Pumiliotoxin (T3D2529)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (25)XML
Targets (25)
Record Information
Version2.0
Creation Date2009-07-03 22:19:12 UTC
Update Date2014-12-24 20:25:39 UTC
Accession NumberT3D2529
Identification
Common NamePumiliotoxin
ClassSmall Molecule
DescriptionPumiliotoxin is a toxin found in poison dart frogs (genus Dendrobates and Phyllobates). It affects the calcium channels, interfering with muscle contraction in the heart and skeletal muscle. (3)
Compound Type
  • Amine
  • Animal Toxin
  • Frog/Toad Toxin
  • Natural Compound
  • Organic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
Pumilitoxin 251d
Chemical FormulaC16H29NO
Average Molecular Mass251.408 g/mol
Monoisotopic Mass251.225 g/mol
CAS Registry Number73376-35-9
IUPAC Name8-methyl-6-(2-methylhexylidene)-octahydroindolizin-8-ol
Traditional Name8-methyl-6-(2-methylhexylidene)-hexahydroindolizin-8-ol
SMILESCCCCC(C)C=C1CN2CCCC2C(C)(O)C1
InChI IdentifierInChI=1S/C16H29NO/c1-4-5-7-13(2)10-14-11-16(3,18)15-8-6-9-17(15)12-14/h10,13,15,18H,4-9,11-12H2,1-3H3/b14-10+
InChI KeyInChIKey=OKTQTXDNHCOLHT-GXDHUFHOSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as pumiliotoxins, homopumiliotoxins, and allopumiliotoxins. These are neurotoxic alkaloids, containing a 8-methyl-octahydroindolizin-8-ol or 1-methyl-octahydro-1H-quinolizin-1-ol moiety.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassPumiliotoxins, homopumiliotoxins, and allopumiliotoxins
Sub ClassNot Available
Direct ParentPumiliotoxins, homopumiliotoxins, and allopumiliotoxins
Alternative Parents
Substituents
  • Pumiliotoxin-skeleton
  • Indolizidine
  • Piperidine
  • N-alkylpyrrolidine
  • Pyrrolidine
  • Tertiary alcohol
  • 1,2-aminoalcohol
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organic oxygen compound
  • Amine
  • Organic nitrogen compound
  • Alcohol
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.27 g/LALOGPS
logP3.38ALOGPS
logP3.26ChemAxon
logS-3ALOGPS
pKa (Strongest Acidic)14.36ChemAxon
pKa (Strongest Basic)10.15ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area23.47 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity78.14 m³·mol⁻¹ChemAxon
Polarizability30.73 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0f89-0090000000-8fda08d9c59c22d280d12019-02-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-001m-9680000000-4d04b469dea5271682ce2019-02-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9300000000-51086adc1c3fca8b3a1c2019-02-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-0090000000-459d5dbba46f2e8e44912019-02-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0ue9-0190000000-5de9dc17a27d085ac5c42019-02-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00el-6950000000-9e91e40295a3072020932019-02-23View Spectrum
Toxicity Profile
Route of ExposureInjection (sting/bite) (5) ; inhalation (smoking) (6)
Mechanism of ToxicityPumiliotoxin affects voltage-gated calcium channels, interfering with muscle contraction in the heart and skeletal muscle. They also may block sodium and potassium channels in cells and inhibit calcium-dependent ATPase. (3, 4, 1, 2)
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesPumiliotoxin is a toxin found in poison dart frogs (genus Dendrobates and Phyllobates). (3)
Minimum Risk LevelNot Available
Health EffectsPumiliotoxin interferes with muscle contraction in the heart and skeletal muscle. (3)
SymptomsSome of the symptoms of pumiliotoxins are partial paralysis, having difficulty moving, being hyperactive and in some cases death. (3)
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID6440480
ChEMBL IDNot Available
ChemSpider IDNot Available
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDPumiliotoxin
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDST3D2529.pdf
