CA2D2_MOUSE
ID CA2D2_MOUSE Reviewed; 1154 AA.
AC Q6PHS9; B2RY16; Q3TPT9; Q3TSS6; Q6REE3; Q8C8R8; Q8CHE9; Q920H5; Q920H6;
AC Q9EQG2; Q9R142;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Voltage-dependent calcium channel subunit alpha-2/delta-2;
DE AltName: Full=Protein ducky;
DE AltName: Full=Voltage-gated calcium channel subunit alpha-2/delta-2;
DE Contains:
DE RecName: Full=Voltage-dependent calcium channel subunit alpha-2-2;
DE Contains:
DE RecName: Full=Voltage-dependent calcium channel subunit delta-2;
DE Flags: Precursor;
GN Name=Cacna2d2; Synonyms=Kiaa0558;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RC STRAIN=TKDU;
RX PubMed=11130987; DOI=10.1007/s003350010211;
RA Barclay J., Rees M.;
RT "Genomic organization of the mouse and human alpha2delta2 voltage-dependent
RT calcium channel subunit genes.";
RL Mamm. Genome 11:1142-1144(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND INVOLVEMENT IN DU.
RC STRAIN=TKDU;
RX PubMed=11487633; DOI=10.1523/jneurosci.21-16-06095.2001;
RA Barclay J., Balaguero N., Mione M., Ackerman S.L., Letts V.A., Brodbeck J.,
RA Canti C., Meir A., Page K.M., Kusumi K., Perez-Reyes E., Lander E.S.,
RA Frankel W.N., Gardiner R.M., Dolphin A.C., Rees M.;
RT "Ducky mouse phenotype of epilepsy and ataxia is associated with mutations
RT in the Cacna2d2 gene and decreased calcium channel current in cerebellar
RT Purkinje cells.";
RL J. Neurosci. 21:6095-6104(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), AND
RP VARIANT ILE-TYR-LYS-ASP-ASN-ARG-ASN-LEU-PHE-GLU-VAL-GLN-GLU-ASN-GLU-PRO-
RP GLN-LYS-LEU-VAL-GLU-LYS-VAL-ALA-GLY-ASP-ILE-GLU-SER-LEU-LEU-ASP-ARG-LYS-
RP VAL-GLN-ALA-LEU-LYS-99 INS.
RC STRAIN=DBA/2J;
RX PubMed=14660671; DOI=10.1074/jbc.m308778200;
RA Brill J., Klocke R., Paul D., Boison D., Gouder N., Klugbauer N.,
RA Hofmann F., Becker C.-M., Becker K.;
RT "entla, a novel epileptic and ataxic Cacna2d2 mutant of the mouse.";
RL J. Biol. Chem. 279:7322-7330(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 788-1154 (ISOFORM 6).
RC STRAIN=C57BL/6J; TISSUE=Hippocampus, Medulla oblongata, and Retina;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4).
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 53-1154 (ISOFORM 5).
RX PubMed=12465718; DOI=10.1093/dnares/9.5.179;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Hara Y., Nagase T., Ohara O.,
RA Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: I.
RT The complete nucleotide sequences of 100 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 9:179-188(2002).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 932-1154.
RX PubMed=10766861; DOI=10.1074/jbc.275.16.12237;
RA Gao B., Sekido Y., Maximov A., Saad M., Forgacs E., Latif F., Wei M.-H.,
RA Lerman M., Lee J.-H., Perez-Reyes E., Bezprozvanny I., Minna J.D.;
RT "Functional properties of a new voltage-dependent calcium channel
RT alpha(2)delta auxiliary subunit gene (CACNA2D2).";
RL J. Biol. Chem. 275:12237-12242(2000).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=10762351; DOI=10.1046/j.1460-9568.2000.01009.x;
RA Hobom M., Dai S., Marais E., Lacinova L., Hofmann F., Klugbauer N.;
RT "Neuronal distribution and functional characterization of the calcium
RT channel alpha2delta-2 subunit.";
RL Eur. J. Neurosci. 12:1217-1226(2000).
RN [9]
RP DISULFIDE BONDS, GLYCOSYLATION, PROTEOLYTIC PROCESSING, AND
RP GABAPENTIN-BINDING.
