B8QG00 · CAHAD_HOFGE
- ProteinHadrucalcin
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids
- Protein existenceEvidence at protein level
- Annotation score4/5
Function
function
This toxin activates ryanodine receptors RyR1 and RyR2 by inducing a long-lasting subconductance state (35% of the full conductance stateon RyR1) (PubMed:19389159, PubMed:27114612).
Furthermore, it triggers calcium release from sarcoplasmic vesicles (11.8 nM are enough to induce a sharp release on RyR1, and 55% of the total calcium is released after toxin (100 nM) addition on RyR1) probably by acting as a cell-penetrating peptide (CPP) (PubMed:19389159).
In addition, it has been shown to dose-dependently stimulate ryanodine binding to RyR1 (EC50=14.8 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 (By similarity).
It acts synergistically with caffeine (PubMed:19389159).
In vivo, intracerebroventricular injection into mice induces neurotoxic symptoms, followed by death (By similarity).
Furthermore, it triggers calcium release from sarcoplasmic vesicles (11.8 nM are enough to induce a sharp release on RyR1, and 55% of the total calcium is released after toxin (100 nM) addition on RyR1) probably by acting as a cell-penetrating peptide (CPP) (PubMed:19389159).
In addition, it has been shown to dose-dependently stimulate ryanodine binding to RyR1 (EC50=14.8 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 (By similarity).
It acts synergistically with caffeine (PubMed:19389159).
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 | 72 | Essential for stimulation of [3H]ryanodine binding to RYR1 | ||||
Sequence: R | ||||||
Site | 74 | Essential for stimulation of [3H]ryanodine binding to RYR1 | ||||
Sequence: R |
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | extracellular region | |
Molecular Function | calcium channel inhibitor activity | |
Molecular Function | toxin activity |
Keywords
- Molecular function
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameHadrucalcin
- Short namesHdCa
Organism names
- Taxonomic lineageEukaryota > Metazoa > Ecdysozoa > Arthropoda > Chelicerata > Arachnida > Scorpiones > Iurida > Iuroidea > Hadrurus
Accessions
- Primary accessionB8QG00
- Secondary accessions
Subcellular Location
PTM/Processing
Features
Showing features for signal, propeptide, peptide, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-27 | |||||
Sequence: MKTSSLTIIFIAVIITIICLNIHDIEA | ||||||
Propeptide | PRO_0000383671 | 28-39 | ||||
Sequence: REIEFNAGRVVR | ||||||
Peptide | PRO_5000433512 | 40-74 | Hadrucalcin | |||
Sequence: SEKDCIKHLQRCRENKDCCSKKCSRRGTNPEKRCR | ||||||
Disulfide bond | 44↔58 | |||||
Sequence: CIKHLQRCRENKDCC | ||||||
Disulfide bond | 51↔62 | |||||
Sequence: CRENKDCCSKKC | ||||||
Disulfide bond | 57↔73 | |||||
Sequence: CCSKKCSRRGTNPEKRC |
Keywords
- PTM
Expression
Tissue specificity
Expressed by the venom gland.
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 64-65 | Essential for stimulation of [3H]ryanodine binding to RYR1 | ||||
Sequence: RR |
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
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length74
- Mass (Da)8,593
- Last updated2009-03-03 v1
- Checksum12D5F2B54C1640A2
Mass Spectrometry
Keywords
- Technical term