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P54289

- CA2D1_HUMAN

UniProt

P54289 - CA2D1_HUMAN

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Protein

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

Gene

CACNA2D1

Organism
Homo sapiens (Human)
Status
Reviewed - 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. Plays an important role in excitation-contraction coupling (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi259 – 2591Divalent metal cationBy similarity
Metal bindingi261 – 2611Divalent metal cationBy similarity
Metal bindingi263 – 2631Divalent metal cationBy similarity

GO - Molecular functioni

  1. metal ion binding Source: UniProtKB-KW
  2. voltage-gated calcium channel activity Source: BHF-UCL

GO - Biological processi

  1. calcium ion transport Source: UniProtKB
  2. regulation of calcium ion transport Source: BHF-UCL
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

Protein family/group databases

TCDBi8.A.18.1.1. the ca(2+) channel auxiliary subunit 2 types 1-4 (cca-2) 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
ProteomesiUP000005640: Chromosome 7

Organism-specific databases

HGNCiHGNC:1399. CACNA2D1.

Subcellular locationi

GO - Cellular componenti

  1. extracellular vesicular exosome Source: UniProtKB
  2. sarcoplasmic reticulum Source: Ensembl
  3. T-tubule Source: Ensembl
  4. voltage-gated calcium channel complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

Orphaneti130. Brugada syndrome.
51083. Familial short QT syndrome.
PharmGKBiPA86.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424Sequence AnalysisAdd
BLAST
Chaini25 – 11031079Voltage-dependent calcium channel subunit alpha-2/delta-1PRO_0000304633Add
BLAST
Chaini25 – 956932Voltage-dependent calcium channel subunit alpha-2-1By similarityPRO_0000005001Add
BLAST
Chaini957 – 1103147Voltage-dependent calcium channel subunit delta-1By similarityPRO_0000005002Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi92 – 921N-linked (GlcNAc...)Sequence Analysis
Glycosylationi136 – 1361N-linked (GlcNAc...)Sequence Analysis
Glycosylationi184 – 1841N-linked (GlcNAc...)Sequence Analysis
Glycosylationi324 – 3241N-linked (GlcNAc...)Sequence Analysis
Glycosylationi348 – 3481N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi404 ↔ 1059Interchain (between alpha-2-1 and delta-1 chains)
Glycosylationi468 – 4681N-linked (GlcNAc...)Sequence Analysis
Glycosylationi475 – 4751N-linked (GlcNAc...)Sequence Analysis
Glycosylationi604 – 6041N-linked (GlcNAc...)Sequence Analysis
Glycosylationi613 – 6131N-linked (GlcNAc...)Sequence Analysis
Glycosylationi675 – 6751N-linked (GlcNAc...)Sequence Analysis
Glycosylationi781 – 7811N-linked (GlcNAc...)Sequence Analysis
Glycosylationi824 – 8241N-linked (GlcNAc...)Sequence Analysis
Glycosylationi888 – 8881N-linked (GlcNAc...)Sequence Analysis
Glycosylationi895 – 8951N-linked (GlcNAc...)Sequence Analysis
Glycosylationi985 – 9851N-linked (GlcNAc...)Sequence Analysis
Glycosylationi998 – 9981N-linked (GlcNAc...)Sequence Analysis

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiP54289.
PaxDbiP54289.
PRIDEiP54289.

PTM databases

PhosphoSiteiP54289.

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

BgeeiP54289.
CleanExiHS_CACNA2D1.
ExpressionAtlasiP54289. baseline and differential.
GenevestigatoriP54289.

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. 17 interactions.
STRINGi9606.ENSP00000349320.

Structurei

3D structure databases

ProteinModelPortaliP54289.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini25 – 10731049ExtracellularSequence AnalysisAdd
BLAST
Topological domaini1095 – 11039CytoplasmicSequence Analysis

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei1074 – 109421HelicalSequence AnalysisAdd
BLAST

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini253 – 430178VWFAPROSITE-ProRule annotationAdd
BLAST
Domaini446 – 556111CacheAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi259 – 2635MIDAS-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.
GeneTreeiENSGT00530000062904.
HOVERGENiHBG057779.
InParanoidiP54289.
KOiK04858.
OMAiDDYTNQI.
OrthoDBiEOG70GMDV.
PhylomeDBiP54289.
TreeFamiTF315824.

