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Database: UniProt/SWISS-PROT
Entry: CAC1E_HUMAN
LinkDB: CAC1E_HUMAN
Original site: CAC1E_HUMAN 
ID   CAC1E_HUMAN             Reviewed;        2313 AA.
AC   Q15878; B1AM12; B1AM13; B1AM14; Q14580; Q14581;
DT   15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT   14-OCT-2008, sequence version 3.
DT   31-JUL-2019, entry version 183.
DE   RecName: Full=Voltage-dependent R-type calcium channel subunit alpha-1E;
DE   AltName: Full=Brain calcium channel II;
DE            Short=BII;
DE   AltName: Full=Calcium channel, L type, alpha-1 polypeptide, isoform 6;
DE   AltName: Full=Voltage-gated calcium channel subunit alpha Cav2.3;
GN   Name=CACNA1E; Synonyms=CACH6, CACNL1A6;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT THR-1955.
RC   TISSUE=Brain;
RX   PubMed=7536609;
RA   Schneider T., Wei X., Olcese R., Costantin J.L., Neely A., Palade P.,
RA   Perez-Reyes E., Qin N., Zhou J., Crawford G.D., Smith R.G.,
RA   Appel S.H., Stefani E., Birnbaumer M.;
RT   "Molecular analysis and functional expression of the human type E
RT   neuronal Ca2+ channel alpha 1 subunit.";
RL   Recept. Channels 2:255-270(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3).
RC   TISSUE=Hippocampus;
RX   PubMed=8071363;
RA   Williams M.E., Marubio L.M., Deal C.R., Hans M., Brust P.F.,
RA   Philipson L.H., Miller R.J., Johnson E.C., Harpold M.M., Ellis S.B.;
RT   "Structure and functional characterization of neuronal alpha 1E
RT   calcium channel subtypes.";
RL   J. Biol. Chem. 269:22347-22357(1994).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA   Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA   Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA   McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA   Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA   Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA   Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA   Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA   Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA   Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA   Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA   Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA   Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA   Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA   Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA   Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA   Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA   Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA   Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA   Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA   Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA   Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA   Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA   Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA   Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [4]
RP   INTERACTION WITH EFHC1.
RX   PubMed=15258581; DOI=10.1038/ng1393;
RA   Suzuki T., Delgado-Escueta A.V., Aguan K., Alonso M.E., Shi J.,
RA   Hara Y., Nishida M., Numata T., Medina M.T., Takeuchi T., Morita R.,
RA   Bai D., Ganesh S., Sugimoto Y., Inazawa J., Bailey J.N., Ochoa A.,
RA   Jara-Prado A., Rasmussen A., Ramos-Peek J., Cordova S.,
RA   Rubio-Donnadieu F., Inoue Y., Osawa M., Kaneko S., Oguni H., Mori Y.,
RA   Yamakawa K.;
RT   "Mutations in EFHC1 cause juvenile myoclonic epilepsy.";
RL   Nat. Genet. 36:842-849(2004).
RN   [5]
RP   FUNCTION, INVOLVEMENT IN EIEE69, VARIANTS EIEE69 PRO-228; ARG-348;
RP   ARG-352; LEU-603; ASP-690; SER-698; THR-700; VAL-701; PRO-702;
RP   THR-702; 829-ARG--CYS-2313 DEL; 1389-ARG--CYS-2313 DEL; PHE-1422;
RP   ASN-1425; ARG-1430 AND GLY-1720, AND CHARACTERIZATION OF VARIANTS
RP   EIEE69 LEU-603; SER-698; VAL-701 AND THR-702.
