CAC1D_MESAU
ID CAC1D_MESAU Reviewed; 1610 AA.
AC Q99244; Q99245;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1999, sequence version 2.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=Voltage-dependent L-type calcium channel subunit alpha-1D;
DE AltName: Full=Calcium channel, L type, alpha-1 polypeptide isoform 2;
DE AltName: Full=Voltage-gated calcium channel subunit alpha Cav1.3;
GN Name=CACNA1D; Synonyms=CACH3, CACN4, CACNL1A2, CCHL1A2;
OS Mesocricetus auratus (Golden hamster).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Mesocricetus.
OX NCBI_TaxID=10036;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM HCA3A).
RC TISSUE=Insulinoma;
RX PubMed=1337146; DOI=10.1210/mend.6.12.1337146;
RA Yaney G.C., Wheeler M.B., Wei X., Perez-Reyes E., Birnbaumer L.,
RA Boyd A.E. III, Moss L.G.;
RT "Cloning of a novel alpha 1-subunit of the voltage-dependent calcium
RT channel from the beta-cell.";
RL Mol. Endocrinol. 6:2143-2152(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1146-1441 (ISOFORMS CACH3B AND CACH3D).
RC TISSUE=Heart;
RX PubMed=2173707; DOI=10.1016/s0021-9258(17)30522-7;
RA Perez-Reyes E., Wei X., Castellano A., Birnbaumer L.;
RT "Molecular diversity of L-type calcium channels. Evidence for alternative
RT splicing of the transcripts of three non-allelic genes.";
RL J. Biol. Chem. 265:20430-20436(1990).
CC -!- FUNCTION: Voltage-sensitive calcium channels (VSCC) mediate the entry
CC of calcium ions into excitable cells and are also involved in a variety
CC of calcium-dependent processes, including muscle contraction, hormone
CC or neurotransmitter release, gene expression, cell motility, cell
CC division and cell death. The isoform alpha-1D gives rise to L-type
CC calcium currents. Long-lasting (L-type) calcium channels belong to the
CC 'high-voltage activated' (HVA) group. They are blocked by
CC dihydropyridines (DHP), phenylalkylamines, and by benzothiazepines.
CC -!- SUBUNIT: Voltage-dependent calcium channels are multisubunit complexes,
CC consisting of alpha-1, alpha-2, beta and delta subunits in a 1:1:1:1
CC ratio. The channel activity is directed by the pore-forming and
CC voltage-sensitive alpha-1 subunit. In many cases, this subunit is
CC sufficient to generate voltage-sensitive calcium channel activity. The
CC auxiliary subunits beta and alpha-2/delta linked by a disulfide bridge
CC regulate the channel activity. Interacts with RIMBP2. Interacts with
CC CABP1 and CABP4, resulting in a near elimination of calcium-dependent
CC inactivation of the channel (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Additional isoforms seem to exist.;
CC Name=HCA3A;
CC IsoId=Q99244-1; Sequence=Displayed;
CC Name=CACH3B;
CC IsoId=Q99244-3; Sequence=Not described;
CC Name=CACH3D;
CC IsoId=Q99244-2; Sequence=VSP_000915;
CC -!- TISSUE SPECIFICITY: Expressed in brain, heart and skeletal muscle.
CC -!- DOMAIN: Each of the four internal repeats contains five hydrophobic
CC transmembrane segments (S1, S2, S3, S5, S6) and one positively charged
CC transmembrane segment (S4). S4 segments probably represent the voltage-
CC sensor and are characterized by a series of positively charged amino
CC acids at every third position.
CC -!- SIMILARITY: Belongs to the calcium channel alpha-1 subunit (TC
CC 1.A.1.11) family. CACNA1D subfamily. {ECO:0000305}.
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DR EMBL; M57969; AAB59702.1; -; mRNA.
DR EMBL; M57970; AAA62807.1; -; mRNA.
DR PIR; A46227; A46227.
DR AlphaFoldDB; Q99244; -.
DR SMR; Q99244; -.
DR STRING; 10036.XP_005077775.1; -.
DR eggNOG; KOG2301; Eukaryota.
DR Proteomes; UP000189706; Unplaced.
