CACNA1A

Voltage-dependent calcium channels 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, and gene expression. Calcium channels are multisubunit complexes composed of alpha-1, beta, alpha-2/delta, and gamma subunits. The channel activity is directed by the pore-forming alpha-1 subunit, whereas, the others act as auxiliary subunits regulating this activity. The distinctive properties of the calcium channel types are related primarily to the expression of a variety of alpha-1 isoforms, alpha-1A, B, C, D, E, and S. This gene encodes the alpha-1A subunit, which is predominantly expressed in neuronal tissue. Mutations in this gene are associated with 2 neurologic disorders, familial hemiplegic migraine and episodic ataxia 2. This gene also exhibits polymorphic variation due to (CAG)n-repeats. Multiple transcript variants encoding different isoforms have been found for this gene. In one set of transcript variants, the (CAG)n-repeats occur in the 3' UTR, and are not associated with any disease. But in another set of variants, an insertion extends the coding region to include the (CAG)n-repeats which encode a polyglutamine tract. Expansion of the (CAG)n-repeats from the normal 4-18 to 21-33 in the coding region is associated with spinocerebellar ataxia 6.

calcium channel BI-1

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 specifically blocked by the spider omega-agatoxin-IVA (AC P54282) (By similarity).
They are however insensitive to dihydropyridines (DHP).

Calcium ion import Source: GO_Central
Calcium ion transmembrane transport Source: UniProtKB
Calcium ion transport Source: GO_Central
Cell death Source: UniProtKB
Cellular response to amyloid-beta Source: ARUK-UCL
Chemical synaptic transmission Source: GO_Central
Membrane depolarization Source: Reactome
Modulation of chemical synaptic transmission Source: ARUK-UCL
Positive regulation of cytosolic calcium ion concentration Source: UniProtKB
Regulation of insulin secretion Source: Reactome
Regulation of ion transmembrane transport Source: UniProtKB-KW
Response to amyloid-beta Source: ARUK-UCL

Cell membrane

Spinocerebellar ataxia 6 (SCA6): Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA6 is an autosomal dominant cerebellar ataxia (ADCA), mainly caused by expansion of a CAG repeat in the coding region of CACNA1A. There seems to be a correlation between the repeat number and earlier onset of the disorder.
Migraine, familial hemiplegic, 1 (FHM1): A subtype of migraine with aura associated with ictal hemiparesis and, in some families, cerebellar ataxia and atrophy. Migraine is a disabling symptom complex of periodic headaches, usually temporal and unilateral. Headaches are often accompanied by irritability, nausea, vomiting and photophobia, preceded by constriction of the cranial arteries. Migraine with aura is characterized by recurrent attacks of reversible neurological symptoms (aura) that precede or accompany the headache. Aura may include a combination of sensory disturbances, such as blurred vision, hallucinations, vertigo, numbness and difficulty in concentrating and speaking.
Episodic ataxia 2 (EA2): An autosomal dominant disorder characterized by acetozolamide-responsive attacks of ataxia, migraine-like symptoms, interictal nystagmus, and cerebellar atrophy.
Developmental and epileptic encephalopathy 42 (DEE42): A form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE42 inheritance is autosomal dominant.

Cytoplasmic: 1-98 aa
Helical: 99-117 aa
Extracellular: 118-135 aa
Helical: 136-155 aa
Cytoplasmic: 156-167 aa
Helical: 168-185 aa
Extracellular: 186-190 aa
Helical: 191-209 aa
Cytoplasmic: 210-228 aa
Helical: 229-248 aa
Extracellular: 249-335 aa
Helical: 336-360 aa
Cytoplasmic: 361-486 aa
Helical: 487-505 aa
Extracellular: 506-520 aa
Helical: 521-540 aa
Cytoplasmic: 541-548 aa
Helical: 549-567 aa
Extracellular: 568-577 aa
Helical: 578-596 aa
Cytoplasmic: 597-615 aa
Helical: 616-635 aa
Extracellular: 636-688 aa
Helical: 689-713 aa
Cytoplasmic: 714-1241 aa
Helical: 1242-1260 aa
Extracellular: 1261-1276 aa
Helical: 1277-1296 aa
Cytoplasmic: 1297-1308 aa
Helical: 1309-1327 aa
Extracellular: 1328-1338 aa
Helical: 1339-1357 aa
Cytoplasmic: 1358-1376 aa
Helical: 1377-1396 aa
Extracellular: 1397-1483 aa
Helical: 1484-1508 aa
Cytoplasmic: 1509-1563 aa
Helical: 1564-1592 aa
Extracellular: 1593-1597 aa
Helical: 1598-1617 aa
Cytoplasmic: 1618-1625 aa
Helical: 1626-1644 aa
Extracellular: 1645-1651 aa
Helical: 1652-1670 aa
Cytoplasmic: 1671-1689 aa
Helical: 1690-1709 aa
Extracellular: 1710-1781 aa
Helical: 1782-1806 aa
Cytoplasmic: 1807-2506 aa