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Q9NY47 (CA2D2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 91. 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-2
Alternative name(s):
Voltage-gated calcium channel subunit alpha-2/delta-2
Gene names
Name:CACNA2D2
Synonyms:KIAA0558
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1150 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. 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). Overexpression induces apoptosis. Ref.10 Ref.11

Subunit structure

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.

Subcellular location

Membrane; Single-pass type I membrane protein Potential. Note: Colocalizes with CACNA1A in lipid raft fractions By similarity.

Tissue specificity

Predominantly present in cerebellar cortex. Present in various lung tumor cell lines, while it is absent in normal lung (at protein level). Highly expressed in heart, lung, testis, pancreas and skeletal muscle. Also expressed in kidney, liver, placenta and brain. Ref.1 Ref.2 Ref.8

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

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 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: Q9NY47-1)

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.
Isoform 2 (identifier: Q9NY47-2)

Also known as: Alpha2delta-2b;

The sequence of this isoform differs from the canonical sequence as follows:
     662-669: LPISKLKD → Y
Isoform 3 (identifier: Q9NY47-3)

The sequence of this isoform differs from the canonical sequence as follows:
     662-669: LPISKLKD → Y
     1076-1077: HS → HCPA
Isoform 4 (identifier: Q9NY47-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-69: Missing.
     662-669: LPISKLKD → Y
     1076-1077: HS → HCPA
Isoform 5 (identifier: Q9NY47-5)

Also known as: Alpha2delta-2c;

The sequence of this isoform differs from the canonical sequence as follows:
     1076-1077: HS → HCPA

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Potential
Chain19 – 11501132Voltage-dependent calcium channel subunit alpha-2/delta-2
PRO_0000304637
Chain19 – 1001983Voltage-dependent calcium channel subunit alpha-2-2 Potential
PRO_0000304638
Chain1002 – 1150149Voltage-dependent calcium channel subunit delta-2 Potential
PRO_0000304639

Regions

Topological domain19 – 11131095Extracellular Potential
Transmembrane1114 – 113421Helical; Potential
Topological domain1135 – 115016Cytoplasmic Potential
Domain291 – 469179VWFA
Domain485 – 57490Cache
Motif297 – 3015MIDAS-like motif

Sites

Metal binding2971Divalent metal cation By similarity
Metal binding2991Divalent metal cation By similarity
Metal binding3011Divalent metal cation By similarity

Amino acid modifications

Glycosylation3861N-linked (GlcNAc...) Ref.12
Glycosylation4181N-linked (GlcNAc...) Potential
Glycosylation5071N-linked (GlcNAc...) Potential
Glycosylation5401N-linked (GlcNAc...) Potential
Glycosylation8611N-linked (GlcNAc...) Potential
Disulfide bond443 ↔ 1098Interchain (between alpha-2-2 and delta-2 chains) By similarity

Natural variations

Alternative sequence1 – 6969Missing in isoform 4.
VSP_028058
Alternative sequence662 – 6698LPISKLKD → Y in isoform 2, isoform 3 and isoform 4.
VSP_028059
Alternative sequence1076 – 10772HS → HCPA in isoform 3, isoform 4 and isoform 5.
VSP_028060
Natural variant1381A → V.
Corresponds to variant rs35497591 [ dbSNP | Ensembl ].
VAR_035048
Natural variant3341E → K.
Corresponds to variant rs743855 [ dbSNP | Ensembl ].
VAR_057782

Experimental info

Sequence conflict6631P → R in CAB86193. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Alpha2delta-2a) [UniParc].

Last modified May 16, 2012. Version 2.
Checksum: 502B86A5E6279AA0

FASTA1,150129,817
        10         20         30         40         50         60 
MAVPARTCGA SRPGPARTAR PWPGCGPHPG PGTRRPTSGP PRPLWLLLPL LPLLAAPGAS 

        70         80         90        100        110        120 
AYSFPQQHTM QHWARRLEQE VDGVMRIFGG VQQLREIYKD NRNLFEVQEN EPQKLVEKVA 

       130        140        150        160        170        180 
GDIESLLDRK VQALKRLADA AENFQKAHRW QDNIKEEDIV YYDAKADAEL DDPESEDVER 

       190        200        210        220        230        240 
GSKASTLRLD FIEDPNFKNK VNYSYAAVQI PTDIYKGSTV ILNELNWTEA LENVFMENRR 

       250        260        270        280        290        300 
QDPTLLWQVF GSATGVTRYY PATPWRAPKK IDLYDVRRRP WYIQGASSPK DMVIIVDVSG 

