CA2D3_RAT
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 03-AUG-2022, entry version 108.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
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 GlyGen; Q8CFG5; 4 sites.
DR iPTMnet; Q8CFG5; -.
DR PhosphoSitePlus; Q8CFG5; -.
DR PaxDb; Q8CFG5; -.
DR PRIDE; Q8CFG5; -.
DR Ensembl; ENSRNOT00000048043; ENSRNOP00000042602; ENSRNOG00000031287.
DR GeneID; 306243; -.
DR KEGG; rno:306243; -.
DR UCSC; RGD:631361; rat.
DR CTD; 55799; -.
DR RGD; 631361; Cacna2d3.
DR eggNOG; KOG2353; Eukaryota.
DR GeneTree; ENSGT00940000155766; -.
DR InParanoid; Q8CFG5; -.
DR OrthoDB; 69856at2759; -.
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 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..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
