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Q7Z3S7 (CA2D4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 86. 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-4
Alternative name(s):
Voltage-gated calcium channel subunit alpha-2/delta-4
Gene names
Name:CACNA2D4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1137 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. Ref.1

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 Probable. Interacts with CACNA1C and CACNB3. Ref.1

Subcellular location

Membrane; Single-pass type I membrane protein Potential.

Tissue specificity

Predominantly expressed in certain types of endocrine cells. Present in the Paneth cells of the small intestine. Also present in the erythroblasts in the fetal liver, in the cells of the zona reticularis of the adrenal gland and in the basophils of the pituitary. Present at low level in some brain regions such as the cerebellum (at protein level). Ref.1

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-2-4 and delta-4 that are disulfide-linked. It is however unclear whether such cleavage really takes place in vivo and has a functional role By similarity.

Involvement in disease

Retinal cone dystrophy 4 (RCD4) [MIM:610478]: Characterized by minimal symptoms except for slowly progressive reduction in visual acuity.
Note: The disease is caused by mutations affecting the gene represented in this entry.

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.

Sequence caution

The sequence AAH48288.1 differs from that shown. Reason: Erroneous translation. Wrong choice of frame.

The sequence AAN06672.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q7Z3S7-1)

Also known as: Alpha2delta-4a;

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: Q7Z3S7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     975-1137: Missing.
Note: No experimental confirmation available. May be due to an intron retention.
Isoform 4 (identifier: Q7Z3S7-4)

Also known as: Alpha2delta-4b;

The sequence of this isoform differs from the canonical sequence as follows:
     1-76: MVCGCSALLP...WGQAKIPLET → MAVALGTRRRDR
Isoform 5 (identifier: Q7Z3S7-5)

Also known as: Alpha2delta-4c;

The sequence of this isoform differs from the canonical sequence as follows:
     1104-1137: ENAQDCGGASDTSASPPLLLLPVCAWGLLPQLLR → VRVEADRGWA...LGGNIRVYAL
Isoform 6 (identifier: Q7Z3S7-6)

Also known as: Alpha2delta-4d;

The sequence of this isoform differs from the canonical sequence as follows:
     1-76: MVCGCSALLP...WGQAKIPLET → MAVALGTRRRDR
     1104-1137: ENAQDCGGASDTSASPPLLLLPVCAWGLLPQLLR → VRVEADRGWA...LGGNIRVYAL
Isoform 7 (identifier: Q7Z3S7-7)

The sequence of this isoform differs from the canonical sequence as follows:
     1-855: Missing.
     872-886: Missing.
     908-911: TGRF → SDYV
     912-1137: Missing.
Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1919 Potential
Chain20 – 11371118Voltage-dependent calcium channel subunit alpha-2/delta-4
PRO_0000304655
Chain20 – 991972Voltage-dependent calcium channel subunit alpha-2-4 Potential
PRO_0000304656
Chain992 – 1137146Voltage-dependent calcium channel subunit delta-4 Potential
PRO_0000304657

Regions

Topological domain20 – 11151096Extracellular Potential
Transmembrane1116 – 113621Helical; Potential
Topological domain11371Cytoplasmic Potential
Domain291 – 473183VWFA
Domain487 – 58094Cache
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

Glycosylation2011N-linked (GlcNAc...) Potential
Glycosylation6641N-linked (GlcNAc...) Potential
Disulfide bond447 ↔ 1097Interchain (between alpha-2-4 and delta-4 chains) By similarity

Natural variations

Alternative sequence1 – 855855Missing in isoform 7.
VSP_044107
Alternative sequence1 – 7676MVCGC…IPLET → MAVALGTRRRDR in isoform 4 and isoform 6.
VSP_028069
Alternative sequence872 – 88615Missing in isoform 7.
VSP_044108
Alternative sequence908 – 9114TGRF → SDYV in isoform 7.
VSP_044109
Alternative sequence912 – 1137226Missing in isoform 7.
VSP_044110
Alternative sequence975 – 1137163Missing in isoform 2.
VSP_028070
Alternative sequence1104 – 113734ENAQD…PQLLR → VRVEADRGWAGFSSPNPLCL GLCPCRQEHIGMPMNTPVPV LLGGNIRVYAL in isoform 5 and isoform 6.
VSP_028071
Natural variant3271I → V. Ref.1 Ref.2
Corresponds to variant rs10735005 [ dbSNP | Ensembl ].
VAR_035049
Natural variant8631R → H.
Corresponds to variant rs36077411 [ dbSNP | Ensembl ].
VAR_035050
Natural variant8691T → M.
Corresponds to variant rs35331095 [ dbSNP | Ensembl ].
VAR_035051

Experimental info

Sequence conflict3681K → N in CAD97678. Ref.2
Sequence conflict6501V → A in AAN06672. Ref.1
Sequence conflict7101T → A in CAD97679. Ref.2
Sequence conflict8791C → Y in AAN06672. Ref.1
Sequence conflict10341G → E in CAD97679. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Alpha2delta-4a) [UniParc].

