CA2D2_HUMAN
ID CA2D2_HUMAN Reviewed; 1150 AA.
AC Q9NY47; A7MD15; Q9NY48; Q9UEW0; Q9Y268;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 16-MAY-2012, sequence version 2.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Voltage-dependent calcium channel subunit alpha-2/delta-2;
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 Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4), AND TISSUE SPECIFICITY.
RX PubMed=9880589; DOI=10.1523/jneurosci.19-02-00684.1999;
RA Klugbauer N., Lacinova L., Marais E., Hobom M., Hofmann F.;
RT "Molecular diversity of the calcium channel alpha2delta subunit.";
RL J. Neurosci. 19:684-691(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND TISSUE SPECIFICITY.
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Thyroid;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=9628581; DOI=10.1093/dnares/5.1.31;
RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N.,
RA Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. IX. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:31-39(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
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 [8]
RP DISULFIDE BONDS, TISSUE SPECIFICITY, AND GABAPENTIN-BINDING.
RX PubMed=11687876; DOI=10.1007/s00232-001-0072-7;
RA Gong H.C., Hang J., Kohler W., Li L., Su T.-Z.;
RT "Tissue-specific expression and gabapentin-binding properties of calcium
RT channel alpha2delta subunit subtypes.";
RL J. Membr. Biol. 184:35-43(2001).
RN [9]
RP ALTERNATIVE SPLICING (ISOFORM 5).
RX PubMed=15000524; DOI=10.1023/b:jobb.0000008028.41056.58;
RA Klugbauer N., Marais E., Hofmann F.;
RT "Calcium channel alpha2delta subunits: differential expression, function,
RT and drug binding.";
RL J. Bioenerg. Biomembr. 35:639-647(2003).
RN [10]
RP FUNCTION.
RX PubMed=12555074; DOI=10.1038/sj.onc.1206134;
RA Carboni G.L., Gao B., Nishizaki M., Xu K., Minna J.D., Roth J.A., Ji L.;
RT "CACNA2D2-mediated apoptosis in NSCLC cells is associated with alterations
RT of the intracellular calcium signaling and disruption of mitochondria
RT membrane integrity.";
RL Oncogene 22:615-626(2003).
RN [11]
RP FUNCTION.
RX PubMed=15111129; DOI=10.1016/j.abb.2004.03.010;
RA Lacinova L., Klugbauer N.;
RT "Modulation of gating currents of the Ca(v)3.1 calcium channel by alpha 2
RT delta 2 and gamma 5 subunits.";
RL Arch. Biochem. Biophys. 425:207-213(2004).
RN [12]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-386.
RC TISSUE=Leukemic T-cell;
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [13]
RP FUNCTION, INVOLVEMENT IN CASVDD, VARIANT CASVDD PRO-1047, AND
RP CHARACTERIZATION OF VARIANT CASVDD PRO-1047.
RX PubMed=23339110; DOI=10.1136/jmedgenet-2012-101223;
RA Edvardson S., Oz S., Abulhijaa F.A., Taher F.B., Shaag A., Zenvirt S.,
RA Dascal N., Elpeleg O.;
RT "Early infantile epileptic encephalopathy associated with a high voltage
RT gated calcium channelopathy.";
RL J. Med. Genet. 50:118-123(2013).
RN [14]
RP INVOLVEMENT IN CASVDD.
RX PubMed=24358150; DOI=10.1371/journal.pone.0082154;
RA Pippucci T., Parmeggiani A., Palombo F., Maresca A., Angius A.,
RA Crisponi L., Cucca F., Liguori R., Valentino M.L., Seri M., Carelli V.;
RT "A novel null homozygous mutation confirms CACNA2D2 as a gene mutated in
RT epileptic encephalopathy.";
RL PLoS ONE 8:E82154-E82154(2013).
RN [15]
RP INVOLVEMENT IN CASVDD, AND VARIANTS CASVDD LEU-261 AND PRO-1053.
RX PubMed=30410802; DOI=10.1155/2018/6308283;
RA Butler K.M., Holt P.J., Milla S.S., da Silva C., Alexander J.J., Escayg A.;
RT "Epileptic encephalopathy and cerebellar atrophy resulting from compound
RT heterozygous CACNA2D2 variants.";
RL Case Rep. Genet. 2018:6308283-6308283(2018).
