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Protein

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

Gene

CACNA2D3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Miscellaneous

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi262Divalent metal cationBy similarity1
Metal bindingi264Divalent metal cationBy similarity1
Metal bindingi266Divalent metal cationBy similarity1

GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • voltage-gated calcium channel activity Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionCalcium channel, Ion channel, Voltage-gated channel
Biological processCalcium transport, Ion transport, Transport
LigandCalcium, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-112308 Presynaptic depolarization and calcium channel opening
R-HSA-5576892 Phase 0 - rapid depolarisation
R-HSA-5576893 Phase 2 - plateau phase

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

EuPathDBiHostDB:ENSG00000157445.14
HGNCiHGNC:15460 CACNA2D3
MIMi606399 gene
neXtProtiNX_Q8IZS8

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini29 – 1068ExtracellularSequence analysisAdd BLAST1040
Transmembranei1069 – 1089HelicalSequence analysisAdd BLAST21
Topological domaini1090 – 1091CytoplasmicSequence analysis2

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi55799
OpenTargetsiENSG00000157445
PharmGKBiPA26013

Chemistry databases

ChEMBLiCHEMBL2363032
DrugBankiDB00381 Amlodipine
DB06712 Nilvadipine
DB00421 Spironolactone

Polymorphism and mutation databases

BioMutaiCACNA2D3
DMDMi74723683

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_0000304648? – 1091Voltage-dependent calcium channel subunit delta-3Sequence analysis
Signal peptidei1 – 28Sequence analysisAdd BLAST28
ChainiPRO_000030464629 – 1091Voltage-dependent calcium channel subunit alpha-2/delta-3Add BLAST1063
ChainiPRO_000030464729 – ?Voltage-dependent calcium channel subunit alpha-2-3Sequence analysis

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi166N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi309N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi412 ↔ 1055Interchain (between alpha-2-3 and delta-3 chains)By similarity
Glycosylationi553N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi632N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi793N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei924PhosphotyrosineBy similarity1

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

EPDiQ8IZS8
PaxDbiQ8IZS8
PeptideAtlasiQ8IZS8
PRIDEiQ8IZS8
ProteomicsDBi71421
71422 [Q8IZS8-2]
71423 [Q8IZS8-3]

PTM databases

iPTMnetiQ8IZS8
PhosphoSitePlusiQ8IZS8

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 Expressed in 163 organ(s), highest expression level in caudate nucleus
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

BioGridi120911, 10 interactors
STRINGi9606.ENSP00000419101

Structurei

3D structure databases

ProteinModelPortaliQ8IZS8
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini256 – 438VWFAPROSITE-ProRule annotationAdd BLAST183
Domaini452 – 549CacheAdd BLAST98

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi262 – 266MIDAS-like motif5

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

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

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

Family and domain databases

Gene3Di3.40.50.410, 1 hit
InterProiView protein in InterPro
IPR013680 VDCC_a2/dsu
IPR013608 VWA_N
IPR002035 VWF_A
IPR036465 vWFA_dom_sf
PfamiView protein in Pfam
PF08473 VGCC_alpha2, 1 hit
PF13768 VWA_3, 1 hit
PF08399 VWA_N, 1 hit
SMARTiView protein in SMART
SM00327 VWA, 1 hit
SUPFAMiSSF53300 SSF53300, 1 hit
PROSITEiView protein in PROSITE
PS50234 VWFA, 1 hit

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

This entry has 3 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B4DSF6B4DSF6_HUMAN
Voltage-dependent calcium channel s...
CACNA2D3
525Annotation score:
C9JAV5C9JAV5_HUMAN
Voltage-dependent calcium channel s...
CACNA2D3
126Annotation score:
F8WAV4F8WAV4_HUMAN
Voltage-dependent calcium channel s...
CACNA2D3
46Annotation score:

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0280641 – 94Missing in isoform 2 and isoform 3. 1 PublicationAdd BLAST94
Alternative sequenceiVSP_028065461 – 466Missing in isoform 3. 1 Publication6
Alternative sequenceiVSP_028066595 – 619KRVLV…SLGVA → FRCGAFQRSWEIFLPRECNH RRRPA in isoform 3. 1 PublicationAdd BLAST25
Alternative sequenceiVSP_028067620 – 1091Missing in isoform 3. 1 PublicationAdd BLAST472

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

Similar proteinsi

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
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120911, 10 interactors
STRINGi9606.ENSP00000419101

Chemistry databases

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
PhosphoSitePlusiQ8IZS8

Polymorphism and mutation databases

BioMutaiCACNA2D3
DMDMi74723683

Proteomic databases

EPDiQ8IZS8
PaxDbiQ8IZS8
PeptideAtlasiQ8IZS8
PRIDEiQ8IZS8
ProteomicsDBi71421
71422 [Q8IZS8-2]
71423 [Q8IZS8-3]

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
DisGeNETi55799
EuPathDBiHostDB:ENSG00000157445.14
GeneCardsiCACNA2D3
HGNCiHGNC:15460 CACNA2D3
HPAiHPA030849
HPA030850
MIMi606399 gene
neXtProtiNX_Q8IZS8
OpenTargetsiENSG00000157445
PharmGKBiPA26013
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

ReactomeiR-HSA-112308 Presynaptic depolarization and calcium channel opening
R-HSA-5576892 Phase 0 - rapid depolarisation
R-HSA-5576893 Phase 2 - plateau phase

Miscellaneous databases

ChiTaRSiCACNA2D3 human
GenomeRNAii55799
PROiPR:Q8IZS8
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000157445 Expressed in 163 organ(s), highest expression level in caudate nucleus
CleanExiHS_CACNA2D3
ExpressionAtlasiQ8IZS8 baseline and differential
GenevisibleiQ8IZS8 HS

Family and domain databases

Gene3Di3.40.50.410, 1 hit
InterProiView protein in InterPro
IPR013680 VDCC_a2/dsu
IPR013608 VWA_N
IPR002035 VWF_A
IPR036465 vWFA_dom_sf
PfamiView protein in Pfam
PF08473 VGCC_alpha2, 1 hit
PF13768 VWA_3, 1 hit
PF08399 VWA_N, 1 hit
SMARTiView protein in SMART
SM00327 VWA, 1 hit
SUPFAMiSSF53300 SSF53300, 1 hit
PROSITEiView protein in PROSITE
PS50234 VWFA, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCA2D3_HUMAN
AccessioniPrimary (citable) accession number: Q8IZS8
Secondary accession number(s): B2RPL6, Q9NY16, Q9NY18
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 11, 2007
Last sequence update: March 1, 2003
Last modified: November 7, 2018
This is version 118 of the entry and version 1 of the sequence. See 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

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