Family and domain databases

Gene3Di3.40.50.410. 1 hit.
InterProiIPR004010. Cache_domain.
IPR013680. VDCC_a2/dsu.
IPR013608. VWA_N.
IPR002035. VWF_A.
[Graphical view]
PfamiPF02743. Cache_1. 1 hit.
PF08473. VGCC_alpha2. 1 hit.
PF00092. VWA. 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 (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. Align

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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti99 – 991R → S in AAA51903. (PubMed:1309651)Curated
Sequence conflicti386 – 3861T → R in AAA51903. (PubMed:1309651)Curated
Sequence conflicti395 – 3951D → E in AAA51903. (PubMed:1309651)Curated
Sequence conflicti635 – 6351L → I no nucleotide entry (PubMed:8107964)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti1019 – 10191E → D.
Corresponds to variant rs9886043 [ dbSNP | Ensembl ].
VAR_053960
Natural varianti1057 – 10571D → A.
Corresponds to variant rs35131433 [ dbSNP | Ensembl ].
VAR_035047

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei531 – 55424Missing in isoform 3 and isoform 4. 1 PublicationVSP_038349Add
BLAST
Alternative sequencei531 – 54919Missing in isoform 2 and isoform 5. 3 PublicationsVSP_038348Add
BLAST
Alternative sequencei644 – 6441Y → SKKGKMKD in isoform 2 and isoform 3. 3 PublicationsVSP_038350

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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_000722.2. [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]
UniGeneiHs.282151.
Hs.743228.

Genome annotation databases

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

Polymorphism databases

DMDMi262527579.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M76559 mRNA. Translation: AAA51903.1 .
CH471091 Genomic DNA. Translation: EAW76990.1 .
BC117468 mRNA. Translation: AAI17469.1 .
BC117470 mRNA. Translation: AAI17471.1 .
CCDSi CCDS5598.1. [P54289-2 ]
PIRi JH0565.
RefSeqi NP_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 ]
UniGenei Hs.282151.
Hs.743228.

3D structure databases

ProteinModelPortali P54289.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 107235. 17 interactions.
STRINGi 9606.ENSP00000349320.

Chemistry

BindingDBi P54289.
ChEMBLi CHEMBL2363032.
DrugBanki DB00381. 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.

Protein family/group databases

TCDBi 8.A.18.1.1. the ca(2+) channel auxiliary subunit 2 types 1-4 (cca-2) family.

PTM databases

PhosphoSitei P54289.

Polymorphism databases

DMDMi 262527579.

Proteomic databases

MaxQBi P54289.
PaxDbi P54289.
PRIDEi P54289.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000356253 ; ENSP00000348589 ; ENSG00000153956 . [P54289-1 ]
ENST00000356860 ; ENSP00000349320 ; ENSG00000153956 . [P54289-2 ]
GeneIDi 781.
KEGGi hsa:781.
UCSCi uc003uhr.1. human. [P54289-2 ]

Organism-specific databases

CTDi 781.
GeneCardsi GC07M081575.
HGNCi HGNC:1399. CACNA2D1.
HPAi HPA008213.
HPA008621.
MIMi 114204. gene.
neXtProti NX_P54289.
Orphaneti 130. Brugada syndrome.
51083. Familial short QT syndrome.
PharmGKBi PA86.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG307080.
GeneTreei ENSGT00530000062904.
HOVERGENi HBG057779.
InParanoidi P54289.
KOi K04858.
OMAi DDYTNQI.
OrthoDBi EOG70GMDV.
PhylomeDBi P54289.
TreeFami TF315824.

Miscellaneous databases

GeneWikii CACNA2D1.
GenomeRNAii 781.
NextBioi 3160.
PROi P54289.
SOURCEi Search...

Gene expression databases

Bgeei P54289.
CleanExi HS_CACNA2D1.
ExpressionAtlasi P54289. baseline and differential.
Genevestigatori P54289.

Family and domain databases

Gene3Di 3.40.50.410. 1 hit.
InterProi IPR004010. Cache_domain.
IPR013680. VDCC_a2/dsu.
IPR013608. VWA_N.
IPR002035. VWF_A.
[Graphical view ]
Pfami PF02743. Cache_1. 1 hit.
PF08473. VGCC_alpha2. 1 hit.
PF00092. VWA. 1 hit.
PF08399. VWA_N. 1 hit.
[Graphical view ]
SMARTi SM00327. VWA. 1 hit.
[Graphical view ]
SUPFAMi SSF53300. SSF53300. 1 hit.
PROSITEi PS50234. VWFA. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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.

Entry informationi

Entry nameiCA2D1_HUMAN
AccessioniPrimary (citable) accession number: P54289
Secondary accession number(s): Q17R45
, Q9UD80, Q9UD81, Q9UD82
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: November 3, 2009
Last modified: October 29, 2014
This is version 144 of the entry and version 3 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

Binds gabapentin, an antiepileptic drug.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  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. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3