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Protein

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

Gene

Cacna2d2

Organism
Mus musculus (Mouse)
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) and possibly T-type (CACNA1G).1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi300Divalent metal cationCurated1
Metal bindingi302Divalent metal cationCurated1
Metal bindingi304Divalent metal cationCurated1

GO - Molecular functioni

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

GO - Biological processi

  • calcium ion transport Source: MGI
  • muscle fiber development Source: MGI
  • neuromuscular junction development Source: MGI
  • positive regulation of organ growth Source: MGI
  • regulation of multicellular organism growth Source: MGI
  • rhythmic synaptic transmission Source: MGI
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-MMU-422356. Regulation of insulin secretion.
R-MMU-5576892. Phase 0 - rapid depolarisation.
R-MMU-5576893. Phase 2 - plateau phase.
R-MMU-5576894. Phase 1 - inactivation of fast Na+ channels.

Names & Taxonomyi

Protein namesi
Recommended name:
Voltage-dependent calcium channel subunit alpha-2/delta-2
Alternative name(s):
Protein ducky
Voltage-gated calcium channel subunit alpha-2/delta-2
Cleaved into the following 2 chains:
Gene namesi
Name:Cacna2d2
Synonyms:Kiaa0558
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:1929813. Cacna2d2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini19 – 1116ExtracellularSequence analysisAdd BLAST1098
Transmembranei1117 – 1137HelicalSequence analysisAdd BLAST21
Topological domaini1138 – 1154CytoplasmicSequence analysisAdd BLAST17

GO - Cellular componenti

  • voltage-gated calcium channel complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Defects in Cacna2d2 are the cause of ducky phenotype (du). Du mice have spike-wave seizures characteristic of absence epilepsy and ataxia, with accompanying decreased calcium channel current in cerebellar Purkinje cells.

Disruption phenotypei

Mice exhibit growth retardation, reduced life span, ataxic gait with apoptosis of cerebellar granule cells followed by Purkinje cell depletion, enhanced susceptibility to seizures, and cardiac abnormalities.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi282R → A: Induces a strong decrease in gabapentin-binding. 1 Publication1
Mutagenesisi300D → A: Abolishes metal-binding and ability to regulate calcium current. 1 Publication1
Mutagenesisi302S → A: Abolishes metal-binding and ability to regulate calcium current. 1 Publication1
Mutagenesisi304S → A: Abolishes metal-binding and ability to regulate calcium current. 1 Publication1

Keywords - Diseasei

Disease mutation

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Sequence analysisAdd BLAST18
ChainiPRO_000030464019 – 1154Voltage-dependent calcium channel subunit alpha-2/delta-2Add BLAST1136
ChainiPRO_000030464119 – 1004Voltage-dependent calcium channel subunit alpha-2-2Sequence analysisAdd BLAST986
ChainiPRO_00003046421005 – 1154Voltage-dependent calcium channel subunit delta-2Sequence analysisAdd BLAST150

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi205N-linked (GlcNAc...)Sequence analysis1
Glycosylationi389N-linked (GlcNAc...)Sequence analysis1
Glycosylationi421N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi446 ↔ 1101Interchain (between alpha-2-2 and delta-2 chains)By similarity
Glycosylationi510N-linked (GlcNAc...)Sequence analysis1
Glycosylationi543N-linked (GlcNAc...)Sequence analysis1
Glycosylationi627N-linked (GlcNAc...)Sequence analysis1
Glycosylationi864N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

N-glycosylated.2 Publications
May be proteolytically processed into subunits alpha-2-2 and delta-2 that are disulfide-linked. It is however unclear whether such cleavage really takes place in vivo and has a functional role. According to PubMed:11306709, it is processed, at least in vitro, while according to PubMed:17052222, it is only poorly processed in vivo.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ6PHS9.
PRIDEiQ6PHS9.

PTM databases

PhosphoSitePlusiQ6PHS9.

Expressioni

Tissue specificityi

Predominantly expressed in brain in a restricted pattern. Also expressed at lower level in kidney and testis Not expressed in lung at any moment of development. In brain, it localizes to sections of P21 brain. Expressed at high level in the cerebellum, with moderate levels in medulla, pons, and striatum. Also expressed in cortex, hippocampus, habenula and nucleus reticularis thalami (nRT). Strongly expressed in cerebellar Purkinje cells.1 Publication

Gene expression databases

BgeeiENSMUSG00000010066.
ExpressionAtlasiQ6PHS9. baseline and differential.
GenevisibleiQ6PHS9. MM.

