CA2D1_RAT
ID CA2D1_RAT Reviewed; 1091 AA.
AC P54290;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 159.
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=Cacnl2a, Cchl2a;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1314383; DOI=10.1073/pnas.89.8.3251;
RA Kim H.L., Kim H., Lee P., King R.G., Chin H.;
RT "Rat brain expresses an alternatively spliced form of the dihydropyridine-
RT sensitive L-type calcium channel alpha 2 subunit.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:3251-3255(1992).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-119, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [3]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-323 AND ASN-973, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24090084; DOI=10.1021/pr400783j;
RA Parker B.L., Thaysen-Andersen M., Solis N., Scott N.E., Larsen M.R.,
RA Graham M.E., Packer N.H., Cordwell S.J.;
RT "Site-specific glycan-peptide analysis for determination of N-glycoproteome
RT heterogeneity.";
RL J. Proteome Res. 12:5791-5800(2013).
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 P54290; P35442: THBS2; Xeno; NbExp=2; IntAct=EBI-2466294, EBI-2466249;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=1;
CC Comment=2 isoforms are produced.;
CC Name=1;
CC IsoId=P54290-1; Sequence=Displayed;
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; M86621; AAA41088.1; -; mRNA.
DR PIR; A44147; A44147.
DR AlphaFoldDB; P54290; -.
DR SMR; P54290; -.
DR IntAct; P54290; 4.
DR MINT; P54290; -.
DR STRING; 10116.ENSRNOP00000034572; -.
DR BindingDB; P54290; -.
DR ChEMBL; CHEMBL3420; -.
DR GlyGen; P54290; 9 sites, 11 N-linked glycans (2 sites).
DR iPTMnet; P54290; -.
DR PhosphoSitePlus; P54290; -.
DR jPOST; P54290; -.
DR PaxDb; P54290; -.
DR PRIDE; P54290; -.
DR RGD; 2247; Cacna2d1.
DR eggNOG; KOG2353; Eukaryota.
DR InParanoid; P54290; -.
DR PhylomeDB; P54290; -.
DR PRO; PR:P54290; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0099025; C:anchored component of postsynaptic membrane; IDA:SynGO.
DR GO; GO:0099029; C:anchored component of presynaptic active zone membrane; IDA:SynGO.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:1990454; C:L-type voltage-gated calcium channel complex; IDA:BHF-UCL.
DR GO; GO:0016529; C:sarcoplasmic reticulum; ISO:RGD.
DR GO; GO:0030315; C:T-tubule; ISO:RGD.
DR GO; GO:0005891; C:voltage-gated calcium channel complex; IDA:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; IMP:RGD.
DR GO; GO:0070588; P:calcium ion transmembrane transport; IDA:BHF-UCL.
DR GO; GO:0061577; P:calcium ion transmembrane transport via high voltage-gated calcium channel; IDA:BHF-UCL.
DR GO; GO:0006816; P:calcium ion transport; ISO:RGD.
DR GO; GO:0060402; P:calcium ion transport into cytosol; IDA:BHF-UCL.
DR GO; GO:0086002; P:cardiac muscle cell action potential involved in contraction; ISO:RGD.
DR GO; GO:1904646; P:cellular response to amyloid-beta; ISO:RGD.
DR GO; GO:0086048; P:membrane depolarization during bundle of His cell action potential; ISO:RGD.
DR GO; GO:1901843; P:positive regulation of high voltage-gated calcium channel activity; IDA:BHF-UCL.
DR GO; GO:1901387; P:positive regulation of voltage-gated calcium channel activity; IDA:RGD.
DR GO; GO:1902514; P:regulation of calcium ion transmembrane transport via high voltage-gated calcium channel; ISO:RGD.
DR GO; GO:0051924; P:regulation of calcium ion transport; ISO:RGD.
DR GO; GO:0086091; P:regulation of heart rate by cardiac conduction; ISO:RGD.
DR GO; GO:0098903; P:regulation of membrane repolarization during action potential; IDA:BHF-UCL.
