ID   CAOP2_OPICA             Reviewed;          66 AA.
AC   P60253;
DT   16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
DT   16-JAN-2004, sequence version 1.
DT   25-MAY-2022, entry version 54.
DE   RecName: Full=Opicalcin-2 {ECO:0000303|PubMed:27114612};
DE            Short=OpCa2 {ECO:0000303|PubMed:27114612};
DE   AltName: Full=Opicalcine-2 {ECO:0000303|PubMed:12958203};
DE   Flags: Precursor;
OS   Opistophthalmus carinatus (African yellow leg scorpion).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC   Scorpiones; Iurida; Scorpionoidea; Scorpionidae; Opistophthalminae;
OC   Opistophthalmus.
OX   NCBI_TaxID=190115;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   TISSUE=Venom gland;
RX   PubMed=12958203; DOI=10.1096/fj.02-1044fje;
RA   Zhu S.-Y., Darbon H., Dyason K., Verdonck F., Tytgat J.;
RT   "Evolutionary origin of inhibitor cystine knot peptides.";
RL   FASEB J. 17:1765-1767(2003).
RN   [2]
RP   FUNCTION, SYNTHESIS OF 34-66, AND 3D-STRUCTURE MODELING.
RX   PubMed=27114612; DOI=10.1085/jgp.201511499;
RA   Xiao L., Gurrola G.B., Zhang J., Valdivia C.R., SanMartin M., Zamudio F.Z.,
RA   Zhang L., Possani L.D., Valdivia H.H.;
RT   "Structure-function relationships of peptides forming the calcin family of
RT   ryanodine receptor ligands.";
RL   J. Gen. Physiol. 147:375-394(2016).
CC   -!- FUNCTION: This toxin stabilizes ryanodine receptor 1 (RyR1) opening in
CC       a long-lasting subconductance state (40% of the full conductance state)
CC       (PubMed:27114612). Furthermore, it triggers calcium release from
CC       sarcoplasmic vesicles (64.2 nM are enough to induce a sharp release,
CC       and 50% of the total calcium is released after toxin (100 nM) addition)
CC       probably by acting as a cell-penetrating peptide (CPP)
CC       (PubMed:27114612). In addition, it has been shown to dose-dependently
CC       stimulate ryanodine binding to RyR1 (EC(50)=3.2 nM) (PubMed:27114612).
CC       It also augments the bell-shaped calcium-[3H]ryanodine binding curve
CC       that is maximal at about 10 uM calcium concentration (PubMed:27114612).
CC       It binds a different site as ryanodine (By similarity). It acts
CC       synergistically with caffeine (By similarity). In vivo,
CC       intracerebroventricular injection into mice induces neurotoxic
CC       symptoms, followed by death (By similarity).
CC       {ECO:0000250|UniProtKB:A0A1L4BJ42, ECO:0000250|UniProtKB:B8QG00,
CC       ECO:0000250|UniProtKB:P59868, ECO:0000250|UniProtKB:P60254,
CC       ECO:0000269|PubMed:27114612}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305}.
CC   -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC       structurally defines this protein as a knottin.
CC       {ECO:0000250|UniProtKB:P59868}.
CC   -!- SIMILARITY: Belongs to the scorpion calcin family. {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   AlphaFoldDB; P60253; -.
DR   SMR; P60253; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0019855; F:calcium channel inhibitor activity; IEA:InterPro.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   InterPro; IPR012632; Scorpion_calcine.
DR   Pfam; PF08099; Toxin_27; 1.
DR   PROSITE; PS60028; SCORPION_CALCINE; 1.
PE   3: Inferred from homology;
KW   Calcium channel impairing toxin; Cleavage on pair of basic residues;
KW   Disulfide bond; Ion channel impairing toxin; Knottin; Neurotoxin;
KW   Ryanodine-sensitive calcium-release channel impairing toxin; Secreted;
KW   Signal; Toxin.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000255"
FT   PROPEP          23..31
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000035353"
FT   CHAIN           34..66
FT                   /note="Opicalcin-2"
FT                   /id="PRO_0000035354"
FT   REGION          55..57
FT                   /note="Essential for stimulation of [3H]ryanodine binding
FT                   to RYR1"
FT                   /evidence="ECO:0000250|UniProtKB:P59868,
FT                   ECO:0000250|UniProtKB:P60254"
FT   SITE            64
FT                   /note="Essential for stimulation of [3H]ryanodine binding
FT                   to RYR1"
FT                   /evidence="ECO:0000250|UniProtKB:P59868"
FT   SITE            66
FT                   /note="Essential for stimulation of [3H]ryanodine binding
FT                   to RYR1"
FT                   /evidence="ECO:0000250|UniProtKB:P59868"
FT   DISULFID        36..50
FT                   /evidence="ECO:0000250|UniProtKB:P59868"
FT   DISULFID        43..54
FT                   /evidence="ECO:0000250|UniProtKB:P59868"
FT   DISULFID        49..65
FT                   /evidence="ECO:0000250|UniProtKB:P59868"
SQ   SEQUENCE   66 AA;  7644 MW;  6DC7632E9F205F5D CRC64;
     MKPSLIIVTF IVVFMTISCV AADDEQETWI EKRGDCLPHL KRCKENNDCC SKKCKRRGAN
     PEKRCR