CA2D2_RAT
ID CA2D2_RAT Reviewed; 1157 AA.
AC Q8CFG6;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 104.
DE RecName: Full=Voltage-dependent calcium channel subunit alpha-2/delta-2;
DE AltName: Full=Voltage-gated calcium channel subunit alpha-2/delta-2;
DE Contains:
DE RecName: Full=Voltage-dependent calcium channel subunit alpha-2-2;
DE Contains:
DE RecName: Full=Voltage-dependent calcium channel subunit delta-2;
DE Flags: Precursor;
GN Name=Cacna2d2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Heart atrium;
RX PubMed=12606261; DOI=10.1016/s0022-2828(02)00313-9;
RA Chu P.-J., Best P.M.;
RT "Molecular cloning of calcium channel alpha(2)delta-subunits from rat atria
RT and the differential regulation of their expression by IGF-1.";
RL J. Mol. Cell. Cardiol. 35:207-215(2003).
RN [2]
RP TISSUE SPECIFICITY.
RX PubMed=16636499; DOI=10.1253/circj.70.610;
RA Hatano S., Yamashita T., Sekiguchi A., Iwasaki Y., Nakazawa K., Sagara K.,
RA Iinuma H., Aizawa T., Fu L.-T.;
RT "Molecular and electrophysiological differences in the L-type Ca2+ channel
RT of the atrium and ventricle of rat hearts.";
RL Jpn. Circ. J. 70:610-614(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. Acts as a regulatory subunit for P/Q-
CC type calcium channel (CACNA1A), N-type (CACNA1B), L-type (CACNA1C OR
CC CACNA1D) and possibly T-type (CACNA1G). Overexpression induces
CC apoptosis (By similarity). {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 (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}. Note=Colocalizes with CACNA1A in lipid
CC raft fractions. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: In heart, it is highly expressed in atrium and at
CC lower level in ventricle. {ECO:0000269|PubMed:12606261,
CC ECO:0000269|PubMed:16636499}.
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: N-glycosylated. {ECO:0000250}.
CC -!- PTM: May be proteolytically processed into subunits alpha-2-2 and
CC delta-2 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 -!- MISCELLANEOUS: Binds gabapentin, an antiepileptic drug. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the calcium channel subunit alpha-2/delta
CC family. {ECO:0000305}.
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DR EMBL; AF486277; AAO14653.1; -; mRNA.
DR RefSeq; NP_783182.1; NM_175592.2.
DR AlphaFoldDB; Q8CFG6; -.
DR SMR; Q8CFG6; -.
DR BioGRID; 256785; 1.
DR IntAct; Q8CFG6; 3.
DR STRING; 10116.ENSRNOP00000021216; -.
DR ChEMBL; CHEMBL3988639; -.
DR GlyGen; Q8CFG6; 7 sites.
DR PaxDb; Q8CFG6; -.
DR GeneID; 300992; -.
DR KEGG; rno:300992; -.
DR UCSC; RGD:631360; rat.
DR CTD; 9254; -.
DR RGD; 631360; Cacna2d2.
DR eggNOG; KOG2353; Eukaryota.
DR InParanoid; Q8CFG6; -.
DR OrthoDB; 510149at2759; -.
DR PhylomeDB; Q8CFG6; -.
DR Reactome; R-RNO-112308; Presynaptic depolarization and calcium channel opening.
DR Reactome; R-RNO-422356; Regulation of insulin secretion.
DR Reactome; R-RNO-5576892; Phase 0 - rapid depolarisation.
DR Reactome; R-RNO-5576893; Phase 2 - plateau phase.
DR PRO; PR:Q8CFG6; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005891; C:voltage-gated calcium channel complex; ISO:RGD.
DR GO; GO:0005246; F:calcium channel regulator activity; TAS:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; IDA:RGD.
DR GO; GO:0006816; P:calcium ion transport; IDA:RGD.
DR GO; GO:0055001; P:muscle cell development; ISO:RGD.
DR GO; GO:0007528; P:neuromuscular junction development; ISO:RGD.
DR GO; GO:0046622; P:positive regulation of organ growth; ISO:RGD.
DR GO; GO:0008016; P:regulation of heart contraction; IMP:RGD.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0040014; P:regulation of multicellular organism growth; ISO:RGD.
DR GO; GO:0060024; P:rhythmic synaptic transmission; ISO:RGD.
