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Protein

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

Gene

CACNA2D3

Organism
Homo sapiens (Human)
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

GO - Biological processi

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

ReactomeiR-HSA-112308. Depolarization of the Presynaptic Terminal Triggers the Opening of Calcium Channels.
R-HSA-5576892. Phase 0 - rapid depolarisation.
R-HSA-5576893. Phase 2 - plateau phase.
R-HSA-5576894. Phase 1 - inactivation of fast Na+ channels.

Protein family/group databases

TCDBi8.A.18.3.1. the ca(2+) channel auxiliary subunit Alpha2Delta types 1-4 (cca-Alpha2Delta) family.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:15460. CACNA2D3.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini29 – 10681040ExtracellularSequence analysisAdd
BLAST
Transmembranei1069 – 108921HelicalSequence analysisAdd
BLAST
Topological domaini1090 – 10912CytoplasmicSequence analysis

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA26013.

Chemistry

ChEMBLiCHEMBL2363032.
DrugBankiDB00381. Amlodipine.
DB06712. Nilvadipine.
DB00421. Spironolactone.

Polymorphism and mutation databases

BioMutaiCACNA2D3.
DMDMi74723683.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini? – 1091Voltage-dependent calcium channel subunit delta-3Sequence analysisPRO_0000304648
Signal peptidei1 – 2828Sequence analysisAdd
BLAST
Chaini29 – 10911063Voltage-dependent calcium channel subunit alpha-2/delta-3PRO_0000304646Add
BLAST
Chaini29 – ?Voltage-dependent calcium channel subunit alpha-2-3Sequence analysisPRO_0000304647

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi166 – 1661N-linked (GlcNAc...)Sequence analysis
Glycosylationi309 – 3091N-linked (GlcNAc...)Sequence analysis
Disulfide bondi412 ↔ 1055Interchain (between alpha-2-3 and delta-3 chains)By similarity
Glycosylationi553 – 5531N-linked (GlcNAc...)Sequence analysis
Glycosylationi632 – 6321N-linked (GlcNAc...)Sequence analysis
Glycosylationi793 – 7931N-linked (GlcNAc...)Sequence analysis
Modified residuei924 – 9241PhosphotyrosineBy similarity

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

PaxDbiQ8IZS8.
PeptideAtlasiQ8IZS8.
PRIDEiQ8IZS8.

PTM databases

iPTMnetiQ8IZS8.
PhosphoSiteiQ8IZS8.

Expressioni

Tissue specificityi

Only detected in brain. Not present in lung, testis, aorta, spleen, jejunum, ventricular muscle and kidney (at protein level). According to PubMed:11687876, it is brain-specific, while according to PubMed:11245980, it is widely expressed.1 Publication

Gene expression databases

BgeeiENSG00000157445.
CleanExiHS_CACNA2D3.
ExpressionAtlasiQ8IZS8. baseline and differential.
GenevisibleiQ8IZS8. HS.

Organism-specific databases

HPAiHPA030849.
HPA030850.

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

STRINGi9606.ENSP00000419101.

Structurei

3D structure databases

ProteinModelPortaliQ8IZS8.
SMRiQ8IZS8. Positions 223-371.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini256 – 438183VWFAPROSITE-ProRule annotationAdd
BLAST
Domaini452 – 54998CacheAdd
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

eggNOGiKOG2353. Eukaryota.
ENOG410XPDX. LUCA.
GeneTreeiENSGT00530000062904.
HOGENOMiHOG000010247.
HOVERGENiHBG107124.
InParanoidiQ8IZS8.
KOiK04860.
OMAiAALDGKC.
OrthoDBiEOG091G00UY.
PhylomeDBiQ8IZS8.
TreeFamiTF315824.

