ID   CAINT_THOIN             Reviewed;          69 AA.
AC   P0DM30;
DT   13-FEB-2019, integrated into UniProtKB/Swiss-Prot.
DT   13-FEB-2019, sequence version 1.
DT   25-MAY-2022, entry version 7.
DE   RecName: Full=Intrepicalcin {ECO:0000303|PubMed:28159581};
DE   AltName: Full=ViCaTx1 {ECO:0000303|PubMed:25659089, ECO:0000303|PubMed:28159581};
DE   Flags: Precursor;
OS   Thorellius intrepidus (Scorpion) (Vaejovis intrepidus).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC   Scorpiones; Iurida; Chactoidea; Vaejovidae; Thorellius.
OX   NCBI_TaxID=1533001;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Venom gland;
RX   PubMed=25659089; DOI=10.1371/journal.pone.0117188;
RA   Quintero-Hernandez V., Ramirez-Carreto S., Romero-Gutierrez M.T.,
RA   Valdez-Velazquez L.L., Becerril B., Possani L.D., Ortiz E.;
RT   "Transcriptome analysis of scorpion species belonging to the Vaejovis
RT   genus.";
RL   PLoS ONE 10:E0117188-E0117188(2015).
RN   [2]
RP   FUNCTION, AND 3D-STRUCTURE MODELING.
RX   PubMed=28159581; DOI=10.1016/j.bbagen.2017.01.032;
RA   Vargas-Jaimes L., Xiao L., Zhang J., Possani L.D., Valdivia H.H.,
RA   Quintero-Hernandez V.;
RT   "Recombinant expression of intrepicalcin from the scorpion Vaejovis
RT   intrepidus and its effect on skeletal ryanodine receptors.";
RL   Biochim. Biophys. Acta 1861:936-946(2017).
CC   -!- FUNCTION: This toxin stabilizes ryanodine receptor 1 (RyR1) opening in
CC       a long-lasting subconductance state (55% of the full conductance state)
CC       (PubMed:28159581). Furthermore, it triggers calcium release from
CC       sarcoplasmic vesicles (45.3 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:28159581). In addition, it has been shown to dose-dependently
CC       stimulate ryanodine binding to RyR1 (EC(50)=17.4 nM) (PubMed:28159581).
CC       It also augments the bell-shaped calcium-[3H]ryanodine binding curve
CC       that is maximal at about 10 uM calcium concentration (PubMed:28159581).
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:28159581}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:25659089}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:28159581}.
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}.
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DR   EMBL; JZ818387; -; NOT_ANNOTATED_CDS; mRNA.
DR   AlphaFoldDB; P0DM30; -.
DR   SMR; P0DM30; -.
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..27
FT                   /evidence="ECO:0000255"
FT   PROPEP          28..36
FT                   /evidence="ECO:0000305"
FT                   /id="PRO_0000446292"
FT   CHAIN           37..69
FT                   /note="Intrepicalcin"
FT                   /id="PRO_0000446293"
FT   REGION          59..60
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            67
FT                   /note="Essential for stimulation of [3H]ryanodine binding
FT                   to RYR1"
FT                   /evidence="ECO:0000250|UniProtKB:P59868"
FT   SITE            69
FT                   /note="Essential for stimulation of [3H]ryanodine binding
FT                   to RYR1"
FT                   /evidence="ECO:0000250|UniProtKB:P59868"
FT   DISULFID        39..53
FT                   /evidence="ECO:0000250|UniProtKB:P59868"
FT   DISULFID        46..57
FT                   /evidence="ECO:0000250|UniProtKB:P59868"
FT   DISULFID        52..68
FT                   /evidence="ECO:0000250|UniProtKB:P59868"
SQ   SEQUENCE   69 AA;  7931 MW;  831EDD04F37E5112 CRC64;
     MRQNTMTIIF IVFIVTFASL TIYGAEASEA NFLERRADCL AHLKLCKKNK DCCSKKCSRR
     GTNPEQRCR