RX   PubMed=30343943; DOI=10.1016/j.ajhg.2018.09.006;
RG   Task Force for Neonatal Genomics;
RG   Deciphering Developmental Disorders Study;
RA   Helbig K.L., Lauerer R.J., Bahr J.C., Souza I.A., Myers C.T.,
RA   Uysal B., Schwarz N., Gandini M.A., Huang S., Keren B., Mignot C.,
RA   Afenjar A., Billette de Villemeur T., Heron D., Nava C., Valence S.,
RA   Buratti J., Fagerberg C.R., Soerensen K.P., Kibaek M., Kamsteeg E.J.,
RA   Koolen D.A., Gunning B., Schelhaas H.J., Kruer M.C., Fox J.,
RA   Bakhtiari S., Jarrar R., Padilla-Lopez S., Lindstrom K., Jin S.C.,
RA   Zeng X., Bilguvar K., Papavasileiou A., Xing Q., Zhu C., Boysen K.,
RA   Vairo F., Lanpher B.C., Klee E.W., Tillema J.M., Payne E.T.,
RA   Cousin M.A., Kruisselbrink T.M., Wick M.J., Baker J., Haan E.,
RA   Smith N., Sadeghpour A., Davis E.E., Katsanis N., Corbett M.A.,
RA   MacLennan A.H., Gecz J., Biskup S., Goldmann E., Rodan L.H.,
RA   Kichula E., Segal E., Jackson K.E., Asamoah A., Dimmock D.,
RA   McCarrier J., Botto L.D., Filloux F., Tvrdik T., Cascino G.D.,
RA   Klingerman S., Neumann C., Wang R., Jacobsen J.C., Nolan M.A.,
RA   Snell R.G., Lehnert K., Sadleir L.G., Anderlid B.M., Kvarnung M.,
RA   Guerrini R., Friez M.J., Lyons M.J., Leonhard J., Kringlen G.,
RA   Casas K., El Achkar C.M., Smith L.A., Rotenberg A., Poduri A.,
RA   Sanchis-Juan A., Carss K.J., Rankin J., Zeman A., Raymond F.L.,
RA   Blyth M., Kerr B., Ruiz K., Urquhart J., Hughes I., Banka S.,
RA   Hedrich U.B.S., Scheffer I.E., Helbig I., Zamponi G.W., Lerche H.,
RA   Mefford H.C.;
RT   "De novo pathogenic variants in CACNA1E cause developmental and
RT   epileptic encephalopathy with contractures, macrocephaly, and
RT   dyskinesias.";
RL   Am. J. Hum. Genet. 103:666-678(2018).
RN   [6]
RP   X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1867-1885.
RX   PubMed=18400181; DOI=10.1016/j.str.2008.01.011;
RA   Mori M.X., Vander Kooi C.W., Leahy D.J., Yue D.T.;
RT   "Crystal structure of the CaV2 IQ domain in complex with
RT   Ca2+/calmodulin: high-resolution mechanistic implications for channel
RT   regulation by Ca2+.";
RL   Structure 16:607-620(2008).
CC   -!- FUNCTION: Voltage-sensitive calcium channels (VSCC) mediate the
CC       entry of calcium ions into excitable cells (PubMed:30343943). They
CC       are also involved in a variety of calcium-dependent processes,
CC       including muscle contraction, hormone or neurotransmitter release,
CC       gene expression, cell motility, cell division and cell death. The
CC       isoform alpha-1E gives rise to R-type calcium currents. R-type
CC       calcium channels belong to the 'high-voltage activated' (HVA)
CC       group and are blocked by nickel. They are however insensitive to
CC       dihydropyridines (DHP). Calcium channels containing alpha-1E
CC       subunit could be involved in the modulation of firing patterns of
CC       neurons which is important for information processing.
CC       {ECO:0000269|PubMed:30343943}.
CC   -!- SUBUNIT: Interacts with EFHC1. Voltage-dependent calcium channels
CC       are multisubunit complexes, consisting of alpha-1, alpha-2, beta
CC       and delta subunits in a 1:1:1:1 ratio. The channel activity is
CC       directed by the pore-forming and voltage-sensitive alpha-1
CC       subunit. In many cases, this subunit is sufficient to generate
CC       voltage-sensitive calcium channel activity. The auxiliary subunits
CC       beta and alpha-2/delta linked by a disulfide bridge regulate the
CC       channel activity. {ECO:0000269|PubMed:15258581}.
