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Protein

Voltage-dependent calcium channel subunit alpha-2/delta-3

Gene

Cacna2d3

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-type calcium channel (CACNA1A), N-type (CACNA1B), L-type (CACNA1C OR CACNA1D) but not T-type (CACNA1G) (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi262 – 2621Divalent metal cationBy similarity
Metal bindingi264 – 2641Divalent metal cationBy similarity
Metal bindingi266 – 2661Divalent metal cationBy similarity

GO - Molecular functioni

  1. calcium channel regulator activity Source: RGD
  2. metal ion binding Source: UniProtKB-KW
  3. voltage-gated calcium channel activity Source: RGD

GO - Biological processi

  1. calcium ion transmembrane transport Source: GO_Central
  2. calcium ion transport Source: RGD
  3. regulation of calcium ion transport Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Calcium channel, Ion channel, Voltage-gated channel

Keywords - Biological processi

Calcium transport, Ion transport, Transport

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

ReactomeiREACT_351378. Adrenaline,noradrenaline inhibits insulin secretion.

Names & Taxonomyi

Protein namesi
Recommended name:
Voltage-dependent calcium channel subunit alpha-2/delta-3
Alternative name(s):
Voltage-gated calcium channel subunit alpha-2/delta-3
Cleaved into the following 2 chains:
Gene namesi
Name:Cacna2d3
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Unplaced

Organism-specific databases

RGDi631361. Cacna2d3.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini34 – 1001968ExtracellularSequence AnalysisAdd
BLAST
Transmembranei1063 – 108321HelicalSequence AnalysisAdd
BLAST
Topological domaini1084 – 10852CytoplasmicSequence Analysis

GO - Cellular componenti

  1. voltage-gated calcium channel complex Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini? – 1085Voltage-dependent calcium channel subunit delta-3Sequence AnalysisPRO_0000304654
Signal peptidei1 – 3333Sequence AnalysisAdd
BLAST
Chaini34 – 10851052Voltage-dependent calcium channel subunit alpha-2/delta-3PRO_0000304652Add
BLAST
Chaini34 – ?Voltage-dependent calcium channel subunit alpha-2-3Sequence AnalysisPRO_0000304653

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi166 – 1661N-linked (GlcNAc...)Sequence Analysis
Glycosylationi309 – 3091N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi412 ↔ 1049Interchain (between alpha-2-3 and delta-3 chains)By similarity
Glycosylationi547 – 5471N-linked (GlcNAc...)Sequence Analysis
Glycosylationi626 – 6261N-linked (GlcNAc...)Sequence Analysis
Modified residuei918 – 9181Phosphotyrosine1 Publication

Post-translational modificationi

N-glycosylated.By similarity
May be proteolytically processed into subunits alpha-2-3 and delta-3 that are disulfide-linked. It is however unclear whether such cleavage really takes place in vivo and has a functional role (By similarity).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ8CFG5.
PRIDEiQ8CFG5.

PTM databases

PhosphoSiteiQ8CFG5.

Expressioni

Tissue specificityi

In heart, it is expressed in atrium but not in ventricle.1 Publication

Inductioni

By IGF1.1 Publication

Gene expression databases

ExpressionAtlasiQ8CFG5. baseline and differential.
GenevestigatoriQ8CFG5.

Interactioni

Subunit structurei

Dimer formed of alpha-2-2 and delta-2 chains; disulfide-linked. Voltage-dependent calcium channels are multisubunit complexes, consisting of alpha-1 (CACNA1), alpha-2 (CACNA2D), beta (CACNB) and delta (CACNA2D) subunits in a 1:1:1:1 ratio (By similarity).By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000042602.

Structurei

3D structure databases

ProteinModelPortaliQ8CFG5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini256 – 438183VWFAPROSITE-ProRule annotationAdd
BLAST
Domaini452 – 54392CacheAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi262 – 2665MIDAS-like motif

Domaini

The MIDAS-like motif in the VWFA domain binds divalent metal cations and is required to promote trafficking of the alpha-1 (CACNA1) subunit to the plasma membrane by an integrin-like switch.By similarity

Sequence similaritiesi

Contains 1 cache domain.Curated
Contains 1 VWFA domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG307080.
HOGENOMiHOG000010247.
HOVERGENiHBG107124.
InParanoidiQ8CFG5.
KOiK04860.
PhylomeDBiQ8CFG5.