RX PubMed=11306709; DOI=10.1124/mol.59.5.1243;
RA Marais E., Klugbauer N., Hofmann F.;
RT "Calcium channel alpha(2)delta subunits-structure and Gabapentin binding.";
RL Mol. Pharmacol. 59:1243-1248(2001).
RN [10]
RP SUBCELLULAR LOCATION, AND INVOLVEMENT IN DU.
RX PubMed=11756448; DOI=10.1074/jbc.m109404200;
RA Brodbeck J., Davies A., Courtney J.-M., Meir A., Balaguero N., Canti C.,
RA Moss F.J., Page K.M., Pratt W.S., Hunt S.P., Barclay J., Rees M.,
RA Dolphin A.C.;
RT "The ducky mutation in Cacna2d2 results in altered Purkinje cell morphology
RT and is associated with the expression of a truncated alpha 2 delta-2
RT protein with abnormal function.";
RL J. Biol. Chem. 277:7684-7693(2002).
RN [11]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15331424; DOI=10.1016/s0002-9440(10)63362-7;
RA Ivanov S.V., Ward J.M., Tessarollo L., McAreavey D., Sachdev V.,
RA Fananapazir L., Banks M.K., Morris N., Djurickovic D., Devor-Henneman D.E.,
RA Wei M.-H., Alvord G.W., Gao B., Richardson J.A., Minna J.D., Rogawski M.A.,
RA Lerman M.I.;
RT "Cerebellar ataxia, seizures, premature death, and cardiac abnormalities in
RT mice with targeted disruption of the Cacna2d2 gene.";
RL Am. J. Pathol. 165:1007-1018(2004).
RN [12]
RP METAL-BINDING, MIDAS-LIKE MOTIF, AND MUTAGENESIS OF ASP-300; SER-302 AND
RP SER-304.
RX PubMed=16061813; DOI=10.1073/pnas.0504183102;
RA Canti C., Nieto-Rostro M., Foucault I., Heblich F., Wratten J.,
RA Richards M.W., Hendrich J., Douglas L., Page K.M., Davies A., Dolphin A.C.;
RT "The metal-ion-dependent adhesion site in the Von Willebrand factor-A
RT domain of alpha2delta subunits is key to trafficking voltage-gated Ca2+
RT channels.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:11230-11235(2005).
RN [13]
RP GLYCOSYLATION, AND LACK OF PROTEOLYTIC PROCESSING.
RX PubMed=17052222; DOI=10.1042/bst0340894;
RA Douglas L., Davies A., Wratten J., Dolphin A.C.;
RT "Do voltage-gated calcium channel alpha2delta subunits require proteolytic
RT processing into alpha2 and delta to be functional?";
RL Biochem. Soc. Trans. 34:894-898(2006).
RN [14]
RP SUBCELLULAR LOCATION, INTERACTION WITH STOML2, GABAPENTIN-BINDING, AND
RP MUTAGENESIS OF ARG-282.
RX PubMed=16928863; DOI=10.1523/jneurosci.2764-06.2006;
RA Davies A., Douglas L., Hendrich J., Wratten J., Tran Van Minh A.,
RA Foucault I., Koch D., Pratt W.S., Saibil H.R., Dolphin A.C.;
RT "The calcium channel alpha2delta-2 subunit partitions with CaV2.1 into
RT lipid rafts in cerebellum: implications for localization and function.";
RL J. Neurosci. 26:8748-8757(2006).
RN [15]
RP INVOLVEMENT IN DU.
RX PubMed=17135419; DOI=10.1523/jneurosci.3080-06.2006;
RA Donato R., Page K.M., Koch D., Nieto-Rostro M., Foucault I., Davies A.,
RA Wilkinson T., Rees M., Edwards F.A., Dolphin A.C.;
RT "The ducky(2J) mutation in Cacna2d2 results in reduced spontaneous Purkinje
RT cell activity and altered gene expression.";
RL J. Neurosci. 26:12576-12586(2006).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Heart;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: The alpha-2/delta subunit of voltage-dependent calcium
CC channels regulates calcium current density and activation/inactivation
CC kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-
CC type calcium channel (CACNA1A), N-type (CACNA1B), L-type (CACNA1C OR
CC CACNA1D) and possibly T-type (CACNA1G). {ECO:0000269|PubMed:15331424}.
