CA2D1_MOUSE
ID CA2D1_MOUSE Reviewed; 1103 AA.
AC O08532; O08533; O08534; O08535; O08536;
DT 26-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Voltage-dependent calcium channel subunit alpha-2/delta-1;
DE AltName: Full=Voltage-gated calcium channel subunit alpha-2/delta-1;
DE Contains:
DE RecName: Full=Voltage-dependent calcium channel subunit alpha-2-1;
DE Contains:
DE RecName: Full=Voltage-dependent calcium channel subunit delta-1;
DE Flags: Precursor;
GN Name=Cacna2d1; Synonyms=Cacna2;
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].
RC TISSUE=Brain;
RX PubMed=8955374; DOI=10.1016/s0014-5793(96)01205-7;
RA Angelotti T., Hofmann F.;
RT "Tissue-specific expression of splice variants of the mouse voltage-gated
RT calcium channel alpha2/delta subunit.";
RL FEBS Lett. 397:331-337(1996).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [3]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-136; ASN-324 AND ASN-781.
RC TISSUE=Myoblast;
RX PubMed=19656770; DOI=10.1074/mcp.m900195-mcp200;
RA Gundry R.L., Raginski K., Tarasova Y., Tchernyshyov I., Bausch-Fluck D.,
RA Elliott S.T., Boheler K.R., Van Eyk J.E., Wollscheid B.;
RT "The mouse C2C12 myoblast cell surface N-linked glycoproteome:
RT identification, glycosite occupancy, and membrane orientation.";
RL Mol. Cell. Proteomics 8:2555-2569(2009).
RN [4]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-136 AND ASN-781.
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Lung, and Spleen;
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. Plays an important role in excitation-
CC contraction coupling (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Dimer formed of alpha-2-1 and delta-1 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 -!- INTERACTION:
CC O08532; P04925: Prnp; NbExp=3; IntAct=EBI-770939, EBI-768613;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=2A;
CC IsoId=O08532-1; Sequence=Displayed;
CC Name=2B;
CC IsoId=O08532-2; Sequence=VSP_050444;
CC Name=2C;
CC IsoId=O08532-3; Sequence=VSP_050445;
CC Name=2D;
CC IsoId=O08532-4; Sequence=VSP_050445, VSP_050446;
CC Name=2E;
CC IsoId=O08532-5; Sequence=VSP_050444, VSP_050446;
CC -!- TISSUE SPECIFICITY: Isoform 2A is expressed in skeletal muscle and
CC aorta. Isoform 2B is expressed in brain. Isoform 2C is expressed in
CC heart. Isoform 2D is expressed in heart and smooth muscle. Isoform 2E
CC is expressed in smooth muscle. All five isoforms are expressed in the
CC cardiovascular system.
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: Proteolytically processed into subunits alpha-2-1 and delta-1 that
CC are disulfide-linked. {ECO:0000250}.
CC -!- MISCELLANEOUS: Binds gabapentin, an antiepileptic drug. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the calcium channel subunit alpha-2/delta
CC family. {ECO:0000305}.
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DR EMBL; U73484; AAB50139.1; -; mRNA.
DR EMBL; U73485; AAB50140.1; -; mRNA.
DR EMBL; U73483; AAB50138.1; -; mRNA.
DR EMBL; U73486; AAB50141.1; -; mRNA.
DR EMBL; U73487; AAB50142.1; -; mRNA.
DR CCDS; CCDS19096.1; -. [O08532-2]
DR CCDS; CCDS51421.1; -. [O08532-1]
DR CCDS; CCDS51422.1; -. [O08532-5]
DR CCDS; CCDS51423.1; -. [O08532-4]
DR CCDS; CCDS80212.1; -. [O08532-3]
DR RefSeq; NP_001104313.1; NM_001110843.1. [O08532-1]
DR RefSeq; NP_001104314.1; NM_001110844.1. [O08532-5]
DR RefSeq; NP_001104315.1; NM_001110845.1. [O08532-4]
DR RefSeq; NP_001104316.1; NM_001110846.1. [O08532-3]
DR RefSeq; NP_033914.1; NM_009784.2. [O08532-2]
DR AlphaFoldDB; O08532; -.
DR SMR; O08532; -.
DR BioGRID; 198437; 7.
DR ComplexPortal; CPX-3191; Skeletal muscle VGCC complex.
DR ComplexPortal; CPX-3194; Cardiac muscle VGCC complex.
DR IntAct; O08532; 8.
DR MINT; O08532; -.
DR STRING; 10090.ENSMUSP00000049457; -.
DR BindingDB; O08532; -.
DR ChEMBL; CHEMBL4676; -.
DR DrugCentral; O08532; -.
DR GlyConnect; 2415; 20 N-Linked glycans (10 sites). [O08532-4]
DR GlyGen; O08532; 8 sites, 10 N-linked glycans (3 sites).
