ID:CA2D2_MOUSE DESCRIPTION: RecName: Full=Voltage-dependent calcium channel subunit alpha-2/delta-2; AltName: Full=Protein ducky; AltName: Full=Voltage-gated calcium channel subunit alpha-2/delta-2; Contains: RecName: Full=Voltage-dependent calcium channel subunit alpha-2-2; Contains: RecName: Full=Voltage-dependent calcium channel subunit delta-2; Flags: Precursor; FUNCTION: The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-type calcium channel (CACNA1A), N-type (CACNA1B), L-type (CACNA1C OR CACNA1D) and possibly T-type (CACNA1G). SUBUNIT: Dimer formed of alpha-2-2 and delta-2 chains; disulfide- linked. Voltage-dependent calcium channels are multisubunit complexes, consisting of alpha-1 (CACNA1), alpha-2 (CACNA2D), beta (CACNB) and delta (CACNA2D) subunits in a 1:1:1:1 ratio (Probable). SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein (Potential). Note=Colocalizes with CACNA1A in lipid raft fractions. TISSUE SPECIFICITY: Predominantly expressed in brain in a restricted pattern. Also expressed at lower level in kidney and testis Not expressed in lung at any moment of development. In brain, it localizes to sections of P21 brain. Expressed at high level in the cerebellum, with moderate levels in medulla, pons, and striatum. Also expressed in cortex, hippocampus, habenula and nucleus reticularis thalami (nRT). Strongly expressed in cerebellar Purkinje cells. DOMAIN: The MIDAS-like motif in the VWFA domain binds divalent metal cations and is required to promote trafficking of the alpha- 1 (CACNA1) subunit to the plasma membrane by an integrin-like switch. PTM: N-glycosylated. PTM: May be proteolytically processed into subunits alpha-2-2 and delta-2 that are disulfide-linked. It is however unclear whether such cleavage really takes place in vivo and has a functional role. According to PubMed:11306709, it is processed, at least in vitro, while according to PubMed:17052222, it is only poorly processed in vivo. DISEASE: Note=Defects in Cacna2d2 are the cause of ducky phenotype (du). Du mice have spike-wave seizures characteristic of absence epilepsy and ataxia, with accompanying decreased calcium channel current in cerebellar Purkinje cells. DISRUPTION PHENOTYPE: Mice exhibit growth retardation, reduced life span, ataxic gait with apoptosis of cerebellar granule cells followed by Purkinje cell depletion, enhanced susceptibility to seizures, and cardiac abnormalities. MISCELLANEOUS: Binds gabapentin, an antiepileptic drug. SIMILARITY: Belongs to the calcium channel subunit alpha-2/delta family. SIMILARITY: Contains 1 cache domain. SIMILARITY: Contains 1 VWFA domain. SEQUENCE CAUTION: Sequence=AAL01651.1; Type=Frameshift; Positions=301;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF00092 - von Willebrand factor type A domain PF08399 - VWA N-terminal PF08473 - Neuronal voltage-dependent calcium channel alpha 2acd PF13519 - von Willebrand factor type A domain PF13768 - von Willebrand factor type A domain
SCOP Domains: 46585 - HR1 repeat 47364 - Domain of the SRP/SRP receptor G-proteins 53300 - vWA-like 56601 - beta-lactamase/transpeptidase-like
ModBase Predicted Comparative 3D Structure on Q6PHS9
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0005244 voltage-gated ion channel activity GO:0005245 voltage-gated calcium channel activity GO:0005262 calcium channel activity GO:0046872 metal ion binding
Biological Process: GO:0006811 ion transport GO:0006816 calcium ion transport GO:0007528 neuromuscular junction development GO:0034765 regulation of ion transmembrane transport GO:0040014 regulation of multicellular organism growth GO:0046622 positive regulation of organ growth GO:0048747 muscle fiber development GO:0060024 rhythmic synaptic transmission GO:0070588 calcium ion transmembrane transport
Cellular Component: GO:0005891 voltage-gated calcium channel complex GO:0016020 membrane GO:0016021 integral component of membrane
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