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{
"metadata": {
"accession": "IPR005452",
"entry_id": null,
"type": "family",
"go_terms": [
{
"identifier": "GO:0005245",
"name": "voltage-gated calcium channel activity",
"category": {
"code": "F",
"name": "molecular_function"
}
},
{
"identifier": "GO:0070588",
"name": "calcium ion transmembrane transport",
"category": {
"code": "P",
"name": "biological_process"
}
},
{
"identifier": "GO:0005891",
"name": "voltage-gated calcium channel complex",
"category": {
"code": "C",
"name": "cellular_component"
}
}
],
"source_database": "interpro",
"member_databases": {
"prints": {
"PR01636": "LVDCCALPHA1D"
}
},
"integrated": null,
"hierarchy": {
"accession": "IPR002077",
"name": "Voltage-dependent calcium channel, alpha-1 subunit",
"type": "Family",
"children": [
{
"accession": "IPR005446",
"name": "Voltage-dependent calcium channel, L-type, alpha-1 subunit",
"type": "Family",
"children": [
{
"accession": "IPR005450",
"name": "Voltage-dependent calcium channel, L-type, alpha-1S subunit",
"type": "Family",
"children": []
},
{
"accession": "IPR005451",
"name": "Voltage-dependent calcium channel, L-type, alpha-1C subunit",
"type": "Family",
"children": []
},
{
"accession": "IPR005452",
"name": "Voltage-dependent calcium channel, L-type, alpha-1D subunit",
"type": "Family",
"children": []
}
]
},
{
"accession": "IPR005447",
"name": "Voltage-dependent calcium channel, N-type, alpha-1 subunit",
"type": "Family",
"children": []
},
{
"accession": "IPR005448",
"name": "Voltage-dependent calcium channel, P/Q-type, alpha-1 A",
"type": "Family",
"children": []
},
{
"accession": "IPR005449",
"name": "Voltage-dependent calcium channel, R-type, alpha-1 subunit",
"type": "Family",
"children": []
}
]
},
"name": {
"name": "Voltage-dependent calcium channel, L-type, alpha-1D subunit",
"short": "LVDCC_a1dsu"
},
"description": [
{
"text": "<p>This entry represents the alpha-1D subunits of the Voltage-dependent calcium channel, L-type (LVDCC), which allow cells to slowly inactivate voltage-gated Ca2+ influx to weak depolarisations [[cite:PUB00007839]]. This property allows them to participate in important physiological functions, such as tonic neurotransmitter release in cochlear inner hair cells [[cite:PUB00007840]]. In addition, these properties make them ideally suited to contribute to subthreshold Ca2+ signalling, for example in hippocampal pyramidal cells [[cite:PUB00007841]]. Mutations in this channel have been associated with autism spectrum disorders and epilepsy [[cite:PUB00100491]].</p>",
"llm": false,
"checked": false,
"updated": false
},
{
"text": "<p>Ca2+ ions are unique in that they not only carry charge but they are also the most widely used of diffusible second messengers. Voltage-dependent Ca2+ channels (VDCC) are a family of molecules that allow cells to couple electrical activity to intracellular Ca2+ signalling. The opening and closing of these channels by depolarizing stimuli, such as action potentials, allows Ca2+ ions to enter neurons down a steep electrochemical gradient, producing transient intracellular Ca2+ signals. Many of the processes that occur in neurons, including transmitter release, gene transcription and metabolism are controlled by Ca2+ influx occurring simultaneously at different cellular locales. The pore is formed by the alpha-1 subunit which incorporates the conduction pore, the voltage sensor and gating apparatus, and the known sites of channel regulation by second messengers, drugs, and toxins [[cite:PUB00036034]]. The activity of this pore is modulated by four tightly-coupled subunits: an intracellular beta subunit; a transmembrane gamma subunit; and a disulphide-linked complex of alpha-2 and delta subunits, which are proteolytically cleaved from the same gene product. Properties of the protein including gating voltage-dependence, G protein modulation and kinase susceptibility can be influenced by these subunits.</p>\r\n\r\n<p>Voltage-gated calcium channels are classified as T, L, N, P, Q and R, and are distinguished by their sensitivity to pharmacological blocks, single-channel conductance kinetics, and voltage-dependence. On the basis of their voltage activation properties, the voltage-gated calcium classes can be further divided into two broad groups: the low (T-type) and high (L, N, P, Q and R-type) threshold-activated channels.</p>",
