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P54289 (CA2D1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 142. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Voltage-dependent calcium channel subunit alpha-2/delta-1
Alternative name(s):
Voltage-gated calcium channel subunit alpha-2/delta-1
Gene names
Name:CACNA2D1
Synonyms:CACNL2A, CCHL2A, MHS3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1103 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

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. Ref.7

Subcellular location

Membrane; Single-pass type I membrane protein Potential.

Tissue specificity

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. Ref.1 Ref.4

Domain

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.

Post-translational modification

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

Miscellaneous

Binds gabapentin, an antiepileptic drug.

Sequence similarities

Belongs to the calcium channel subunit alpha-2/delta family.

Contains 1 cache domain.

Contains 1 VWFA domain.

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P54289-1)

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.
Isoform 2 (identifier: P54289-2)

Also known as: Alpha-2b;

The sequence of this isoform differs from the canonical sequence as follows:
     531-549: Missing.
     644-644: Y → SKKGKMKD
Isoform 3 (identifier: P54289-3)

Also known as: Alpha-2c;

The sequence of this isoform differs from the canonical sequence as follows:
     531-554: Missing.
     644-644: Y → SKKGKMKD
Isoform 4 (identifier: P54289-4)

Also known as: Alpha-2d;

The sequence of this isoform differs from the canonical sequence as follows:
     531-554: Missing.
Isoform 5 (identifier: P54289-5)

Also known as: Alpha-2e;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Potential
Chain25 – 11031079Voltage-dependent calcium channel subunit alpha-2/delta-1
PRO_0000304633
Chain25 – 956932Voltage-dependent calcium channel subunit alpha-2-1 By similarity
PRO_0000005001
Chain957 – 1103147Voltage-dependent calcium channel subunit delta-1 By similarity
PRO_0000005002

Regions

Topological domain25 – 10731049Extracellular Potential
Transmembrane1074 – 109421Helical; Potential
Topological domain1095 – 11039Cytoplasmic Potential
Domain253 – 430178VWFA
Domain446 – 556111Cache
Motif259 – 2635MIDAS-like motif

Sites

Metal binding2591Divalent metal cation By similarity
Metal binding2611Divalent metal cation By similarity
Metal binding2631Divalent metal cation By similarity

Amino acid modifications

Glycosylation921N-linked (GlcNAc...) Potential
Glycosylation1361N-linked (GlcNAc...) Potential
Glycosylation1841N-linked (GlcNAc...) Potential
Glycosylation3241N-linked (GlcNAc...) Potential
Glycosylation3481N-linked (GlcNAc...) Potential
Glycosylation4681N-linked (GlcNAc...) Potential
Glycosylation4751N-linked (GlcNAc...) Potential
Glycosylation6041N-linked (GlcNAc...) Potential
Glycosylation6131N-linked (GlcNAc...) Potential
Glycosylation6751N-linked (GlcNAc...) Potential
Glycosylation7811N-linked (GlcNAc...) Potential
Glycosylation8241N-linked (GlcNAc...) Potential
Glycosylation8881N-linked (GlcNAc...) Potential
Glycosylation8951N-linked (GlcNAc...) Potential
Glycosylation9851N-linked (GlcNAc...) Potential
Glycosylation9981N-linked (GlcNAc...) Potential
Disulfide bond404 ↔ 1059Interchain (between alpha-2-1 and delta-1 chains) Ref.7

Natural variations

Alternative sequence531 – 55424Missing in isoform 3 and isoform 4.
VSP_038349
Alternative sequence531 – 54919Missing in isoform 2 and isoform 5.
VSP_038348
Alternative sequence6441Y → SKKGKMKD in isoform 2 and isoform 3.
VSP_038350
Natural variant10191E → D.
Corresponds to variant rs9886043 [ dbSNP | Ensembl ].
VAR_053960
Natural variant10571D → A.
Corresponds to variant rs35131433 [ dbSNP | Ensembl ].
VAR_035047

Experimental info

Sequence conflict991R → S in AAA51903. Ref.1
Sequence conflict3861T → R in AAA51903. Ref.1
Sequence conflict3951D → E in AAA51903. Ref.1
Sequence conflict6351L → I no nucleotide entry Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Alpha-2a) [UniParc].

