CA2D1_RABIT
ID CA2D1_RABIT Reviewed; 1106 AA.
AC P13806;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 146.
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 Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2458626; DOI=10.1126/science.2458626;
RA Ellis S.B., Williams M.E., Ways N.R., Brenner R., Sharp A.H., Leung A.T.,
RA Campbell K.P., McKenna E., Koch W.J., Hui A., Schwartz A., Harpold M.M.;
RT "Sequence and expression of mRNAs encoding the alpha 1 and alpha 2 subunits
RT of a DHP-sensitive calcium channel.";
RL Science 241:1661-1664(1988).
RN [2]
RP PROTEIN SEQUENCE OF 27-47.
RX PubMed=2558713; DOI=10.1021/bi00445a044;
RA Hamilton S.L., Hawkes M.J., Brush K., Cook R., Chang R.J., Smilowitz H.M.;
RT "Subunit composition of the purified dihydropyridine binding protein from
RT skeletal muscle.";
RL Biochemistry 28:7820-7828(1989).
RN [3]
RP PROTEIN SEQUENCE OF 961-973.
RX PubMed=1847144; DOI=10.1016/s0021-9258(18)49986-3;
RA Jay S.D., Sharp A.H., Kahl S.D., Vedvick T.S., Harpold M.M., Campbell K.P.;
RT "Structural characterization of the dihydropyridine-sensitive calcium
RT channel alpha 2-subunit and the associated delta peptides.";
RL J. Biol. Chem. 266:3287-3293(1991).
RN [4]
RP PROTEIN SEQUENCE OF 961-975; 992-1000 AND 1033-1050, PROTEOLYTIC
RP PROCESSING, AND SUBUNIT.
RX PubMed=2168391; DOI=10.1016/s0021-9258(18)77174-3;
RA de Jongh K.S., Warner C., Catterall W.A.;
RT "Subunits of purified calcium channels. Alpha 2 and delta are encoded by
RT the same gene.";
RL J. Biol. Chem. 265:14738-14741(1990).
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.
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.
CC {ECO:0000269|PubMed:2168391}.
CC -!- INTERACTION:
CC P13806; P07293: CACNA1S; NbExp=3; IntAct=EBI-9683767, EBI-8613624;
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=P13806-1; Sequence=Displayed;
CC -!- TISSUE SPECIFICITY: Skeletal muscle.
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:0000269|PubMed:2168391}.
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; M21948; AAA81562.1; -; mRNA.
DR PIR; S10579; CHRBA2.
DR RefSeq; NP_001075745.1; NM_001082276.1. [P13806-1]
DR PDB; 3JBR; EM; 4.20 A; F=1-39, F=56-661, F=956-1106.
DR PDB; 5GJV; EM; 3.60 A; F=1-1106.
DR PDB; 5GJW; EM; 3.90 A; F=1-1106.
DR PDB; 6JP5; EM; 2.90 A; F=1-1074.
DR PDB; 6JP8; EM; 2.70 A; F=29-1075.
DR PDB; 6JPA; EM; 2.60 A; F=29-1075.
DR PDB; 6JPB; EM; 2.90 A; F=29-1075.
DR PDB; 7JPK; EM; 3.00 A; F=1-1106.
DR PDB; 7JPL; EM; 3.40 A; F=1-1106.
DR PDB; 7JPV; EM; 3.40 A; F=1-1106.
DR PDB; 7JPW; EM; 3.20 A; F=1-1106.
DR PDB; 7JPX; EM; 2.90 A; F=1-1106.
DR PDBsum; 3JBR; -.
DR PDBsum; 5GJV; -.
DR PDBsum; 5GJW; -.
DR PDBsum; 6JP5; -.
DR PDBsum; 6JP8; -.
DR PDBsum; 6JPA; -.
DR PDBsum; 6JPB; -.
DR PDBsum; 7JPK; -.
DR PDBsum; 7JPL; -.
DR PDBsum; 7JPV; -.
DR PDBsum; 7JPW; -.
DR PDBsum; 7JPX; -.
DR AlphaFoldDB; P13806; -.
DR SMR; P13806; -.
DR ComplexPortal; CPX-3189; Skeletal muscle VGCC complex.
DR DIP; DIP-61880N; -.
DR IntAct; P13806; 3.
DR STRING; 9986.ENSOCUP00000024431; -.
DR GeneID; 100009105; -.
DR KEGG; ocu:100009105; -.
DR CTD; 781; -.
DR eggNOG; KOG2353; Eukaryota.
DR InParanoid; P13806; -.
DR OrthoDB; 510149at2759; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:1990454; C:L-type voltage-gated calcium channel complex; IDA:UniProtKB.
DR GO; GO:0030315; C:T-tubule; IDA:UniProtKB.
DR GO; GO:0005262; F:calcium channel activity; IEA:UniProtKB-KW.