CC   -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1; Synonyms=Alpha-1E;
CC         IsoId=Q15878-1; Sequence=Displayed;
CC       Name=2; Synonyms=Alpha-1E-1;
CC         IsoId=Q15878-2; Sequence=VSP_000937, VSP_024817;
CC       Name=3; Synonyms=Alpha-1E-3;
CC         IsoId=Q15878-3; Sequence=VSP_024817;
CC   -!- TISSUE SPECIFICITY: Expressed in neuronal tissues and in kidney.
CC   -!- DOMAIN: Each of the four internal repeats contains five
CC       hydrophobic transmembrane segments (S1, S2, S3, S5, S6) and one
CC       positively charged transmembrane segment (S4). S4 segments
CC       probably represent the voltage-sensor and are characterized by a
CC       series of positively charged amino acids at every third position.
CC   -!- DISEASE: Epileptic encephalopathy, early infantile, 69 (EIEE69)
CC       [MIM:618285]: A form of epileptic encephalopathy, a heterogeneous
CC       group of severe childhood onset epilepsies characterized by
CC       refractory seizures, neurodevelopmental impairment, and poor
CC       prognosis. Development is normal prior to seizure onset, after
CC       which cognitive and motor delays become apparent. EIEE69 is an
CC       autosomal dominant form characterized by early-onset refractory
CC       seizures, hypotonia, and profoundly impaired development often
CC       associated with macrocephaly, hyperkinetic movements, and
CC       contractures. The disorder can sometimes result in early death.
CC       Some patients may have a favorable seizure response to topiramate
CC       medication. {ECO:0000269|PubMed:30343943}. Note=The disease is
CC       caused by mutations affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the calcium channel alpha-1 subunit (TC
CC       1.A.1.11) family. CACNA1E subfamily. {ECO:0000305}.
DR   EMBL; L27745; AAA72125.1; -; mRNA.
DR   EMBL; L29384; AAA59204.1; -; mRNA.
DR   EMBL; L29385; AAA59205.1; -; mRNA.
DR   EMBL; AL161734; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL359270; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL160059; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL590998; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS53443.1; -. [Q15878-3]
DR   CCDS; CCDS55664.1; -. [Q15878-1]
DR   CCDS; CCDS55665.1; -. [Q15878-2]
DR   PIR; A54972; A54972.
DR   PIR; B54972; B54972.
DR   RefSeq; NP_000712.2; NM_000721.3. [Q15878-3]
DR   RefSeq; NP_001192222.1; NM_001205293.1. [Q15878-1]
DR   RefSeq; NP_001192223.1; NM_001205294.1. [Q15878-2]
DR   PDB; 3BXL; X-ray; 2.30 A; B=1867-1887.
DR   PDBsum; 3BXL; -.
DR   SMR; Q15878; -.
DR   BioGrid; 107231; 2.
DR   IntAct; Q15878; 1.
DR   STRING; 9606.ENSP00000356545; -.
DR   BindingDB; Q15878; -.
DR   ChEMBL; CHEMBL1687682; -.
DR   GuidetoPHARMACOLOGY; 534; -.
DR   iPTMnet; Q15878; -.
DR   PhosphoSitePlus; Q15878; -.
DR   BioMuta; CACNA1E; -.
DR   DMDM; 209572758; -.
DR   EPD; Q15878; -.
DR   jPOST; Q15878; -.
DR   MaxQB; Q15878; -.
DR   PaxDb; Q15878; -.
DR   PeptideAtlas; Q15878; -.
DR   PRIDE; Q15878; -.