CC -!- SUBUNIT: Dimer formed of alpha-2-2 and delta-2 chains; disulfide-
CC linked. Voltage-dependent calcium channels are multisubunit complexes,
CC consisting of alpha-1 (CACNA1), alpha-2 (CACNA2D), beta (CACNB) and
CC delta (CACNA2D) subunits in a 1:1:1:1 ratio (Probable).
CC {ECO:0000305|PubMed:11306709}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}. Note=Colocalizes with CACNA1A in lipid
CC raft fractions. {ECO:0000269|PubMed:11756448,
CC ECO:0000269|PubMed:16928863}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1; Synonyms=Alpha2delta-2a;
CC IsoId=Q6PHS9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6PHS9-2; Sequence=VSP_028061, VSP_028062;
CC Name=3; Synonyms=Alpha2delta-2c;
CC IsoId=Q6PHS9-3; Sequence=VSP_028063;
CC Name=4; Synonyms=Alpha2delta-2b;
CC IsoId=Q6PHS9-4; Sequence=VSP_028061;
CC Name=5;
CC IsoId=Q6PHS9-5; Sequence=VSP_028061, VSP_028062, VSP_028063;
CC Name=6;
CC IsoId=Q6PHS9-6; Sequence=VSP_028062, VSP_028063;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in brain in a restricted
CC pattern. Also expressed at lower level in kidney and testis Not
CC expressed in lung at any moment of development. In brain, it localizes
CC to sections of P21 brain. Expressed at high level in the cerebellum,
CC with moderate levels in medulla, pons, and striatum. Also expressed in
CC cortex, hippocampus, habenula and nucleus reticularis thalami (nRT).
CC Strongly expressed in cerebellar Purkinje cells.
CC {ECO:0000269|PubMed:10762351}.
CC -!- DOMAIN: The MIDAS-like motif in the VWFA domain binds divalent metal
CC cations and is required to promote trafficking of the alpha-1 (CACNA1)
CC subunit to the plasma membrane by an integrin-like switch.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:11306709,
CC ECO:0000269|PubMed:17052222}.
CC -!- PTM: May be proteolytically processed into subunits alpha-2-2 and
CC delta-2 that are disulfide-linked. It is however unclear whether such
CC cleavage really takes place in vivo and has a functional role.
CC According to PubMed:11306709, it is processed, at least in vitro, while
CC according to PubMed:17052222, it is only poorly processed in vivo.
CC {ECO:0000269|PubMed:11306709}.
CC -!- DISEASE: Note=Defects in Cacna2d2 are the cause of ducky phenotype
CC (du). Du mice have spike-wave seizures characteristic of absence
CC epilepsy and ataxia, with accompanying decreased calcium channel
CC current in cerebellar Purkinje cells. {ECO:0000269|PubMed:11487633,
CC ECO:0000269|PubMed:11756448, ECO:0000269|PubMed:14660671,
CC ECO:0000269|PubMed:17135419}.
CC -!- DISRUPTION PHENOTYPE: Mice exhibit growth retardation, reduced life
CC span, ataxic gait with apoptosis of cerebellar granule cells followed
CC by Purkinje cell depletion, enhanced susceptibility to seizures, and
CC cardiac abnormalities. {ECO:0000269|PubMed:15331424}.
CC -!- MISCELLANEOUS: Binds gabapentin, an antiepileptic drug.
CC -!- SIMILARITY: Belongs to the calcium channel subunit alpha-2/delta
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL01651.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF247139; AAG47846.1; -; mRNA.
DR EMBL; AF247141; AAL01650.1; -; mRNA.
DR EMBL; AF247142; AAL01651.1; ALT_FRAME; mRNA.
DR EMBL; AY502107; AAR89454.1; -; mRNA.
DR EMBL; AK044603; BAC31998.1; -; mRNA.
DR EMBL; AK164143; BAE37646.1; -; mRNA.
DR EMBL; AK161839; BAE36599.1; -; mRNA.