General References
  1. Tamburini R, Albuquerque EX, Daly JW, Kauffman FC: Inhibition of calcium-dependent ATPase from sarcoplasmic reticulum by a new class of indolizidine alkaloids, pumiliotoxins A, B, and 251D. J Neurochem. 1981 Sep;37(3):775-80. [6456330 ]
  2. Vandendriessche T, Abdel-Mottaleb Y, Maertens C, Cuypers E, Sudau A, Nubbemeyer U, Mebs D, Tytgat J: Modulation of voltage-gated Na+ and K+ channels by pumiliotoxin 251D: a "joint venture" alkaloid from arthropods and amphibians. Toxicon. 2008 Mar 1;51(3):334-44. Epub 2007 Oct 24. [18061227 ]
  3. Wikipedia. Pumiliotoxin. Last Updated 5 October 2008. [Link]
  4. Wikipedia. Pumiliotoxin 251D. Last Updated 13 May 2009. [Link]
  5. Wikipedia. Spider toxin. Last Updated 9 January 2009. [Link]
  6. Wikipedia. Frog. Last Updated 10 August 2009. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Potassium voltage-gated channel subfamily A member 1
General Function:
Voltage-gated potassium channel activity
Specific Function:
Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the kidney (PubMed:19903818). Contributes to the regulation of the membrane potential and nerve signaling, and prevents neuronal hyperexcitability (PubMed:17156368). Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:19912772). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:12077175, PubMed:17156368). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation of delayed rectifier potassium channels (PubMed:12077175, PubMed:17156368). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA1 forms a delayed-rectifier potassium channel that opens in response to membrane depolarization, followed by slow spontaneous channel closure (PubMed:19912772, PubMed:19968958, PubMed:19307729, PubMed:19903818). In contrast, a heterotetrameric channel formed by KCNA1 and KCNA4 shows rapid inactivation (PubMed:17156368). Regulates neuronal excitability in hippocampus, especially in mossy fibers and medial perforant path axons, preventing neuronal hyperexcitability. Response to toxins that are selective for KCNA1, respectively for KCNA2, suggests that heteromeric potassium channels composed of both KCNA1 and KCNA2 play a role in pacemaking and regulate the output of deep cerebellar nuclear neurons (By similarity). May function as down-stream effector for G protein-coupled receptors and inhibit GABAergic inputs to basolateral amygdala neurons (By similarity). May contribute to the regulation of neurotransmitter release, such as gamma-aminobutyric acid (GABA) release (By similarity). Plays a role in regulating the generation of action potentials and preventing hyperexcitability in myelinated axons of the vagus nerve, and thereby contributes to the regulation of heart contraction (By similarity). Required for normal neuromuscular responses (PubMed:11026449, PubMed:17136396). Regulates the frequency of neuronal action potential firing in response to mechanical stimuli, and plays a role in the perception of pain caused by mechanical stimuli, but does not play a role in the perception of pain due to heat stimuli (By similarity). Required for normal responses to auditory stimuli and precise location of sound sources, but not for sound perception (By similarity). The use of toxins that block specific channels suggest that it contributes to the regulation of the axonal release of the neurotransmitter dopamine (By similarity). Required for normal postnatal brain development and normal proliferation of neuronal precursor cells in the brain (By similarity). Plays a role in the reabsorption of Mg(2+) in the distal convoluted tubules in the kidney and in magnesium ion homeostasis, probably via its effect on the membrane potential (PubMed:23903368, PubMed:19307729).
