CA2D4_MOUSE
ID CA2D4_MOUSE Reviewed; 1116 AA.
AC Q5RJF7;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 107.
DE RecName: Full=Voltage-dependent calcium channel subunit alpha-2/delta-4;
DE AltName: Full=Voltage-gated calcium channel subunit alpha-2/delta-4;
DE Contains:
DE RecName: Full=Voltage-dependent calcium channel subunit alpha-2-4;
DE Contains:
DE RecName: Full=Voltage-dependent calcium channel subunit delta-4;
DE Flags: Precursor;
GN Name=Cacna2d4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP IDENTIFICATION.
RX PubMed=15536090; DOI=10.1074/jbc.m411501200;
RA Obermair G.J., Kugler G., Baumgartner S., Tuluc P., Grabner M.,
RA Flucher B.E.;
RT "The Ca2+ channel alpha2delta-1 subunit determines Ca2+ current kinetics in
RT skeletal muscle but not targeting of alpha1S or excitation-contraction
RT coupling.";
RL J. Biol. Chem. 280:2229-2237(2005).
RN [3]
RP INVOLVEMENT IN CONE-ROD DYSFUNCTION.
RX PubMed=16877424; DOI=10.1167/iovs.06-0271;
RA Wycisk K.A., Budde B., Feil S., Skosyrski S., Buzzi F., Neidhardt J.,
RA Glaus E., Nurnberg P., Ruether K., Berger W.;
RT "Structural and functional abnormalities of retinal ribbon synapses due to
RT Cacna2d4 mutation.";
RL Invest. Ophthalmol. Vis. Sci. 47:3523-3530(2006).
CC -!- FUNCTION: The alpha-2/delta subunit of voltage-dependent calcium
CC channels regulates calcium current density and activation/inactivation
CC kinetics of the calcium channel. {ECO:0000250}.
CC -!- SUBUNIT: Dimer formed of alpha-2-2 and delta-2 chains; disulfide-
CC linked. Voltage-dependent calcium channels are multisubunit complexes,
CC consisting of alpha-1 (CACNA1), alpha-2 (CACNA2D), beta (CACNB) and
CC delta (CACNA2D) subunits in a 1:1:1:1 ratio (Probable). Interacts with
CC CACNA1C and CACNB3 (By similarity). {ECO:0000250, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q5RJF7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5RJF7-2; Sequence=VSP_044323;
CC -!- DOMAIN: The MIDAS-like motif in the VWFA domain binds divalent metal
CC cations and is required to promote trafficking of the alpha-1 (CACNA1)
CC subunit to the plasma membrane by an integrin-like switch.
CC {ECO:0000250}.
CC -!- PTM: May be proteolytically processed into subunits alpha-2-4 and
CC delta-4 that are disulfide-linked. It is however unclear whether such
CC cleavage really takes place in vivo and has a functional role (By
CC similarity). {ECO:0000250}.
CC -!- DISEASE: Note=Defects in Cacna2d4 are a cause of cone-rod dysfunction.
CC Mice display affected retinal ribbon-type synapses. The retinopathy is
CC accompanied by a substantial loss in the activities of the second-order
CC neurons. Rod photoreceptor responses are maintained with reduced
CC amplitude, whereas cone activities are absent.
CC {ECO:0000269|PubMed:16877424}.
CC -!- SIMILARITY: Belongs to the calcium channel subunit alpha-2/delta
CC family. {ECO:0000305}.
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DR EMBL; AC115816; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BK005394; DAA05529.1; -; mRNA.
DR CCDS; CCDS51886.2; -. [Q5RJF7-1]
DR CCDS; CCDS85143.2; -. [Q5RJF7-2]
DR RefSeq; NP_001028554.2; NM_001033382.2. [Q5RJF7-1]
DR AlphaFoldDB; Q5RJF7; -.
DR SMR; Q5RJF7; -.
DR BioGRID; 235483; 1.
DR STRING; 10090.ENSMUSP00000044660; -.
DR GlyGen; Q5RJF7; 3 sites.
DR iPTMnet; Q5RJF7; -.
DR PhosphoSitePlus; Q5RJF7; -.
DR PaxDb; Q5RJF7; -.
DR PRIDE; Q5RJF7; -.
DR Antibodypedia; 22099; 213 antibodies from 24 providers.
DR Ensembl; ENSMUST00000186622; ENSMUSP00000140197; ENSMUSG00000041460. [Q5RJF7-2]
DR Ensembl; ENSMUST00000238905; ENSMUSP00000158949; ENSMUSG00000041460. [Q5RJF7-1]
DR GeneID; 319734; -.
DR KEGG; mmu:319734; -.
DR CTD; 93589; -.
DR MGI; MGI:2442632; Cacna2d4.
DR VEuPathDB; HostDB:ENSMUSG00000041460; -.
DR eggNOG; KOG2353; Eukaryota.
DR GeneTree; ENSGT00940000155997; -.
DR InParanoid; Q5RJF7; -.
DR OMA; MLMWIIL; -.
DR OrthoDB; 69856at2759; -.
DR PhylomeDB; Q5RJF7; -.
DR BioGRID-ORCS; 319734; 3 hits in 73 CRISPR screens.
DR ChiTaRS; Cacna2d4; mouse.
DR PRO; PR:Q5RJF7; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q5RJF7; protein.