DR   ProteomicsDB; 60800; -. [Q15878-1]
DR   ProteomicsDB; 60801; -. [Q15878-2]
DR   ProteomicsDB; 60802; -. [Q15878-3]
DR   Ensembl; ENST00000358338; ENSP00000351101; ENSG00000198216. [Q15878-2]
DR   Ensembl; ENST00000367567; ENSP00000356539; ENSG00000198216. [Q15878-3]
DR   Ensembl; ENST00000367570; ENSP00000356542; ENSG00000198216. [Q15878-3]
DR   Ensembl; ENST00000367573; ENSP00000356545; ENSG00000198216. [Q15878-1]
DR   Ensembl; ENST00000621551; ENSP00000483914; ENSG00000198216. [Q15878-1]
DR   Ensembl; ENST00000621791; ENSP00000481619; ENSG00000198216. [Q15878-2]
DR   GeneID; 777; -.
DR   KEGG; hsa:777; -.
DR   UCSC; uc001gow.5; human. [Q15878-1]
DR   CTD; 777; -.
DR   DisGeNET; 777; -.
DR   GeneCards; CACNA1E; -.
DR   HGNC; HGNC:1392; CACNA1E.
DR   HPA; CAB079032; -.
DR   HPA; HPA042515; -.
DR   MIM; 601013; gene.
DR   MIM; 618285; phenotype.
DR   neXtProt; NX_Q15878; -.
DR   OpenTargets; ENSG00000198216; -.
DR   PharmGKB; PA26009; -.
DR   eggNOG; ENOG410INF5; Eukaryota.
DR   eggNOG; ENOG410YD06; LUCA.
DR   GeneTree; ENSGT00940000155601; -.
DR   HOGENOM; HOG000231530; -.
DR   InParanoid; Q15878; -.
DR   KO; K04852; -.
DR   OMA; ISVRHMV; -.
DR   OrthoDB; 1566576at2759; -.
DR   PhylomeDB; Q15878; -.
DR   TreeFam; TF312805; -.
DR   Reactome; R-HSA-112308; Presynaptic depolarization and calcium channel opening.
DR   Reactome; R-HSA-422356; Regulation of insulin secretion.
DR   ChiTaRS; CACNA1E; human.
DR   EvolutionaryTrace; Q15878; -.
DR   GeneWiki; R-type_calcium_channel; -.
DR   GenomeRNAi; 777; -.
DR   PRO; PR:Q15878; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   Bgee; ENSG00000198216; Expressed in 70 organ(s), highest expression level in caudate nucleus.
DR   ExpressionAtlas; Q15878; baseline and differential.
DR   Genevisible; Q15878; HS.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0005891; C:voltage-gated calcium channel complex; TAS:ProtInc.
DR   GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR   GO; GO:0005245; F:voltage-gated calcium channel activity; IDA:MGI.
DR   GO; GO:0022843; F:voltage-gated cation channel activity; IDA:UniProtKB.
DR   GO; GO:0070509; P:calcium ion import; IBA:GO_Central.
DR   GO; GO:0006816; P:calcium ion transport; IBA:GO_Central.
DR   GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR   GO; GO:0051899; P:membrane depolarization; TAS:Reactome.
DR   GO; GO:0050796; P:regulation of insulin secretion; TAS:Reactome.
DR   GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR   Gene3D; 1.20.120.350; -; 4.
DR   InterPro; IPR002048; EF_hand_dom.
DR   InterPro; IPR031649; GPHH_dom.
DR   InterPro; IPR005821; Ion_trans_dom.
DR   InterPro; IPR014873; VDCC_a1su_IQ.
DR   InterPro; IPR005449; VDCC_R_a1su.
DR   InterPro; IPR002077; VDCCAlpha1.
DR   InterPro; IPR027359; Volt_channel_dom_sf.
DR   PANTHER; PTHR45628:SF5; PTHR45628:SF5; 1.
DR   Pfam; PF08763; Ca_chan_IQ; 1.
DR   Pfam; PF16905; GPHH; 1.
DR   Pfam; PF00520; Ion_trans; 4.
DR   PRINTS; PR00167; CACHANNEL.
DR   PRINTS; PR01633; RVDCCALPHA1.
DR   SMART; SM01062; Ca_chan_IQ; 1.
