CAHEM_HEMLE
ID CAHEM_HEMLE Reviewed; 66 AA.
AC A0A1L4BJ42;
DT 13-FEB-2019, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2017, sequence version 1.
DT 25-MAY-2022, entry version 13.
DE RecName: Full=Hemicalcin {ECO:0000303|PubMed:17291197};
DE Short=HCa {ECO:0000303|PubMed:17291197};
DE Short=HmCa {ECO:0000303|PubMed:27114612};
DE Flags: Precursor;
OS Hemiscorpius lepturus (Scorpion).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Iurida; Scorpionoidea; Hemiscorpiidae.
OX NCBI_TaxID=520031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=27914888; DOI=10.1016/j.toxicon.2016.11.261;
RA Kazemi-Lomedasht F., Khalaj V., Bagheri K.P., Behdani M., Shahbazzadeh D.;
RT "The first report on transcriptome analysis of the venom gland of Iranian
RT scorpion, Hemiscorpius lepturus.";
RL Toxicon 125:123-130(2016).
RN [2]
RP PROTEIN SEQUENCE OF 34-66, FUNCTION, BIOASSAY, TOXIC DOSE, SUBCELLULAR
RP LOCATION, MASS SPECTROMETRY, AND 3D-STRUCTURE MODELING.
RC TISSUE=Venom;
RX PubMed=17291197; DOI=10.1042/bj20061404;
RA Shahbazzadeh D., Srairi-Abid N., Feng W., Ram N., Borchani L., Ronjat M.,
RA Akbari A., Pessah I.N., De Waard M., El Ayeb M.;
RT "Hemicalcin, a new toxin from the Iranian scorpion Hemiscorpius lepturus
RT which is active on ryanodine-sensitive Ca2+ channels.";
RL Biochem. J. 404:89-96(2007).
RN [3]
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 (20% and 38% of the full
CC conductance state have been found) (PubMed:17291197, PubMed:27114612).
CC It promotes an increase in the opening probability at intermediate
CC concentration (PubMed:17291197). Furthermore, it triggers calcium
CC release from sarcoplasmic vesicles (68 nM are enough to induce a sharp
CC release, and 45% of the total calcium is released after toxin (100 nM)
CC addition) probably by acting as a cell-penetrating peptide (CPP)
CC (PubMed:17291197, PubMed:27114612). In addition, it has been shown to
CC dose-dependently stimulate ryanodine binding to RyR1 (EC(50)=6.9-71 nM)
CC (PubMed:17291197, PubMed:27114612). It also augments the bell-shaped
CC calcium-[3H]ryanodine binding curve that is maximal at about 10 uM
CC calcium concentration (PubMed:27114612). It binds a different site as
CC ryanodine (By similarity). It acts synergistically with caffeine (By
CC similarity). In vivo, intracerebroventricular injection into mice
CC induces neurotoxic symptoms, followed by death (PubMed:17291197).
CC {ECO:0000250|UniProtKB:P21817, ECO:0000250|UniProtKB:P59868,
CC ECO:0000250|UniProtKB:P60254, ECO:0000269|PubMed:17291197,
CC ECO:0000269|PubMed:27114612}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:17291197}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:17291197}.
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=3788.09; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:17291197};
CC -!- TOXIC DOSE: LD(50) is 15 ug/kg by intracerebroventricular injection
CC into mice. {ECO:0000269|PubMed:17291197}.
CC -!- SIMILARITY: Belongs to the scorpion calcin family. {ECO:0000305}.
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DR EMBL; KX874539; API81327.1; -; mRNA.
DR AlphaFoldDB; A0A1L4BJ42; -.
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; Cleavage on pair of basic residues;
KW Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW Knottin; Neurotoxin;
KW Ryanodine-sensitive calcium-release channel impairing toxin; Secreted;
KW Signal; Toxin.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT PROPEP 22..33
FT /evidence="ECO:0000305"
FT /id="PRO_0000446294"
FT CHAIN 34..66
FT /note="Hemicalcin"
FT /evidence="ECO:0000269|PubMed:17291197"
FT /id="PRO_5012476333"
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; 7650 MW; C29EC489ABA490F4 CRC64;
MRASLFIVIF VVSFITISCL STDDEEARWI EKRGDCLPHL KLCKADKDCC SKKCKRRGTN
PEKRCR