Last modified May 18, 2010. Version 2.
Checksum: BF7FD169E1AF34F7

FASTA1,137127,938
        10         20         30         40         50         60 
MVCGCSALLP LPNPRPTMPA TPNFLANPSS SSRWIPLQPM PVAWAFVQKT SALLWLLLLG 

        70         80         90        100        110        120 
TSLSPAWGQA KIPLETVKLW ADTFGGDLYN TVTKYSGSLL LQKKYKDVES SLKIEEVDGL 

       130        140        150        160        170        180 
ELVRKFSEDM ENMLRRKVEA VQNLVEAAEE ADLNHEFNES LVFDYYNSVL INERDEKGNF 

       190        200        210        220        230        240 
VELGAEFLLE SNAHFSNLPV NTSISSVQLP TNVYNKDPDI LNGVYMSEAL NAVFVENFQR 

       250        260        270        280        290        300 
DPTLTWQYFG SATGFFRIYP GIKWTPDENG VITFDCRNRG WYIQAATSPK DIVILVDVSG 

       310        320        330        340        350        360 
SMKGLRMTIA KHTITTILDT LGENDFINII AYNDYVHYIE PCFKGILVQA DRDNREHFKL 

       370        380        390        400        410        420 
LVEELMVKGV GVVDQALREA FQILKQFQEA KQGSLCNQAI MLISDGAVED YEPVFEKYNW 

       430        440        450        460        470        480 
PDCKVRVFTY LIGREVSFAD RMKWIACNNK GYYTQISTLA DTQENVMEYL HVLSRPMVIN 

       490        500        510        520        530        540 
HDHDIIWTEA YMDSKLLSSQ AQSLTLLTTV AMPVFSKKNE TRSHGILLGV VGSDVALREL 

       550        560        570        580        590        600 
MKLAPRYKLG VHGYAFLNTN NGYILSHPDL RPLYREGKKL KPKPNYNSVD LSEVEWEDQA 

       610        620        630        640        650        660 
ESLRTAMINR ETGTLSMDVK VPMDKGKRVL FLTNDYFFTD ISDTPFSLGV VLSRGHGEYI 

       670        680        690        700        710        720 
LLGNTSVEEG LHDLLHPDLA LAGDWIYCIT DIDPDHRKLS QLEAMIRFLT RKDPDLECDE 

       730        740        750        760        770        780 
ELVREVLFDA VVTAPMEAYW TALALNMSEE SEHVVDMAFL GTRAGLLRSS LFVGSEKVSD 

       790        800        810        820        830        840 
RKFLTPEDEA SVFTLDRFPL WYRQASEHPA GSFVFNLRWA EGPESAGEPM VVTASTAVAV 

       850        860        870        880        890        900 
TVDKRTAIAA AAGVQMKLEF LQRKFWAATR QCSTVDGPCT QSCEDSDLDC FVIDNNGFIL 

       910        920        930        940        950        960 
ISKRSRETGR FLGEVDGAVL TQLLSMGVFS QVTMYDYQAM CKPSSHHHSA AQPLVSPISA 

       970        980        990       1000       1010       1020 
FLTATRWLLQ ELVLFLLEWS VWGSWYDRGA EAKSVFHHSH KHKKQDPLQP CDTEYPVFVY 

      1030       1040       1050       1060       1070       1080 
QPAIREANGI VECGPCQKVF VVQQIPNSNL LLLVTDPTCD CSIFPPVLQE ATEVKYNASV 

      1090       1100       1110       1120       1130 
KCDRMRSQKL RRRPDSCHAF HPEENAQDCG GASDTSASPP LLLLPVCAWG LLPQLLR 

« Hide

Isoform 2 [UniParc].

Checksum: 4C32DE661B46D266
Show »

FASTA974109,597
Isoform 4 (Alpha2delta-4b) [UniParc].

Checksum: B7D8BA5A62F9D13D
Show »

FASTA1,073121,156
Isoform 5 (Alpha2delta-4c) [UniParc].