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 (Probable).1 Publication

Protein-protein interaction databases

IntActiQ6PHS9. 1 interactor.
STRINGi10090.ENSMUSP00000082173.

Structurei

3D structure databases

ProteinModelPortaliQ6PHS9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini294 – 472VWFAPROSITE-ProRule annotationAdd BLAST179
Domaini488 – 577CacheAdd BLAST90

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi300 – 304MIDAS-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.

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.
HOVERGENiHBG057779.
InParanoidiQ6PHS9.
KOiK04859.
PhylomeDBiQ6PHS9.
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.
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 (6)i

Sequence statusi: Complete.

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

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q6PHS9-1) [UniParc]FASTAAdd to basket
Also known as: Alpha2delta-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
MAVPARTCGA SWPGPVRTAR PWPGRGPRPC PDPRGPASGP ARPLLLLLPP
60 70 80 90 100
LLLLPLLTAP GASAYSFPQQ HTMQHWARRL EQEIDGVMRI FGGVQQLREI
110 120 130 140 150
YKDNRNLFEV QENEPQKLVE KVAGDIESLL DRKVQALKRL ADAAENFQKA
160 170 180 190 200
HRWQDNIKEE DIMYYDAKAD AELDDPESED MERGSKTSAL RLDFIEDPNF
210 220 230 240 250
KNKVNYSYTA VQIPTDIYKG STVILNELNW TEALENVFIE NRRQDPTLLW
260 270 280 290 300
QVFGSATGVT RYYPATPWRA PKKIDLYDVR RRPWYIQGAS SPKDMVIIVD
310 320 330 340 350
VSGSVSGLTL KLMKTSVCEM LDTLSDDDYV NVASFNEKAQ PVSCFTHLVQ
360 370 380 390 400
ANVRNKKVFK EAVQGMVAKG TTGYKAGFEY AFDQLQNSNI TRANCNKMIM
410 420 430 440 450
MFTDGGEDRV QDVFEKYNWP NRTVRVFTFS VGQHNYDVTP LQWMACTNKG
460 470 480 490 500
YYFEIPSIGA IRINTQEYLD VLGRPMVLAG KDAKQVQWTN VYEDALGLGL
510 520 530 540 550
VVTGTLPVFN LTQDGPGEKK NQLILGVMGI DVALNDIKRL TPNYTLGANG
560 570 580 590 600
YVFAIDLNGY VLLHPNLKPQ TTNFREPVTL DFLDAELEDE NKEEIRRSMI
610 620 630 640 650
DGDKGHKQIR TLVKSLDERY IDEVIRNYTW VPIRSTNYSL GLVLPPYSTY
660 670 680 690 700
YLQANLSDQI LQVKLPISKL KDFEFLLPSS FESEGHVFIA PREYCKDLNA
710 720 730 740 750
SDNNTEFLKN FIELMEKVTP DSKQCNNFLL HNLILDTGIT QQLVERVWRD
760 770 780 790 800
QDLNTYSLLA VFAATDGGIT RVFPNKAAED WTENPEPFNA SFYRRSLDNH
810 820 830 840 850
GYIFKPPHQD SLLRPLELEN DTVGVLVSTA VELSLGRRTL RPAVVGVKLD
860 870 880 890 900
LEAWAEKFKV LASNRTHQDQ PQKCGPSSHC EMDCEVNNED LLCVLIDDGG
910 920 930 940 950
FLVLSNQNHQ WDQVGRFFSE VDANLMLALY NNSFYTRKES YDYQAACAPQ
960 970 980 990 1000
PPGNLGAAPR GVFVPTIADF LNLAWWTSAA AWSLFQQLLY GLIYHSWFQA
1010 1020 1030 1040 1050
DPAEAEGSPE TRESSCVMKQ TQYYFGSVNA SYNAIIDCGN CSRLFHAQRL
1060 1070 1080 1090 1100
TNTNLLFVVA EKPLCSQCEA GRLLQKETHS DGPEQCELVQ RPRYRRGPHI
1110 1120 1130 1140 1150
CFDYNATEDT SDCGRGASFP PSLGVLVSLQ LLLLLGLPPR PQPQVHSFAA

SRHL
Length:1,154
Mass (Da):130,385
Last modified:July 5, 2004 - v1
Checksum:iAE4F646D89A96053
GO
Isoform 2 (identifier: Q6PHS9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     665-672: LPISKLKD → Y
     873-873: K → KQ