Gene Name:
KCNA1
Uniprot ID:
Q09470
Molecular Weight:
56465.01 Da
References
  1. Tamburini R, Albuquerque EX, Daly JW, Kauffman FC: Inhibition of calcium-dependent ATPase from sarcoplasmic reticulum by a new class of indolizidine alkaloids, pumiliotoxins A, B, and 251D. J Neurochem. 1981 Sep;37(3):775-80. [6456330 ]
  2. Vandendriessche T, Abdel-Mottaleb Y, Maertens C, Cuypers E, Sudau A, Nubbemeyer U, Mebs D, Tytgat J: Modulation of voltage-gated Na+ and K+ channels by pumiliotoxin 251D: a "joint venture" alkaloid from arthropods and amphibians. Toxicon. 2008 Mar 1;51(3):334-44. Epub 2007 Oct 24. [18061227 ]
  3. Wikipedia. Pumiliotoxin 251D. Last Updated 13 May 2009. [Link]
Target Details
2. Potassium voltage-gated channel subfamily A member 2
General Function:
Voltage-gated potassium channel activity
Specific Function:
Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the cardiovascular system. Prevents aberrant action potential firing and regulates neuronal output. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:19912772, PubMed:8495559, PubMed:11211111, PubMed:23769686). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:8495559, PubMed:20220134). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation of delayed rectifier potassium channels. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA2 forms a delayed-rectifier potassium channel that opens in response to membrane depolarization, followed by slow spontaneous channel closure (PubMed:19912772, PubMed:23769686). In contrast, a heteromultimer formed by KCNA2 and KCNA4 shows rapid inactivation (PubMed:8495559). Regulates neuronal excitability and plays a role as pacemaker in the regulation of neuronal action potentials (By similarity). KCNA2-containing channels play a presynaptic role and prevent hyperexcitability and aberrant action potential firing (By similarity). Response to toxins that are selective for KCNA2-containing potassium channels suggests that in Purkinje cells, dendritic subthreshold KCNA2-containing potassium channels prevent random spontaneous calcium spikes, suppressing dendritic hyperexcitability without hindering the generation of somatic action potentials, and thereby play an important role in motor coordination (By similarity). Plays a role in the induction of long-term potentiation of neuron excitability in the CA3 layer of the hippocampus (By similarity). May function as down-stream effector for G protein-coupled receptors and inhibit GABAergic inputs to basolateral amygdala neurons (By similarity). May contribute to the regulation of neurotransmitter release, such as gamma-aminobutyric acid (GABA) (By similarity). Contributes to the regulation of the axonal release of the neurotransmitter dopamine (By similarity). Reduced KCNA2 expression plays a role in the perception of neuropathic pain after peripheral nerve injury, but not acute pain (By similarity). Plays a role in the regulation of the time spent in non-rapid eye movement (NREM) sleep (By similarity).
Gene Name:
KCNA2
Uniprot ID:
P16389
Molecular Weight:
56716.21 Da
References
  1. Tamburini R, Albuquerque EX, Daly JW, Kauffman FC: Inhibition of calcium-dependent ATPase from sarcoplasmic reticulum by a new class of indolizidine alkaloids, pumiliotoxins A, B, and 251D. J Neurochem. 1981 Sep;37(3):775-80. [6456330 ]
  2. Vandendriessche T, Abdel-Mottaleb Y, Maertens C, Cuypers E, Sudau A, Nubbemeyer U, Mebs D, Tytgat J: Modulation of voltage-gated Na+ and K+ channels by pumiliotoxin 251D: a "joint venture" alkaloid from arthropods and amphibians. Toxicon. 2008 Mar 1;51(3):334-44. Epub 2007 Oct 24. [18061227 ]
  3. Wikipedia. Pumiliotoxin 251D. Last Updated 13 May 2009. [Link]
Target Details
3. Potassium voltage-gated channel subfamily A member 3
General Function:
Voltage-gated ion channel activity
Specific Function:
Mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient.
Gene Name:
KCNA3
Uniprot ID:
P22001
Molecular Weight:
63841.09 Da
References
  1. Tamburini R, Albuquerque EX, Daly JW, Kauffman FC: Inhibition of calcium-dependent ATPase from sarcoplasmic reticulum by a new class of indolizidine alkaloids, pumiliotoxins A, B, and 251D. J Neurochem. 1981 Sep;37(3):775-80. [6456330 ]
  2. Vandendriessche T, Abdel-Mottaleb Y, Maertens C, Cuypers E, Sudau A, Nubbemeyer U, Mebs D, Tytgat J: Modulation of voltage-gated Na+ and K+ channels by pumiliotoxin 251D: a "joint venture" alkaloid from arthropods and amphibians. Toxicon. 2008 Mar 1;51(3):334-44. Epub 2007 Oct 24. [18061227 ]
  3. Wikipedia. Pumiliotoxin 251D. Last Updated 13 May 2009. [Link]
Target Details
4. Potassium voltage-gated channel subfamily H member 1
General Function:
Phosphorelay sensor kinase activity
Specific Function:
Pore-forming (alpha) subunit of a voltage-gated delayed rectifier potassium channel (PubMed:22732247). Channel properties may be modulated by subunit assembly, but not by cyclic nucleotides (By similarity). Mediates IK(NI) current in myoblasts (PubMed:9738473). Involved in the regulation of cell proliferation and differentiation, in particular adipogenic and osteogenic differentiation in bone marrow-derived mesenchymal stem cells (MSCs) (PubMed:23881642).