Checksum: AEE808DF16BAE995
Show »

FASTA1,154129,938
Isoform 6 (Alpha2delta-4d) [UniParc].

Checksum: 145BCC542E24E4C4
Show »

FASTA1,090123,155
Isoform 7 [UniParc].

Checksum: 6189BCF6FD9B7870
Show »

FASTA414,955

References

« Hide 'large scale' references
[1]"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] (ISOFORMS 1; 4; 5 AND 6), FUNCTION, TISSUE SPECIFICITY, LACK OF GABAPENTIN-BINDING, INTERACTION WITH CACNA1C AND CACNB3, VARIANT VAL-327.
[2]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT VAL-327.
Tissue: Retina.
[3]"The finished DNA sequence of human chromosome 12."
Scherer S.E., Muzny D.M., 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., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. expand/collapse author list , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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 7).
Tissue: Blood.
[5]"Mutation in the auxiliary calcium-channel subunit CACNA2D4 causes autosomal recessive cone dystrophy."
Wycisk K.A., Zeitz C., Feil S., Wittmer M., Forster U., Neidhardt J., Wissinger B., Zrenner E., Wilke R., Kohl S., Berger W.
Am. J. Hum. Genet. 79:973-977(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN RDC4.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF516695 mRNA. Translation: AAN06672.1. Different initiation.
BX537436 mRNA. Translation: CAD97678.1.
BX537437 mRNA. Translation: CAD97679.1.
AC005342 Genomic DNA. No translation available.
AC005343 Genomic DNA. No translation available.
BC048288 mRNA. Translation: AAH48288.1. Sequence problems.
CCDSCCDS44785.1. [Q7Z3S7-1]
RefSeqNP_758952.4. NM_172364.4. [Q7Z3S7-1]
UniGeneHs.13768.

3D structure databases

ProteinModelPortalQ7Z3S7.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000372169.

Chemistry

ChEMBLCHEMBL2363032.

Protein family/group databases

TCDB8.A.18.4.1. the ca(2+) channel auxiliary subunit 2 types 1-4 (cca-2) family.

PTM databases

PhosphoSiteQ7Z3S7.

Polymorphism databases

DMDM296434419.

Proteomic databases

PaxDbQ7Z3S7.
PRIDEQ7Z3S7.

Protocols and materials databases

DNASU93589.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000382722; ENSP00000372169; ENSG00000151062. [Q7Z3S7-1]
ENST00000545595; ENSP00000442329; ENSG00000151062. [Q7Z3S7-7]
ENST00000585708; ENSP00000467697; ENSG00000151062. [Q7Z3S7-6]
ENST00000586184; ENSP00000465060; ENSG00000151062. [Q7Z3S7-5]
ENST00000588077; ENSP00000468530; ENSG00000151062. [Q7Z3S7-4]
GeneID93589.
KEGGhsa:93589.
UCSCuc009zdt.1. human. [Q7Z3S7-1]

Organism-specific databases

CTD93589.
GeneCardsGC12M001901.
H-InvDBHIX0010321.
HIX0171624.
HGNCHGNC:20202. CACNA2D4.
HPAHPA031952.
MIM608171. gene.
610478. phenotype.
neXtProtNX_Q7Z3S7.
Orphanet1872. Cone rod dystrophy.
215. Congenital stationary night blindness.
PharmGKBPA130546913.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG307080.
HOGENOMHOG000010247.
HOVERGENHBG107124.
InParanoidQ7Z3S7.
KOK04861.
OMAFTMDHFP.
PhylomeDBQ7Z3S7.
TreeFamTF315824.

Gene expression databases

ArrayExpressQ7Z3S7.
BgeeQ7Z3S7.
CleanExHS_CACNA2D4.
GenevestigatorQ7Z3S7.

Family and domain databases

Gene3D3.40.50.410. 1 hit.
InterProIPR004010. Cache_domain.
IPR013608. VWA_N.
IPR002035. VWF_A.
[Graphical view]
PfamPF02743. Cache_1. 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

GenomeRNAi93589.
NextBio78139.
PROQ7Z3S7.
SOURCESearch...

Entry information

Entry nameCA2D4_HUMAN
AccessionPrimary (citable) accession number: Q7Z3S7
Secondary accession number(s): Q7Z3S8, Q86XZ5, Q8IZS9
Entry history
Integrated into UniProtKB/Swiss-Prot: September 11, 2007
Last sequence update: May 18, 2010
Last modified: July 9, 2014
This is version 86 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 12

Human chromosome 12: entries, gene names and cross-references to MIM