ACTPA_HETCR
ID ACTPA_HETCR Reviewed; 175 AA.
AC P58691; Q5I4H2;
DT 31-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 2.
DT 03-AUG-2022, entry version 85.
DE RecName: Full=DELTA-stichotoxin-Hcr4a {ECO:0000303|PubMed:22683676};
DE Short=DELTA-SHTX-Hcr4a {ECO:0000303|PubMed:22683676};
DE AltName: Full=Cytolysin RTX-A {ECO:0000303|PubMed:10645476};
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] OF 5-175, AND HEMOLYTIC ACTIVITY.
RX PubMed=16530241; DOI=10.1016/j.toxicon.2005.12.014;
RA Il'ina A.P., Lipkin A., Barsova E., Issaeva M., Leychenko E., Guzev K.,
RA Monastyrnaia M.M., Lukyanov S., Kozlovskaya E.;
RT "Amino acid sequence of RTX-A's isoform actinoporin from the sea anemone,
RT Radianthus macrodactylus.";
RL Toxicon 47:517-520(2006).
RN [2]
RP PROTEIN SEQUENCE OF 1-30, AND FUNCTION.
RX PubMed=10645476;
RA Monastyrnaia M.M., Zykova T.A., Kozlovskaya E.P.;
RT "Isolation and characteristics of high molecular weight cytolysins from the
RT sea anemone Radianthus macrodactylus.";
RL Bioorg. Khim. 25:733-741(1999).
RN [3]
RP PROTEIN SEQUENCE OF 1-30, AND TOXIC DOSE.
RX PubMed=12165324; DOI=10.1016/s0041-0101(02)00139-3;
RA Monastyrnaia M.M., Zykova T.A., Apalikova O.V., Shwets T.V.,
RA Kozlovskaya E.P.;
RT "Biologically active polypeptides from the tropical sea anemone Radianthus
RT macrodactylus.";
RL Toxicon 40:1197-1217(2002).
RN [4]
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 [5]
RP 3D-STRUCTURE MODELING.
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 [6]
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.
CC {ECO:0000269|PubMed:10645476}.
CC -!- SUBUNIT: Tetramer in the presence of a lipidic interface. Monomer, in
CC soluble state (By similarity). {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 -!- TOXIC DOSE: LD(50) is 50 ug/kg by intraperitoneal injection into mice.
CC {ECO:0000269|PubMed:12165324}.
CC -!- MISCELLANEOUS: Hemolytic activity is 3.5 x 10(4) HU/mg.
CC -!- SIMILARITY: Belongs to the actinoporin family. Sea anemone subfamily.
CC {ECO:0000305}.
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DR EMBL; AY855350; AAW47930.1; -; mRNA.
DR AlphaFoldDB; P58691; -.
DR SMR; P58691; -.
DR TCDB; 1.C.38.1.10; the pore-forming equinatoxin (equinatoxin) family.
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..175
FT /note="DELTA-stichotoxin-Hcr4a"
FT /id="PRO_0000221533"
FT REGION 1..10
FT /note="Plays an important role in the hemolytic activity"
FT /evidence="ECO:0000250|UniProtKB:P07845"
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:0000250|UniProtKB:P07845"
FT BINDING 85
FT /ligand="phosphocholine"
FT /ligand_id="ChEBI:CHEBI:295975"
FT /evidence="ECO:0000250|UniProtKB:P07845"
FT BINDING 103
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 131
FT /ligand="phosphocholine"
FT /ligand_id="ChEBI:CHEBI:295975"
FT /evidence="ECO:0000250|UniProtKB:P07845"
FT BINDING 135
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 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 CONFLICT 11..30
FT /note="SLTFQILDKVLAELGQVSRK -> GLGLKILIEVLGEGXVKVKI (in
FT Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 175 AA; 19275 MW; C3D9D267D8662FCA CRC64;
ALAGAIIAGA SLTFQILDKV LAELGQVSRK IAIGIDNESG GSWTAMNAYF RSGTTDVILP
EFVPNQKALL YSGRKNRGPD TTGAVGALAY YMSNGNTLGV MFSVPFDYNL YSNWWDVKVY
SGKRRADQAM YEDLYYSNPY RGDNGWHQKN LGYGLKMKGI MTSAGEAIME IRISR