DR   PROSITE; PS50222; EF_HAND_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Calcium; Calcium channel;
KW   Calcium transport; Complete proteome; Disease mutation;
KW   Disulfide bond; Epilepsy; Glycoprotein; Ion channel; Ion transport;
KW   Membrane; Metal-binding; Phosphoprotein; Polymorphism;
KW   Reference proteome; Repeat; Transmembrane; Transmembrane helix;
KW   Transport; Voltage-gated channel.
FT   CHAIN         1   2313       Voltage-dependent R-type calcium channel
FT                                subunit alpha-1E.
FT                                /FTId=PRO_0000053938.
FT   TOPO_DOM      1     89       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM     90    108       Helical; Name=S1 of repeat I.
FT   TOPO_DOM    109    127       Extracellular. {ECO:0000255}.
FT   TRANSMEM    128    146       Helical; Name=S2 of repeat I.
FT   TOPO_DOM    147    158       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    159    173       Helical; Name=S3 of repeat I.
FT   TOPO_DOM    174    185       Extracellular. {ECO:0000255}.
FT   TRANSMEM    186    205       Helical; Name=S4 of repeat I.
FT   TOPO_DOM    206    223       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    224    244       Helical; Name=S5 of repeat I.
FT   TOPO_DOM    245    326       Extracellular. {ECO:0000255}.
FT   TRANSMEM    327    350       Helical; Name=S6 of repeat I.
FT   TOPO_DOM    351    476       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    477    496       Helical; Name=S1 of repeat II.
FT   TOPO_DOM    497    509       Extracellular. {ECO:0000255}.
FT   TRANSMEM    510    529       Helical; Name=S2 of repeat II.
FT   TOPO_DOM    530    538       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    539    557       Helical; Name=S3 of repeat II.
FT   TOPO_DOM    558    567       Extracellular. {ECO:0000255}.
FT   TRANSMEM    568    586       Helical; Name=S4 of repeat II.
FT   TOPO_DOM    587    605       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    606    625       Helical; Name=S5 of repeat II.
FT   TOPO_DOM    626    678       Extracellular. {ECO:0000255}.
FT   TRANSMEM    679    703       Helical; Name=S6 of repeat II.
FT   TOPO_DOM    704   1148       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM   1149   1165       Helical; Name=S1 of repeat III.
FT   TOPO_DOM   1166   1189       Extracellular. {ECO:0000255}.
FT   TRANSMEM   1190   1209       Helical; Name=S2 of repeat III.
FT   TOPO_DOM   1210   1217       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM   1218   1240       Helical; Name=S3 of repeat III.
FT   TOPO_DOM   1241   1254       Extracellular. {ECO:0000255}.
FT   TRANSMEM   1255   1272       Helical; Name=S4 of repeat III.
FT   TOPO_DOM   1273   1291       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM   1292   1311       Helical; Name=S5 of repeat III.
FT   TOPO_DOM   1312   1398       Extracellular. {ECO:0000255}.
FT   TRANSMEM   1399   1422       Helical; Name=S6 of repeat III.
FT   TOPO_DOM   1423   1479       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM   1480   1498       Helical; Name=S1 of repeat IV.
FT   TOPO_DOM   1499   1513       Extracellular. {ECO:0000255}.
FT   TRANSMEM   1514   1533       Helical; Name=S2 of repeat IV.
FT   TOPO_DOM   1534   1541       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM   1542   1560       Helical; Name=S3 of repeat IV.
FT   TOPO_DOM   1561   1571       Extracellular. {ECO:0000255}.
FT   TRANSMEM   1572   1590       Helical; Name=S4 of repeat IV.
FT   TOPO_DOM   1591   1609       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM   1610   1629       Helical; Name=S5 of repeat IV.
FT   TOPO_DOM   1630   1698       Extracellular. {ECO:0000255}.
FT   TRANSMEM   1699   1724       Helical; Name=S6 of repeat IV.
FT   TOPO_DOM   1725   2313       Cytoplasmic. {ECO:0000255}.
