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Protein

Voltage-dependent calcium channel subunit alpha-2/delta-1

Gene

CACNA2D1

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. Plays an important role in excitation-contraction coupling (By similarity).By similarity

Miscellaneous

Binds gabapentin, an antiepileptic drug.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi259Divalent metal cationBy similarity1
Metal bindingi261Divalent metal cationBy similarity1
Metal bindingi263Divalent metal cationBy similarity1

GO - Molecular functioni

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

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-5576892 Phase 0 - rapid depolarisation
R-HSA-5576893 Phase 2 - plateau phase

Protein family/group databases

TCDBi8.A.18.1.1 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-1
Alternative name(s):
Voltage-gated calcium channel subunit alpha-2/delta-1
Cleaved into the following 2 chains:
Gene namesi
Name:CACNA2D1
Synonyms:CACNL2A, CCHL2A, MHS3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000153956.15
HGNCiHGNC:1399 CACNA2D1
MIMi114204 gene
neXtProtiNX_P54289

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 domaini25 – 1073ExtracellularSequence analysisAdd BLAST1049
Transmembranei1074 – 1094HelicalSequence analysisAdd BLAST21
Topological domaini1095 – 1103CytoplasmicSequence analysis9

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi781
MalaCardsiCACNA2D1
OpenTargetsiENSG00000153956
Orphaneti130 Brugada syndrome
51083 Familial short QT syndrome
PharmGKBiPA86

Chemistry databases

ChEMBLiCHEMBL1919
DrugBankiDB00381 Amlodipine
DB04838 Cyclandelate
DB01023 Felodipine
DB00996 Gabapentin
DB00308 Ibutilide
DB00270 Isradipine
DB00653 Magnesium Sulfate
DB00622 Nicardipine
DB01115 Nifedipine
DB06712 Nilvadipine
DB00401 Nisoldipine
DB01054 Nitrendipine
DB00421 Spironolactone
DB04922 XP13512

Polymorphism and mutation databases

BioMutaiCACNA2D1
DMDMi262527579

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Sequence analysisAdd BLAST24
ChainiPRO_000030463325 – 1103Voltage-dependent calcium channel subunit alpha-2/delta-1Add BLAST1079
ChainiPRO_000000500125 – 956Voltage-dependent calcium channel subunit alpha-2-1By similarityAdd BLAST932
ChainiPRO_0000005002957 – 1103Voltage-dependent calcium channel subunit delta-1By similarityAdd BLAST147

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi92N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei119PhosphoserineBy similarity1
Glycosylationi136N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi184N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi324N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi348N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi404 ↔ 1059Interchain (between alpha-2-1 and delta-1 chains)
Glycosylationi468N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi475N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi604N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi613N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi675N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi781N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi824N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi888N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi895N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi985N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi998N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

Proteolytically processed into subunits alpha-2-1 and delta-1 that are disulfide-linked.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP54289
MaxQBiP54289
PaxDbiP54289
PeptideAtlasiP54289
PRIDEiP54289
ProteomicsDBi56675
56676 [P54289-2]
56677 [P54289-3]
56678 [P54289-4]
56679 [P54289-5]

PTM databases

GlyConnecti1895
iPTMnetiP54289
PhosphoSitePlusiP54289
SwissPalmiP54289

Expressioni

Tissue specificityi

Isoform 1 is expressed in skeletal muscle. Isoform 2 is expressed in the central nervous system. Isoform 2, isoform 4 and isoform 5 are expressed in neuroblastoma cells. Isoform 3, isoform 4 and isoform 5 are expressed in the aorta.2 Publications

Gene expression databases

BgeeiENSG00000153956 Expressed in 204 organ(s), highest expression level in biceps brachii
CleanExiHS_CACNA2D1
ExpressionAtlasiP54289 baseline and differential
GenevisibleiP54289 HS

Organism-specific databases

HPAiHPA008213
HPA008621

Interactioni

Subunit structurei

Dimer formed of alpha-2-1 and delta-1 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