Family and domain databases

Gene3Di3.40.50.410. 1 hit.
InterProiIPR004010. Cache_domain.
IPR013608. VWA_N.
IPR002035. VWF_A.
[Graphical view]
PfamiPF02743. Cache_1. 1 hit.
PF08399. VWA_N. 1 hit.
[Graphical view]
SMARTiSM00327. VWA. 1 hit.
[Graphical view]
SUPFAMiSSF53300. SSF53300. 1 hit.
PROSITEiPS50234. VWFA. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q8CFG5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAGPGSLCCA SRGASALLAT ALLYAALGDV VRSEQQIPLS VVKLWASAFG
60 70 80 90 100
GEIKSIAAKY SGSQLLQKKY KEYEKDVAIE EIDGLQLVKK LAKNMEEMFH
110 120 130 140 150
KKSEAVRRLV EAAEEAHLKH EFDADLQYEY FNAVLINERD KDGNFLELGK
160 170 180 190 200
EFILAPNDHF NNLPVNISLS DVQVPTNMYN KDPAIVNGVY WSESLNKVFV
210 220 230 240 250
DNFDRDPSLI WQYFGSAKGF FRQYPGIKWE PDENGVIAFD CRNRKWYIQA
260 270 280 290 300
ATSPKDVVIL VDVSGSMKGL RLTIAKQTVS SILDTLGDDD FFNIITYNEE
310 320 330 340 350
LHYVEPCLNG TLVQADRTNK EHFREHLDKL FAKGIGMLDI ALNEAFNVLS
360 370 380 390 400
DFNHTGQGSI CSQAIMLITD GAVDTYDTIF AKYNWPERKV RIFTYLIGRE
410 420 430 440 450
AAFADNLKWM ACANKGFFTQ ISTLADVQEN VMEYLHVLSR PKVIDQEHDV
460 470 480 490 500
VWTEAYIDST LADDQGLVLM TTVAMPVFSK QNETRSKGIL LGVVGTDVPV
510 520 530 540 550
KELLKTIPKY KLGIHGYAFA ITNNGYILTH PELRPLYEEG KKRRKPNYSS
560 570 580 590 600
VDLSEVEWED RDDVLRNAMV NRKTGKFSME VKKTVDKGKR VLVMTNDYYY
610 620 630 640 650
TDIKGAPFSL GVALSRGHGK YFFRGNVTIE EGLHDLEHPD VSLADEWSYC
660 670 680 690 700
NTDLHPEHRH LSQLEAIKLY LKGKEPLLQC DKELIQEVLF DAVVSAPIEA
710 720 730 740 750
YWTSLALNKS ENSDKGVEVA FLGTRTGLSR INLFVGAEQL TNQDFLKARD
760 770 780 790 800
KENIFNADHF PLWYRRAAEQ IPGSFVYSIP FSTGTVNKSN VVTASTSIQL
810 820 830 840 850
LDERKSPVVA AVGIQMKLEF FQRKFWTASR QCASLDGKCS ISCDDETVNC
860 870 880 890 900
YLIDNNGFIL VSEDYTQTGD FFGEVEGAVM NKLLTMGSFK RITLYDYQAM
910 920 930 940 950
CRANKESSDS AHGLLDPYKA FLSAAKWIVT ELVLFLVEFN LCSWWHSDMT
960 970 980 990 1000
AKAQKLKQTL EPCDTEYPAF VSERTIKETT GNIACEDCSK SFVIQQIPSS
1010 1020 1030 1040 1050
NLFMVVVDSS CLCESVAPIT MAPIEIRYNE SLKCERLKAQ KIRRRPESCH
1060 1070 1080
GFHPEENARE CGGASSLQAQ VALLLLPLVS SLFSR
Length:1,085
Mass (Da):122,204
Last modified:March 1, 2003 - v1
Checksum:i9584F533E318002A
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF486278 mRNA. Translation: AAO14654.1.
RefSeqiNP_783185.1. NM_175595.2.
UniGeneiRn.229510.

Genome annotation databases

GeneIDi306243.
KEGGirno:306243.
UCSCiRGD:631361. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF486278 mRNA. Translation: AAO14654.1.
RefSeqiNP_783185.1. NM_175595.2.
UniGeneiRn.229510.

3D structure databases

ProteinModelPortaliQ8CFG5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000042602.

PTM databases

PhosphoSiteiQ8CFG5.

Proteomic databases

PaxDbiQ8CFG5.
PRIDEiQ8CFG5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi306243.
KEGGirno:306243.
UCSCiRGD:631361. rat.

Organism-specific databases

CTDi55799.
RGDi631361. Cacna2d3.

Phylogenomic databases

eggNOGiNOG307080.
HOGENOMiHOG000010247.
HOVERGENiHBG107124.
InParanoidiQ8CFG5.
KOiK04860.
PhylomeDBiQ8CFG5.

Enzyme and pathway databases

ReactomeiREACT_351378. Adrenaline,noradrenaline inhibits insulin secretion.

Miscellaneous databases

NextBioi655665.
PROiQ8CFG5.

Gene expression databases

ExpressionAtlasiQ8CFG5. baseline and differential.
GenevestigatoriQ8CFG5.

Family and domain databases

Gene3Di3.40.50.410. 1 hit.
InterProiIPR004010. Cache_domain.
IPR013608. VWA_N.
IPR002035. VWF_A.
[Graphical view]
PfamiPF02743. Cache_1. 1 hit.
PF08399. VWA_N. 1 hit.
[Graphical view]
SMARTiSM00327. VWA. 1 hit.
[Graphical view]
SUPFAMiSSF53300. SSF53300. 1 hit.
PROSITEiPS50234. VWFA. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning of calcium channel alpha(2)delta-subunits from rat atria and the differential regulation of their expression by IGF-1."
    Chu P.-J., Best P.M.
    J. Mol. Cell. Cardiol. 35:207-215(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INDUCTION.
    Strain: Sprague-Dawley.
    Tissue: Heart atrium.
  2. "Quantitative phosphoproteomics of vasopressin-sensitive renal cells: regulation of aquaporin-2 phosphorylation at two sites."
    Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.
    Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-918, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiCA2D3_RAT
AccessioniPrimary (citable) accession number: Q8CFG5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 11, 2007
Last sequence update: March 1, 2003
Last modified: April 29, 2015
This is version 76 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

In contrast to CACNA2D1 and CACNA2D2, it does not bind gabapentin, an antiepileptic drug.By similarity

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.