DR GO; GO:0005891; C:voltage-gated calcium channel complex; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; IEA:InterPro.
DR GO; GO:0045762; P:positive regulation of adenylate cyclase activity; ISS:UniProtKB.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR Gene3D; 1.20.120.350; -; 4.
DR InterPro; IPR031649; GPHH_dom.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR005452; LVDCC_a1dsu.
DR InterPro; IPR014873; VDCC_a1su_IQ.
DR InterPro; IPR005446; VDCC_L_a1su.
DR InterPro; IPR002077; VDCCAlpha1.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR Pfam; PF08763; Ca_chan_IQ; 1.
DR Pfam; PF16905; GPHH; 1.
DR Pfam; PF00520; Ion_trans; 4.
DR PRINTS; PR00167; CACHANNEL.
DR PRINTS; PR01630; LVDCCALPHA1.
DR PRINTS; PR01636; LVDCCALPHA1D.
PE 2: Evidence at transcript level;
KW Alternative splicing; Calcium; Calcium channel; Calcium transport;
KW Disulfide bond; Glycoprotein; Ion channel; Ion transport; Membrane;
KW Metal-binding; Phosphoprotein; Reference proteome; Repeat; Transmembrane;
KW Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..1610
FT /note="Voltage-dependent L-type calcium channel subunit
FT alpha-1D"
FT /id="PRO_0000053934"
FT TOPO_DOM 1..125
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 126..144
FT /note="Helical; Name=S1 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 145..162
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 163..182
FT /note="Helical; Name=S2 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 183..194
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 195..213
FT /note="Helical; Name=S3 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 214..234
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 235..253
FT /note="Helical; Name=S4 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 254..272
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 273..292
FT /note="Helical; Name=S5 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 293..380
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 381..405
FT /note="Helical; Name=S6 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 406..522
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 523..542
FT /note="Helical; Name=S1 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 543..557
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 558..576
FT /note="Helical; Name=S2 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 577..584
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 585..603
FT /note="Helical; Name=S3 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 604..613
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 614..632
FT /note="Helical; Name=S4 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 633..651
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 652..672
FT /note="Helical; Name=S5 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 673..726
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 727..751
FT /note="Helical; Name=S6 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 752..884
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 885..903
FT /note="Helical; Name=S1 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 904..919
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 920..939
FT /note="Helical; Name=S2 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 940..951
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 952..970
FT /note="Helical; Name=S3 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 971..976
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 977..996
FT /note="Helical; Name=S4 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 997..1015
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1016..1035
FT /note="Helical; Name=S5 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1036..1125
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1126..1146
FT /note="Helical; Name=S6 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1147..1203
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1204..1222
FT /note="Helical; Name=S1 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1223..1237
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1238..1257