DR GO; GO:0005246; F:calcium channel regulator activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005244; F:voltage-gated ion channel activity; IEA:UniProtKB-KW.
DR GO; GO:0098703; P:calcium ion import across plasma membrane; IDA:BHF-UCL.
DR GO; GO:0070588; P:calcium ion transmembrane transport; IC:ComplexPortal.
DR GO; GO:0045933; P:positive regulation of muscle contraction; IC:ComplexPortal.
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 3D-structure; Alternative splicing; Calcium; Calcium channel;
KW Calcium transport; Direct protein sequencing; 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..26
FT /evidence="ECO:0000269|PubMed:2558713"
FT CHAIN 27..1106
FT /note="Voltage-dependent calcium channel subunit alpha-
FT 2/delta-1"
FT /id="PRO_0000304636"
FT CHAIN 27..960
FT /note="Voltage-dependent calcium channel subunit alpha-2-1"
FT /id="PRO_0000005007"
FT CHAIN 961..1106
FT /note="Voltage-dependent calcium channel subunit delta-1"
FT /id="PRO_0000005008"
FT TOPO_DOM 27..1076
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1077..1097
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1098..1106
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 255..432
FT /note="VWFA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00219"
FT DOMAIN 448..539
FT /note="Cache"
FT MOTIF 261..265
FT /note="MIDAS-like motif"
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 BINDING 265
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT MOD_RES 121
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P54290"
FT CARBOHYD 94
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 138
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 186
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 326
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 350
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 615
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 784
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 891
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 406..1062
FT /note="Interchain (between alpha-2-1 and delta-1 chains)"
FT /evidence="ECO:0000250"
FT CONFLICT 45
FT /note="D -> S (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 32..39
FT /evidence="ECO:0007829|PDB:6JPA"
FT TURN 40..42
FT /evidence="ECO:0007829|PDB:6JPA"
FT HELIX 44..54
FT /evidence="ECO:0007829|PDB:6JPA"
FT HELIX 56..66
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 67..74
FT /evidence="ECO:0007829|PDB:6JPA"
FT HELIX 79..110
FT /evidence="ECO:0007829|PDB:6JPA"
FT TURN 119..121
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 127..131
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 144..146
FT /evidence="ECO:0007829|PDB:7JPX"
FT STRAND 155..159
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 161..165
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 167..169
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 172..174
FT /evidence="ECO:0007829|PDB:6JPA"
FT HELIX 179..187
FT /evidence="ECO:0007829|PDB:6JPA"
FT HELIX 188..191
FT /evidence="ECO:0007829|PDB:6JPA"
FT HELIX 192..201
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 208..212
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 217..222
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 229..233
FT /evidence="ECO:0007829|PDB:6JPA"
FT TURN 240..242
FT /evidence="ECO:0007829|PDB:6JPA"
FT HELIX 244..250
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 254..261
FT /evidence="ECO:0007829|PDB:6JPA"
FT HELIX 264..266
FT /evidence="ECO:0007829|PDB:6JPA"
FT HELIX 269..283
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 289..305
FT /evidence="ECO:0007829|PDB:6JPA"
FT HELIX 314..323
FT /evidence="ECO:0007829|PDB:6JPA"
FT HELIX 337..346
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 356..365
FT /evidence="ECO:0007829|PDB:6JPA"
FT HELIX 372..378
FT /evidence="ECO:0007829|PDB:6JPA"
FT TURN 379..381
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 384..393
FT /evidence="ECO:0007829|PDB:6JPA"
FT HELIX 399..407
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 411..415
FT /evidence="ECO:0007829|PDB:6JPA"
FT HELIX 418..420
FT /evidence="ECO:0007829|PDB:6JPA"
FT TURN 421..424
FT /evidence="ECO:0007829|PDB:6JPA"
FT HELIX 429..432
FT /evidence="ECO:0007829|PDB:6JPA"
FT HELIX 434..437
FT /evidence="ECO:0007829|PDB:6JPA"
FT HELIX 440..443
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 460..469
FT /evidence="ECO:0007829|PDB:6JPA"
FT TURN 474..477
