UniProtKB - A0A1L4BJ42 (CAHEM_HEMLE)
Hemicalcin
Functioni
This toxin stabilizes ryanodine receptor 1 (RyR1) opening in a long-lasting subconductance state (20% and 38% of the full conductance state have been found) (PubMed:17291197, PubMed:27114612).
It promotes an increase in the opening probability at intermediate concentration (PubMed:17291197).
Furthermore, it triggers calcium release from sarcoplasmic vesicles (68 nM are enough to induce a sharp release, and 45% of the total calcium is released after toxin (100 nM) addition) probably by acting as a cell-penetrating peptide (CPP) (PubMed:17291197, PubMed:27114612).
In addition, it has been shown to dose-dependently stimulate ryanodine binding to RyR1 (EC(50)=6.9-71 nM) (PubMed:17291197, PubMed:27114612).
It also augments the bell-shaped calcium-[3H]ryanodine binding curve that is maximal at about 10 µM calcium concentration (PubMed:27114612).
It binds a different site as ryanodine (By similarity).
It acts synergistically with caffeine (By similarity).
In vivo, intracerebroventricular injection into mice induces neurotoxic symptoms, followed by death (PubMed:17291197).
By similarity2 PublicationsSites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 64 | Essential for stimulation of [3H]ryanodine binding to RYR1By similarity | 1 | |
Sitei | 66 | Essential for stimulation of [3H]ryanodine binding to RYR1By similarity | 1 |
GO - Molecular functioni
- calcium channel inhibitor activity Source: InterPro
- toxin activity Source: UniProtKB-KW
Keywordsi
Molecular function | Calcium channel impairing toxin, Ion channel impairing toxin, Neurotoxin, Ryanodine-sensitive calcium-release channel impairing toxin, Toxin |
Names & Taxonomyi
Protein namesi | Recommended name: Hemicalcin1 PublicationShort name: HCa1 Publication Short name: HmCa1 Publication |
Organismi | Hemiscorpius lepturus (Scorpion) |
Taxonomic identifieri | 520031 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Ecdysozoa › Arthropoda › Chelicerata › Arachnida › Scorpiones › Iurida › Scorpionoidea › Hemiscorpiidae › |
Subcellular locationi
Extracellular region or secreted
- Secreted 1 Publication
Extracellular region or secreted
- extracellular region Source: UniProtKB-SubCell
Keywords - Cellular componenti
SecretedPathology & Biotechi
Toxic dosei
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 21 | Sequence analysisAdd BLAST | 21 | |
PropeptideiPRO_0000446294 | 22 – 33 | CuratedAdd BLAST | 12 | |
ChainiPRO_5012476333 | 34 – 66 | Hemicalcin1 PublicationAdd BLAST | 33 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 36 ↔ 50 | By similarity | ||
Disulfide bondi | 43 ↔ 54 | By similarity | ||
Disulfide bondi | 49 ↔ 65 | By similarity |
Keywords - PTMi
Cleavage on pair of basic residues, Disulfide bondExpressioni
Tissue specificityi
Structurei
3D structure databases
AlphaFoldDBi | A0A1L4BJ42 |
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 55 – 57 | Essential for stimulation of [3H]ryanodine binding to RYR1By similarity | 3 |
Domaini
Sequence similaritiesi
Keywords - Domaini
Knottin, SignalFamily and domain databases
InterProi | View protein in InterPro IPR012632, Scorpion_calcine |
Pfami | View protein in Pfam PF08099, Toxin_27, 1 hit |
PROSITEi | View protein in PROSITE PS60028, SCORPION_CALCINE, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MRASLFIVIF VVSFITISCL STDDEEARWI EKRGDCLPHL KLCKADKDCC
60
SKKCKRRGTN PEKRCR
Mass spectrometryi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | KX874539 mRNA Translation: API81327.1 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | KX874539 mRNA Translation: API81327.1 |
3D structure databases
AlphaFoldDBi | A0A1L4BJ42 |
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Family and domain databases
InterProi | View protein in InterPro IPR012632, Scorpion_calcine |
Pfami | View protein in Pfam PF08099, Toxin_27, 1 hit |
PROSITEi | View protein in PROSITE PS60028, SCORPION_CALCINE, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | CAHEM_HEMLE | |
Accessioni | A0A1L4BJ42Primary (citable) accession number: A0A1L4BJ42 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 13, 2019 |
Last sequence update: | March 15, 2017 | |
Last modified: | May 25, 2022 | |
This is version 13 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Animal Toxin Annotation Program |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencingDocuments
- SIMILARITY comments
Index of protein domains and families