CAHAD_HOFGE
ID CAHAD_HOFGE Reviewed; 74 AA.
AC B8QG00; P85499;
DT 22-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 1.
DT 03-AUG-2022, entry version 29.
DE RecName: Full=Hadrucalcin {ECO:0000303|Ref.2};
DE Short=HdCa {ECO:0000303|PubMed:19389159, ECO:0000303|Ref.2};
DE Flags: Precursor;
OS Hoffmannihadrurus gertschi (Scorpion) (Hadrurus gertschi).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Iurida; Iuroidea; Hadrurus.
OX NCBI_TaxID=380989;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 40-74, FUNCTION ON RYR1 AND
RP RYR2, SUBCELLULAR LOCATION, AND MASS SPECTROMETRY.
RC TISSUE=Telson, and Venom;
RX PubMed=19389159; DOI=10.1111/j.1476-5381.2009.00147.x;
RA Schwartz E.F., Capes E.M., Diego-Garcia E., Zamudio F.Z., Fuentes O.,
RA Possani L.D., Valdivia H.H.;
RT "Characterization of hadrucalcin, a peptide from Hadrurus gertschi scorpion
RT venom with pharmacological activity on ryanodine receptors.";
RL Br. J. Pharmacol. 157:392-403(2009).
RN [2]
RP FUNCTION.
RA Capes E.M., Schwartz E.F., Diego-Garcia E., Zamudio F.Z., Possani L.D.,
RA Valdivia H.H.;
RT "Hadrucalcin, a novel member of the Calcin scorpion toxin family, rapidly
RT penetrates cellular membranes to bind ryanodine receptors and alter calcium
RT release.";
RL Biophys. J. 94:2631-2631(2008).
RN [3]
RP FUNCTION, SYNTHESIS OF 40-74, 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 activates ryanodine receptors RyR1 and RyR2 by
CC inducing a long-lasting subconductance state (35% of the full
CC conductance stateon RyR1) (PubMed:19389159, PubMed:27114612).
CC Furthermore, it triggers calcium release from sarcoplasmic vesicles
CC (11.8 nM are enough to induce a sharp release on RyR1, and 55% of the
CC total calcium is released after toxin (100 nM) addition on RyR1)
CC probably by acting as a cell-penetrating peptide (CPP)
CC (PubMed:19389159). In addition, it has been shown to dose-dependently
CC stimulate ryanodine binding to RyR1 (EC(50)=14.8 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 (PubMed:19389159). In vivo,
CC intracerebroventricular injection into mice induces neurotoxic
CC symptoms, followed by death (By similarity).
CC {ECO:0000250|UniProtKB:A0A1L4BJ42, ECO:0000250|UniProtKB:P59868,
CC ECO:0000250|UniProtKB:P60254, ECO:0000269|PubMed:19389159,
CC ECO:0000269|PubMed:27114612, ECO:0000269|Ref.2}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:19389159}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:19389159}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000250|UniProtKB:P59868}.
CC -!- MASS SPECTROMETRY: Mass=4190.5; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:19389159};
CC -!- SIMILARITY: Belongs to the scorpion calcin family. {ECO:0000255}.
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DR EMBL; EU496812; ACC99422.1; -; mRNA.
DR AlphaFoldDB; B8QG00; -.
DR SMR; B8QG00; -.
DR TCDB; 8.B.16.1.3; the maurocalcine (maca) family.
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 1: Evidence at protein level;
KW Calcium channel impairing toxin; Direct protein sequencing; Disulfide bond;
KW 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..39
FT /evidence="ECO:0000255, ECO:0000269|PubMed:19389159"
FT /id="PRO_0000383671"
FT PEPTIDE 40..74
FT /note="Hadrucalcin"
FT /evidence="ECO:0000269|PubMed:19389159"
FT /id="PRO_5000433512"
FT REGION 64..65
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 72
FT /note="Essential for stimulation of [3H]ryanodine binding
FT to RYR1"
FT /evidence="ECO:0000250|UniProtKB:P59868"
FT SITE 74
FT /note="Essential for stimulation of [3H]ryanodine binding
FT to RYR1"
FT /evidence="ECO:0000250|UniProtKB:P59868"
FT DISULFID 44..58
FT /evidence="ECO:0000250|UniProtKB:P59868"
FT DISULFID 51..62
FT /evidence="ECO:0000250|UniProtKB:P59868"
FT DISULFID 57..73
FT /evidence="ECO:0000250|UniProtKB:P59868"
SQ SEQUENCE 74 AA; 8593 MW; 12D5F2B54C1640A2 CRC64;
MKTSSLTIIF IAVIITIICL NIHDIEAREI EFNAGRVVRS EKDCIKHLQR CRENKDCCSK
KCSRRGTNPE KRCR