Gene Name:
KCNH1
Uniprot ID:
O95259
Molecular Weight:
111421.76 Da
References
  1. Tamburini R, Albuquerque EX, Daly JW, Kauffman FC: Inhibition of calcium-dependent ATPase from sarcoplasmic reticulum by a new class of indolizidine alkaloids, pumiliotoxins A, B, and 251D. J Neurochem. 1981 Sep;37(3):775-80. [6456330 ]
  2. Vandendriessche T, Abdel-Mottaleb Y, Maertens C, Cuypers E, Sudau A, Nubbemeyer U, Mebs D, Tytgat J: Modulation of voltage-gated Na+ and K+ channels by pumiliotoxin 251D: a "joint venture" alkaloid from arthropods and amphibians. Toxicon. 2008 Mar 1;51(3):334-44. Epub 2007 Oct 24. [18061227 ]
  3. Wikipedia. Pumiliotoxin 251D. Last Updated 13 May 2009. [Link]
Target Details
5. Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
General Function:
Protein homodimerization activity
Specific Function:
Key regulator of striated muscle performance by acting as the major Ca(2+) ATPase responsible for the reuptake of cytosolic Ca(2+) into the sarcoplasmic reticulum. Catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Contributes to calcium sequestration involved in muscular excitation/contraction.
Gene Name:
ATP2A1
Uniprot ID:
O14983
Molecular Weight:
110251.36 Da
References
  1. Tamburini R, Albuquerque EX, Daly JW, Kauffman FC: Inhibition of calcium-dependent ATPase from sarcoplasmic reticulum by a new class of indolizidine alkaloids, pumiliotoxins A, B, and 251D. J Neurochem. 1981 Sep;37(3):775-80. [6456330 ]
  2. Vandendriessche T, Abdel-Mottaleb Y, Maertens C, Cuypers E, Sudau A, Nubbemeyer U, Mebs D, Tytgat J: Modulation of voltage-gated Na+ and K+ channels by pumiliotoxin 251D: a "joint venture" alkaloid from arthropods and amphibians. Toxicon. 2008 Mar 1;51(3):334-44. Epub 2007 Oct 24. [18061227 ]
  3. Wikipedia. Pumiliotoxin 251D. Last Updated 13 May 2009. [Link]
Target Details
6. Sarcoplasmic/endoplasmic reticulum calcium ATPase 2
General Function:
S100 protein binding
Specific Function:
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Isoform 2 is involved in the regulation of the contraction/relaxation cycle.
Gene Name:
ATP2A2
Uniprot ID:
P16615
Molecular Weight:
114755.765 Da
References
  1. Tamburini R, Albuquerque EX, Daly JW, Kauffman FC: Inhibition of calcium-dependent ATPase from sarcoplasmic reticulum by a new class of indolizidine alkaloids, pumiliotoxins A, B, and 251D. J Neurochem. 1981 Sep;37(3):775-80. [6456330 ]
  2. Vandendriessche T, Abdel-Mottaleb Y, Maertens C, Cuypers E, Sudau A, Nubbemeyer U, Mebs D, Tytgat J: Modulation of voltage-gated Na+ and K+ channels by pumiliotoxin 251D: a "joint venture" alkaloid from arthropods and amphibians. Toxicon. 2008 Mar 1;51(3):334-44. Epub 2007 Oct 24. [18061227 ]
  3. Wikipedia. Pumiliotoxin 251D. Last Updated 13 May 2009. [Link]
Target Details
7. Sarcoplasmic/endoplasmic reticulum calcium ATPase 3
General Function:
Metal ion binding
Specific Function:
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium. Transports calcium ions from the cytosol into the sarcoplasmic/endoplasmic reticulum lumen. Contributes to calcium sequestration involved in muscular excitation/contraction.