FT   REPEAT       76    354       I.
FT   REPEAT      462    706       II.
FT   REPEAT     1140   1426       III.
FT   REPEAT     1463   1726       IV.
FT   DOMAIN     1739   1774       EF-hand. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00448}.
FT   CA_BIND     426    437       {ECO:0000255|PROSITE-ProRule:PRU00448}.
FT   CA_BIND    1752   1763       {ECO:0000255|PROSITE-ProRule:PRU00448}.
FT   REGION      374    391       Binding to the beta subunit.
FT                                {ECO:0000250}.
FT   COMPBIAS    716    721       Poly-Glu.
FT   COMPBIAS    748    753       Poly-Arg.
FT   COMPBIAS    767    772       Poly-Arg.
FT   COMPBIAS   1228   1231       Poly-Val.
FT   COMPBIAS   2284   2288       Poly-Arg.
FT   SITE        309    309       Calcium ion selectivity and permeability.
FT                                {ECO:0000250}.
FT   SITE        657    657       Calcium ion selectivity and permeability.
FT                                {ECO:0000250}.
FT   SITE       1372   1372       Calcium ion selectivity and permeability.
FT                                {ECO:0000250}.
FT   SITE       1663   1663       Calcium ion selectivity and permeability.
FT                                {ECO:0000250}.
FT   MOD_RES      14     14       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q61290}.
FT   MOD_RES      19     19       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q61290}.
FT   MOD_RES     427    427       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q61290}.
FT   MOD_RES     440    440       Phosphothreonine.
FT                                {ECO:0000250|UniProtKB:Q61290}.
FT   MOD_RES     736    736       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q07652}.
FT   MOD_RES     745    745       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q61290}.
FT   MOD_RES     793    793       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q07652}.
FT   MOD_RES     815    815       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q61290}.
FT   MOD_RES     855    855       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q61290}.
FT   MOD_RES     947    947       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q07652}.
FT   MOD_RES    1097   1097       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q07652}.
FT   MOD_RES    1734   1734       Phosphoserine; by PKA. {ECO:0000255}.
FT   MOD_RES    2094   2094       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q61290}.
FT   MOD_RES    2113   2113       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q07652}.
FT   CARBOHYD    254    254       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   1566   1566       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   1571   1571       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   VAR_SEQ     748    766       Missing (in isoform 2).
FT                                {ECO:0000303|PubMed:8071363}.
FT                                /FTId=VSP_000937.
FT   VAR_SEQ    1967   2009       Missing (in isoform 2 and isoform 3).
FT                                {ECO:0000303|PubMed:8071363}.
FT                                /FTId=VSP_024817.
FT   VARIANT     228    228       L -> P (in EIEE69).
FT                                {ECO:0000269|PubMed:30343943}.
FT                                /FTId=VAR_081838.
FT   VARIANT     348    348       G -> R (in EIEE69).
FT                                {ECO:0000269|PubMed:30343943}.
FT                                /FTId=VAR_081839.
FT   VARIANT     352    352       G -> R (in EIEE69).
FT                                {ECO:0000269|PubMed:30343943}.
FT                                /FTId=VAR_081840.
FT   VARIANT     603    603       I -> L (in EIEE69; gain-of-function
FT                                variant affecting channel activity;
FT                                results in hyperpolarizing shift in half
FT                                activation voltage).
FT                                {ECO:0000269|PubMed:30343943}.
FT                                /FTId=VAR_081841.
FT   VARIANT     690    690       G -> D (in EIEE69).
FT                                {ECO:0000269|PubMed:30343943}.
FT                                /FTId=VAR_081842.
FT   VARIANT     698    698       F -> S (in EIEE69; gain-of-function
FT                                variant affecting channel activity;
FT                                shifts the voltage dependence of
FT                                activation toward more negative
FT                                potentials and slows the fast
FT                                inactivation time course).
FT                                {ECO:0000269|PubMed:30343943}.
FT                                /FTId=VAR_081843.