DR EMBL; BC056389; AAH56389.1; -; mRNA.
DR EMBL; BC158058; AAI58059.1; -; mRNA.
DR EMBL; AB093246; BAC41430.1; -; mRNA.
DR EMBL; AF169633; AAD48037.1; -; mRNA.
DR CCDS; CCDS52916.1; -. [Q6PHS9-1]
DR CCDS; CCDS52917.1; -. [Q6PHS9-2]
DR CCDS; CCDS72304.1; -. [Q6PHS9-3]
DR CCDS; CCDS72305.1; -. [Q6PHS9-5]
DR RefSeq; NP_001167518.1; NM_001174047.1. [Q6PHS9-3]
DR RefSeq; NP_001167520.1; NM_001174049.1. [Q6PHS9-4]
DR RefSeq; NP_001167521.1; NM_001174050.1. [Q6PHS9-2]
DR RefSeq; NP_064659.2; NM_020263.3. [Q6PHS9-1]
DR RefSeq; XP_011241201.1; XM_011242899.2. [Q6PHS9-6]
DR AlphaFoldDB; Q6PHS9; -.
DR SMR; Q6PHS9; -.
DR BioGRID; 208183; 2.
DR IntAct; Q6PHS9; 2.
DR MINT; Q6PHS9; -.
DR STRING; 10090.ENSMUSP00000132512; -.
DR GlyConnect; 2436; 2 N-Linked glycans (1 site). [Q6PHS9-2]
DR GlyConnect; 2821; 10 N-Linked glycans (4 sites).
DR GlyGen; Q6PHS9; 9 sites, 10 N-linked glycans (4 sites).
DR PhosphoSitePlus; Q6PHS9; -.
DR MaxQB; Q6PHS9; -.
DR PaxDb; Q6PHS9; -.
DR PRIDE; Q6PHS9; -.
DR ProteomicsDB; 281732; -. [Q6PHS9-1]
DR ProteomicsDB; 281733; -. [Q6PHS9-2]
DR ProteomicsDB; 281734; -. [Q6PHS9-3]
DR ProteomicsDB; 281735; -. [Q6PHS9-4]
DR ProteomicsDB; 281736; -. [Q6PHS9-5]
DR ProteomicsDB; 281737; -. [Q6PHS9-6]
DR Antibodypedia; 30959; 155 antibodies from 29 providers.
DR DNASU; 56808; -.
DR Ensembl; ENSMUST00000010210; ENSMUSP00000010210; ENSMUSG00000010066. [Q6PHS9-2]
DR Ensembl; ENSMUST00000085092; ENSMUSP00000082173; ENSMUSG00000010066. [Q6PHS9-1]
DR Ensembl; ENSMUST00000166799; ENSMUSP00000126029; ENSMUSG00000010066. [Q6PHS9-6]
DR Ensembl; ENSMUST00000168532; ENSMUSP00000132512; ENSMUSG00000010066. [Q6PHS9-3]
DR Ensembl; ENSMUST00000170737; ENSMUSP00000125943; ENSMUSG00000010066. [Q6PHS9-5]
DR GeneID; 56808; -.
DR KEGG; mmu:56808; -.
DR UCSC; uc009rli.2; mouse. [Q6PHS9-2]
DR UCSC; uc009rlj.2; mouse. [Q6PHS9-4]
DR UCSC; uc012haf.1; mouse. [Q6PHS9-1]
DR UCSC; uc057apw.1; mouse. [Q6PHS9-3]
DR UCSC; uc057apx.1; mouse. [Q6PHS9-5]
DR CTD; 9254; -.
DR MGI; MGI:1929813; Cacna2d2.
DR VEuPathDB; HostDB:ENSMUSG00000010066; -.
DR eggNOG; KOG2353; Eukaryota.
DR GeneTree; ENSGT00940000156238; -.
DR HOGENOM; CLU_004660_0_0_1; -.
DR InParanoid; Q6PHS9; -.
DR OMA; HCEMDCD; -.
DR OrthoDB; 510149at2759; -.
DR PhylomeDB; Q6PHS9; -.
DR TreeFam; TF315824; -.
DR Reactome; R-MMU-112308; Presynaptic depolarization and calcium channel opening.