FT /note="Helical; Name=S2 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1258..1264
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1265..1286
FT /note="Helical; Name=S3 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1287..1311
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1312..1331
FT /note="Helical; Name=S4 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1332..1350
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1351..1370
FT /note="Helical; Name=S5 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1371..1437
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1438..1462
FT /note="Helical; Name=S6 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1463..1610
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 112..408
FT /note="I"
FT REPEAT 508..754
FT /note="II"
FT REPEAT 871..1153
FT /note="III"
FT REPEAT 1190..1465
FT /note="IV"
FT REGION 1..99
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 428..445
FT /note="Binding to the beta subunit"
FT /evidence="ECO:0000250"
FT REGION 448..487
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 765..846
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1073..1163
FT /note="Dihydropyridine binding"
FT /evidence="ECO:0000250"
FT REGION 1418..1484
FT /note="Dihydropyridine binding"
FT /evidence="ECO:0000250"
FT REGION 1430..1473
FT /note="Phenylalkylamine binding"
FT /evidence="ECO:0000250"
FT COMPBIAS 34..54
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 63..99
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 461..487
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 765..787
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 788..802
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 803..821
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 822..836
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 363
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT BINDING 704
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT BINDING 1099
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT CARBOHYD 154
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 224
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 328
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1261..1303
FT /note="GYFSDAWNTFDSLIVIGSIIDVALSEADPTESESLPLPTATPG -> HYFTD
FT AWNTFDALIVVGSVVDIAITEVN (in isoform CACH3D)"
FT /evidence="ECO:0000303|PubMed:2173707"
FT /id="VSP_000915"
SQ SEQUENCE 1610 AA; 182328 MW; B3B2E3794D936F79 CRC64;
MMMMMMKKMQ HQRQQQEDHA NEANYARGTR PPISGEGPTS QPNSSKQTVL SWQAAIDAAR
QAKAAQTMST SAPPPVGSLS QRKRQQYAKS KKQGNSSNSR PARALFCLSL NNPIRRACIS
IVEWKPFDIF ILLAIFANCV ALAIYIPFPE DDSNSTNHNL EKVEYAFLII FTVETFLKII
AYGLLLHPNA YVRNGWNLLD FVIVIVGLFS VILEQLTKET EGGNHSSGKS GGFDVKALRA
FRVLRPLRLV SGVPSLQVVL NSIIKAMVPL LHIALLVLFV IIIYAIIGLE LFIGKMHKTC
FFADSDIVAE EDPAPCAFSG NGRQCAVNGT ECRSGWVGPN GGITNFDNFA FAMLTVFQCI
TMEGWTDVLY WMNDAMGFEL PWVYFVSLVI FGSFFVLNLV LGVLSGEFSK EREKAKARGD
FQKLRENEQL EEDLKGYLDW ITQAEDIDPE NEEEGGEEGK RNTSMPTSET ESVNTENVSG
EGETQGSCGS LCQAISKSKL SRRWRRWNRF NRRRCRAAVK SVTFYWLVIV LVFLNTLTIS
SEHYNQPDWL TQIQDIANKV LLALFTCEML VKMYSLGLQA YFVSLFNRFD CFVVCGGITE
TILVELELMS PLGVSVFRCV RLLRIFKVTR HWTSLSNLVA SLLNSMKSIA SLLLLLFLFI
IIFSLLGMQL FGGKFNFDET QTKRSTFDNF PQALLTVFQI LTGEDWNAVM YDGIMAYGGP
SSSGMIVCIY FIILFICGNY ILLNVFLAIA VDNLADAESL NTAQKEEAEE KERKKIARKE
SLENKKNNKP EVNQIANSDN KVTIDDYQEE TEDKDPYPPC DVPVGEEEEE EEEEPEVPAG
PRPRRISELN MKEKIVPIPE GSAFFILSKT NPIRVGCHKL INHHIFTNLI LVFIMLSSAA
LAAEDPIRSH SFRNTILGYF DYAFTAIFTV EILLKMTTFG AFLHKGAFCR NYFNLLDMLV
VGVSLVSFGI QSSAISVVKI LRVLRVLRPL RAINRAKGLK HVVQCVFVAI RTIGNIMIVT
TLLQFMFACI GVQLFKGKFY RCTDEAKSNP EECRGLFILY KDGDVDSPVV RERIWQNSDF
NFDNVLSAMM ALFTVSTFEG WPALLYKAID SNGENAGPVY NHRVEISIFF IIYIIIVAFF
MMNIFVGFVI VTFQEQGEKE YKNCELDKNQ RQCVEYALKA RPLRRYIPKN PYQYKFWYVV
NSSPFEYMMF VLIMLNTLCL AMQHYEQSKM FNDAMDILNM VFTGVFTVEM VLKVIAFKPK
GYFSDAWNTF DSLIVIGSII DVALSEADPT ESESLPLPTA TPGNSEESNR ISITFFRLFR
VMRLVKLLSR GEGIRTLLWT FIKSFQALPY VALLIAMLFF IYAVIGMQMF GKVAMRDNNQ
INRNNNFQTF PQAVLLLFRC ATGEAWQEIM LACLPGKLCD PDSDYNPGEE YTCGSNFAIV
YFISFYMLCA FLIINLFVAV IMDNFDYLTR DWSILGPHHL DEFKRIWSEY DPEAKGRIKH
LDVVTLLRRI QPPLGFGKLC PHRVACKRLV AMNMPLNSDG TVMFNATLFA LVRTALKIKT
EGNLEQANEE LRAVIKKIWK KTSMKLLDQV VPPAGGQCGL CFLSPSRSRS
