P59868 · CAIMP_PANIM
- ProteinImperacalcin
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
This toxin affects the activity of ryanodine receptors 1, 2 and 3 (RyR1, RyR2 and RyR3) (PubMed:11867448, PubMed:1334561, PubMed:9565405).
At lower concentrations the toxin increases full openings of the RyRs, and at higher concentrations it inhibits full openings and induces openings to subconductance levels (30% of the full conductance state) and reduces the number of full conductance openings (PubMed:27114612, PubMed:9565405).
The different actions may be attributed to the toxins binding at different sites on the RyRs, with binding at a high-affinity site mediating the increase in full openings and the induction of subconductance states evoked upon binding to a lower-affinity site (PubMed:14699105).
Furthermore, it triggers calcium release from sarcoplasmic vesicles (11.7 nM are enough to induce a sharp release, and 70% of the total calcium is released after toxin (100 nM) addition) probably by acting as a cell-penetrating peptide (CPP) (PubMed:1334561, PubMed:27114612).
In addition, it has been shown to dose-dependently stimulate ryanodine binding to RyR1 (EC50=8.7 nM) (PubMed:27114612).
It also augments the bell-shaped calcium-[3H]ryanodine binding curve that is maximal at about 10 uM calcium concentration (PubMed:27114612).
It binds a different site as ryanodine (PubMed:9565405).
It acts synergistically with caffeine (By similarity).
In vivo, intracerebroventricular injection into mice induces neurotoxic symptoms, followed by death (By similarity).
At lower concentrations the toxin increases full openings of the RyRs, and at higher concentrations it inhibits full openings and induces openings to subconductance levels (30% of the full conductance state) and reduces the number of full conductance openings (PubMed:27114612, PubMed:9565405).
The different actions may be attributed to the toxins binding at different sites on the RyRs, with binding at a high-affinity site mediating the increase in full openings and the induction of subconductance states evoked upon binding to a lower-affinity site (PubMed:14699105).
Furthermore, it triggers calcium release from sarcoplasmic vesicles (11.7 nM are enough to induce a sharp release, and 70% of the total calcium is released after toxin (100 nM) addition) probably by acting as a cell-penetrating peptide (CPP) (PubMed:1334561, PubMed:27114612).
In addition, it has been shown to dose-dependently stimulate ryanodine binding to RyR1 (EC50=8.7 nM) (PubMed:27114612).
It also augments the bell-shaped calcium-[3H]ryanodine binding curve that is maximal at about 10 uM calcium concentration (PubMed:27114612).
It binds a different site as ryanodine (PubMed:9565405).
It acts synergistically with caffeine (By similarity).
In vivo, intracerebroventricular injection into mice induces neurotoxic symptoms, followed by death (By similarity).
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 6 | Important for stimulation of [3H]ryanodine binding to RYR1 | ||||
Sequence: H | ||||||
Site | 7 | Essential for stimulation of [3H]ryanodine binding to RYR1 | ||||
Sequence: L | ||||||
Site | 11 | Important for stimulation of [3H]ryanodine binding to RYR1 | ||||
Sequence: K | ||||||
Site | 30 | Important for stimulation of [3H]ryanodine binding to RYR1 | ||||
Sequence: K | ||||||
Site | 31 | Essential for stimulation of [3H]ryanodine binding to RYR1 | ||||
Sequence: R | ||||||
Site | 33 | Essential for stimulation of [3H]ryanodine binding to RYR1 | ||||
Sequence: R |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | extracellular region | |
Molecular Function | calcium channel inhibitor activity | |
Molecular Function | toxin activity |
Keywords
- Molecular function
Names & Taxonomy
Protein names
- Recommended nameImperacalcin
- Short namesIpCa
- Alternative names
Organism names
- Taxonomic lineageEukaryota > Metazoa > Ecdysozoa > Arthropoda > Chelicerata > Arachnida > Scorpiones > Iurida > Scorpionoidea > Scorpionidae > Pandininae > Pandinus
Accessions
- Primary accessionP59868
Subcellular Location
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 1 | 1.18-fold decrease of stimulation of [3H]ryanodine binding to RYR1. | ||||
Sequence: G → A | ||||||
Mutagenesis | 2 | 2.33-fold increase of stimulation of [3H]ryanodine binding to RYR1. | ||||
Sequence: D → A | ||||||
Mutagenesis | 3 | Linear IpCa; Loss of stimulation of [3H]ryanodine binding to RYR1. | ||||