BioGridi107235, 50 interactors
ComplexPortaliCPX-3192 Skeletal muscle VGCC complex
CPX-3195 Cardiac muscle VGCC complex
IntActiP54289, 9 interactors
STRINGi9606.ENSP00000349320

Chemistry databases

BindingDBiP54289

Structurei

3D structure databases

ProteinModelPortaliP54289
SMRiP54289
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini253 – 430VWFAPROSITE-ProRule annotationAdd BLAST178
Domaini446 – 556CacheAdd BLAST111

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi259 – 263MIDAS-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
HOVERGENiHBG057779
InParanoidiP54289
KOiK04858
OMAiHIGWWAT
OrthoDBiEOG091G00UY
PhylomeDBiP54289
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
PF00092 VWA, 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 (5+)i

Sequence statusi: Complete.

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

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 5 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P54289-1) [UniParc]FASTAAdd to basket
Also known as: Alpha-2a

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
MAAGCLLALT LTLFQSLLIG PSSEEPFPSA VTIKSWVDKM QEDLVTLAKT
60 70 80 90 100
ASGVNQLVDI YEKYQDLYTV EPNNARQLVE IAARDIEKLL SNRSKALVRL
110 120 130 140 150
ALEAEKVQAA HQWREDFASN EVVYYNAKDD LDPEKNDSEP GSQRIKPVFI
160 170 180 190 200
EDANFGRQIS YQHAAVHIPT DIYEGSTIVL NELNWTSALD EVFKKNREED
210 220 230 240 250
PSLLWQVFGS ATGLARYYPA SPWVDNSRTP NKIDLYDVRR RPWYIQGAAS
260 270 280 290 300
PKDMLILVDV SGSVSGLTLK LIRTSVSEML ETLSDDDFVN VASFNSNAQD
310 320 330 340 350
VSCFQHLVQA NVRNKKVLKD AVNNITAKGI TDYKKGFSFA FEQLLNYNVS
360 370 380 390 400
RANCNKIIML FTDGGEERAQ EIFNKYNKDK KVRVFTFSVG QHNYDRGPIQ
410 420 430 440 450
WMACENKGYY YEIPSIGAIR INTQEYLDVL GRPMVLAGDK AKQVQWTNVY
460 470 480 490 500
LDALELGLVI TGTLPVFNIT GQFENKTNLK NQLILGVMGV DVSLEDIKRL
510 520 530 540 550
TPRFTLCPNG YYFAIDPNGY VLLHPNLQPK PIGVGIPTIN LRKRRPNIQN
560 570 580 590 600
PKSQEPVTLD FLDAELENDI KVEIRNKMID GESGEKTFRT LVKSQDERYI
610 620 630 640 650
DKGNRTYTWT PVNGTDYSLA LVLPTYSFYY IKAKLEETIT QARYSETLKP
660 670 680 690 700
DNFEESGYTF IAPRDYCNDL KISDNNTEFL LNFNEFIDRK TPNNPSCNAD
710 720 730 740 750
LINRVLLDAG FTNELVQNYW SKQKNIKGVK ARFVVTDGGI TRVYPKEAGE
760 770 780 790 800
NWQENPETYE DSFYKRSLDN DNYVFTAPYF NKSGPGAYES GIMVSKAVEI
810 820 830 840 850
YIQGKLLKPA VVGIKIDVNS WIENFTKTSI RDPCAGPVCD CKRNSDVMDC
860 870 880 890 900
VILDDGGFLL MANHDDYTNQ IGRFFGEIDP SLMRHLVNIS VYAFNKSYDY
910 920 930 940 950
QSVCEPGAAP KQGAGHRSAY VPSVADILQI GWWATAAAWS ILQQFLLSLT
960 970 980 990 1000
FPRLLEAVEM EDDDFTASLS KQSCITEQTQ YFFDNDSKSF SGVLDCGNCS
1010 1020 1030 1040 1050
RIFHGEKLMN TNLIFIMVES KGTCPCDTRL LIQAEQTSDG PNPCDMVKQP
1060 1070 1080 1090 1100
RYRKGPDVCF DNNVLEDYTD CGGVSGLNPS LWYIIGIQFL LLWLVSGSTH