RN [16]
RP INVOLVEMENT IN CASVDD.
RX PubMed=29997391; DOI=10.1038/s41436-018-0089-2;
RA Valence S., Cochet E., Rougeot C., Garel C., Chantot-Bastaraud S.,
RA Lainey E., Afenjar A., Barthez M.A., Bednarek N., Doummar D., Faivre L.,
RA Goizet C., Haye D., Heron B., Kemlin I., Lacombe D., Milh M., Moutard M.L.,
RA Riant F., Robin S., Roubertie A., Sarda P., Toutain A., Villard L.,
RA Ville D., Billette de Villemeur T., Rodriguez D., Burglen L.;
RT "Exome sequencing in congenital ataxia identifies two new candidate genes
RT and highlights a pathophysiological link between some congenital ataxias
RT and early infantile epileptic encephalopathies.";
RL Genet. Med. 21:553-563(2019).
RN [17]
RP VARIANT CYS-371.
RX PubMed=33798445; DOI=10.1016/j.ajhg.2021.03.013;
RA Courage C., Oliver K.L., Park E.J., Cameron J.M., Grabinska K.A., Muona M.,
RA Canafoglia L., Gambardella A., Said E., Afawi Z., Baykan B., Brandt C.,
RA di Bonaventura C., Chew H.B., Criscuolo C., Dibbens L.M., Castellotti B.,
RA Riguzzi P., Labate A., Filla A., Giallonardo A.T., Berecki G.,
RA Jackson C.B., Joensuu T., Damiano J.A., Kivity S., Korczyn A., Palotie A.,
RA Striano P., Uccellini D., Giuliano L., Andermann E., Scheffer I.E.,
RA Michelucci R., Bahlo M., Franceschetti S., Sessa W.C., Berkovic S.F.,
RA Lehesjoki A.E.;
RT "Progressive myoclonus epilepsies-Residual unsolved cases have marked
RT genetic heterogeneity including dolichol-dependent protein glycosylation
RT pathway genes.";
RL Am. J. Hum. Genet. 108:722-738(2021).
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) (PubMed:15111129,
CC PubMed:23339110). Overexpression induces apoptosis.
CC {ECO:0000269|PubMed:12555074, ECO:0000269|PubMed:15111129,
CC ECO:0000269|PubMed:23339110}.
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 (By similarity).
CC {ECO:0000250}.
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:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1; Synonyms=Alpha2delta-2a;
CC IsoId=Q9NY47-1; Sequence=Displayed;
CC Name=2; Synonyms=Alpha2delta-2b;
CC IsoId=Q9NY47-2; Sequence=VSP_028059;
CC Name=3;
CC IsoId=Q9NY47-3; Sequence=VSP_028059, VSP_028060;
CC Name=4;
CC IsoId=Q9NY47-4; Sequence=VSP_028058, VSP_028059, VSP_028060;
CC Name=5; Synonyms=Alpha2delta-2c;
CC IsoId=Q9NY47-5; Sequence=VSP_028060;
CC -!- TISSUE SPECIFICITY: Predominantly present in cerebellar cortex. Present
CC in various lung tumor cell lines, while it is absent in normal lung (at
CC protein level). Highly expressed in heart, lung, testis, pancreas and
CC skeletal muscle. Also expressed in kidney, liver, placenta and brain.
CC {ECO:0000269|PubMed:10766861, ECO:0000269|PubMed:11687876,
CC ECO:0000269|PubMed:9880589}.
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 {ECO:0000250}.
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 (By
CC similarity). {ECO:0000250}.
CC -!- DISEASE: Cerebellar atrophy with seizures and variable developmental
CC delay (CASVDD) [MIM:618501]: An autosomal recessive neurologic disorder
CC characterized by cerebellar ataxia, atrophy of the cerebellar vermis,
CC severe refractory seizures with early onset, and global developmental
CC delay compatible with epileptic encephalopathy in most patients.
CC Disease severity is variable and normal cognitive development has also
CC been reported. {ECO:0000269|PubMed:23339110,
CC ECO:0000269|PubMed:24358150, ECO:0000269|PubMed:29997391,
CC ECO:0000269|PubMed:30410802}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Binds gabapentin, an antiepileptic drug.