Gene Name:
ATP2A3
Uniprot ID:
Q93084
Molecular Weight:
113976.23 Da
References
  1. Tamburini R, Albuquerque EX, Daly JW, Kauffman FC: Inhibition of calcium-dependent ATPase from sarcoplasmic reticulum by a new class of indolizidine alkaloids, pumiliotoxins A, B, and 251D. J Neurochem. 1981 Sep;37(3):775-80. [6456330 ]
  2. Vandendriessche T, Abdel-Mottaleb Y, Maertens C, Cuypers E, Sudau A, Nubbemeyer U, Mebs D, Tytgat J: Modulation of voltage-gated Na+ and K+ channels by pumiliotoxin 251D: a "joint venture" alkaloid from arthropods and amphibians. Toxicon. 2008 Mar 1;51(3):334-44. Epub 2007 Oct 24. [18061227 ]
  3. Wikipedia. Pumiliotoxin 251D. Last Updated 13 May 2009. [Link]
Target Details
8. Sodium channel protein type 2 subunit alpha
General Function:
Voltage-gated sodium channel activity
Specific Function:
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
Gene Name:
SCN2A
Uniprot ID:
Q99250
Molecular Weight:
227972.64 Da
References
  1. Tamburini R, Albuquerque EX, Daly JW, Kauffman FC: Inhibition of calcium-dependent ATPase from sarcoplasmic reticulum by a new class of indolizidine alkaloids, pumiliotoxins A, B, and 251D. J Neurochem. 1981 Sep;37(3):775-80. [6456330 ]
  2. Vandendriessche T, Abdel-Mottaleb Y, Maertens C, Cuypers E, Sudau A, Nubbemeyer U, Mebs D, Tytgat J: Modulation of voltage-gated Na+ and K+ channels by pumiliotoxin 251D: a "joint venture" alkaloid from arthropods and amphibians. Toxicon. 2008 Mar 1;51(3):334-44. Epub 2007 Oct 24. [18061227 ]
  3. Wikipedia. Pumiliotoxin 251D. Last Updated 13 May 2009. [Link]
Target Details
9. Sodium channel protein type 4 subunit alpha
General Function:
Voltage-gated sodium channel activity
Specific Function:
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. This sodium channel may be present in both denervated and innervated skeletal muscle.
Gene Name:
SCN4A
Uniprot ID:
P35499
Molecular Weight:
208059.175 Da
References
  1. Tamburini R, Albuquerque EX, Daly JW, Kauffman FC: Inhibition of calcium-dependent ATPase from sarcoplasmic reticulum by a new class of indolizidine alkaloids, pumiliotoxins A, B, and 251D. J Neurochem. 1981 Sep;37(3):775-80. [6456330 ]
  2. Vandendriessche T, Abdel-Mottaleb Y, Maertens C, Cuypers E, Sudau A, Nubbemeyer U, Mebs D, Tytgat J: Modulation of voltage-gated Na+ and K+ channels by pumiliotoxin 251D: a "joint venture" alkaloid from arthropods and amphibians. Toxicon. 2008 Mar 1;51(3):334-44. Epub 2007 Oct 24. [18061227 ]
  3. Wikipedia. Pumiliotoxin 251D. Last Updated 13 May 2009. [Link]
Target Details
10. Sodium channel protein type 5 subunit alpha
General Function:
Voltage-gated sodium channel activity involved in sa node cell action potential
Specific Function:
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential. Channel inactivation is regulated by intracellular calcium levels.
Gene Name:
SCN5A
Uniprot ID:
Q14524
Molecular Weight:
226937.475 Da
References
  1. Tamburini R, Albuquerque EX, Daly JW, Kauffman FC: Inhibition of calcium-dependent ATPase from sarcoplasmic reticulum by a new class of indolizidine alkaloids, pumiliotoxins A, B, and 251D. J Neurochem. 1981 Sep;37(3):775-80. [6456330 ]
  2. Vandendriessche T, Abdel-Mottaleb Y, Maertens C, Cuypers E, Sudau A, Nubbemeyer U, Mebs D, Tytgat J: Modulation of voltage-gated Na+ and K+ channels by pumiliotoxin 251D: a "joint venture" alkaloid from arthropods and amphibians. Toxicon. 2008 Mar 1;51(3):334-44. Epub 2007 Oct 24. [18061227 ]
  3. Wikipedia. Pumiliotoxin 251D. Last Updated 13 May 2009. [Link]
Target Details
11. Sodium channel subunit beta-1
General Function:
Voltage-gated sodium channel activity involved in purkinje myocyte action potential
Specific Function:
Crucial in the assembly, expression, and functional modulation of the heterotrimeric complex of the sodium channel. The subunit beta-1 can modulate multiple alpha subunit isoforms from brain, skeletal muscle, and heart. Its association with neurofascin may target the sodium channels to the nodes of Ranvier of developing axons and retain these channels at the nodes in mature myelinated axons.Isoform 2: Cell adhesion molecule that plays a critical role in neuronal migration and pathfinding during brain development. Stimulates neurite outgrowth.