Last modified November 3, 2009. Version 3.
Checksum: 0749685DE9DB0700

FASTA1,103124,568
        10         20         30         40         50         60 
MAAGCLLALT LTLFQSLLIG PSSEEPFPSA VTIKSWVDKM QEDLVTLAKT ASGVNQLVDI 

        70         80         90        100        110        120 
YEKYQDLYTV EPNNARQLVE IAARDIEKLL SNRSKALVRL ALEAEKVQAA HQWREDFASN 

       130        140        150        160        170        180 
EVVYYNAKDD LDPEKNDSEP GSQRIKPVFI EDANFGRQIS YQHAAVHIPT DIYEGSTIVL 

       190        200        210        220        230        240 
NELNWTSALD EVFKKNREED PSLLWQVFGS ATGLARYYPA SPWVDNSRTP NKIDLYDVRR 

       250        260        270        280        290        300 
RPWYIQGAAS PKDMLILVDV SGSVSGLTLK LIRTSVSEML ETLSDDDFVN VASFNSNAQD 

       310        320        330        340        350        360 
VSCFQHLVQA NVRNKKVLKD AVNNITAKGI TDYKKGFSFA FEQLLNYNVS RANCNKIIML 

       370        380        390        400        410        420 
FTDGGEERAQ EIFNKYNKDK KVRVFTFSVG QHNYDRGPIQ WMACENKGYY YEIPSIGAIR 

       430        440        450        460        470        480 
INTQEYLDVL GRPMVLAGDK AKQVQWTNVY LDALELGLVI TGTLPVFNIT GQFENKTNLK 

       490        500        510        520        530        540 
NQLILGVMGV DVSLEDIKRL TPRFTLCPNG YYFAIDPNGY VLLHPNLQPK PIGVGIPTIN 

       550        560        570        580        590        600 
LRKRRPNIQN PKSQEPVTLD FLDAELENDI KVEIRNKMID GESGEKTFRT LVKSQDERYI 

       610        620        630        640        650        660 
DKGNRTYTWT PVNGTDYSLA LVLPTYSFYY IKAKLEETIT QARYSETLKP DNFEESGYTF 

       670        680        690        700        710        720 
IAPRDYCNDL KISDNNTEFL LNFNEFIDRK TPNNPSCNAD LINRVLLDAG FTNELVQNYW 

       730        740        750        760        770        780 
SKQKNIKGVK ARFVVTDGGI TRVYPKEAGE NWQENPETYE DSFYKRSLDN DNYVFTAPYF 

       790        800        810        820        830        840 
NKSGPGAYES GIMVSKAVEI YIQGKLLKPA VVGIKIDVNS WIENFTKTSI RDPCAGPVCD 

       850        860        870        880        890        900 
CKRNSDVMDC VILDDGGFLL MANHDDYTNQ IGRFFGEIDP SLMRHLVNIS VYAFNKSYDY 

       910        920        930        940        950        960 
QSVCEPGAAP KQGAGHRSAY VPSVADILQI GWWATAAAWS ILQQFLLSLT FPRLLEAVEM 

       970        980        990       1000       1010       1020 
EDDDFTASLS KQSCITEQTQ YFFDNDSKSF SGVLDCGNCS RIFHGEKLMN TNLIFIMVES 

      1030       1040       1050       1060       1070       1080 
KGTCPCDTRL LIQAEQTSDG PNPCDMVKQP RYRKGPDVCF DNNVLEDYTD CGGVSGLNPS 

      1090       1100 
LWYIIGIQFL LLWLVSGSTH RLL 

« Hide

Isoform 2 (Alpha-2b) [UniParc].

Checksum: DBD649BAC7871934
Show »

FASTA1,091123,183
Isoform 3 (Alpha-2c) [UniParc].

Checksum: 55B5E049C472FD0C
Show »

FASTA1,086122,629
Isoform 4 (Alpha-2d) [UniParc].

Checksum: AFC36093EB8EE8D3
Show »

FASTA1,079121,889
Isoform 5 (Alpha-2e) [UniParc].

