CA2D3_MOUSE
ID CA2D3_MOUSE Reviewed; 1091 AA.
AC Q9Z1L5;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Voltage-dependent calcium channel subunit alpha-2/delta-3;
DE AltName: Full=Voltage-gated calcium channel subunit alpha-2/delta-3;
DE Contains:
DE RecName: Full=Voltage-dependent calcium channel subunit alpha-2-3;
DE Contains:
DE RecName: Full=Voltage-dependent calcium channel subunit delta-3;
DE Flags: Precursor;
GN Name=Cacna2d3;
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], FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
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 FUNCTION.
RX PubMed=10200414; DOI=10.1111/j.1469-7793.1999.0639u.x;
RA Lacinova L., Klugbauer N., Hofmann F.;
RT "Absence of modulation of the expressed calcium channel alpha1G subunit by
RT alpha2delta subunits.";
RL J. Physiol. (Lond.) 516:639-645(1999).
RN [3]
RP TISSUE SPECIFICITY.
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 [4]
RP DISULFIDE BONDS, GLYCOSYLATION, PROTEOLYTIC PROCESSING, AND LACK OF
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
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) but not T-type (CACNA1G). {ECO:0000269|PubMed:10200414,
CC ECO:0000269|PubMed:9880589}.
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}.
CC -!- TISSUE SPECIFICITY: Brain-specific. Predominantly expressed in the
CC caudate putamen, entorhinal complex, hippocampus and cortex.
CC {ECO:0000269|PubMed:11687876, 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: N-glycosylated. {ECO:0000269|PubMed:11306709}.
CC -!- PTM: May be proteolytically processed into subunits alpha-2-3 and
CC delta-3 that are disulfide-linked. It is however unclear whether such
CC cleavage really takes place in vivo and has a functional role.
CC {ECO:0000269|PubMed:11306709}.
CC -!- MISCELLANEOUS: In contrast to CACNA2D1 and CACNA2D2, it does not bind
CC gabapentin, an antiepileptic drug.
CC -!- SIMILARITY: Belongs to the calcium channel subunit alpha-2/delta
CC family. {ECO:0000305}.
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DR EMBL; AJ010949; CAA09423.1; -; mRNA.
DR PIR; T30256; T30256.
DR RefSeq; NP_033915.1; NM_009785.1.
DR AlphaFoldDB; Q9Z1L5; -.
DR SMR; Q9Z1L5; -.
DR IntAct; Q9Z1L5; 2.
DR MINT; Q9Z1L5; -.
DR STRING; 10090.ENSMUSP00000022567; -.
DR GlyConnect; 2822; 3 N-Linked glycans (2 sites).
DR GlyGen; Q9Z1L5; 4 sites, 3 N-linked glycans (2 sites).
DR PhosphoSitePlus; Q9Z1L5; -.
DR MaxQB; Q9Z1L5; -.
DR PaxDb; Q9Z1L5; -.
DR PeptideAtlas; Q9Z1L5; -.
DR PRIDE; Q9Z1L5; -.
DR ProteomicsDB; 273813; -.
DR Antibodypedia; 31444; 117 antibodies from 21 providers.
DR DNASU; 12294; -.
DR Ensembl; ENSMUST00000022567; ENSMUSP00000022567; ENSMUSG00000021991.
DR GeneID; 12294; -.
DR KEGG; mmu:12294; -.
DR UCSC; uc007sui.1; mouse.
DR CTD; 55799; -.
DR MGI; MGI:1338890; Cacna2d3.
DR VEuPathDB; HostDB:ENSMUSG00000021991; -.
DR eggNOG; KOG2353; Eukaryota.
DR GeneTree; ENSGT00940000155766; -.
DR HOGENOM; CLU_004660_1_1_1; -.
DR InParanoid; Q9Z1L5; -.
DR OMA; RTMQVPC; -.
DR OrthoDB; 69856at2759; -.
DR PhylomeDB; Q9Z1L5; -.
DR TreeFam; TF315824; -.
DR Reactome; R-MMU-112308; Presynaptic depolarization and calcium channel opening.
DR BioGRID-ORCS; 12294; 1 hit in 67 CRISPR screens.
DR ChiTaRS; Cacna2d3; mouse.
DR PRO; PR:Q9Z1L5; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q9Z1L5; protein.
DR Bgee; ENSMUSG00000021991; Expressed in caudate-putamen and 148 other tissues.
DR ExpressionAtlas; Q9Z1L5; baseline and differential.