Gene Name:
SCN1B
Uniprot ID:
Q07699
Molecular Weight:
24706.955 Da
References
  1. Tamburini R, Albuquerque EX, Daly JW, Kauffman FC: Inhibition of calcium-dependent ATPase from sarcoplasmic reticulum by a new class of indolizidine alkaloids, pumiliotoxins A, B, and 251D. J Neurochem. 1981 Sep;37(3):775-80. [6456330 ]
  2. Vandendriessche T, Abdel-Mottaleb Y, Maertens C, Cuypers E, Sudau A, Nubbemeyer U, Mebs D, Tytgat J: Modulation of voltage-gated Na+ and K+ channels by pumiliotoxin 251D: a "joint venture" alkaloid from arthropods and amphibians. Toxicon. 2008 Mar 1;51(3):334-44. Epub 2007 Oct 24. [18061227 ]
  3. Wikipedia. Pumiliotoxin 251D. Last Updated 13 May 2009. [Link]
Target Details
12. Voltage-dependent L-type calcium channel subunit alpha-1C
General Function:
Voltage-gated calcium channel activity
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1C gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1C subunit play an important role in excitation-contraction coupling in the heart. The various isoforms display marked differences in the sensitivity to DHP compounds. Binding of calmodulin or CABP1 at the same regulatory sites results in an opposit effects on the channel function.
Gene Name:
CACNA1C
Uniprot ID:
Q13936
Molecular Weight:
248974.1 Da
References
  1. Wikipedia. Pumiliotoxin. Last Updated 5 October 2008. [Link]
Target Details
13. Voltage-dependent L-type calcium channel subunit alpha-1D
General Function:
Voltage-gated calcium channel activity involved sa node cell action potential
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1D gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA).
Gene Name:
CACNA1D
Uniprot ID:
Q01668
Molecular Weight:
245138.75 Da
References
  1. Wikipedia. Pumiliotoxin. Last Updated 5 October 2008. [Link]
Target Details
14. Voltage-dependent L-type calcium channel subunit alpha-1F
General Function:
Voltage-gated calcium channel activity
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1F gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA).
Gene Name:
CACNA1F
Uniprot ID:
O60840
Molecular Weight:
220675.9 Da
References
  1. Wikipedia. Pumiliotoxin. Last Updated 5 October 2008. [Link]
Target Details
15. Voltage-dependent L-type calcium channel subunit alpha-1S
General Function:
Voltage-gated calcium channel activity
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1S gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1S subunit play an important role in excitation-contraction coupling in skeletal muscle.
Gene Name:
CACNA1S
Uniprot ID:
Q13698
Molecular Weight:
212348.1 Da
References
  1. Wikipedia. Pumiliotoxin. Last Updated 5 October 2008. [Link]
Target Details
16. Voltage-dependent L-type calcium channel subunit beta-1
General Function:
Voltage-gated calcium channel activity
Specific Function:
The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting.
Gene Name:
CACNB1
Uniprot ID:
Q02641
Molecular Weight:
65712.995 Da
References
  1. Wikipedia. Pumiliotoxin. Last Updated 5 October 2008. [Link]
Target Details
17. Voltage-dependent L-type calcium channel subunit beta-2
General Function:
Voltage-gated calcium channel activity
Specific Function:
The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting.
Gene Name:
CACNB2
Uniprot ID:
Q08289
Molecular Weight:
73579.925 Da
References
  1. Wikipedia. Pumiliotoxin. Last Updated 5 October 2008. [Link]
Target Details
18. Voltage-dependent L-type calcium channel subunit beta-3
General Function:
Voltage-gated calcium channel activity
Specific Function:
The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting.
Gene Name:
CACNB3
Uniprot ID:
P54284
Molecular Weight:
54531.425 Da
References
  1. Wikipedia. Pumiliotoxin. Last Updated 5 October 2008. [Link]
Target Details
19. Voltage-dependent L-type calcium channel subunit beta-4
General Function:
Voltage-gated calcium channel activity
Specific Function:
The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting.
