ID   BDS5D_HETCR             Reviewed;          41 AA.
AC   C0HL54;
DT   18-JUL-2018, integrated into UniProtKB/Swiss-Prot.
DT   18-JUL-2018, sequence version 1.
DT   25-MAY-2022, entry version 8.
DE   RecName: Full=Pi-stichotoxin-Hcr5d {ECO:0000303|PubMed:29684594};
DE            Short=Pi-SHTX-Hcr5d {ECO:0000305|PubMed:29684594};
DE   AltName: Full=APETx-like peptide {ECO:0000303|PubMed:32326130};
DE   AltName: Full=Pi-AnmTX Hcr 1b-4 {ECO:0000303|PubMed:29684594};
DE            Short=Hcr 1b-4 {ECO:0000303|PubMed:32326130};
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   PROTEIN SEQUENCE, FUNCTION, MASS SPECTROMETRY, IDENTIFICATION BY MASS
RP   SPECTROMETRY, AND PRESENCE OF DISULFIDE BONDS.
RX   PubMed=29684594; DOI=10.1016/j.peptides.2018.04.013;
RA   Kalina R., Gladkikh I., Dmitrenok P., Chernikov O., Koshelev S.,
RA   Kvetkina A., Kozlov S., Kozlovskaya E., Monastyrnaya M.;
RT   "New APETx-like peptides from sea anemone Heteractis crispa modulate ASIC1a
RT   channels.";
RL   Peptides 104:41-49(2018).
RN   [2]
RP   FUNCTION, AND 3D-STRUCTURE MODELING IN COMPLEX WITH RAT ASIC1A.
RX   PubMed=32326130; DOI=10.3390/toxins12040266;
RA   Kalina R.S., Koshelev S.G., Zelepuga E.A., Kim N.Y., Kozlov S.A.,
RA   Kozlovskaya E.P., Monastyrnaya M.M., Gladkikh I.N.;
RT   "APETx-Like peptides from the sea anemone Heteractis crispa, diverse in
RT   their effect on ASIC1a and ASIC3 ion channels.";
RL   Toxins 12:0-0(2020).
CC   -!- FUNCTION: Toxin with different activities on acid-sensing ion channels
CC       1 and 3 (PubMed:32326130). It weakly and reversibly inhibits rat
CC       homomeric ASIC1 (isoform ASIC1a) (IC(50)=1.25 uM), while it potentiates
CC       rat homomeric ASIC3 (EC(50)=1.53 uM) (PubMed:29684594,
CC       PubMed:32326130). ASIC1a current inhibition is not complete, and
CC       reaches a maximum of 86% inhibition (PubMed:32326130). On ASIC3, this
CC       toxin does not activate the channel itself, but produces a remarkable
CC       potentiation of the transient current resulting from the acidic pulse
CC       (PubMed:32326130). At the maximal applied concentration, it elicits
CC       responses that are twice as high as those produced by extracellular
CC       protons (PubMed:32326130). Molecular modeling interaction with ASIC1a
CC       suggests that this peptide hinders the collapse of acidic pockets and
CC       stabilize nonconducting channels state (PubMed:32326130).
CC       {ECO:0000269|PubMed:29684594, ECO:0000269|PubMed:32326130}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}. Nematocyst {ECO:0000305}.
CC   -!- PTM: Contains disulfide bonds. {ECO:0000269|PubMed:29684594}.
CC   -!- MASS SPECTROMETRY: Mass=4693.9; Method=MALDI;
CC       Evidence={ECO:0000269|PubMed:29684594};
CC   -!- SIMILARITY: Belongs to the sea anemone type 3 (BDS) potassium channel
CC       toxin family. {ECO:0000305}.
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DR   AlphaFoldDB; C0HL54; -.
DR   SMR; C0HL54; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0042151; C:nematocyst; IEA:UniProtKB-SubCell.
DR   GO; GO:0008200; F:ion channel inhibitor activity; IEA:InterPro.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   Gene3D; 2.20.20.10; -; 1.
DR   InterPro; IPR012414; BDS_K_chnl_tox.
DR   InterPro; IPR023355; Myo_ane_neurotoxin_sf.
DR   Pfam; PF07936; Defensin_4; 1.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW   Nematocyst; Proton-gated sodium channel impairing toxin; Secreted; Toxin.
FT   PEPTIDE         1..41
FT                   /note="Pi-stichotoxin-Hcr5d"
FT                   /evidence="ECO:0000269|PubMed:29684594"
FT                   /id="PRO_0000444939"
FT   DISULFID        4..37
FT                   /evidence="ECO:0000250|UniProtKB:P61541"
FT   DISULFID        6..30
FT                   /evidence="ECO:0000250|UniProtKB:P61541"
FT   DISULFID        20..38
FT                   /evidence="ECO:0000250|UniProtKB:P61541"
SQ   SEQUENCE   41 AA;  4703 MW;  2B556F04CAEE13BB CRC64;
     GTPCDCYGYT GVYWFMLSRC PSGYGYNLSC HYFMGICCVK R