DR Bgee; ENSMUSG00000041460; Expressed in retinal neural layer and 56 other tissues.
DR ExpressionAtlas; Q5RJF7; baseline and differential.
DR GO; GO:0005891; C:voltage-gated calcium channel complex; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; ISO:MGI.
DR GO; GO:0070588; P:calcium ion transmembrane transport; ISO:MGI.
DR GO; GO:0050908; P:detection of light stimulus involved in visual perception; ISO:MGI.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.410; -; 1.
DR InterPro; IPR013680; VDCC_a2/dsu.
DR InterPro; IPR013608; VWA_N.
DR InterPro; IPR002035; VWF_A.
DR InterPro; IPR036465; vWFA_dom_sf.
DR Pfam; PF08473; VGCC_alpha2; 1.
DR Pfam; PF13768; VWA_3; 1.
DR Pfam; PF08399; VWA_N; 1.
DR SMART; SM00327; VWA; 1.
DR SUPFAM; SSF53300; SSF53300; 1.
DR PROSITE; PS50234; VWFA; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Calcium; Calcium channel; Calcium transport;
KW Cone-rod dystrophy; Disulfide bond; Glycoprotein; Ion channel;
KW Ion transport; Membrane; Metal-binding; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix; Transport; Voltage-gated channel.
FT SIGNAL 1..47
FT /evidence="ECO:0000255"
FT CHAIN 48..1116
FT /note="Voltage-dependent calcium channel subunit alpha-
FT 2/delta-4"
FT /id="PRO_0000304658"
FT CHAIN 48..970
FT /note="Voltage-dependent calcium channel subunit alpha-2-4"
FT /evidence="ECO:0000255"
FT /id="PRO_0000304659"
FT CHAIN 971..1116
FT /note="Voltage-dependent calcium channel subunit delta-4"
FT /evidence="ECO:0000255"
FT /id="PRO_0000304660"
FT TOPO_DOM 48..1094
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1095..1115
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1116
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 270..452
FT /note="VWFA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00219"
FT DOMAIN 466..559
FT /note="Cache"
FT MOTIF 276..280
FT /note="MIDAS-like motif"
FT BINDING 276
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT BINDING 278
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT BINDING 280
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT CARBOHYD 180
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 643
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 725
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 426..1076
FT /note="Interchain (between alpha-2-4 and delta-4 chains)"
FT /evidence="ECO:0000250"
FT VAR_SEQ 528..552
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_044323"
SQ SEQUENCE 1116 AA; 125991 MW; 731AE2A4B090B143 CRC64;
MARCPMLSSS HNQDHSGRWT AVWTSLWKTP IILWLLLSDT SLPTVRGQTT VPLETVKLWA
DTFGRNLYNT VTRYSGSLLL QKKYKDAEPS LKIKEVDGLE LVKKFSEDME TMLRRKVEAV
ESLVEAAEEA DLNHEFNASL VFNYYNSVLI NEKDDKGNYV ELGAEFLLES DAHFSNLRVN
VSMSSVQLPT NVYNKDPDIL NGVYMSEALN PVFVENFQRD PTLTWQYFGS STGFFRIYPG
IKWMPDENGV IAFDCRNRGW YIQAATSPKD IVILVDISGS MKGLRMAIAK HTITTILDTL
GENDFVNIIA YNDYVHYIEP CFKGILVQAD RDNREHFKQL VDELMVKGVG VVSQALIEAF
EILKQFQESK QGSLCNQAIM LITDGAVEDY EPVFETYNWP DRKVRVFTYL IGREVTFADR
MKWIACNNKG YYTQISTLAD AQESVMEYLH VLSRPMVINH DHDIIWTEAY MDSRLFTSEA
QSLMLLTTVA MPVFSKKNET RSHGILLGVV GSDVTLRELM KLAPRYKLGV HGYAFLNTNN
GYILSHPDLR PLYREGKKLR PKPNYNSVDL SEVEWEDQAE ILRTAMINGE TGSHSMDVKV
PLDKGKRVLF LTNDYFFTDI SDTPFSLGVV LTRGHGEYIL LGNTSVEEGL HDLLHPDLTL
ASDWIYCITD IDPDHRKLSQ LEAVVRFLTG VDPDLECDEE LVREVLFDAV VTAPMEAYWT
ALALNISEES EPGVDVAFLG TRAGLLRRSL FVGSEKVSDR KFLTPEDEAS IFTMDHFPLW
YRQASEQPPG SFVFNLRWAE GPDSPGKPVA VRASTAVTVT VDGKTAIAAA VGIQMQADYL
QRQFWAAMQQ CNAVEGPCLK SCEDTDLDCF VIDNNGFVLI SERPQEMGRL LGEADGALMK
QLLSMGVFSR VTMYDYQAMC KPPDHHHSAA ESLFSPLSAF LMVARWLLHE CLLFLLEWSA
WGSWQDKGSE AKSVFHHSHK HKKQDLLHPC DTEYPVFVHQ TAIQEANGII ECGGCQKTFV
MQQIPRSNLL LLVTDRTCDC SAHSPILQEA TEVKYNASVK CDRMRSQKPR RRPGSCHAFH
PEENAQDCGG ASDTLPSSPL LLLSLGAWLL PPQLLW