Gene Name:
CACNB4
Uniprot ID:
O00305
Molecular Weight:
58168.625 Da
References
  1. Wikipedia. Pumiliotoxin. Last Updated 5 October 2008. [Link]
Target Details
20. Voltage-dependent N-type calcium channel subunit alpha-1B
General Function:
Voltage-gated calcium channel activity
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1B gives rise to N-type calcium currents. N-type calcium channels belong to the 'high-voltage activated' (HVA) group and are blocked by omega-conotoxin-GVIA (omega-CTx-GVIA) and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to dihydropyridines (DHP), and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing alpha-1B subunit may play a role in directed migration of immature neurons.
Gene Name:
CACNA1B
Uniprot ID:
Q00975
Molecular Weight:
262493.84 Da
References
  1. Wikipedia. Pumiliotoxin. Last Updated 5 October 2008. [Link]
Target Details
21. Voltage-dependent P/Q-type calcium channel subunit alpha-1A
General Function:
Voltage-gated calcium channel activity
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1A gives rise to P and/or Q-type calcium currents. P/Q-type calcium channels belong to the 'high-voltage activated' (HVA) group and are blocked by the funnel toxin (Ftx) and by the omega-agatoxin-IVA (omega-Aga-IVA). They are however insensitive to dihydropyridines (DHP), and omega-conotoxin-GVIA (omega-CTx-GVIA).
Gene Name:
CACNA1A
Uniprot ID:
O00555
Molecular Weight:
282362.39 Da
References
  1. Wikipedia. Pumiliotoxin. Last Updated 5 October 2008. [Link]
Target Details
22. Voltage-dependent R-type calcium channel subunit alpha-1E
General Function:
Voltage-gated calcium channel activity
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1E gives rise to R-type calcium currents. R-type calcium channels belong to the 'high-voltage activated' (HVA) group and are blocked by nickel, and partially by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to dihydropyridines (DHP), omega-conotoxin-GVIA (omega-CTx-GVIA), and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing alpha-1E subunit could be involved in the modulation of firing patterns of neurons which is important for information processing.
Gene Name:
CACNA1E
Uniprot ID:
Q15878
Molecular Weight:
261729.05 Da
References
  1. Wikipedia. Pumiliotoxin. Last Updated 5 October 2008. [Link]
Target Details
23. Voltage-dependent T-type calcium channel subunit alpha-1G
General Function:
Scaffold protein binding
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1G gives rise to T-type calcium currents. T-type calcium channels belong to the "low-voltage activated (LVA)" group and are strongly blocked by mibefradil. A particularity of this type of channel is an opening at quite negative potentials and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes.
Gene Name:
CACNA1G
Uniprot ID:
O43497
Molecular Weight:
262468.62 Da
References
  1. Wikipedia. Pumiliotoxin. Last Updated 5 October 2008. [Link]
Target Details
24. Voltage-dependent T-type calcium channel subunit alpha-1H
General Function:
Scaffold protein binding
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1H gives rise to T-type calcium currents. T-type calcium channels belong to the "low-voltage activated (LVA)" group and are strongly blocked by nickel and mibefradil. A particularity of this type of channels is an opening at quite negative potentials, and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes.
Gene Name:
CACNA1H
Uniprot ID:
O95180
Molecular Weight:
259160.2 Da
References
  1. Wikipedia. Pumiliotoxin. Last Updated 5 October 2008. [Link]
Target Details
25. Voltage-dependent T-type calcium channel subunit alpha-1I
General Function:
Voltage-gated calcium channel activity
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. Isoform alpha-1I gives rise to T-type calcium currents. T-type calcium channels belong to the "low-voltage activated (LVA)" group and are strongly blocked by nickel and mibefradil. A particularity of this type of channels is an opening at quite negative potentials, and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes. Gates in voltage ranges similar to, but higher than alpha 1G or alpha 1H (By similarity).
Gene Name:
CACNA1I
Uniprot ID:
Q9P0X4
Molecular Weight:
245100.8 Da
References
  1. Wikipedia. Pumiliotoxin. Last Updated 5 October 2008. [Link]