DR iPTMnet; O08532; -.
DR PhosphoSitePlus; O08532; -.
DR MaxQB; O08532; -.
DR PaxDb; O08532; -.
DR PeptideAtlas; O08532; -.
DR PRIDE; O08532; -.
DR ProteomicsDB; 265477; -. [O08532-1]
DR ProteomicsDB; 265478; -. [O08532-2]
DR ProteomicsDB; 265479; -. [O08532-3]
DR ProteomicsDB; 265480; -. [O08532-4]
DR ProteomicsDB; 265481; -. [O08532-5]
DR Antibodypedia; 2200; 282 antibodies from 35 providers.
DR DNASU; 12293; -.
DR Ensembl; ENSMUST00000039370; ENSMUSP00000049457; ENSMUSG00000040118. [O08532-1]
DR Ensembl; ENSMUST00000078272; ENSMUSP00000077391; ENSMUSG00000040118. [O08532-2]
DR Ensembl; ENSMUST00000101581; ENSMUSP00000099117; ENSMUSG00000040118. [O08532-5]
DR Ensembl; ENSMUST00000115281; ENSMUSP00000110936; ENSMUSG00000040118. [O08532-4]
DR Ensembl; ENSMUST00000180204; ENSMUSP00000136260; ENSMUSG00000040118. [O08532-4]
DR Ensembl; ENSMUST00000199704; ENSMUSP00000142881; ENSMUSG00000040118. [O08532-3]
DR GeneID; 12293; -.
DR KEGG; mmu:12293; -.
DR UCSC; uc008wmx.2; mouse. [O08532-2]
DR UCSC; uc008wmy.2; mouse. [O08532-5]
DR UCSC; uc008wna.2; mouse. [O08532-1]
DR UCSC; uc008wnb.2; mouse. [O08532-3]
DR CTD; 781; -.
DR MGI; MGI:88295; Cacna2d1.
DR VEuPathDB; HostDB:ENSMUSG00000040118; -.
DR eggNOG; KOG2353; Eukaryota.
DR GeneTree; ENSGT00940000155209; -.
DR InParanoid; O08532; -.
DR OMA; FWMNSFM; -.
DR OrthoDB; 510149at2759; -.
DR PhylomeDB; O08532; -.
DR TreeFam; TF315824; -.
DR BioGRID-ORCS; 12293; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Cacna2d1; mouse.
DR PRO; PR:O08532; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; O08532; protein.
DR Bgee; ENSMUSG00000040118; Expressed in triceps brachii and 232 other tissues.
DR ExpressionAtlas; O08532; baseline and differential.
DR Genevisible; O08532; MM.
DR GO; GO:0099025; C:anchored component of postsynaptic membrane; ISO:MGI.
DR GO; GO:0099029; C:anchored component of presynaptic active zone membrane; ISO:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:1990454; C:L-type voltage-gated calcium channel complex; ISS:BHF-UCL.
DR GO; GO:0016529; C:sarcoplasmic reticulum; IDA:MGI.
DR GO; GO:0030315; C:T-tubule; IDA:MGI.
DR GO; GO:0005891; C:voltage-gated calcium channel complex; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; ISO:MGI.
DR GO; GO:0086057; F:voltage-gated calcium channel activity involved in bundle of His cell action potential; ISO:MGI.
DR GO; GO:0070588; P:calcium ion transmembrane transport; ISS:BHF-UCL.
DR GO; GO:0061577; P:calcium ion transmembrane transport via high voltage-gated calcium channel; ISS:BHF-UCL.
DR GO; GO:0006816; P:calcium ion transport; ISO:MGI.
DR GO; GO:0060402; P:calcium ion transport into cytosol; ISS:BHF-UCL.
DR GO; GO:0086002; P:cardiac muscle cell action potential involved in contraction; ISS:BHF-UCL.
DR GO; GO:1904646; P:cellular response to amyloid-beta; ISO:MGI.
DR GO; GO:0086048; P:membrane depolarization during bundle of His cell action potential; ISO:MGI.
DR GO; GO:1901843; P:positive regulation of high voltage-gated calcium channel activity; ISS:BHF-UCL.
DR GO; GO:0045933; P:positive regulation of muscle contraction; IC:ComplexPortal.
DR GO; GO:1901387; P:positive regulation of voltage-gated calcium channel activity; ISO:MGI.
DR GO; GO:1902514; P:regulation of calcium ion transmembrane transport via high voltage-gated calcium channel; ISO:MGI.
DR GO; GO:0051924; P:regulation of calcium ion transport; IMP:MGI.
DR GO; GO:0086091; P:regulation of heart rate by cardiac conduction; ISS:BHF-UCL.
DR GO; GO:0098903; P:regulation of membrane repolarization during action potential; ISS:BHF-UCL.
DR GO; GO:0060307; P:regulation of ventricular cardiac muscle cell membrane repolarization; ISS:BHF-UCL.