RLL
Length:1,103
Mass (Da):124,568
Last modified:November 3, 2009 - v3
Checksum:i0749685DE9DB0700
GO
Isoform 2 (identifier: P54289-2) [UniParc]FASTAAdd to basket
Also known as: Alpha-2b

The sequence of this isoform differs from the canonical sequence as follows:
     531-549: Missing.
     644-644: Y → SKKGKMKD

Show »
Length:1,091
Mass (Da):123,183
Checksum:iDBD649BAC7871934
GO
Isoform 3 (identifier: P54289-3) [UniParc]FASTAAdd to basket
Also known as: Alpha-2c

The sequence of this isoform differs from the canonical sequence as follows:
     531-554: Missing.
     644-644: Y → SKKGKMKD

Show »
Length:1,086
Mass (Da):122,629
Checksum:i55B5E049C472FD0C
GO
Isoform 4 (identifier: P54289-4) [UniParc]FASTAAdd to basket
Also known as: Alpha-2d

The sequence of this isoform differs from the canonical sequence as follows:
     531-554: Missing.

Show »
Length:1,079
Mass (Da):121,889
Checksum:iAFC36093EB8EE8D3
GO
Isoform 5 (identifier: P54289-5) [UniParc]FASTAAdd to basket
Also known as: Alpha-2e

The sequence of this isoform differs from the canonical sequence as follows:
     531-549: Missing.

Show »
Length:1,084
Mass (Da):122,443
Checksum:i972A0FB832A88313
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E7ERK3E7ERK3_HUMAN
Voltage-dependent calcium channel s...
CACNA2D1
309Annotation score:
H0Y715H0Y715_HUMAN
Voltage-dependent calcium channel s...
CACNA2D1
280Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti99R → S in AAA51903 (PubMed:1309651).Curated1
Sequence conflicti386T → R in AAA51903 (PubMed:1309651).Curated1
Sequence conflicti395D → E in AAA51903 (PubMed:1309651).Curated1
Sequence conflicti635L → I no nucleotide entry (PubMed:8107964).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0539601019E → D. Corresponds to variant dbSNP:rs9886043Ensembl.1
Natural variantiVAR_0350471057D → A. Corresponds to variant dbSNP:rs35131433Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_038349531 – 554Missing in isoform 3 and isoform 4. 1 PublicationAdd BLAST24
Alternative sequenceiVSP_038348531 – 549Missing in isoform 2 and isoform 5. 3 PublicationsAdd BLAST19
Alternative sequenceiVSP_038350644Y → SKKGKMKD in isoform 2 and isoform 3. 3 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M76559 mRNA Translation: AAA51903.1
CH471091 Genomic DNA Translation: EAW76990.1
BC117468 mRNA Translation: AAI17469.1
BC117470 mRNA Translation: AAI17471.1
CCDSiCCDS5598.1 [P54289-2]
PIRiJH0565
RefSeqiNP_000713.2, NM_000722.3 [P54289-2]
XP_005250627.1, XM_005250570.2 [P54289-1]
XP_005250629.1, XM_005250572.2 [P54289-3]
XP_005250630.1, XM_005250573.2 [P54289-5]
XP_005250631.1, XM_005250574.2 [P54289-4]
UniGeneiHs.282151
Hs.592625
Hs.743228