       310        320        330        340        350        360 
SVSGLTLKLM KTSVCEMLDT LSDDDYVNVA SFNEKAQPVS CFTHLVQANV RNKKVFKEAV 

       370        380        390        400        410        420 
QGMVAKGTTG YKAGFEYAFD QLQNSNITRA NCNKMIMMFT DGGEDRVQDV FEKYNWPNRT 

       430        440        450        460        470        480 
VRVFTFSVGQ HNYDVTPLQW MACANKGYYF EIPSIGAIRI NTQEYLDVLG RPMVLAGKEA 

       490        500        510        520        530        540 
KQVQWTNVYE DALGLGLVVT GTLPVFNLTQ DGPGEKKNQL ILGVMGIDVA LNDIKRLTPN 

       550        560        570        580        590        600 
YTLGANGYVF AIDLNGYVLL HPNLKPQTTN FREPVTLDFL DAELEDENKE EIRRSMIDGN 

       610        620        630        640        650        660 
KGHKQIRTLV KSLDERYIDE VTRNYTWVPI RSTNYSLGLV LPPYSTFYLQ ANLSDQILQV 

       670        680        690        700        710        720 
KLPISKLKDF EFLLPSSFES EGHVFIAPRE YCKDLNASDN NTEFLKNFIE LMEKVTPDSK 

       730        740        750        760        770        780 
QCNNFLLHNL ILDTGITQQL VERVWRDQDL NTYSLLAVFA ATDGGITRVF PNKAAEDWTE 

       790        800        810        820        830        840 
NPEPFNASFY RRSLDNHGYV FKPPHQDALL RPLELENDTV GILVSTAVEL SLGRRTLRPA 

       850        860        870        880        890        900 
VVGVKLDLEA WAEKFKVLAS NRTHQDQPQK CGPNSHCEMD CEVNNEDLLC VLIDDGGFLV 

       910        920        930        940        950        960 
LSNQNHQWDQ VGRFFSEVDA NLMLALYNNS FYTRKESYDY QAACAPQPPG NLGAAPRGVF 

       970        980        990       1000       1010       1020 
VPTVADFLNL AWWTSAAAWS LFQQLLYGLI YHSWFQADPA EAEGSPETRE SSCVMKQTQY 

      1030       1040       1050       1060       1070       1080 
YFGSVNASYN AIIDCGNCSR LFHAQRLTNT NLLFVVAEKP LCSQCEAGRL LQKETHSDGP 

      1090       1100       1110       1120       1130       1140 
EQCELVQRPR YRRGPHICFD YNATEDTSDC GRGASFPPSL GVLVSLQLLL LLGLPPRPQP 

      1150 
QVLVHASRRL 

« Hide

Isoform 2 (Alpha2delta-2b) [UniParc].

Checksum: 492556C9919A0CE5
Show »

FASTA1,143129,085
Isoform 3 [UniParc].

Checksum: 9ADA4807FC70971B
Show »

FASTA1,145129,269
Isoform 4 [UniParc].

Checksum: EEC474836B7EDA85
Show »

FASTA1,076122,117
Isoform 5 (Alpha2delta-2c) [UniParc].

Checksum: 5C1121092C1CE0A6
Show »

FASTA1,152130,001

References

« Hide 'large scale' references
[1]"Molecular diversity of the calcium channel alpha2delta subunit."
Klugbauer N., Lacinova L., Marais E., Hobom M., Hofmann F.
J. Neurosci. 19:684-691(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4), TISSUE SPECIFICITY.
[2]"Functional properties of a new voltage-dependent calcium channel alpha(2)delta auxiliary subunit gene (CACNA2D2)."
Gao B., Sekido Y., Maximov A., Saad M., Forgacs E., Latif F., Wei M.-H., Lerman M., Lee J.-H., Perez-Reyes E., Bezprozvanny I., Minna J.D.
J. Biol. Chem. 275:12237-12242(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TISSUE SPECIFICITY.
[3]"Neuronal distribution and functional characterization of the calcium channel alpha2delta-2 subunit."
Hobom M., Dai S., Marais E., Lacinova L., Hofmann F., Klugbauer N.
Eur. J. Neurosci. 12:1217-1226(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
Tissue: Thyroid.
[4]"Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro."
Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 5:31-39(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Brain.
[5]"The DNA sequence, annotation and analysis of human chromosome 3."
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. expand/collapse author list , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]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 (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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 3).
[8]"Tissue-specific expression and gabapentin-binding properties of calcium channel alpha2delta subunit subtypes."
Gong H.C., Hang J., Kohler W., Li L., Su T.-Z.
J. Membr. Biol. 184:35-43(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: DISULFIDE BONDS, TISSUE SPECIFICITY, GABAPENTIN-BINDING.
[9]"Calcium channel alpha2delta subunits: differential expression, function, and drug binding."
Klugbauer N., Marais E., Hofmann F.
J. Bioenerg. Biomembr. 35:639-647(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING (ISOFORM 5).
[10]"CACNA2D2-mediated apoptosis in NSCLC cells is associated with alterations of the intracellular calcium signaling and disruption of mitochondria membrane integrity."
Carboni G.L., Gao B., Nishizaki M., Xu K., Minna J.D., Roth J.A., Ji L.
Oncogene 22:615-626(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"Modulation of gating currents of the Ca(v)3.1 calcium channel by alpha 2 delta 2 and gamma 5 subunits."
Lacinova L., Klugbauer N.
Arch. Biochem. Biophys. 425:207-213(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[12]"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins."
Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D.
Nat. Biotechnol. 27:378-386(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-386.
Tissue: Leukemic T-cell.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF042792 mRNA. Translation: AAB96913.1.
AF042793 mRNA. Translation: AAB96914.1.
AF040709 mRNA. Translation: AAC70914.1.
AJ251367 mRNA. Translation: CAB86192.1.
AJ251368 mRNA. Translation: CAB86193.1.
AB011130 mRNA. Translation: BAA25484.1.
AL450422 Genomic DNA. No translation available.
Z75742 Genomic DNA. No translation available.
Z75743 Genomic DNA. No translation available.
Z84492 Genomic DNA. No translation available.
Z84494 Genomic DNA. No translation available.
Z84495 Genomic DNA. No translation available.
CH471055 Genomic DNA. Translation: EAW65121.1.
BC152438 mRNA. Translation: AAI52439.1.
RefSeqNP_001005505.1. NM_001005505.1.
NP_001167522.1. NM_001174051.1.
NP_006021.2. NM_006030.2.
UniGeneHs.476273.
Hs.674666.

3D structure databases

ProteinModelPortalQ9NY47.
SMRQ9NY47. Positions 284-469.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114678. 1 interaction.
IntActQ9NY47. 1 interaction.
STRING9606.ENSP00000390329.

Chemistry

ChEMBLCHEMBL2363032.
DrugBankDB00996. Gabapentin.

Protein family/group databases

TCDB8.A.18.2.1. the ca(2+) channel auxiliary subunit 2 types 1-4 (cca-2) family.

PTM databases

PhosphoSiteQ9NY47.

Polymorphism databases

DMDM387912827.

Proteomic databases

PaxDbQ9NY47.
PRIDEQ9NY47.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000266039; ENSP00000266039; ENSG00000007402. [Q9NY47-3]
ENST00000360963; ENSP00000354228; ENSG00000007402. [Q9NY47-4]
ENST00000424201; ENSP00000390329; ENSG00000007402. [Q9NY47-2]
ENST00000479441; ENSP00000418081; ENSG00000007402. [Q9NY47-1]
GeneID9254.
KEGGhsa:9254.
UCSCuc003dap.3. human. [Q9NY47-2]
uc003daq.3. human. [Q9NY47-1]

Organism-specific databases

CTD9254.
GeneCardsGC03M050400.
HGNCHGNC:1400. CACNA2D2.
HPAHPA034771.
MIM607082. gene.
neXtProtNX_Q9NY47.
Orphanet1934. Early infantile epileptic encephalopathy.
PharmGKBPA26012.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG307080.
HOGENOMHOG000004860.
HOVERGENHBG057779.
InParanoidQ9NY47.
KOK04859.
TreeFamTF315824.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
REACT_13685. Neuronal System.

Gene expression databases

ArrayExpressQ9NY47.
BgeeQ9NY47.
CleanExHS_CACNA2D2.
GenevestigatorQ9NY47.

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

GeneWikiCACNA2D2.
GenomeRNAi9254.
NextBio34689.
PROQ9NY47.
SOURCESearch...

Entry information

Entry nameCA2D2_HUMAN
AccessionPrimary (citable) accession number: Q9NY47
Secondary accession number(s): A7MD15 expand/collapse secondary AC list , Q9NY48, Q9UEW0, Q9Y268
Entry history
Integrated into UniProtKB/Swiss-Prot: September 11, 2007
Last sequence update: May 16, 2012
Last modified: April 16, 2014
This is version 91 of the entry and version 2 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 3

Human chromosome 3: entries, gene names and cross-references to MIM