FT   VARIANT     700    700       A -> T (in EIEE69).
FT                                {ECO:0000269|PubMed:30343943}.
FT                                /FTId=VAR_081844.
FT   VARIANT     701    701       I -> V (in EIEE69; gain-of-function
FT                                variant affecting channel activity;
FT                                shifts the voltage dependence of
FT                                activation toward more negative
FT                                potentials and slows the fast
FT                                inactivation time course).
FT                                {ECO:0000269|PubMed:30343943}.
FT                                /FTId=VAR_081845.
FT   VARIANT     702    702       A -> P (in EIEE69).
FT                                {ECO:0000269|PubMed:30343943}.
FT                                /FTId=VAR_081846.
FT   VARIANT     702    702       A -> T (in EIEE69; gain-of-function
FT                                variant affecting channel activity;
FT                                shifts the voltage dependence of
FT                                activation toward more negative
FT                                potentials and slows the fast
FT                                inactivation time course).
FT                                {ECO:0000269|PubMed:30343943}.
FT                                /FTId=VAR_081847.
FT   VARIANT     829   2313       Missing (in EIEE69; unknown pathological
FT                                significance).
FT                                {ECO:0000269|PubMed:30343943}.
FT                                /FTId=VAR_081848.
FT   VARIANT     859    859       D -> E (in dbSNP:rs35737760).
FT                                /FTId=VAR_031912.
FT   VARIANT    1389   2313       Missing (in EIEE69; unknown pathological
FT                                significance).
FT                                {ECO:0000269|PubMed:30343943}.
FT                                /FTId=VAR_081849.
FT   VARIANT    1422   1422       I -> F (in EIEE69).
FT                                {ECO:0000269|PubMed:30343943}.
FT                                /FTId=VAR_081850.
FT   VARIANT    1425   1425       T -> N (in EIEE69).
FT                                {ECO:0000269|PubMed:30343943}.
FT                                /FTId=VAR_081851.
FT   VARIANT    1430   1430       G -> R (in EIEE69).
FT                                {ECO:0000269|PubMed:30343943}.
FT                                /FTId=VAR_081852.
FT   VARIANT    1720   1720       A -> G (in EIEE69).
FT                                {ECO:0000269|PubMed:30343943}.
FT                                /FTId=VAR_081853.
FT   VARIANT    1955   1955       A -> T (in dbSNP:rs704326).
FT                                {ECO:0000269|PubMed:7536609}.
FT                                /FTId=VAR_046996.
FT   CONFLICT    648    648       M -> I (in Ref. 1; AAA72125).
FT                                {ECO:0000305}.
FT   CONFLICT    836    838       LAL -> WP (in Ref. 1; AAA72125).
FT                                {ECO:0000305}.
FT   CONFLICT   2077   2077       R -> P (in Ref. 2; AAA59204/AAA59205).
FT                                {ECO:0000305}.
FT   CONFLICT   2084   2084       G -> R (in Ref. 2; AAA59204/AAA59205).
FT                                {ECO:0000305}.
FT   CONFLICT   2206   2206       C -> W (in Ref. 2; AAA59204/AAA59205).
FT                                {ECO:0000305}.
FT   CONFLICT   2219   2219       S -> R (in Ref. 2; AAA59204/AAA59205).
FT                                {ECO:0000305}.
FT   CONFLICT   2245   2245       G -> V (in Ref. 2; AAA59204/AAA59205).
FT                                {ECO:0000305}.
FT   HELIX      1868   1882       {ECO:0000244|PDB:3BXL}.