DR Genevisible; Q9Z1L5; MM.
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; ISO:MGI.
DR GO; GO:0006816; P:calcium ion transport; ISO:MGI.
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; 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 Calcium; Calcium channel; Calcium transport; Disulfide bond; Glycoprotein;
KW Ion channel; Ion transport; Membrane; Metal-binding; Phosphoprotein;
KW Reference proteome; Signal; Transmembrane; Transmembrane helix; Transport;
KW Voltage-gated channel.
FT SIGNAL 1..33
FT /evidence="ECO:0000255"
FT CHAIN 34..1091
FT /note="Voltage-dependent calcium channel subunit alpha-
FT 2/delta-3"
FT /id="PRO_0000304649"
FT CHAIN 34..?
FT /note="Voltage-dependent calcium channel subunit alpha-2-3"
FT /evidence="ECO:0000255"
FT /id="PRO_0000304650"
FT CHAIN ?..1091
FT /note="Voltage-dependent calcium channel subunit delta-3"
FT /evidence="ECO:0000255"
FT /id="PRO_0000304651"
FT TOPO_DOM 34..1068
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1069..1089
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1090..1091
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 256..438
FT /note="VWFA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00219"
FT DOMAIN 452..549
FT /note="Cache"
FT MOTIF 262..266
FT /note="MIDAS-like motif"
FT BINDING 262
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT BINDING 264
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT BINDING 266
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT MOD_RES 924
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q8CFG5"
FT CARBOHYD 166
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 309
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 553
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 632
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 412..1055
FT /note="Interchain (between alpha-2-3 and delta-3 chains)"
FT /evidence="ECO:0000250"
SQ SEQUENCE 1091 AA; 122778 MW; 7AEE2BDA10077A0A CRC64;
MAGPGSLCCA SRGASALLAT ALLYAALGDV VRSEQQIPLS VVKLWASAFG GEIKSIAAKY
SGSQLLQKKY KEYEKDVAIE EIDGLQLVKK LAKIMEEMFH KKSEAVRRLV EAAEEAHLKH
EFDADLQYEY FNAVLINERD KDGNFLELGK EFILAPNDHF NNLPVNISLS DVQVPTNMYN
KDPAIVNGVY WSESLNKVFV DNFDRDPSLI WQYFGSAKGF FRQYPGIKWE PDENGVIAFD
CRNRKWYIQA ATSPKDVVIL VDVSGSMKGL RLTIAKQTVS SILDTLGDDD FFNIITYNEE
LHYVEPCLNG TLVQADRTNK EHFREHLDKL FAKGIGMLDI ALNEAFNILS DFNHTGQGSI
CSQAIMLITD GAVDTYDTIF AKYNWPDRKV RIFTYLIGRE AAFADNLKWM ACANKGFFTQ
ISTLADVQEN VMEYLHVLSR PKVIDQEHDV VWTEAYIDST LPQAQKLADD QGLVLMTTVA
MPVFSKQNET RSKGILLGVV GTDVPVKELL KTIPKYKLGI HGYAFAITNN GYILTHPELR
PLYEEGKKRR KPNYSSVDLS EVEWEDRDDV LRNAMVNRKT GKFSMEVKKT VDKGKRVLVM
TNDYYYTDIK GTPFSLGVAL SRGHGKYFFR GNVTIEEGLH DLEHPDVSLA DEWSYCNTDL
HPEHRHLSQL EAIKLYLKGK EPLLQCDKEL IQEVLFDAVV SAPIEAYWTS LALNKSENSD
KGVEVAFLGT RTGLSRINLF VGAEQLTNQD FLKAGDKENI FNADHFPLWY RRAAEQIAGS
FVYSIPFSTG TVNKSNVVTA STSIQLLDER KSPVVAAVGI QMKLEFFQRK FWTASRQCAS
LDGKCSISCD DETVNCYLID NNGFILVSED YTQTGDFFGE VEGAVMNKLL TMGSFKRITL
YDYQAMCRAN KESSDSAHGL LDPYKAFLSA AKWIMTELVL FLVEFNLCSW WHSDMTAKAQ
KLKQTLEPCD TEYPAFVSER TIKETTGNIA CEDCSKSFVI QQIPSSNLFM VVVDSSCLCE
SVAPITMAPI EIRYNESLKC ERLKAQKIRR RPESCHGFHP EENARECGGA SSLQAQAALL
LLPLVSSLFS R