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; PF13768; VWA_3; 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 Disulfide bond; Glycoprotein; Ion channel; Ion transport; Membrane;
KW Metal-binding; Phosphoprotein; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix; Transport; Voltage-gated channel.
FT SIGNAL 1..24
FT /evidence="ECO:0000250"
FT CHAIN 25..1103
FT /note="Voltage-dependent calcium channel subunit alpha-
FT 2/delta-1"
FT /id="PRO_0000304634"
FT CHAIN 25..957
FT /note="Voltage-dependent calcium channel subunit alpha-2-1"
FT /id="PRO_0000005003"
FT CHAIN 958..1103
FT /note="Voltage-dependent calcium channel subunit delta-1"
FT /id="PRO_0000005004"
FT TOPO_DOM 25..1073
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1074..1094
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1095..1103
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 253..430
FT /note="VWFA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00219"
FT DOMAIN 446..537
FT /note="Cache"
FT MOTIF 259..263
FT /note="MIDAS-like motif"
FT BINDING 259
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT BINDING 261
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT BINDING 263
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT MOD_RES 119
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P54290"
FT CARBOHYD 92
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 136
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973,
FT ECO:0000269|PubMed:19656770"
FT CARBOHYD 184
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 324
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19656770"
FT CARBOHYD 348
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 613
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 781
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973,
FT ECO:0000269|PubMed:19656770"
FT CARBOHYD 888
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 404..1059
FT /note="Interchain (between alpha-2-1 and delta-1 chains)"
FT /evidence="ECO:0000250"
FT VAR_SEQ 531..554
FT /note="Missing (in isoform 2C and isoform 2D)"
FT /evidence="ECO:0000305"
FT /id="VSP_050445"
FT VAR_SEQ 531..549
FT /note="Missing (in isoform 2B and isoform 2E)"
FT /evidence="ECO:0000305"
FT /id="VSP_050444"
FT VAR_SEQ 644
FT /note="Y -> SKKGKMKD (in isoform 2D and isoform 2E)"
FT /evidence="ECO:0000305"
FT /id="VSP_050446"
SQ SEQUENCE 1103 AA; 124630 MW; 103773B4735120D4 CRC64;
MAAGCLLALT LTLFQSGLIG PSSEEPFPSP VTIKSWVDKM QEDLVTLAKT ASGVTQLADI
YEKYQDLYTV EPNNARQLVE IAARDIEKLL SNRSKALVRL AMEAEKVQAA HQWREDFASN
EVVYYNAKDD LDPERNESEP GSQRIKPVFI EDANFGRQIS YQHAAVHIPT DIYEGSTIVL
NELNWTSALD EVFKRNRDED PTLLWQVFGS ATGLARYYPA SPWVDNSRTP NKIDLYDVRR
RPWYIQGAAS PKDMLILVDV SGSVSGLTLK LIRTSVSEML ETLSDDDFVN VASFNSNAQD
VSCFQHLVQA NVRNKKVLKD AVNNITAKGI TDYKKGFSFA FEQLLNYNVS RANCNKIIML
FTDGGEERAQ EIFAKYNKDK KVRVFTFSVG QHNYDRGPIQ WMACENKGYY YEIPSIGAIR
INTQEYLDVL GRPMVLAGDK AKQVQWTNVY LDALELGLVI TGTLPVFNVT GQSENKTNLK
NQLILGVMGV DVSLEDIKRL TPRFTLCPNG YYFAIDPNGY VLLHPNLQPK PIGVGIPTIN
LRKRRPNVQN PKSQEPVTLD FLDAELENEI KVEIRNKMID GESGEKTFRT LVKSQDERYI
DKGNRTYTWT PVNGTDYSLA LVLPTYSFYY IKAKLEETIT QARYSETLKP DNFEESGYTF
IAPREYCNDL KPSDNNTEFL LNFNEFIDRK TPNNPSCNTD LINRILLDAG FTNELVQNYW
SKQKNIKGVK ARFVVTDGGI TRVYPKEAGE NWQENPETYE DSFYKRSLDN DNYVFTAPYF
NKSGPGAYES GIMVSKAVEL YIQGKLLKPA VVGIKIDVNS WIENFTKTSI RDPCAGPVCD
CKRNSDVMDC VILDDGGFLL MANHDDYTNQ IGRFFGEIDP SMMRHLVNIS LYAFNKSYDY
QSVCDPGAAP KQGAGHRSAY VPSIADILQI GWWATAAAWS ILQQLLLSLT FPRLLEAVEM
EEDDFTASLS KQSCITEQTQ YFFKNDTKSF SGLLDCGNCS RIFHVEKLMN TNLVFIMVES
KGTCPCDTRL LMQAEQTSDG PDPCDMVKQP RYRKGPDVCF DNNVLEDYTD CGGVSGLNPS
LWSIFGLQFI LLWLVSGSRH YLL