FT /evidence="ECO:0007829|PDB:6JPA"
FT HELIX 482..484
FT /evidence="ECO:0007829|PDB:7JPW"
FT STRAND 485..495
FT /evidence="ECO:0007829|PDB:6JPA"
FT HELIX 496..499
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 506..508
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 513..517
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 521..525
FT /evidence="ECO:0007829|PDB:6JPA"
FT HELIX 543..545
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 548..550
FT /evidence="ECO:0007829|PDB:7JPV"
FT HELIX 563..566
FT /evidence="ECO:0007829|PDB:6JPA"
FT HELIX 574..579
FT /evidence="ECO:0007829|PDB:6JPA"
FT TURN 580..583
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 586..595
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 602..613
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 615..618
FT /evidence="ECO:0007829|PDB:7JPK"
FT STRAND 622..627
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 631..636
FT /evidence="ECO:0007829|PDB:6JPA"
FT HELIX 641..646
FT /evidence="ECO:0007829|PDB:6JPA"
FT HELIX 653..655
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 657..659
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 661..664
FT /evidence="ECO:0007829|PDB:7JPX"
FT STRAND 670..673
FT /evidence="ECO:0007829|PDB:6JPA"
FT HELIX 679..692
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 698..700
FT /evidence="ECO:0007829|PDB:7JPX"
FT HELIX 702..712
FT /evidence="ECO:0007829|PDB:6JPA"
FT HELIX 714..721
FT /evidence="ECO:0007829|PDB:6JPA"
FT TURN 722..725
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 730..734
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 737..739
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 745..748
FT /evidence="ECO:0007829|PDB:6JPA"
FT HELIX 751..753
FT /evidence="ECO:0007829|PDB:6JPA"
FT TURN 761..763
FT /evidence="ECO:0007829|PDB:6JPA"
FT HELIX 765..772
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 774..779
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 786..788
FT /evidence="ECO:0007829|PDB:7JPX"
FT TURN 791..793
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 796..800
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 803..807
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 813..819
FT /evidence="ECO:0007829|PDB:6JPA"
FT HELIX 821..829
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 849..856
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 860..870
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 875..877
FT /evidence="ECO:0007829|PDB:7JPV"
FT HELIX 878..880
FT /evidence="ECO:0007829|PDB:6JPA"
FT HELIX 883..891
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 896..907
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 975..985
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 991..994
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 997..1001
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 1007..1010
FT /evidence="ECO:0007829|PDB:6JPA"
FT TURN 1012..1015
FT /evidence="ECO:0007829|PDB:7JPK"
FT STRAND 1017..1022
FT /evidence="ECO:0007829|PDB:6JPA"
FT HELIX 1024..1026
FT /evidence="ECO:0007829|PDB:6JPA"
FT STRAND 1039..1041
FT /evidence="ECO:0007829|PDB:7JPX"
FT HELIX 1046..1049
FT /evidence="ECO:0007829|PDB:6JPA"
SQ SEQUENCE 1106 AA; 125043 MW; B00DE7F3C877B618 CRC64;
MAAGRPLAWT LTLWQAWLIL IGPSSEEPFP SAVTIKSWVD KMQEDLVTLA KTASGVHQLV
DIYEKYQDLY TVEPNNARQL VEIAARDIEK LLSNRSKALV RLALEAEKVQ AAHQWREDFA
SNEVVYYNAK DDLDPEKNDS EPGSQRIKPV FIDDANFRRQ VSYQHAAVHI PTDIYEGSTI
VLNELNWTSA LDDVFKKNRE EDPSLLWQVF GSATGLARYY PASPWVDNSR TPNKIDLYDV
RRRPWYIQGA ASPKDMLILV DVSGSVSGLT LKLIRTSVSE MLETLSDDDF VNVASFNSNA
QDVSCFQHLV QANVRNKKVL KDAVNNITAK GITDYKKGFS FAFEQLLNYN VSRANCNKII
MLFTDGGEER AQEIFAKYNK DKKVRVFTFS VGQHNYDRGP IQWMACENKG YYYEIPSIGA
IRINTQEYLD VLGRPMVLAG DKAKQVQWTN VYLDALELGL VITGTLPVFN ITGQFENKTN
LKNQLILGVM GVDVSLEDIK RLTPRFTLCP NGYYFAIDPN GYVLLHPNLQ PKPIGVGIPT
INLRKRRPNV QNPKSQEPVT LDFLDAELEN DIKVEIRNKM IDGESGEKTF RTLVKSQDER
YIDKGNRTYT WTPVNGTDYS SLALVLPTYS FYYIKAKIEE TITQARYSET LKPDNFEESG
YTFLAPRDYC SDLKPSDNNT EFLLNFNEFI DRKTPNNPSC NTDLINRVLL DAGFTNELVQ
NYWSKQKNIK GVKARFVVTD GGITRVYPKE AGENWQENPE TYEDSFYKRS LDNDNYVFTA
PYFNKSGPGA YESGIMVSKA VEIYIQGKLL KPAVVGIKID VNSWIENFTK TSIRDPCAGP
VCDCKRNSDV MDCVILDDGG FLLMANHDDY TNQIGRFFGE IDPSLMRHLV NISVYAFNKS
YDYQSVCEPG AAPKQGAGHR SAYVPSIADI LQIGWWATAA AWSILQQFLL SLTFPRLLEA
ADMEDDDFTA SMSKQSCITE QTQYFFDNDS KSFSGVLDCG NCSRIFHVEK LMNTNLIFIM
VESKGTCPCD TRLLIQAEQT SDGPDPCDMV KQPRYRKGPD VCFDNNVLED YTDCGGVSGL
NPSLWSIIGI QFVLLWLVSG SRHCLL