DR GO; GO:0060307; P:regulation of ventricular cardiac muscle cell membrane repolarization; ISO:RGD.
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..1091
FT /note="Voltage-dependent calcium channel subunit alpha-
FT 2/delta-1"
FT /id="PRO_0000304635"
FT CHAIN 25..944
FT /note="Voltage-dependent calcium channel subunit alpha-2-1"
FT /evidence="ECO:0000250"
FT /id="PRO_0000005005"
FT CHAIN 945..1091
FT /note="Voltage-dependent calcium channel subunit delta-1"
FT /evidence="ECO:0000250"
FT /id="PRO_0000005006"
FT TOPO_DOM 25..1061
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1062..1082
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1083..1091
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 252..429
FT /note="VWFA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00219"
FT DOMAIN 445..536
FT /note="Cache"
FT MOTIF 258..262
FT /note="MIDAS-like motif"
FT BINDING 258
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT BINDING 260
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT BINDING 262
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:0007744|PubMed:22673903"
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:0000255"
FT CARBOHYD 184
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 323
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0007744|PubMed:24090084"
FT CARBOHYD 347
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 593
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 769
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 876
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 973
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0007744|PubMed:24090084"
FT DISULFID 403..1047
FT /note="Interchain (between alpha-2-1 and delta-1 chains)"
FT /evidence="ECO:0000250"
SQ SEQUENCE 1091 AA; 123823 MW; 7054907D9D343B34 CRC64;
MAAGCLLALT LTLFQSWLIG PSSEEPFPSP VTIKSWVDKM QEDLVTLAKT ASGVTQLADI
YEKYQDLYTV EPNNARQLVE IAARDIEKLL SNRSKALVRL AMEAEKVQAA HQWREDFASN
EVVYYNAKDD LDPERNESES GSQRIKPVFI EDANFGRQIS YQHAAVHIPT DIYEGSTIVL
NELNWTSALD EVFKRNRDED PTLLWQVFAA DRLARYYPAS PWVDNSRTPN KIDLYDVRRR
PWYIQGAASP KDMLILVDVS GSVSGLTLKL IRTSVSEMLE TLSDDDFVNV ASFNSNAQDV
SCFQHLVQAN VRNKKVLKDA VNNITAKGIT DYKKGFTFAF EQLLNYNVSR ANCNKIIMLF
TDGGEERAQE IFAKYNKDKK VRVFTFSVGQ HNYDRGPIQW MACENKGYYY EIPSIGAIRI
NTQEYLDVLG RPMVLAGDKA KQVQWTNVYL DALELGLVIT GTLPVFNVTG QSENKTNLKN
QLILGVMGVD VSLEDIKRLT PRFTLCPNGY YFAIDPNGYV LLHPNLQPKN PKSQEPVTLD
FLDAELENDI KVEIRNKMID GESGEKTFRT LVKSQDERYI DKGNRTYTWT PVNGTDYRYL
ALVLPTYSFY YIKAKIEETI TQARSKKGKM KDSETLKPDN FEESGYTFIA PREYCNDLKP
SDNNTEFLLN FNEFIDRKTP NNPSCNTDLI NRILLDAGFT NELVQNYWSK QKNIKGVKAR
FVVTDGGITR VYPKEAGENW QENPETYEDS FYKRSLDNDN YVFTAPYFNK SGPGAYESGI
MVSKAVELYI QGKLLKPAVV GIKIDVNSWI ENFTKTSIRD PCAGPVCDCK RNSDVMDCVI
LDDGGFLLMA NHDDYTNQIG RFFGEIDPRM MRHLVNISLY AFNKSYDYQS VCDPGAAPKQ
GAGHRSAYVP SITDILQIGW WATAAAWSIL QQLLLSLTFP RLLEAVEMEE DDFTASLSKQ
SCITEQTQYF FKNDTKSFSG LLDCGNCSRI FHVEKLMNTN LVFIMVESKG TCPCDTRLLM
QAEQTSDGPD PCDMVKQPRY RKGPDVCFDN NVLEDYTDCG GVSGLNPSLW SIFGLQFILL
WLVSGSRHYL W
