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   27-MAR-2024, entry version 112.
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   GlyCosmos; Q8CFG6; 7 sites, No reported glycans.
DR   GlyGen; Q8CFG6; 7 sites.
DR   PhosphoSitePlus; Q8CFG6; -.
DR   PaxDb; 10116-ENSRNOP00000021216; -.
DR   GeneID; 300992; -.
DR   KEGG; rno:300992; -.
DR   UCSC; RGD:631360; rat.
DR   AGR; RGD:631360; -.
DR   CTD; 9254; -.
DR   RGD; 631360; Cacna2d2.
DR   eggNOG; KOG2353; Eukaryota.
DR   InParanoid; Q8CFG6; -.
DR   OrthoDB; 2971287at2759; -.
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:0035265; P:organ growth; ISO:RGD.
DR   GO; GO:0046622; P:positive regulation of organ growth; ISO:RGD.
DR   GO; GO:0040014; P:regulation of multicellular organism growth; ISO:RGD.
DR   GO; GO:0060024; P:rhythmic synaptic transmission; ISO:RGD.
DR   CDD; cd01463; vWA_VGCC_like; 1.
DR   Gene3D; 3.30.450.20; PAS domain; 1.
DR   Gene3D; 3.40.50.410; von Willebrand factor, type A domain; 1.
DR   InterPro; IPR013680; VDCC_a2/dsu.
DR   InterPro; IPR013608; VWA_N.
DR   InterPro; IPR002035; VWF_A.
DR   InterPro; IPR036465; vWFA_dom_sf.
DR   PANTHER; PTHR10166; VOLTAGE-DEPENDENT CALCIUM CHANNEL SUBUNIT ALPHA-2/DELTA-RELATED; 1.
DR   PANTHER; PTHR10166:SF7; VOLTAGE-DEPENDENT CALCIUM CHANNEL SUBUNIT ALPHA-2_DELTA-2; 1.
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; vWA-like; 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
//