DR Reactome; R-MMU-422356; Regulation of insulin secretion.
DR Reactome; R-MMU-5576892; Phase 0 - rapid depolarisation.
DR Reactome; R-MMU-5576893; Phase 2 - plateau phase.
DR BioGRID-ORCS; 56808; 0 hits in 72 CRISPR screens.
DR ChiTaRS; Cacna2d2; mouse.
DR PRO; PR:Q6PHS9; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q6PHS9; protein.
DR Bgee; ENSMUSG00000010066; Expressed in lateral septal nucleus and 206 other tissues.
DR ExpressionAtlas; Q6PHS9; baseline and differential.
DR Genevisible; Q6PHS9; MM.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005891; C:voltage-gated calcium channel complex; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; IDA:MGI.
DR GO; GO:0006816; P:calcium ion transport; ISO:MGI.
DR GO; GO:0055001; P:muscle cell development; IMP:MGI.
DR GO; GO:0007528; P:neuromuscular junction development; IMP:MGI.
DR GO; GO:0035265; P:organ growth; IMP:MGI.
DR GO; GO:0046622; P:positive regulation of organ growth; IMP:MGI.
DR GO; GO:0008016; P:regulation of heart contraction; ISO:MGI.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0040014; P:regulation of multicellular organism growth; IMP:MGI.
DR GO; GO:0060024; P:rhythmic synaptic transmission; IMP:MGI.
DR Gene3D; 3.40.50.410; -; 1.
DR InterPro; IPR013680; VDCC_a2/dsu.
DR InterPro; IPR013608; VWA_N.
DR InterPro; IPR002035; VWF_A.
DR InterPro; IPR036465; vWFA_dom_sf.
DR Pfam; PF08473; VGCC_alpha2; 1.
DR Pfam; PF00092; VWA; 1.
DR Pfam; PF08399; VWA_N; 1.
DR SMART; SM00327; VWA; 1.
DR SUPFAM; SSF53300; SSF53300; 1.
DR PROSITE; PS50234; VWFA; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Calcium channel; Calcium transport;
KW Disease variant; Disulfide bond; Glycoprotein; Ion channel; Ion transport;
KW Membrane; Metal-binding; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix; Transport; Voltage-gated channel.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..1154
FT /note="Voltage-dependent calcium channel subunit alpha-
FT 2/delta-2"
FT /id="PRO_0000304640"
FT CHAIN 19..1004
FT /note="Voltage-dependent calcium channel subunit alpha-2-2"
FT /evidence="ECO:0000255"
FT /id="PRO_0000304641"
FT CHAIN 1005..1154
FT /note="Voltage-dependent calcium channel subunit delta-2"
FT /evidence="ECO:0000255"
FT /id="PRO_0000304642"
FT TOPO_DOM 19..1116
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1117..1137
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1138..1154
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 294..472
FT /note="VWFA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00219"
FT DOMAIN 488..577
FT /note="Cache"
FT REGION 1..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 300..304
FT /note="MIDAS-like motif"
FT COMPBIAS 20..37
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 300
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000305"
FT BINDING 302
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000305"
FT BINDING 304
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000305"
FT CARBOHYD 205
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 389
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 421
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 510
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 543
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 627
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 864
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 446..1101
FT /note="Interchain (between alpha-2-2 and delta-2 chains)"
FT /evidence="ECO:0000250"
FT VAR_SEQ 665..672
FT /note="LPISKLKD -> Y (in isoform 2, isoform 4 and isoform
FT 5)"
FT /evidence="ECO:0000303|PubMed:12465718,
FT ECO:0000303|PubMed:14660671, ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_028061"
FT VAR_SEQ 873
FT /note="K -> KQ (in isoform 2, isoform 5 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:12465718,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_028062"
FT VAR_SEQ 1079..1080
FT /note="HS -> HCPA (in isoform 3, isoform 5 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:11130987,
FT ECO:0000303|PubMed:11487633, ECO:0000303|PubMed:12465718,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_028063"
FT VARIANT 99
FT /note="E -> EIYKDNRNLFEVQENEPQKLVEKVAGDIESLLDRKVQALK (in
FT du; variant allele entla)"
FT MUTAGEN 282
FT /note="R->A: Induces a strong decrease in gabapentin-
FT binding."