Family and domain databases

Gene3Di3.40.50.410. 1 hit.
InterProiIPR013680. VDCC_a2/dsu.
IPR013608. VWA_N.
IPR002035. VWF_A.
[Graphical view]
PfamiPF08473. VGCC_alpha2. 1 hit.
PF13768. VWA_3. 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]

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8IZS8-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAGPGSPRRA SRGASALLAA 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 FFNIIAYNEE
310 320 330 340 350
LHYVEPCLNG TLVQADRTNK EHFREHLDKL FAKGIGMLDI ALNEAFNILS
360 370 380 390 400
DFNHTGQGSI CSQAIMLITD GAVDTYDTIF AKYNWPDRKV RIFTYLIGRE
410 420 430 440 450
AAFADNLKWM ACANKGFFTQ ISTLADVQEN VMEYLHVLSR PKVIDQEHDV
460 470 480 490 500
VWTEAYIDST LPQAQKLTDD QGPVLMTTVA MPVFSKQNET RSKGILLGVV
510 520 530 540 550
GTDVPVKELL KTIPKYKLGI HGYAFAITNN GYILTHPELR LLYEEGKKRR
560 570 580 590 600
KPNYSSVDLS EVEWEDRDDV LRNAMVNRKT GKFSMEVKKT VDKGKRVLVM
610 620 630 640 650
TNDYYYTDIK GTPFSLGVAL SRGHGKYFFR GNVTIEEGLH DLEHPDVSLA
660 670 680 690 700
DEWSYCNTDL HPEHRHLSQL EAIKLYLKGK EPLLQCDKEL IQEVLFDAVV
710 720 730 740 750
SAPIEAYWTS LALNKSENSD KGVEVAFLGT RTGLSRINLF VGAEQLTNQD
760 770 780 790 800
FLKAGDKENI FNADHFPLWY RRAAEQIPGS FVYSIPFSTG PVNKSNVVTA
810 820 830 840 850
STSIQLLDER KSPVVAAVGI QMKLEFFQRK FWTASRQCAS LDGKCSISCD
860 870 880 890 900
DETVNCYLID NNGFILVSED YTQTGDFFGE IEGAVMNKLL TMGSFKRITL
910 920 930 940 950
YDYQAMCRAN KESSDGAHGL LDPYNAFLSA VKWIMTELVL FLVEFNLCSW
960 970 980 990 1000
WHSDMTAKAQ KLKQTLEPCD TEYPAFVSER TIKETTGNIA CEDCSKSFVI
1010 1020 1030 1040 1050
QQIPSSNLFM VVVDSSCLCE SVAPITMAPI EIRYNESLKC ERLKAQKIRR
1060 1070 1080 1090
RPESCHGFHP EENARECGGA PSLQAQTVLL LLPLLLMLFS R
Length:1,091
Mass (Da):123,011
Last modified:March 1, 2003 - v1
Checksum:i4E5E50BD38F05082
GO
Isoform 2 (identifier: Q8IZS8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-94: Missing.

Show »
Length:997
Mass (Da):112,997
Checksum:iB56D13133FD67B8D
GO
Isoform 3 (identifier: Q8IZS8-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-94: Missing.
     461-466: Missing.
     595-619: KRVLVMTNDYYYTDIKGTPFSLGVA → FRCGAFQRSWEIFLPRECNHRRRPA
     620-1091: Missing.

Show »
Length:519
Mass (Da):59,527
Checksum:i198D13AF246286C6
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 9494Missing in isoform 2 and isoform 3. 1 PublicationVSP_028064Add
BLAST
Alternative sequencei461 – 4666Missing in isoform 3. 1 PublicationVSP_028065
Alternative sequencei595 – 61925KRVLV…SLGVA → FRCGAFQRSWEIFLPRECNH RRRPA in isoform 3. 1 PublicationVSP_028066Add
BLAST
Alternative sequencei620 – 1091472Missing in isoform 3. 1 PublicationVSP_028067Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ272268 mRNA. Translation: CAB75962.1.
AJ272213 mRNA. Translation: CAB75878.1.
AF516696 mRNA. Translation: AAN06673.1.
BC137502 mRNA. Translation: AAI37503.1.
BC137505 mRNA. Translation: AAI37506.1.
CCDSiCCDS54598.1. [Q8IZS8-1]
RefSeqiNP_060868.2. NM_018398.2. [Q8IZS8-1]
UniGeneiHs.656687.