CC -!- SIMILARITY: Belongs to the calcium channel subunit alpha-2/delta
CC family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF042792; AAB96913.1; -; mRNA.
DR EMBL; AF042793; AAB96914.1; -; mRNA.
DR EMBL; AF040709; AAC70914.1; -; mRNA.
DR EMBL; AJ251367; CAB86192.1; -; mRNA.
DR EMBL; AJ251368; CAB86193.1; -; mRNA.
DR EMBL; AB011130; BAA25484.1; -; mRNA.
DR EMBL; AL450422; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z75742; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z75743; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z84492; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z84494; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z84495; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471055; EAW65121.1; -; Genomic_DNA.
DR EMBL; BC152438; AAI52439.1; -; mRNA.
DR CCDS; CCDS33763.1; -. [Q9NY47-2]
DR CCDS; CCDS54588.1; -. [Q9NY47-1]
DR CCDS; CCDS63647.1; -. [Q9NY47-3]
DR CCDS; CCDS77748.1; -. [Q9NY47-4]
DR RefSeq; NP_001005505.1; NM_001005505.2. [Q9NY47-3]
DR RefSeq; NP_001167522.1; NM_001174051.2. [Q9NY47-1]
DR RefSeq; NP_001278030.1; NM_001291101.1. [Q9NY47-4]
DR RefSeq; NP_006021.2; NM_006030.3. [Q9NY47-2]
DR AlphaFoldDB; Q9NY47; -.
DR SMR; Q9NY47; -.
DR BioGRID; 114678; 101.
DR IntAct; Q9NY47; 16.
DR STRING; 9606.ENSP00000418081; -.
DR BindingDB; Q9NY47; -.
DR ChEMBL; CHEMBL3896; -.
DR DrugBank; DB01244; Bepridil.
DR DrugBank; DB13746; Bioallethrin.
DR DrugBank; DB11148; Butamben.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB00153; Ergocalciferol.
DR DrugBank; DB01023; Felodipine.
DR DrugBank; DB00996; Gabapentin.
DR DrugBank; DB08872; Gabapentin enacarbil.
DR DrugBank; DB00270; Isradipine.
DR DrugBank; DB01054; Nitrendipine.
DR DrugBank; DB00421; Spironolactone.
DR DrugCentral; Q9NY47; -.
DR TCDB; 8.A.18.2.1; the ca(2+) channel auxiliary subunit Alpha2Delta types 1-4 (cca-Alpha2Delta) family.
DR CarbonylDB; Q9NY47; -.
DR GlyGen; Q9NY47; 6 sites.
DR iPTMnet; Q9NY47; -.
DR PhosphoSitePlus; Q9NY47; -.
DR BioMuta; CACNA2D2; -.
DR DMDM; 387912827; -.
DR EPD; Q9NY47; -.
DR jPOST; Q9NY47; -.
DR MassIVE; Q9NY47; -.
DR MaxQB; Q9NY47; -.
DR PaxDb; Q9NY47; -.
DR PeptideAtlas; Q9NY47; -.
DR PRIDE; Q9NY47; -.
DR ProteomicsDB; 83169; -. [Q9NY47-1]
DR ProteomicsDB; 83170; -. [Q9NY47-2]
DR ProteomicsDB; 83171; -. [Q9NY47-3]
DR ProteomicsDB; 83172; -. [Q9NY47-4]
DR ProteomicsDB; 83173; -. [Q9NY47-5]
DR Antibodypedia; 30959; 155 antibodies from 29 providers.
DR DNASU; 9254; -.
DR Ensembl; ENST00000266039.7; ENSP00000266039.3; ENSG00000007402.12. [Q9NY47-3]
DR Ensembl; ENST00000360963.7; ENSP00000354228.3; ENSG00000007402.12. [Q9NY47-4]
DR Ensembl; ENST00000424201.7; ENSP00000390329.2; ENSG00000007402.12. [Q9NY47-2]
DR Ensembl; ENST00000479441.1; ENSP00000418081.1; ENSG00000007402.12. [Q9NY47-1]
DR GeneID; 9254; -.
DR KEGG; hsa:9254; -.