FT /evidence="ECO:0000269|PubMed:16928863"
FT MUTAGEN 300
FT /note="D->A: Abolishes metal-binding and ability to
FT regulate calcium current."
FT /evidence="ECO:0000269|PubMed:16061813"
FT MUTAGEN 302
FT /note="S->A: Abolishes metal-binding and ability to
FT regulate calcium current."
FT /evidence="ECO:0000269|PubMed:16061813"
FT MUTAGEN 304
FT /note="S->A: Abolishes metal-binding and ability to
FT regulate calcium current."
FT /evidence="ECO:0000269|PubMed:16061813"
FT CONFLICT 657
FT /note="S -> R (in Ref. 1; AAG47846, 2; AAL01650 and 3;
FT AAR89454)"
FT /evidence="ECO:0000305"
FT CONFLICT 704
FT /note="N -> S (in Ref. 1; AAG47846, 2; AAL01650 and 3;
FT AAR89454)"
FT /evidence="ECO:0000305"
FT CONFLICT 710
FT /note="N -> D (in Ref. 1; AAG47846, 2; AAL01650 and 3;
FT AAR89454)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1154 AA; 130385 MW; AE4F646D89A96053 CRC64;
MAVPARTCGA SWPGPVRTAR PWPGRGPRPC PDPRGPASGP ARPLLLLLPP LLLLPLLTAP
GASAYSFPQQ HTMQHWARRL EQEIDGVMRI FGGVQQLREI YKDNRNLFEV QENEPQKLVE
KVAGDIESLL DRKVQALKRL ADAAENFQKA HRWQDNIKEE DIMYYDAKAD AELDDPESED
MERGSKTSAL RLDFIEDPNF KNKVNYSYTA VQIPTDIYKG STVILNELNW TEALENVFIE
NRRQDPTLLW QVFGSATGVT RYYPATPWRA PKKIDLYDVR RRPWYIQGAS SPKDMVIIVD
VSGSVSGLTL KLMKTSVCEM LDTLSDDDYV NVASFNEKAQ PVSCFTHLVQ ANVRNKKVFK
EAVQGMVAKG TTGYKAGFEY AFDQLQNSNI TRANCNKMIM MFTDGGEDRV QDVFEKYNWP
NRTVRVFTFS VGQHNYDVTP LQWMACTNKG YYFEIPSIGA IRINTQEYLD VLGRPMVLAG
KDAKQVQWTN VYEDALGLGL VVTGTLPVFN LTQDGPGEKK NQLILGVMGI DVALNDIKRL
TPNYTLGANG YVFAIDLNGY VLLHPNLKPQ TTNFREPVTL DFLDAELEDE NKEEIRRSMI
DGDKGHKQIR TLVKSLDERY IDEVIRNYTW VPIRSTNYSL GLVLPPYSTY YLQANLSDQI
LQVKLPISKL KDFEFLLPSS FESEGHVFIA PREYCKDLNA SDNNTEFLKN FIELMEKVTP
DSKQCNNFLL HNLILDTGIT QQLVERVWRD QDLNTYSLLA VFAATDGGIT RVFPNKAAED
WTENPEPFNA SFYRRSLDNH GYIFKPPHQD SLLRPLELEN DTVGVLVSTA VELSLGRRTL
RPAVVGVKLD LEAWAEKFKV LASNRTHQDQ PQKCGPSSHC EMDCEVNNED LLCVLIDDGG
FLVLSNQNHQ WDQVGRFFSE VDANLMLALY NNSFYTRKES YDYQAACAPQ PPGNLGAAPR
GVFVPTIADF LNLAWWTSAA AWSLFQQLLY GLIYHSWFQA DPAEAEGSPE TRESSCVMKQ
TQYYFGSVNA SYNAIIDCGN CSRLFHAQRL TNTNLLFVVA EKPLCSQCEA GRLLQKETHS
DGPEQCELVQ RPRYRRGPHI CFDYNATEDT SDCGRGASFP PSLGVLVSLQ LLLLLGLPPR
PQPQVHSFAA SRHL
