 44..50
FT /evidence="ECO:0007829|PDB:2KS4"
FT STRAND 52..54
FT /evidence="ECO:0007829|PDB:2KS4"
FT STRAND 62..64
FT /evidence="ECO:0007829|PDB:2KS4"
FT STRAND 68..75
FT /evidence="ECO:0007829|PDB:2KS4"
FT STRAND 77..82
FT /evidence="ECO:0007829|PDB:2KS4"
FT STRAND 84..93
FT /evidence="ECO:0007829|PDB:2KS4"
FT TURN 94..96
FT /evidence="ECO:0007829|PDB:2KS4"
FT STRAND 97..105
FT /evidence="ECO:0007829|PDB:2KS4"
FT TURN 109..111
FT /evidence="ECO:0007829|PDB:2KS4"
FT STRAND 117..124
FT /evidence="ECO:0007829|PDB:2KS4"
FT HELIX 129..136
FT /evidence="ECO:0007829|PDB:2KS4"
FT TURN 153..155
FT /evidence="ECO:0007829|PDB:2KS4"
FT STRAND 156..161
FT /evidence="ECO:0007829|PDB:2KS4"
FT STRAND 164..167
FT /evidence="ECO:0007829|PDB:2KS4"
FT STRAND 170..174
FT /evidence="ECO:0007829|PDB:2KS4"
SQ SEQUENCE 176 AA; 19391 MW; 4879B6C5A3547B62 CRC64;
SELAGTIIDG ASLTFEVLDK VLGELGKVSR KIAVGIDNES GGTWTALNAY FRSGTTDVIL
PEVVPNTKAL LYSGRKSSGP VATGAVAAFA YYMSNGNTLG VMFSVPFDYN WYSNWWDVKI
YPGKRRADQG MYEDMYYGNP YRGDNGWYQK NLGYGLRMKG IMTSAGEAKM QIKISR
