ACTS2_HETCR
ID ACTS2_HETCR Reviewed; 177 AA.
AC P0C1F8;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 16-SEP-2015, sequence version 2.
DT 03-AUG-2022, entry version 60.
DE RecName: Full=DELTA-stichotoxin-Hcr4b {ECO:0000303|PubMed:22683676};
DE Short=DELTA-SHTX-Hcr4b {ECO:0000303|PubMed:22683676};
DE AltName: Full=Cytolysin RTX-S II {ECO:0000303|PubMed:15302538};
DE Short=RTX-SII {ECO:0000303|PubMed:20692277};
OS Heteractis crispa (Leathery sea anemone) (Radianthus macrodactylus).
OC Eukaryota; Metazoa; Cnidaria; Anthozoa; Hexacorallia; Actiniaria;
OC Stichodactylidae; Heteractis.
OX NCBI_TaxID=175771;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=20692277; DOI=10.1016/j.toxicon.2010.07.011;
RA Monastyrnaya M., Leychenko E., Isaeva M., Likhatskaya G., Zelepuga E.,
RA Kostina E., Trifonov E., Nurminski E., Kozlovskaya E.;
RT "Actinoporins from the sea anemones, tropical Radianthus macrodactylus and
RT northern Oulactis orientalis: comparative analysis of structure-function
RT relationships.";
RL Toxicon 56:1299-1314(2010).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 7-147, PROTEIN SEQUENCE OF
RP 1-15, TOXIC DOSE, HEMOLYTIC ACTIVITY, AND MASS SPECTROMETRY.
RX PubMed=15302538; DOI=10.1016/j.toxicon.2004.06.006;
RA Klyshko E.V., Issaeva M.P., Monastyrnaia M.M., Il'ina A.P., Guzev K.V.,
RA Vakorina T.I., Dmitrenok P.S., Zykova T.A., Kozlovskaya E.P.;
RT "Isolation, properties and partial amino acid sequence of a new actinoporin
RT from the sea anemone Radianthus macrodactylus.";
RL Toxicon 44:315-324(2004).
RN [3]
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 [4]
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).
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 (By similarity). Preincubation with exogenous
CC sphingomyeline causes complete loss of hemolytic activity.
CC {ECO:0000250}.
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 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:0000250|UniProtKB:P61914}.
CC -!- MASS SPECTROMETRY: Mass=19280; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:15302538};
CC -!- TOXIC DOSE: LD(50) is 70 ug/kg by intraperitoneal injection into mice.
CC {ECO:0000269|PubMed:15302538}.
CC -!- MISCELLANEOUS: Hemolytic activity is 3.6 x 10(4) HU/mg.
CC -!- SIMILARITY: Belongs to the actinoporin family. Sea anemone subfamily.
CC {ECO:0000305}.
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DR AlphaFoldDB; P0C1F8; -.
DR SMR; P0C1F8; -.
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 Cytolysis; Direct protein sequencing; Hemolysis; Ion transport; Membrane;
KW Nematocyst; Secreted; Target cell membrane; Target membrane; Toxin;
KW Transmembrane; Transport.
FT CHAIN 1..177
FT /note="DELTA-stichotoxin-Hcr4b"
FT /id="PRO_0000239199"
FT REGION 3..12
FT /note="Plays an important role in the hemolytic activity"
FT /evidence="ECO:0000250|UniProtKB:P07845"
FT REGION 11..30
FT /note="N-terminal region"
FT /evidence="ECO:0000250|UniProtKB:P61914"
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 BINDING 54
FT /ligand="phosphocholine"
FT /ligand_id="ChEBI:CHEBI:295975"
FT /evidence="ECO:0000250|UniProtKB:P07845"
FT BINDING 87
FT /ligand="phosphocholine"
FT /ligand_id="ChEBI:CHEBI:295975"
FT /evidence="ECO:0000250|UniProtKB:P07845"
FT BINDING 105
FT /ligand="phosphocholine"
FT /ligand_id="ChEBI:CHEBI:295975"
FT /evidence="ECO:0000250|UniProtKB:P07845"
FT BINDING 107
FT /ligand="phosphocholine"
FT /ligand_id="ChEBI:CHEBI:295975"
FT /evidence="ECO:0000250|UniProtKB:P07845"
FT BINDING 133
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 BINDING 138
FT /ligand="phosphocholine"
FT /ligand_id="ChEBI:CHEBI:295975"
FT /evidence="ECO:0000250|UniProtKB:P07845"
FT SITE 113
FT /note="Important in the initial contact with the lipid
FT membrane"
FT /evidence="ECO:0000250|UniProtKB:P61914"
FT SITE 143
FT /note="Interacts with the lipid membrane"
FT /evidence="ECO:0000250"
SQ SEQUENCE 177 AA; 19386 MW; 5D8631E0CC44423A CRC64;
SAALAGTITL GASLGFQILD KVLGELGKVS RKIAVGVDNE SGGSWTALNA YFRSGTTDVI
LPEFVPNQKA LLYSGRKDTG PVATGAVAAF AYYMSNGHTL GVMFSVPFDY NLYSNWWDVK
IYSGKRRADQ AMYEDMYYGN PYRGDNGWHQ KNLGYGLKMK GIMTSAVEAI LEIRISR