Checksum: 972A0FB832A88313
Show »

FASTA1,084122,443

References

« Hide 'large scale' references
[1]"Structure and functional expression of alpha 1, alpha 2, and beta subunits of a novel human neuronal calcium channel subtype."
Williams M.E., Feldman D.H., McCue A.F., Brenner R., Velicelebi G., Ellis S.B., Harpold M.M.
Neuron 8:71-84(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY.
[2]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Cerebellum.
[4]"Human neuronal voltage-dependent calcium channels: studies on subunit structure and role in channel assembly."
Brust P.F., Simerson S., McCue A.F., Deal C.R., Schoonmaker S., Williams M.E., Velicelebi G., Johnson E.C., Harpold M.M., Ellis S.B.
Neuropharmacology 32:1089-1102(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 528-648 (ISOFORMS 1; 2; 3; 4 AND 5), TISSUE SPECIFICITY, ALTERNATIVE SPLICING.
Tissue: Neuroblastoma.
[5]"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-136; ASN-324 AND ASN-675.
Tissue: Plasma.
[6]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-348; ASN-475 AND ASN-824.
Tissue: Liver.
[7]"Identification of a disulfide bridge essential for structure and function of the voltage-gated Ca(2+) channel alpha(2)delta-1 auxiliary subunit."
Calderon-Rivera A., Andrade A., Hernandez-Hernandez O., Gonzalez-Ramirez R., Sandoval A., Rivera M., Gomora J.C., Felix R.
Cell Calcium 51:22-30(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERCHAIN DISULFIDE BOND, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M76559 mRNA. Translation: AAA51903.1.
CH471091 Genomic DNA. Translation: EAW76990.1.
BC117468 mRNA. Translation: AAI17469.1.
BC117470 mRNA. Translation: AAI17471.1.
CCDSCCDS5598.1. [P54289-2]
PIRJH0565.
RefSeqNP_000713.2. NM_000722.2. [P54289-2]
XP_005250627.1. XM_005250570.1. [P54289-1]
XP_005250629.1. XM_005250572.1. [P54289-3]
XP_005250630.1. XM_005250573.1. [P54289-5]
XP_005250631.1. XM_005250574.1. [P54289-4]
UniGeneHs.282151.
Hs.743228.

3D structure databases

ProteinModelPortalP54289.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107235. 4 interactions.
STRING9606.ENSP00000349320.

Chemistry

BindingDBP54289.
ChEMBLCHEMBL1919.
DrugBankDB01023. Felodipine.
DB00996. Gabapentin.
DB00308. Ibutilide.
DB00270. Isradipine.
DB00653. Magnesium Sulfate.
DB01115. Nifedipine.

Protein family/group databases

TCDB8.A.18.1.1. the ca(2+) channel auxiliary subunit 2 types 1-4 (cca-2) family.

PTM databases

PhosphoSiteP54289.

Polymorphism databases

DMDM262527579.

Proteomic databases

MaxQBP54289.
PaxDbP54289.
PRIDEP54289.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000356253; ENSP00000348589; ENSG00000153956. [P54289-1]
ENST00000356860; ENSP00000349320; ENSG00000153956. [P54289-2]
GeneID781.
KEGGhsa:781.
UCSCuc003uhr.1. human. [P54289-2]

Organism-specific databases

CTD781.
GeneCardsGC07M081575.
HGNCHGNC:1399. CACNA2D1.
HPAHPA008213.
HPA008621.
MIM114204. gene.
neXtProtNX_P54289.
Orphanet51083. Familial short QT syndrome.
PharmGKBPA86.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG307080.
HOVERGENHBG057779.
KOK04858.
OMADDYTNQI.
OrthoDBEOG70GMDV.
PhylomeDBP54289.
TreeFamTF315824.

Gene expression databases

ArrayExpressP54289.
BgeeP54289.
CleanExHS_CACNA2D1.
GenevestigatorP54289.

Family and domain databases

Gene3D3.40.50.410. 1 hit.
InterProIPR004010. Cache_domain.
IPR013680. VDCC_a2/dsu.
IPR013608. VWA_N.
IPR002035. VWF_A.
[Graphical view]
PfamPF02743. Cache_1. 1 hit.
PF08473. VGCC_alpha2. 1 hit.
PF00092. VWA. 1 hit.
PF08399. VWA_N. 1 hit.
[Graphical view]
SMARTSM00327. VWA. 1 hit.
[Graphical view]
SUPFAMSSF53300. SSF53300. 1 hit.
PROSITEPS50234. VWFA. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiCACNA2D1.
GenomeRNAi781.
NextBio3160.
PROP54289.
SOURCESearch...

Entry information

Entry nameCA2D1_HUMAN
AccessionPrimary (citable) accession number: P54289
Secondary accession number(s): Q17R45 expand/collapse secondary AC list , Q9UD80, Q9UD81, Q9UD82
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: November 3, 2009
Last modified: July 9, 2014
This is version 142 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM