Q8IZS8 (CA2D3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Voltage-dependent calcium channel subunit alpha-2/delta-3

Alternative name(s):
Voltage-gated calcium channel subunit alpha-2/delta-3

Cleaved into the following 2 chains:

1. Voltage-dependent calcium channel subunit alpha-2-3
2. Voltage-dependent calcium channel subunit delta-3

Gene names

Name:

CACNA2D3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1091 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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) but not T-type (CACNA1G) By similarity.
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.
Tissue specificity	Only detected in brain. Not present in lung, testis, aorta, spleen, jejunum, ventricular muscle and kidney (at protein level). According to Ref.4, it is brain-specific, while according to Ref.1, it is widely expressed. 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	N-glycosylated By similarity. May be proteolytically processed into subunits alpha-2-3 and delta-3 that are disulfide-linked. It is however unclear whether such cleavage really takes place in vivo and has a functional role By similarity.
Miscellaneous	In contrast to CACNA2D1 and CACNA2D2, it does not bind gabapentin, an antiepileptic drug.
Sequence similarities	Belongs to the calcium channel subunit alpha-2/delta family. Contains 1 cache domain. Contains 1 VWFA domain.

Ontologies

Keywords
Biological process	Calcium transport Ion transport Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing
Domain	Signal Transmembrane Transmembrane helix
Ligand	Calcium Metal-binding
Molecular function	Calcium channel Ion channel Voltage-gated channel
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW voltage-gated calcium channel activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8IZS8-1)

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: Q8IZS8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-94: Missing.

Isoform 3 (identifier: Q8IZS8-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-94: Missing.
     461-466: Missing.
     595-619: KRVLVMTNDYYYTDIKGTPFSLGVA → FRCGAFQRSWEIFLPRECNHRRRPA
     620-1091: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 28	28	Potential
	Chain	29 – 1091	1063	Voltage-dependent calcium channel subunit alpha-2/delta-3		PRO_0000304646
	Chain	29 – ?		Voltage-dependent calcium channel subunit alpha-2-3 Potential		PRO_0000304647
	Chain	? – 1091		Voltage-dependent calcium channel subunit delta-3 Potential		PRO_0000304648
Regions
	Topological domain	29 – 1068	1040	Extracellular Potential
	Transmembrane	1069 – 1089	21	Helical; Potential
	Topological domain	1090 – 1091	2	Cytoplasmic Potential
	Domain	256 – 438	183	VWFA
	Domain	452 – 549	98	Cache
	Motif	262 – 266	5	MIDAS-like motif
Sites
	Metal binding	262	1	Divalent metal cation By similarity
	Metal binding	264	1	Divalent metal cation By similarity
	Metal binding	266	1	Divalent metal cation By similarity
Amino acid modifications
	Glycosylation	166	1	N-linked (GlcNAc...) Potential
	Glycosylation	309	1	N-linked (GlcNAc...) Potential
	Glycosylation	553	1	N-linked (GlcNAc...) Potential
	Glycosylation	632	1	N-linked (GlcNAc...) Potential
	Glycosylation	793	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 94	94	Missing in isoform 2 and isoform 3.		VSP_028064
	Alternative sequence	461 – 466	6	Missing in isoform 3.		VSP_028065
	Alternative sequence	595 – 619	25	KRVLV…SLGVA → FRCGAFQRSWEIFLPRECNH RRRPA in isoform 3.		VSP_028066
	Alternative sequence	620 – 1091	472	Missing in isoform 3.		VSP_028067

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2003. Version 1. Checksum: 4E5E50BD38F05082	FASTA	1,091	123,011
	10 20 30 40 50 60 MAGPGSPRRA SRGASALLAA ALLYAALGDV VRSEQQIPLS VVKLWASAFG GEIKSIAAKY 70 80 90 100 110 120 SGSQLLQKKY KEYEKDVAIE EIDGLQLVKK LAKNMEEMFH KKSEAVRRLV EAAEEAHLKH 130 140 150 160 170 180 EFDADLQYEY FNAVLINERD KDGNFLELGK EFILAPNDHF NNLPVNISLS DVQVPTNMYN 190 200 210 220 230 240 KDPAIVNGVY WSESLNKVFV DNFDRDPSLI WQYFGSAKGF FRQYPGIKWE PDENGVIAFD 250 260 270 280 290 300 CRNRKWYIQA ATSPKDVVIL VDVSGSMKGL RLTIAKQTVS SILDTLGDDD FFNIIAYNEE 310 320 330 340 350 360 LHYVEPCLNG TLVQADRTNK EHFREHLDKL FAKGIGMLDI ALNEAFNILS DFNHTGQGSI 370 380 390 400 410 420 CSQAIMLITD GAVDTYDTIF AKYNWPDRKV RIFTYLIGRE AAFADNLKWM ACANKGFFTQ 430 440 450 460 470 480 ISTLADVQEN VMEYLHVLSR PKVIDQEHDV VWTEAYIDST LPQAQKLTDD QGPVLMTTVA 490 500 510 520 530 540 MPVFSKQNET RSKGILLGVV GTDVPVKELL KTIPKYKLGI HGYAFAITNN GYILTHPELR 550 560 570 580 590 600 LLYEEGKKRR KPNYSSVDLS EVEWEDRDDV LRNAMVNRKT GKFSMEVKKT VDKGKRVLVM 610 620 630 640 650 660 TNDYYYTDIK GTPFSLGVAL SRGHGKYFFR GNVTIEEGLH DLEHPDVSLA DEWSYCNTDL 670 680 690 700 710 720 HPEHRHLSQL EAIKLYLKGK EPLLQCDKEL IQEVLFDAVV SAPIEAYWTS LALNKSENSD 730 740 750 760 770 780 KGVEVAFLGT RTGLSRINLF VGAEQLTNQD FLKAGDKENI FNADHFPLWY RRAAEQIPGS 790 800 810 820 830 840 FVYSIPFSTG PVNKSNVVTA STSIQLLDER KSPVVAAVGI QMKLEFFQRK FWTASRQCAS 850 860 870 880 890 900 LDGKCSISCD DETVNCYLID NNGFILVSED YTQTGDFFGE IEGAVMNKLL TMGSFKRITL 910 920 930 940 950 960 YDYQAMCRAN KESSDGAHGL LDPYNAFLSA VKWIMTELVL FLVEFNLCSW WHSDMTAKAQ 970 980 990 1000 1010 1020 KLKQTLEPCD TEYPAFVSER TIKETTGNIA CEDCSKSFVI QQIPSSNLFM VVVDSSCLCE 1030 1040 1050 1060 1070 1080 SVAPITMAPI EIRYNESLKC ERLKAQKIRR RPESCHGFHP EENARECGGA PSLQAQTVLL 1090 LLPLLLMLFS R
	Isoform 2 [UniParc]. Checksum: B56D13133FD67B8D	FASTA	997	112,997
	10 20 30 40 50 60 MEEMFHKKSE AVRRLVEAAE EAHLKHEFDA DLQYEYFNAV LINERDKDGN FLELGKEFIL 70 80 90 100 110 120 APNDHFNNLP VNISLSDVQV PTNMYNKDPA IVNGVYWSES LNKVFVDNFD RDPSLIWQYF 130 140 150 160 170 180 GSAKGFFRQY PGIKWEPDEN GVIAFDCRNR KWYIQAATSP KDVVILVDVS GSMKGLRLTI 190 200 210 220 230 240 AKQTVSSILD TLGDDDFFNI IAYNEELHYV EPCLNGTLVQ ADRTNKEHFR EHLDKLFAKG 250 260 270 280 290 300 IGMLDIALNE AFNILSDFNH TGQGSICSQA IMLITDGAVD TYDTIFAKYN WPDRKVRIFT 310 320 330 340 350 360 YLIGREAAFA DNLKWMACAN KGFFTQISTL ADVQENVMEY LHVLSRPKVI DQEHDVVWTE 370 380 390 400 410 420 AYIDSTLPQA QKLTDDQGPV LMTTVAMPVF SKQNETRSKG ILLGVVGTDV PVKELLKTIP 430 440 450 460 470 480 KYKLGIHGYA FAITNNGYIL THPELRLLYE EGKKRRKPNY SSVDLSEVEW EDRDDVLRNA 490 500 510 520 530 540 MVNRKTGKFS MEVKKTVDKG KRVLVMTNDY YYTDIKGTPF SLGVALSRGH GKYFFRGNVT 550 560 570 580 590 600 IEEGLHDLEH PDVSLADEWS YCNTDLHPEH RHLSQLEAIK LYLKGKEPLL QCDKELIQEV 610 620 630 640 650 660 LFDAVVSAPI EAYWTSLALN KSENSDKGVE VAFLGTRTGL SRINLFVGAE QLTNQDFLKA 670 680 690 700 710 720 GDKENIFNAD HFPLWYRRAA EQIPGSFVYS IPFSTGPVNK SNVVTASTSI QLLDERKSPV 730 740 750 760 770 780 VAAVGIQMKL EFFQRKFWTA SRQCASLDGK CSISCDDETV NCYLIDNNGF ILVSEDYTQT 790 800 810 820 830 840 GDFFGEIEGA VMNKLLTMGS FKRITLYDYQ AMCRANKESS DGAHGLLDPY NAFLSAVKWI 850 860 870 880 890 900 MTELVLFLVE FNLCSWWHSD MTAKAQKLKQ TLEPCDTEYP AFVSERTIKE TTGNIACEDC 910 920 930 940 950 960 SKSFVIQQIP SSNLFMVVVD SSCLCESVAP ITMAPIEIRY NESLKCERLK AQKIRRRPES 970 980 990 CHGFHPEENA RECGGAPSLQ AQTVLLLLPL LLMLFSR
	Isoform 3 [UniParc]. Checksum: 198D13AF246286C6	FASTA	519	59,527
	10 20 30 40 50 60 MEEMFHKKSE AVRRLVEAAE EAHLKHEFDA DLQYEYFNAV LINERDKDGN FLELGKEFIL 70 80 90 100 110 120 APNDHFNNLP VNISLSDVQV PTNMYNKDPA IVNGVYWSES LNKVFVDNFD RDPSLIWQYF 130 140 150 160 170 180 GSAKGFFRQY PGIKWEPDEN GVIAFDCRNR KWYIQAATSP KDVVILVDVS GSMKGLRLTI 190 200 210 220 230 240 AKQTVSSILD TLGDDDFFNI IAYNEELHYV EPCLNGTLVQ ADRTNKEHFR EHLDKLFAKG 250 260 270 280 290 300 IGMLDIALNE AFNILSDFNH TGQGSICSQA IMLITDGAVD TYDTIFAKYN WPDRKVRIFT 310 320 330 340 350 360 YLIGREAAFA DNLKWMACAN KGFFTQISTL ADVQENVMEY LHVLSRPKVI DQEHDVVWTE 370 380 390 400 410 420 AYIDSTLTDD QGPVLMTTVA MPVFSKQNET RSKGILLGVV GTDVPVKELL KTIPKYKLGI 430 440 450 460 470 480 HGYAFAITNN GYILTHPELR LLYEEGKKRR KPNYSSVDLS EVEWEDRDDV LRNAMVNRKT 490 500 510 GKFSMEVKKT VDKGFRCGAF QRSWEIFLPR ECNHRRRPA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning a calcium channel alpha2delta-3 subunit gene from a putative tumor suppressor gene region at chromosome 3p21.1 in conventional renal cell carcinoma." Hanke S., Bugert P., Chudek J., Kovacs G. Gene 264:69-75(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3). Tissue: Brain.
[2]	"Molecular cloning and characterization of the human voltage-gated calcium channel alpha(2)delta-4 subunit." Qin N., Yagel S., Momplaisir M.-L., Codd E.E., D'Andrea M.R. Mol. Pharmacol. 62:485-496(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[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 1).
[4]	"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: TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ272268 mRNA. Translation: CAB75962.1. AJ272213 mRNA. Translation: CAB75878.1. AF516696 mRNA. Translation: AAN06673.1. BC137502 mRNA. Translation: AAI37503.1. BC137505 mRNA. Translation: AAI37506.1.
IPI	IPI00302181. IPI00790775. IPI00796068.
RefSeq	NP_060868.2. NM_018398.2.
UniGene	Hs.656687.
3D structure databases
ProteinModelPortal	Q8IZS8.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000288197.
Protein family/group databases
TCDB	8.A.18.3.1. Ca2+ channel auxiliary subunit alpha2delta types 1-4 (CCA-alpha2delta) family.
PTM databases
PhosphoSite	Q8IZS8.
Polymorphism databases
DMDM	74723683.
Proteomic databases
PaxDb	Q8IZS8.
PRIDE	Q8IZS8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000288197; ENSP00000288197; ENSG00000157445. ENST00000415676; ENSP00000389506; ENSG00000157445. ENST00000471363; ENSP00000418228; ENSG00000157445. ENST00000474759; ENSP00000419101; ENSG00000157445. ENST00000490478; ENSP00000417279; ENSG00000157445.
GeneID	55799.
KEGG	hsa:55799.
UCSC	uc003dhf.3. human.
Organism-specific databases
CTD	55799.
GeneCards	GC03P054131.
HGNC	HGNC:15460. CACNA2D3.
HPA	HPA030850.
MIM	606399. gene.
neXtProt	NX_Q8IZS8.
PharmGKB	PA26013.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG307080.
HOGENOM	HOG000010247.
HOVERGEN	HBG107124.
InParanoid	Q8IZS8.
KO	K04860.
OMA	KTIPKYK.
OrthoDB	EOG479F69.
Enzyme and pathway databases
Reactome	REACT_13685. Neuronal System.
Gene expression databases
ArrayExpress	Q8IZS8.
Bgee	Q8IZS8.
CleanEx	HS_CACNA2D3.
Genevestigator	Q8IZS8.
Family and domain databases
InterPro	IPR004010. Cache_domain. IPR013608. VWA_N. IPR002035. VWF_A. [Graphical view]
Pfam	PF02743. Cache_1. 1 hit. PF08399. VWA_N. 1 hit. [Graphical view]
SMART	SM00327. VWA. 1 hit. [Graphical view]
PROSITE	PS50234. VWFA. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q8IZS8.
ChEMBL	CHEMBL3763.
GenomeRNAi	55799.
NextBio	60933.
SOURCE	Search...

Entry information

Entry name

CA2D3_HUMAN

Accession

Primary (citable) accession number: Q8IZS8
Secondary accession number(s): B2RPL6, Q9NY16, Q9NY18

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 11, 2007
Last sequence update:	March 1, 2003
Last modified:	May 1, 2013
This is version 69 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.