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   27-MAR-2024, entry version 167.
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 (By similarity). Plays an important
CC       role in excitation-contraction coupling (By similarity).
CC       {ECO:0000250|UniProtKB:P54289}.
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}. Cell membrane
CC       {ECO:0000250|UniProtKB:P54289}.
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   GlyCosmos; P54290; 9 sites, 11 glycans.
DR   GlyGen; P54290; 9 sites, 11 N-linked glycans (2 sites).
DR   iPTMnet; P54290; -.
DR   PhosphoSitePlus; P54290; -.
DR   SwissPalm; P54290; -.
DR   jPOST; P54290; -.
DR   PaxDb; 10116-ENSRNOP00000034572; -.
DR   AGR; RGD:2247; -.
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:0098978; C:glutamatergic synapse; IDA:SynGO.
DR   GO; GO:1990454; C:L-type voltage-gated calcium channel complex; IDA:BHF-UCL.
DR   GO; GO:0098992; C:neuronal dense core vesicle; ISO:RGD.
DR   GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR   GO; GO:0045211; C:postsynaptic membrane; IDA:SynGO.
DR   GO; GO:0048787; C:presynaptic active zone membrane; IDA:SynGO.
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: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   CDD; cd01463; vWA_VGCC_like; 1.
DR   Gene3D; 3.30.450.20; PAS domain; 1.
DR   Gene3D; 3.40.50.410; von Willebrand factor, type A domain; 1.
DR   InterPro; IPR013680; VDCC_a2/dsu.
DR   InterPro; IPR013608; VWA_N.
DR   InterPro; IPR002035; VWF_A.
DR   InterPro; IPR036465; vWFA_dom_sf.
DR   PANTHER; PTHR10166; VOLTAGE-DEPENDENT CALCIUM CHANNEL SUBUNIT ALPHA-2/DELTA-RELATED; 1.
DR   PANTHER; PTHR10166:SF6; VOLTAGE-DEPENDENT CALCIUM CHANNEL SUBUNIT ALPHA-2_DELTA-1; 1.
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; vWA-like; 1.
DR   PROSITE; PS50234; VWFA; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Calcium; Calcium channel; Calcium transport;
KW   Cell membrane; Disulfide bond; Glycoprotein; Ion channel; Ion transport;
KW   Membrane; Metal-binding; Phosphoprotein; Reference proteome; Signal;
KW   Transmembrane; 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
//