Genome annotation databases

EnsembliENST00000288197; ENSP00000288197; ENSG00000157445. [Q8IZS8-1]
ENST00000415676; ENSP00000389506; ENSG00000157445. [Q8IZS8-1]
ENST00000471363; ENSP00000418228; ENSG00000157445. [Q8IZS8-3]
ENST00000474759; ENSP00000419101; ENSG00000157445. [Q8IZS8-1]
ENST00000490478; ENSP00000417279; ENSG00000157445. [Q8IZS8-2]
ENST00000620722; ENSP00000478969; ENSG00000157445. [Q8IZS8-3]
GeneIDi55799.
KEGGihsa:55799.
UCSCiuc003dhf.3. human. [Q8IZS8-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ272268 mRNA. Translation: CAB75962.1.
AJ272213 mRNA. Translation: CAB75878.1.
AF516696 mRNA. Translation: AAN06673.1.
BC137502 mRNA. Translation: AAI37503.1.
BC137505 mRNA. Translation: AAI37506.1.
CCDSiCCDS54598.1. [Q8IZS8-1]
RefSeqiNP_060868.2. NM_018398.2. [Q8IZS8-1]
UniGeneiHs.656687.

3D structure databases

ProteinModelPortaliQ8IZS8.
SMRiQ8IZS8. Positions 223-371.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000419101.

Chemistry

ChEMBLiCHEMBL2363032.
DrugBankiDB00381. Amlodipine.
DB06712. Nilvadipine.
DB00421. Spironolactone.

Protein family/group databases

TCDBi8.A.18.3.1. the ca(2+) channel auxiliary subunit Alpha2Delta types 1-4 (cca-Alpha2Delta) family.

PTM databases

iPTMnetiQ8IZS8.
PhosphoSiteiQ8IZS8.

Polymorphism and mutation databases

BioMutaiCACNA2D3.
DMDMi74723683.

Proteomic databases

PaxDbiQ8IZS8.
PeptideAtlasiQ8IZS8.
PRIDEiQ8IZS8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000288197; ENSP00000288197; ENSG00000157445. [Q8IZS8-1]
ENST00000415676; ENSP00000389506; ENSG00000157445. [Q8IZS8-1]
ENST00000471363; ENSP00000418228; ENSG00000157445. [Q8IZS8-3]
ENST00000474759; ENSP00000419101; ENSG00000157445. [Q8IZS8-1]
ENST00000490478; ENSP00000417279; ENSG00000157445. [Q8IZS8-2]
ENST00000620722; ENSP00000478969; ENSG00000157445. [Q8IZS8-3]
GeneIDi55799.
KEGGihsa:55799.
UCSCiuc003dhf.3. human. [Q8IZS8-1]

Organism-specific databases

CTDi55799.
GeneCardsiCACNA2D3.
HGNCiHGNC:15460. CACNA2D3.
HPAiHPA030849.
HPA030850.
MIMi606399. gene.
neXtProtiNX_Q8IZS8.
PharmGKBiPA26013.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2353. Eukaryota.
ENOG410XPDX. LUCA.
GeneTreeiENSGT00530000062904.
HOGENOMiHOG000010247.
HOVERGENiHBG107124.
InParanoidiQ8IZS8.
KOiK04860.
OMAiAALDGKC.
OrthoDBiEOG091G00UY.
PhylomeDBiQ8IZS8.
TreeFamiTF315824.

Enzyme and pathway databases

ReactomeiR-HSA-112308. Depolarization of the Presynaptic Terminal Triggers the Opening of Calcium Channels.
R-HSA-5576892. Phase 0 - rapid depolarisation.
R-HSA-5576893. Phase 2 - plateau phase.
R-HSA-5576894. Phase 1 - inactivation of fast Na+ channels.

Miscellaneous databases

ChiTaRSiCACNA2D3. human.
GenomeRNAii55799.
PROiQ8IZS8.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000157445.
CleanExiHS_CACNA2D3.
ExpressionAtlasiQ8IZS8. baseline and differential.
GenevisibleiQ8IZS8. HS.

Family and domain databases

Gene3Di3.40.50.410. 1 hit.
InterProiIPR013680. VDCC_a2/dsu.
IPR013608. VWA_N.
IPR002035. VWF_A.
[Graphical view]
PfamiPF08473. VGCC_alpha2. 1 hit.
PF13768. VWA_3. 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...

Entry informationi

Entry nameiCA2D3_HUMAN
AccessioniPrimary (citable) accession number: Q8IZS8
Secondary accession number(s): B2RPL6, Q9NY16, Q9NY18
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 11, 2007
Last sequence update: March 1, 2003
Last modified: September 7, 2016
This is version 102 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

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 one 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.