Show »
Length:1,148
Mass (Da):129,781
Checksum:i9B49FF0547F82851
GO
Isoform 3 (identifier: Q6PHS9-3) [UniParc]FASTAAdd to basket
Also known as: Alpha2delta-2c

The sequence of this isoform differs from the canonical sequence as follows:
     1079-1080: HS → HCPA

Show »
Length:1,156
Mass (Da):130,569
Checksum:iADB4926D2EA690E8
GO
Isoform 4 (identifier: Q6PHS9-4) [UniParc]FASTAAdd to basket
Also known as: Alpha2delta-2b

The sequence of this isoform differs from the canonical sequence as follows:
     665-672: LPISKLKD → Y

Show »
Length:1,147
Mass (Da):129,653
Checksum:i9DEBB0CE22DCD170
GO
Isoform 5 (identifier: Q6PHS9-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     665-672: LPISKLKD → Y
     873-873: K → KQ
     1079-1080: HS → HCPA

Show »
Length:1,150
Mass (Da):129,965
Checksum:iCC37C76BB5CE5EB9
GO
Isoform 6 (identifier: Q6PHS9-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     873-873: K → KQ
     1079-1080: HS → HCPA

Show »
Length:1,157
Mass (Da):130,697
Checksum:i8AB34388111AFD12
GO

Sequence cautioni

The sequence AAL01651 differs from that shown. Reason: Frameshift at position 301.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti657S → R in AAG47846 (PubMed:11130987).Curated1
Sequence conflicti657S → R in AAL01650 (PubMed:11487633).Curated1
Sequence conflicti657S → R in AAR89454 (PubMed:14660671).Curated1
Sequence conflicti704N → S in AAG47846 (PubMed:11130987).Curated1
Sequence conflicti704N → S in AAL01650 (PubMed:11487633).Curated1
Sequence conflicti704N → S in AAR89454 (PubMed:14660671).Curated1
Sequence conflicti710N → D in AAG47846 (PubMed:11130987).Curated1
Sequence conflicti710N → D in AAL01650 (PubMed:11487633).Curated1
Sequence conflicti710N → D in AAR89454 (PubMed:14660671).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti99E → EIYKDNRNLFEVQENEPQKL VEKVAGDIESLLDRKVQALK in du; variant allele entla. 1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_028061665 – 672LPISKLKD → Y in isoform 2, isoform 4 and isoform 5. 4 Publications8
Alternative sequenceiVSP_028062873K → KQ in isoform 2, isoform 5 and isoform 6. 2 Publications1
Alternative sequenceiVSP_0280631079 – 1080HS → HCPA in isoform 3, isoform 5 and isoform 6. 4 Publications2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF247139 mRNA. Translation: AAG47846.1.
AF247141 mRNA. Translation: AAL01650.1.
AF247142 mRNA. Translation: AAL01651.1. Frameshift.
AY502107 mRNA. Translation: AAR89454.1.
AK044603 mRNA. Translation: BAC31998.1.
AK164143 mRNA. Translation: BAE37646.1.
AK161839 mRNA. Translation: BAE36599.1.
BC056389 mRNA. Translation: AAH56389.1.
BC158058 mRNA. Translation: AAI58059.1.
AB093246 mRNA. Translation: BAC41430.1.
AF169633 mRNA. Translation: AAD48037.1.
CCDSiCCDS52916.1. [Q6PHS9-1]
CCDS52917.1. [Q6PHS9-2]
CCDS72304.1. [Q6PHS9-3]
CCDS72305.1. [Q6PHS9-5]
RefSeqiNP_001167518.1. NM_001174047.1. [Q6PHS9-3]
NP_001167519.1. NM_001174048.1. [Q6PHS9-5]
NP_001167520.1. NM_001174049.1. [Q6PHS9-4]
NP_001167521.1. NM_001174050.1. [Q6PHS9-2]
NP_064659.2. NM_020263.3. [Q6PHS9-1]
XP_011241201.1. XM_011242899.2. [Q6PHS9-6]
UniGeneiMm.273084.