"llm": false,
"checked": false,
"updated": false
},
{
"text": "<p>L-type calcium channels are formed from alpha-1S, alpha-1C, alpha-1D, and alpha-1F subunits. They are widely distributed and are well characterised in the heart, smooth and skeletal muscle, and some neurons. Their primary functions are in both excitation-contraction and excitation-secretion coupling. In skeletal muscle, the L-type calcium channels act as a voltage sensor for excitation-contraction coupling, and in cardiac muscle, they provide a pathway for calcium influx. Mutations affecting L-type channel subunits result in three diseases: (1) muscular dystrophy, which is characterised by a lack of functional skeletal muscle; (2) hypokalaemic periodic paralysis, which is characterised by episodic attacks of skeletal muscle weakness; and (3) malignant hyperthermia, which is the main cause of death due to anaesthesia. 1,4-dihydropyridines act as antagonists of these channels [[cite:PUB00036043], [cite:PUB00071805]].</p>",
"llm": false,
"checked": false,
"updated": false
},
{
"text": "<p>The alpha-1 subunit forms the pore for the import of extracellular calcium ions and, though regulated by the other subunits, is primarily responsible for the pharmacological properties of the channel [[cite:PUB00036040]]. It shares sequence characteristics with all voltage-dependent cation channels, and exploits the same 6-helix bundle structural motif -in both sodium and calcium channels, this motif is repeated 4 times within the sequence to give a 24-helix bundle. Within each of these repeats, 5 of the transmembrane (TM) segments (S1, S2, S3, S5, S6) are hydrophobic, while the other (S4) is positively charged and serves as the voltage-sensor. Several genes encoding alpha-1 subunits have been identified and can be divided into three functionally distinct families based on sequence homology -Cav1, Cav2 and Cav3 [[cite:PUB00036041]]. The Cav1 family forms channels mediating L-type calcium currents, the Cav2 family mediates P/Q-, N-, and R-type calcium currents, while the Cav3 family mediates T-type calcium currents.</p>",
"llm": false,
"checked": false,
"updated": false
}
],
"wikipedia": null,
"literature": {
"PUB00071805": {
"PMID": 15336981,
"ISBN": null,
"volume": "322",
"issue": "4",
"year": 2004,
"title": "L-type Ca2+ channels in Ca2+ channelopathies.",
"URL": null,
"raw_pages": "1341-6",
"medline_journal": "Biochem Biophys Res Commun",
"ISO_journal": "Biochem. Biophys. Res. Commun.",
"authors": [
"Striessnig J",
"Hoda JC",
"Koschak A",
"Zaghetto F",
"Mullner C",
"Sinnegger-Brauns MJ",
"Wild C",
"Watschinger K",
"Trockenbacher A",
"Pelster G."
],
"DOI_URL": "http://dx.doi.org/10.1016/j.bbrc.2004.08.039"
},
"PUB00007839": {
"PMID": 11285265,
"ISBN": null,
"volume": "276",
"issue": "25",
"year": 2001,
"title": "alpha 1D (Cav1.3) subunits can form l-type Ca2+ channels activating at negative voltages.",
"URL": null,
"raw_pages": "22100-6",
"medline_journal": "J Biol Chem",
"ISO_journal": "J. Biol. Chem.",
"authors": [
"Koschak A",
"Reimer D",
"Huber I",
"Grabner M",
"Glossmann H",
"Engel J",
"Striessnig J."
],
"DOI_URL": "http://dx.doi.org/10.1074/jbc.M101469200"
},
"PUB00036043": {
"PMID": 12825828,
"ISBN": null,
"volume": "23",
"issue": "3",
"year": 2003,
"title": "1,4-Dihydropyridines as calcium channel ligands and privileged structures.",
"URL": null,
"raw_pages": "293-303",
"medline_journal": "Cell Mol Neurobiol",
"ISO_journal": "Cell. Mol. Neurobiol.",
"authors": [
"Triggle DJ."