DR MANE-Select; ENST00000424201.7; ENSP00000390329.2; NM_006030.4; NP_006021.2. [Q9NY47-2]
DR UCSC; uc003dap.4; human. [Q9NY47-1]
DR CTD; 9254; -.
DR DisGeNET; 9254; -.
DR GeneCards; CACNA2D2; -.
DR HGNC; HGNC:1400; CACNA2D2.
DR HPA; ENSG00000007402; Tissue enriched (lung).
DR MalaCards; CACNA2D2; -.
DR MIM; 607082; gene.
DR MIM; 618501; phenotype.
DR neXtProt; NX_Q9NY47; -.
DR OpenTargets; ENSG00000007402; -.
DR PharmGKB; PA26012; -.
DR VEuPathDB; HostDB:ENSG00000007402; -.
DR eggNOG; KOG2353; Eukaryota.
DR GeneTree; ENSGT00940000156238; -.
DR HOGENOM; CLU_004660_0_0_1; -.
DR InParanoid; Q9NY47; -.
DR OMA; HCEMDCD; -.
DR OrthoDB; 510149at2759; -.
DR TreeFam; TF315824; -.
DR PathwayCommons; Q9NY47; -.
DR Reactome; R-HSA-112308; Presynaptic depolarization and calcium channel opening.
DR Reactome; R-HSA-400042; Adrenaline,noradrenaline inhibits insulin secretion.
DR Reactome; R-HSA-422356; Regulation of insulin secretion.
DR Reactome; R-HSA-5576892; Phase 0 - rapid depolarisation.
DR Reactome; R-HSA-5576893; Phase 2 - plateau phase.
DR Reactome; R-HSA-9662360; Sensory processing of sound by inner hair cells of the cochlea.
DR SignaLink; Q9NY47; -.
DR BioGRID-ORCS; 9254; 9 hits in 1071 CRISPR screens.
DR ChiTaRS; CACNA2D2; human.
DR GeneWiki; CACNA2D2; -.
DR GenomeRNAi; 9254; -.
DR Pharos; Q9NY47; Tclin.
DR PRO; PR:Q9NY47; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9NY47; protein.
DR Bgee; ENSG00000007402; Expressed in lower lobe of lung and 162 other tissues.
DR ExpressionAtlas; Q9NY47; baseline and differential.
DR Genevisible; Q9NY47; HS.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005891; C:voltage-gated calcium channel complex; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; IBA:GO_Central.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
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; Epilepsy; Glycoprotein; Ion channel;
KW Ion transport; Membrane; Metal-binding; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix; Transport; Voltage-gated channel.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..1150
FT /note="Voltage-dependent calcium channel subunit alpha-
FT 2/delta-2"
FT /id="PRO_0000304637"
FT CHAIN 19..1001
FT /note="Voltage-dependent calcium channel subunit alpha-2-2"
FT /evidence="ECO:0000255"
FT /id="PRO_0000304638"
FT CHAIN 1002..1150
FT /note="Voltage-dependent calcium channel subunit delta-2"
FT /evidence="ECO:0000255"
FT /id="PRO_0000304639"
FT TOPO_DOM 19..1113
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1114..1134
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1135..1150
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 291..469
FT /note="VWFA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00219"
FT DOMAIN 485..574
FT /note="Cache"
FT REGION 1..41
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 297..301
FT /note="MIDAS-like motif"
FT COMPBIAS 20..41
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 297
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT BINDING 299
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT BINDING 301
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT CARBOHYD 386
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 418
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 507
