ID   CA2D3_RAT               Reviewed;        1085 AA.
AC   Q8CFG5;
DT   11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 1.
DT   27-MAR-2024, entry version 115.
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   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], TISSUE SPECIFICITY, AND INDUCTION.
RC   STRAIN=Sprague-Dawley; TISSUE=Heart atrium;
RX   PubMed=12606261; DOI=10.1016/s0022-2828(02)00313-9;
RA   Chu P.-J., Best P.M.;
RT   "Molecular cloning of calcium channel alpha(2)delta-subunits from rat atria
RT   and the differential regulation of their expression by IGF-1.";
RL   J. Mol. Cell. Cardiol. 35:207-215(2003).
RN   [2]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-918, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA   Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.;
RT   "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT   regulation of aquaporin-2 phosphorylation at two sites.";
RL   Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
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) (By similarity). {ECO:0000250}.
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: In heart, it is expressed in atrium but not in
CC       ventricle. {ECO:0000269|PubMed:12606261}.
CC   -!- INDUCTION: By IGF1. {ECO:0000269|PubMed:12606261}.
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:0000250}.
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 (By
CC       similarity). {ECO:0000250}.
CC   -!- MISCELLANEOUS: In contrast to CACNA2D1 and CACNA2D2, it does not bind
CC       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; AF486278; AAO14654.1; -; mRNA.
DR   RefSeq; NP_783185.1; NM_175595.2.
DR   AlphaFoldDB; Q8CFG5; -.
DR   SMR; Q8CFG5; -.
DR   STRING; 10116.ENSRNOP00000042602; -.
DR   GlyCosmos; Q8CFG5; 4 sites, No reported glycans.
DR   GlyGen; Q8CFG5; 4 sites.
DR   iPTMnet; Q8CFG5; -.
DR   PhosphoSitePlus; Q8CFG5; -.
DR   PaxDb; 10116-ENSRNOP00000042602; -.
DR   Ensembl; ENSRNOT00000048043.4; ENSRNOP00000042602.4; ENSRNOG00000031287.5.
DR   GeneID; 306243; -.
DR   KEGG; rno:306243; -.
DR   UCSC; RGD:631361; rat.
DR   AGR; RGD:631361; -.
DR   CTD; 55799; -.
DR   RGD; 631361; Cacna2d3.
DR   eggNOG; KOG2353; Eukaryota.
DR   GeneTree; ENSGT00940000155766; -.
DR   InParanoid; Q8CFG5; -.
DR   OrthoDB; 2971287at2759; -.
DR   PhylomeDB; Q8CFG5; -.
DR   Reactome; R-RNO-112308; Presynaptic depolarization and calcium channel opening.
DR   PRO; PR:Q8CFG5; -.
DR   Proteomes; UP000002494; Chromosome 16.
DR   GO; GO:0005891; C:voltage-gated calcium channel complex; IBA:GO_Central.
DR   GO; GO:0005246; F:calcium channel regulator activity; TAS:RGD.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0005245; F:voltage-gated calcium channel activity; IDA:RGD.
DR   GO; GO:0006816; P:calcium ion transport; IDA:RGD.
DR   GO; GO:1990314; P:cellular response to insulin-like growth factor stimulus; IEP:RGD.
DR   CDD; cd12912; PDC2_MCP_like; 1.
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:SF25; VOLTAGE-DEPENDENT CALCIUM CHANNEL SUBUNIT ALPHA-2_DELTA-3; 1.
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; vWA-like; 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..1085
FT                   /note="Voltage-dependent calcium channel subunit alpha-
FT                   2/delta-3"
FT                   /id="PRO_0000304652"
FT   CHAIN           34..?
FT                   /note="Voltage-dependent calcium channel subunit alpha-2-3"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000304653"
FT   CHAIN           ?..1085
FT                   /note="Voltage-dependent calcium channel subunit delta-3"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000304654"
FT   TOPO_DOM        34..1062
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1063..1083
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1084..1085
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          256..438
FT                   /note="VWFA"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00219"
FT   DOMAIN          452..543
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         918
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0007744|PubMed:16641100"
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        547
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        626
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        412..1049
FT                   /note="Interchain (between alpha-2-3 and delta-3 chains)"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   1085 AA;  122204 MW;  9584F533E318002A CRC64;
     MAGPGSLCCA SRGASALLAT ALLYAALGDV VRSEQQIPLS VVKLWASAFG GEIKSIAAKY
     SGSQLLQKKY KEYEKDVAIE EIDGLQLVKK LAKNMEEMFH KKSEAVRRLV EAAEEAHLKH
     EFDADLQYEY FNAVLINERD KDGNFLELGK EFILAPNDHF NNLPVNISLS DVQVPTNMYN
     KDPAIVNGVY WSESLNKVFV DNFDRDPSLI WQYFGSAKGF FRQYPGIKWE PDENGVIAFD
     CRNRKWYIQA ATSPKDVVIL VDVSGSMKGL RLTIAKQTVS SILDTLGDDD FFNIITYNEE
     LHYVEPCLNG TLVQADRTNK EHFREHLDKL FAKGIGMLDI ALNEAFNVLS DFNHTGQGSI
     CSQAIMLITD GAVDTYDTIF AKYNWPERKV RIFTYLIGRE AAFADNLKWM ACANKGFFTQ
     ISTLADVQEN VMEYLHVLSR PKVIDQEHDV VWTEAYIDST LADDQGLVLM TTVAMPVFSK
     QNETRSKGIL LGVVGTDVPV KELLKTIPKY KLGIHGYAFA ITNNGYILTH PELRPLYEEG
     KKRRKPNYSS VDLSEVEWED RDDVLRNAMV NRKTGKFSME VKKTVDKGKR VLVMTNDYYY
     TDIKGAPFSL GVALSRGHGK YFFRGNVTIE EGLHDLEHPD VSLADEWSYC NTDLHPEHRH
     LSQLEAIKLY LKGKEPLLQC DKELIQEVLF DAVVSAPIEA YWTSLALNKS ENSDKGVEVA
     FLGTRTGLSR INLFVGAEQL TNQDFLKARD KENIFNADHF PLWYRRAAEQ IPGSFVYSIP
     FSTGTVNKSN VVTASTSIQL LDERKSPVVA AVGIQMKLEF FQRKFWTASR QCASLDGKCS
     ISCDDETVNC YLIDNNGFIL VSEDYTQTGD FFGEVEGAVM NKLLTMGSFK RITLYDYQAM
     CRANKESSDS AHGLLDPYKA FLSAAKWIVT ELVLFLVEFN LCSWWHSDMT AKAQKLKQTL
     EPCDTEYPAF VSERTIKETT GNIACEDCSK SFVIQQIPSS NLFMVVVDSS CLCESVAPIT
     MAPIEIRYNE SLKCERLKAQ KIRRRPESCH GFHPEENARE CGGASSLQAQ VALLLLPLVS
     SLFSR
//