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; PF00092; VWA; 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 Calcium; Calcium channel; Calcium transport; Disulfide bond; Glycoprotein;
KW Ion channel; Ion transport; Membrane; Metal-binding; Reference proteome;
KW Signal; Transmembrane; Transmembrane helix; Transport;
KW Voltage-gated channel.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..1157
FT /note="Voltage-dependent calcium channel subunit alpha-
FT 2/delta-2"
FT /id="PRO_0000304643"
FT CHAIN 19..1004
FT /note="Voltage-dependent calcium channel subunit alpha-2-2"
FT /evidence="ECO:0000255"
FT /id="PRO_0000304644"
FT CHAIN 1005..1157
FT /note="Voltage-dependent calcium channel subunit delta-2"
FT /evidence="ECO:0000255"
FT /id="PRO_0000304645"
FT TOPO_DOM 19..1119
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1120..1140
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1141..1157
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 294..472
FT /note="VWFA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00219"
FT DOMAIN 488..577
FT /note="Cache"
FT REGION 1..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 300..304
FT /note="MIDAS-like motif"
FT COMPBIAS 20..37
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 300
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT BINDING 302
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT BINDING 304
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT CARBOHYD 205
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 389
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 421
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 510
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 543
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 627
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 864
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 446..1104
FT /note="Interchain (between alpha-2-2 and delta-2 chains)"
FT /evidence="ECO:0000250"
SQ SEQUENCE 1157 AA; 130776 MW; 5E81446A1E1EBAF3 CRC64;
MAVPARTCGA SWPGPVRTAR PWPGRGPRPC PDPRGPASGP ARPLLLLLPP LLLLPLLTAP
GASAYSFPQQ HTMQHWARRL EQEIDGVMRI FGGVQQLREI YKDNRNLFDV QENEPQKLVE
KVAGDIESLL DRKVQALKRL ADAAENFQKA HRWQDNIKEE DIMYYDAKAD AELDDPESED
MERGSKTSAL RLDFIEEPNF KNKVNYSYTA VQIPTDIYKG STVILNELNW TEALENVFIE
NRRQDPTLLW QVFGSATGVT RYYPATPWRA PKKIDLYDVR RRPWYIQGAS SPKDMVIIVD
VSGSVSGLTL KLMKTSVCEM LDTLSDDDYV NVASFNEKAQ PVSCFTHLVQ ANVRNKKVFK
EAVQGMVAKG TTGYKAGFEY AFDQLQNSNI TRANCNKMIM MFTDGGEDRV QDVFEKYNWP
NRTVRVFTFS VGQHNYDVTP LQWMACTNKG YYFEIPSIGA IRINTQEYLD VLGRPMVLAG
KDAKQVQWTN VYEDALGLGL VVTGTLPVFN LTQDGPGDKK NQLILGVMGI DVALNDIKRL
TPNYTLGANG YVFAIDLNGY VLLHPNLKPQ ITNFREPVTL DFLDAELEDE NKEEIRRSMI
DGDKGHKQIR TLVKSLDERY IDEVIRNYTW VPIRSTNYSL GLVLPPYSTY YLQANLSDQI
LQVKLPISKL KDFEFLLPSS FESEGHVFIA PREYCKDLNA SDNNTEFLKN FIELMEKVTP
DSKQCNNFLL HNLILDTGIT QQLVERVWRD QDLNTYSLLA VFAATDGGIT RVFPNKAAED
WTENPEPFNA SFYRRSLDNR GYIFKPPHQD SLLRPLELEN DTVGVLVSTA VELSLGRRTL
RPAVVGVKLD LEAWAEKFKV LASNRTHQDQ PQKQCGPSSH CEMDCEVNNE DLLCVLIDDG
GFLVLSNQNH QWDQVGRFFS EVDANLMLAL YNNSFYTRKE SYDYQAACAP QPPGNLGAAP
RGVFVPTIAD FLNLAWWTSA AAWSLFQQLL YGLIYHSWFQ ADPAEAEGSP ETRESSCVMK
QTQYYFGSVN ASYNAIIDCG NCSRLFHAQR LTNTNLLFVV AEKPLCSQCE VGRLLQKETH
CPADGPEQCE LVQRPRYRTG PHICFDYNAT EDTSDCGRGA SFPPSLGVLV SLQLLLLLGL
PPRPQPQIHS FTPSRRL