Genome annotation databases

EnsembliENST00000356253; ENSP00000348589; ENSG00000153956 [P54289-1]
ENST00000356860; ENSP00000349320; ENSG00000153956 [P54289-2]
GeneIDi781
KEGGihsa:781
UCSCiuc003uhr.2 human [P54289-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M76559 mRNA Translation: AAA51903.1
CH471091 Genomic DNA Translation: EAW76990.1
BC117468 mRNA Translation: AAI17469.1
BC117470 mRNA Translation: AAI17471.1
CCDSiCCDS5598.1 [P54289-2]
PIRiJH0565
RefSeqiNP_000713.2, NM_000722.3 [P54289-2]
XP_005250627.1, XM_005250570.2 [P54289-1]
XP_005250629.1, XM_005250572.2 [P54289-3]
XP_005250630.1, XM_005250573.2 [P54289-5]
XP_005250631.1, XM_005250574.2 [P54289-4]
UniGeneiHs.282151
Hs.592625
Hs.743228

3D structure databases

ProteinModelPortaliP54289
SMRiP54289
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107235, 50 interactors
ComplexPortaliCPX-3192 Skeletal muscle VGCC complex
CPX-3195 Cardiac muscle VGCC complex
IntActiP54289, 9 interactors
STRINGi9606.ENSP00000349320

Chemistry databases

BindingDBiP54289
ChEMBLiCHEMBL1919
DrugBankiDB00381 Amlodipine
DB04838 Cyclandelate
DB01023 Felodipine
DB00996 Gabapentin
DB00308 Ibutilide
DB00270 Isradipine
DB00653 Magnesium Sulfate
DB00622 Nicardipine
DB01115 Nifedipine
DB06712 Nilvadipine
DB00401 Nisoldipine
DB01054 Nitrendipine
DB00421 Spironolactone
DB04922 XP13512

Protein family/group databases

TCDBi8.A.18.1.1 the ca(2+) channel auxiliary subunit Alpha2Delta types 1-4 (cca-Alpha2Delta) family

PTM databases

GlyConnecti1895
iPTMnetiP54289
PhosphoSitePlusiP54289
SwissPalmiP54289

Polymorphism and mutation databases

BioMutaiCACNA2D1
DMDMi262527579

Proteomic databases

EPDiP54289
MaxQBiP54289
PaxDbiP54289
PeptideAtlasiP54289
PRIDEiP54289
ProteomicsDBi56675
56676 [P54289-2]
56677 [P54289-3]
56678 [P54289-4]
56679 [P54289-5]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000356253; ENSP00000348589; ENSG00000153956 [P54289-1]
ENST00000356860; ENSP00000349320; ENSG00000153956 [P54289-2]
GeneIDi781
KEGGihsa:781
UCSCiuc003uhr.2 human [P54289-1]

Organism-specific databases

CTDi781
DisGeNETi781
EuPathDBiHostDB:ENSG00000153956.15
GeneCardsiCACNA2D1
HGNCiHGNC:1399 CACNA2D1
HPAiHPA008213
HPA008621
MalaCardsiCACNA2D1
MIMi114204 gene
neXtProtiNX_P54289
OpenTargetsiENSG00000153956
Orphaneti130 Brugada syndrome
51083 Familial short QT syndrome
PharmGKBiPA86
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2353 Eukaryota
ENOG410XPDX LUCA
GeneTreeiENSGT00530000062904
HOVERGENiHBG057779
InParanoidiP54289
KOiK04858
OMAiHIGWWAT
OrthoDBiEOG091G00UY
PhylomeDBiP54289
TreeFamiTF315824

Enzyme and pathway databases

ReactomeiR-HSA-5576892 Phase 0 - rapid depolarisation
R-HSA-5576893 Phase 2 - plateau phase

Miscellaneous databases

ChiTaRSiCACNA2D1 human
GeneWikiiCACNA2D1
GenomeRNAii781
PROiPR:P54289
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000153956 Expressed in 204 organ(s), highest expression level in biceps brachii
CleanExiHS_CACNA2D1
ExpressionAtlasiP54289 baseline and differential
GenevisibleiP54289 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
PF00092 VWA, 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 nameiCA2D1_HUMAN
AccessioniPrimary (citable) accession number: P54289
Secondary accession number(s): Q17R45
, Q9UD80, Q9UD81, Q9UD82
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: November 3, 2009
Last modified: November 7, 2018
This is version 181 of the entry and version 3 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 entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
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