Genome annotation databases

EnsembliENSMUST00000010210; ENSMUSP00000010210; ENSMUSG00000010066. [Q6PHS9-2]
ENSMUST00000085092; ENSMUSP00000082173; ENSMUSG00000010066. [Q6PHS9-1]
ENSMUST00000166799; ENSMUSP00000126029; ENSMUSG00000010066. [Q6PHS9-6]
ENSMUST00000168532; ENSMUSP00000132512; ENSMUSG00000010066. [Q6PHS9-3]
ENSMUST00000170737; ENSMUSP00000125943; ENSMUSG00000010066. [Q6PHS9-5]
GeneIDi56808.
KEGGimmu:56808.
UCSCiuc009rli.2. mouse. [Q6PHS9-2]
uc009rlj.2. mouse. [Q6PHS9-4]
uc012haf.1. mouse. [Q6PHS9-1]
uc057apw.1. mouse. [Q6PHS9-3]
uc057apx.1. mouse. [Q6PHS9-5]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF247139 mRNA. Translation: AAG47846.1.
AF247141 mRNA. Translation: AAL01650.1.
AF247142 mRNA. Translation: AAL01651.1. Frameshift.
AY502107 mRNA. Translation: AAR89454.1.
AK044603 mRNA. Translation: BAC31998.1.
AK164143 mRNA. Translation: BAE37646.1.
AK161839 mRNA. Translation: BAE36599.1.
BC056389 mRNA. Translation: AAH56389.1.
BC158058 mRNA. Translation: AAI58059.1.
AB093246 mRNA. Translation: BAC41430.1.
AF169633 mRNA. Translation: AAD48037.1.
CCDSiCCDS52916.1. [Q6PHS9-1]
CCDS52917.1. [Q6PHS9-2]
CCDS72304.1. [Q6PHS9-3]
CCDS72305.1. [Q6PHS9-5]
RefSeqiNP_001167518.1. NM_001174047.1. [Q6PHS9-3]
NP_001167519.1. NM_001174048.1. [Q6PHS9-5]
NP_001167520.1. NM_001174049.1. [Q6PHS9-4]
NP_001167521.1. NM_001174050.1. [Q6PHS9-2]
NP_064659.2. NM_020263.3. [Q6PHS9-1]
XP_011241201.1. XM_011242899.2. [Q6PHS9-6]
UniGeneiMm.273084.

3D structure databases

ProteinModelPortaliQ6PHS9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ6PHS9. 1 interactor.
STRINGi10090.ENSMUSP00000082173.

PTM databases

PhosphoSitePlusiQ6PHS9.

Proteomic databases

PaxDbiQ6PHS9.
PRIDEiQ6PHS9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000010210; ENSMUSP00000010210; ENSMUSG00000010066. [Q6PHS9-2]
ENSMUST00000085092; ENSMUSP00000082173; ENSMUSG00000010066. [Q6PHS9-1]
ENSMUST00000166799; ENSMUSP00000126029; ENSMUSG00000010066. [Q6PHS9-6]
ENSMUST00000168532; ENSMUSP00000132512; ENSMUSG00000010066. [Q6PHS9-3]
ENSMUST00000170737; ENSMUSP00000125943; ENSMUSG00000010066. [Q6PHS9-5]
GeneIDi56808.
KEGGimmu:56808.
UCSCiuc009rli.2. mouse. [Q6PHS9-2]
uc009rlj.2. mouse. [Q6PHS9-4]
uc012haf.1. mouse. [Q6PHS9-1]
uc057apw.1. mouse. [Q6PHS9-3]
uc057apx.1. mouse. [Q6PHS9-5]

Organism-specific databases

CTDi9254.
MGIiMGI:1929813. Cacna2d2.
RougeiSearch...

Phylogenomic databases

eggNOGiKOG2353. Eukaryota.
ENOG410XPDX. LUCA.
GeneTreeiENSGT00530000062904.
HOVERGENiHBG057779.
InParanoidiQ6PHS9.
KOiK04859.
PhylomeDBiQ6PHS9.
TreeFamiTF315824.

Enzyme and pathway databases

ReactomeiR-MMU-422356. Regulation of insulin secretion.
R-MMU-5576892. Phase 0 - rapid depolarisation.
R-MMU-5576893. Phase 2 - plateau phase.
R-MMU-5576894. Phase 1 - inactivation of fast Na+ channels.

Miscellaneous databases

PROiQ6PHS9.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000010066.
ExpressionAtlasiQ6PHS9. baseline and differential.
GenevisibleiQ6PHS9. MM.

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.
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]
ProtoNetiSearch...

Entry informationi

Entry nameiCA2D2_MOUSE
AccessioniPrimary (citable) accession number: Q6PHS9
Secondary accession number(s): B2RY16
, Q3TPT9, Q3TSS6, Q6REE3, Q8C8R8, Q8CHE9, Q920H5, Q920H6, Q9EQG2, Q9R142
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 11, 2007
Last sequence update: July 5, 2004
Last modified: November 2, 2016
This is version 103 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Binds gabapentin, an antiepileptic drug.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.