],
"DOI_URL": "http://dx.doi.org/10.1023/A:1023632419813"
},
"PUB00036040": {
"PMID": 11031246,
"ISBN": null,
"volume": "16",
"issue": null,
"year": 2000,
"title": "Structure and regulation of voltage-gated Ca2+ channels.",
"URL": null,
"raw_pages": "521-55",
"medline_journal": "Annu Rev Cell Dev Biol",
"ISO_journal": "Annu. Rev. Cell Dev. Biol.",
"authors": [
"Catterall WA."
],
"DOI_URL": "http://dx.doi.org/10.1146/annurev.cellbio.16.1.521"
},
"PUB00036041": {
"PMID": 10774722,
"ISBN": null,
"volume": "25",
"issue": "3",
"year": 2000,
"title": "Nomenclature of voltage-gated calcium channels.",
"URL": null,
"raw_pages": "533-5",
"medline_journal": "Neuron",
"ISO_journal": "Neuron",
"authors": [
"Ertel EA",
"Campbell KP",
"Harpold MM",
"Hofmann F",
"Mori Y",
"Perez-Reyes E",
"Schwartz A",
"Snutch TP",
"Tanabe T",
"Birnbaumer L",
"Tsien RW",
"Catterall WA."
],
"DOI_URL": "http://dx.doi.org/10.1016/S0896-6273(00)81057-0"
},
"PUB00036034": {
"PMID": 14657414,
"ISBN": null,
"volume": "55",
"issue": "4",
"year": 2003,
"title": "International Union of Pharmacology. XL. Compendium of voltage-gated ion channels: calcium channels.",
"URL": null,
"raw_pages": "579-81",
"medline_journal": "Pharmacol Rev",
"ISO_journal": "Pharmacol. Rev.",
"authors": [
"Catterall WA",
"Striessnig J",
"Snutch TP",
"Perez-Reyes E; International Union of Pharmacology."
],
"DOI_URL": "http://dx.doi.org/10.1124/pr.55.4.8"
},
"PUB00007841": {
"PMID": 8930286,
"ISBN": null,
"volume": "76",
"issue": "5",
"year": 1996,
"title": "Dihydropyridine-sensitive, voltage-gated Ca2+ channels contribute to the resting intracellular Ca2+ concentration of hippocampal CA1 pyramidal neurons.",
"URL": null,
"raw_pages": "3460-70",
"medline_journal": "J Neurophysiol",
"ISO_journal": "J. Neurophysiol.",
"authors": [
"Magee JC",
"Avery RB",
"Christie BR",
"Johnston D."
],
"DOI_URL": "http://intl-jn.physiology.org/cgi/content/abstract/76/5/3460"
},
"PUB00007840": {
"PMID": 10639174,
"ISBN": null,
"volume": "97",
"issue": "2",
"year": 2000,
"title": "Kinetics of exocytosis and endocytosis at the cochlear inner hair cell afferent synapse of the mouse.",
"URL": null,
"raw_pages": "883-8",
"medline_journal": "Proc Natl Acad Sci U S A",
"ISO_journal": "Proc. Natl. Acad. Sci. U.S.A.",
"authors": [
"Moser T",
"Beutner D."
],
"DOI_URL": "http://dx.doi.org/10.1073/pnas.97.2.883"
},
"PUB00100491": {
"PMID": 28472301,
"ISBN": null,
"volume": "26",
"issue": "15",
"year": 2017,
"title": "New gain-of-function mutation shows CACNA1D as recurrently mutated gene in autism spectrum disorders and epilepsy.",
"URL": null,
"raw_pages": "2923-2932",
"medline_journal": "Hum Mol Genet",
"ISO_journal": "Hum Mol Genet",
"authors": [
"Pinggera A",
"Mackenroth L",
"Rump A",
"Schallner J",
"Beleggia F",
"Wollnik B",
"Striessnig J."
],
"DOI_URL": null
}
},
"set_info": null,
"overlaps_with": [
{
"accession": "IPR027359",
"name": "Voltage-dependent channel domain superfamily",
"type": "homologous_superfamily"
}
],
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"matches": 6459,
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"structural_models": {
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},
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"taxa": 1459
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"is_llm": false,
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}
}