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 540
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 624
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 861
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 443..1098
FT /note="Interchain (between alpha-2-2 and delta-2 chains)"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..69
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:9880589"
FT /id="VSP_028058"
FT VAR_SEQ 662..669
FT /note="LPISKLKD -> Y (in isoform 2, isoform 3 and isoform
FT 4)"
FT /evidence="ECO:0000303|PubMed:10762351,
FT ECO:0000303|PubMed:10766861, ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9628581, ECO:0000303|PubMed:9880589"
FT /id="VSP_028059"
FT VAR_SEQ 1076..1077
FT /note="HS -> HCPA (in isoform 3, isoform 4 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:10766861,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:9628581,
FT ECO:0000303|PubMed:9880589"
FT /id="VSP_028060"
FT VARIANT 138
FT /note="A -> V (in dbSNP:rs35497591)"
FT /id="VAR_035048"
FT VARIANT 261
FT /note="P -> L (in CASVDD; unknown pathological
FT significance; dbSNP:rs1211603072)"
FT /evidence="ECO:0000269|PubMed:30410802"
FT /id="VAR_083105"
FT VARIANT 334
FT /note="E -> K (in dbSNP:rs743855)"
FT /id="VAR_057782"
FT VARIANT 371
FT /note="Y -> C (found in a patient with progressive
FT myoclonus epilepsy and developmental delay; unknown
FT pathological significance)"
FT /evidence="ECO:0000269|PubMed:33798445"
FT /id="VAR_085040"
FT VARIANT 1047
FT /note="L -> P (in CASVDD; impaired regulation of current
FT density and inactivation kinetics of N- and L-type calcium
FT channels; dbSNP:rs587776948)"
FT /evidence="ECO:0000269|PubMed:23339110"
FT /id="VAR_083106"
FT VARIANT 1053
FT /note="L -> P (in CASVDD; unknown pathological
FT significance; dbSNP:rs1575578837)"
FT /evidence="ECO:0000269|PubMed:30410802"
FT /id="VAR_083107"
FT CONFLICT 663
FT /note="P -> R (in Ref. 3; CAB86193)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1150 AA; 129817 MW; 502B86A5E6279AA0 CRC64;
MAVPARTCGA SRPGPARTAR PWPGCGPHPG PGTRRPTSGP PRPLWLLLPL LPLLAAPGAS
AYSFPQQHTM QHWARRLEQE VDGVMRIFGG VQQLREIYKD NRNLFEVQEN EPQKLVEKVA
GDIESLLDRK VQALKRLADA AENFQKAHRW QDNIKEEDIV YYDAKADAEL DDPESEDVER
GSKASTLRLD FIEDPNFKNK VNYSYAAVQI PTDIYKGSTV ILNELNWTEA LENVFMENRR
QDPTLLWQVF GSATGVTRYY PATPWRAPKK IDLYDVRRRP WYIQGASSPK DMVIIVDVSG
SVSGLTLKLM KTSVCEMLDT LSDDDYVNVA SFNEKAQPVS CFTHLVQANV RNKKVFKEAV
QGMVAKGTTG YKAGFEYAFD QLQNSNITRA NCNKMIMMFT DGGEDRVQDV FEKYNWPNRT
VRVFTFSVGQ HNYDVTPLQW MACANKGYYF EIPSIGAIRI NTQEYLDVLG RPMVLAGKEA
KQVQWTNVYE DALGLGLVVT GTLPVFNLTQ DGPGEKKNQL ILGVMGIDVA LNDIKRLTPN
YTLGANGYVF AIDLNGYVLL HPNLKPQTTN FREPVTLDFL DAELEDENKE EIRRSMIDGN
KGHKQIRTLV KSLDERYIDE VTRNYTWVPI RSTNYSLGLV LPPYSTFYLQ ANLSDQILQV
KLPISKLKDF EFLLPSSFES EGHVFIAPRE YCKDLNASDN NTEFLKNFIE LMEKVTPDSK
QCNNFLLHNL ILDTGITQQL VERVWRDQDL NTYSLLAVFA ATDGGITRVF PNKAAEDWTE
NPEPFNASFY RRSLDNHGYV FKPPHQDALL RPLELENDTV GILVSTAVEL SLGRRTLRPA
VVGVKLDLEA WAEKFKVLAS NRTHQDQPQK CGPNSHCEMD CEVNNEDLLC VLIDDGGFLV
LSNQNHQWDQ VGRFFSEVDA NLMLALYNNS FYTRKESYDY QAACAPQPPG NLGAAPRGVF
VPTVADFLNL AWWTSAAAWS LFQQLLYGLI YHSWFQADPA EAEGSPETRE SSCVMKQTQY
YFGSVNASYN AIIDCGNCSR LFHAQRLTNT NLLFVVAEKP LCSQCEAGRL LQKETHSDGP
EQCELVQRPR YRRGPHICFD YNATEDTSDC GRGASFPPSL GVLVSLQLLL LLGLPPRPQP
QVLVHASRRL