Sequence: C → A | ||||||
Mutagenesis | 4 | 1.93-fold decrease of stimulation of [3H]ryanodine binding to RYR1. | ||||
Sequence: L → A | ||||||
Mutagenesis | 5 | 1.43-fold decrease of stimulation of [3H]ryanodine binding to RYR1. | ||||
Sequence: P → A | ||||||
Mutagenesis | 6 | 20.72-fold decrease of stimulation of [3H]ryanodine binding to RYR1. | ||||
Sequence: H → A | ||||||
Mutagenesis | 7 | 97.51-fold decrease of stimulation of [3H]ryanodine binding to RYR1. | ||||
Sequence: L → A | ||||||
Mutagenesis | 8 | 4.60-fold decrease of stimulation of [3H]ryanodine binding to RYR1. | ||||
Sequence: K → A | ||||||
Mutagenesis | 9 | 25.62-fold decrease of stimulation of [3H]ryanodine binding to RYR1. | ||||
Sequence: R → A | ||||||
Mutagenesis | 10 | Linear IpCa; Loss of stimulation of [3H]ryanodine binding to RYR1. | ||||
Sequence: C → A | ||||||
Mutagenesis | 11 | 6.83-fold decrease of stimulation of [3H]ryanodine binding to RYR1. | ||||
Sequence: K → A | ||||||
Mutagenesis | 13 | 3.08-fold increase of stimulation of [3H]ryanodine binding to RYR1. | ||||
Sequence: D → A | ||||||
Mutagenesis | 14 | 1.14-fold decrease of stimulation of [3H]ryanodine binding to RYR1. | ||||
Sequence: N → A | ||||||
Mutagenesis | 15 | 2.73-fold increase of stimulation of [3H]ryanodine binding to RYR1. | ||||
Sequence: D → A | ||||||
Mutagenesis | 16 | Linear IpCa; Loss of stimulation of [3H]ryanodine binding to RYR1. | ||||
Sequence: C → A | ||||||
Mutagenesis | 17 | Linear IpCa; Loss of stimulation of [3H]ryanodine binding to RYR1. | ||||
Sequence: C → A | ||||||
Mutagenesis | 18 | 1.16-fold decrease of stimulation of [3H]ryanodine binding to RYR1. | ||||
Sequence: G → A | ||||||
Mutagenesis | 19 | 4.96-fold decrease of stimulation of [3H]ryanodine binding to RYR1. | ||||
Sequence: K → A | ||||||
Mutagenesis | 20 | 16.91-fold decrease of stimulation of [3H]ryanodine binding to RYR1. | ||||
Sequence: K → A | ||||||
Mutagenesis | 21 | Linear IpCa; Loss of stimulation of [3H]ryanodine binding to RYR1. | ||||
Sequence: C → A | ||||||
Mutagenesis | 22 | 69.92-fold decrease of stimulation of [3H]ryanodine binding to RYR1. | ||||
Sequence: K → A | ||||||
Mutagenesis | 23 | 418.48-fold decrease of stimulation of [3H]ryanodine binding to RYR1. | ||||
Sequence: R → A | ||||||
Mutagenesis | 24 | Loss of stimulation of [3H]ryanodine binding to RYR1. | ||||
Sequence: R → A | ||||||
Mutagenesis | 25 | 23.96-fold decrease of stimulation of [3H]ryanodine binding to RYR1. | ||||
Sequence: G → A | ||||||
Mutagenesis | 26 | 11.52-fold decrease of stimulation of [3H]ryanodine binding to RYR1. | ||||
Sequence: T → A | ||||||
Mutagenesis | 27 | 20.09-fold decrease of stimulation of [3H]ryanodine binding to RYR1. | ||||
Sequence: N → A | ||||||
Mutagenesis | 29 | 2.35-fold increase of stimulation of [3H]ryanodine binding to RYR1. | ||||
Sequence: E → A | ||||||
Mutagenesis | 30 | 21.69-fold decrease of stimulation of [3H]ryanodine binding to RYR1. | ||||
Sequence: K → A | ||||||
Mutagenesis | 31 | Loss of stimulation of [3H]ryanodine binding to RYR1. | ||||
Sequence: R → A | ||||||
Mutagenesis | 32 | Linear IpCa; Loss of stimulation of [3H]ryanodine binding to RYR1. | ||||
Sequence: C → A | ||||||
Mutagenesis | 33 | Loss of stimulation of [3H]ryanodine binding to RYR1. | ||||
Sequence: R → A |
PTM/Processing
Features
Showing features for peptide, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Peptide | PRO_0000044949 | 1-33 | Imperacalcin | |||
Sequence: GDCLPHLKRCKADNDCCGKKCKRRGTNAEKRCR | ||||||
Disulfide bond | 3↔17 | |||||
Sequence: CLPHLKRCKADNDCC | ||||||
Disulfide bond | 10↔21 | |||||
Sequence: CKADNDCCGKKC | ||||||
Disulfide bond | 16↔32 | |||||
Sequence: CCGKKCKRRGTNAEKRC |
Keywords
- PTM
Expression
Tissue specificity
Expressed by the venom gland.
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 8-9 | Important for stimulation of [3H]ryanodine binding to RYR1 | ||||
Sequence: KR | ||||||
Region | 19-20 | Important for stimulation of [3H]ryanodine binding to RYR1 | ||||
Sequence: KK | ||||||
Region | 22-24 | Essential for stimulation of [3H]ryanodine binding to RYR1 | ||||
Sequence: KRR | ||||||
Region | 25-27 | Important for stimulation of [3H]ryanodine binding to RYR1 | ||||
Sequence: GTN |
Domain
The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin.
Sequence similarities
Belongs to the scorpion calcin family.
Keywords
- Domain