SQ   SEQUENCE   2313 AA;  261731 MW;  CCC7F309C27C42F1 CRC64;
     MARFGEAVVA RPGSGDGDSD QSRNRQGTPV PASGQAAAYK QTKAQRARTM ALYNPIPVRQ
     NCFTVNRSLF IFGEDNIVRK YAKKLIDWPP FEYMILATII ANCIVLALEQ HLPEDDKTPM
     SRRLEKTEPY FIGIFCFEAG IKIVALGFIF HKGSYLRNGW NVMDFIVVLS GILATAGTHF
     NTHVDLRTLR AVRVLRPLKL VSGIPSLQIV LKSIMKAMVP LLQIGLLLFF AILMFAIIGL
     EFYSGKLHRA CFMNNSGILE GFDPPHPCGV QGCPAGYECK DWIGPNDGIT QFDNILFAVL
     TVFQCITMEG WTTVLYNTND ALGATWNWLY FIPLIIIGSF FVLNLVLGVL SGEFAKERER
     VENRRAFMKL RRQQQIEREL NGYRAWIDKA EEVMLAEENK NAGTSALEVL RRATIKRSRT
     EAMTRDSSDE HCVDISSVGT PLARASIKSA KVDGVSYFRH KERLLRISIR HMVKSQVFYW
     IVLSLVALNT ACVAIVHHNQ PQWLTHLLYY AEFLFLGLFL LEMSLKMYGM GPRLYFHSSF
     NCFDFGVTVG SIFEVVWAIF RPGTSFGISV LRALRLLRIF KITKYWASLR NLVVSLMSSM
     KSIISLLFLL FLFIVVFALL GMQLFGGRFN FNDGTPSANF DTFPAAIMTV FQILTGEDWN
     EVMYNGIRSQ GGVSSGMWSA IYFIVLTLFG NYTLLNVFLA IAVDNLANAQ ELTKDEQEEE
     EAFNQKHALQ KAKEVSPMSA PNMPSIERDR RRRHHMSMWE PRSSHLRERR RRHHMSVWEQ
     RTSQLRKHMQ MSSQEALNRE EAPTMNPLNP LNPLSSLNPL NAHPSLYRRP RAIEGLALGL
     ALEKFEEERI SRGGSLKGDG GDRSSALDNQ RTPLSLGQRE PPWLARPCHG NCDPTQQEAG
     GGEAVVTFED RARHRQSQRR SRHRRVRTEG KESSSASRSR SASQERSLDE AMPTEGEKDH
     ELRGNHGAKE PTIQEERAQD LRRTNSLMVS RGSGLAGGLD EADTPLVLPH PELEVGKHVV
     LTEQEPEGSS EQALLGNVQL DMGRVISQSE PDLSCITANT DKATTESTSV TVAIPDVDPL
     VDSTVVHISN KTDGEASPLK EAEIREDEEE VEKKKQKKEK RETGKAMVPH SSMFIFSTTN
     PIRRACHYIV NLRYFEMCIL LVIAASSIAL AAEDPVLTNS ERNKVLRYFD YVFTGVFTFE
     MVIKMIDQGL ILQDGSYFRD LWNILDFVVV VGALVAFALA NALGTNKGRD IKTIKSLRVL
     RVLRPLKTIK RLPKLKAVFD CVVTSLKNVF NILIVYKLFM FIFAVIAVQL FKGKFFYCTD
     SSKDTEKECI GNYVDHEKNK MEVKGREWKR HEFHYDNIIW ALLTLFTVST GEGWPQVLQH
     SVDVTEEDRG PSRSNRMEMS IFYVVYFVVF PFFFVNIFVA LIIITFQEQG DKMMEECSLE
     KNERACIDFA ISAKPLTRYM PQNRHTFQYR VWHFVVSPSF EYTIMAMIAL NTVVLMMKYY
     SAPCTYELAL KYLNIAFTMV FSLECVLKVI AFGFLNYFRD TWNIFDFITV IGSITEIILT
     DSKLVNTSGF NMSFLKLFRA ARLIKLLRQG YTIRILLWTF VQSFKALPYV CLLIAMLFFI
     YAIIGMQVFG NIKLDEESHI NRHNNFRSFF GSLMLLFRSA TGEAWQEIML SCLGEKGCEP
     DTTAPSGQNE NERCGTDLAY VYFVSFIFFC SFLMLNLFVA VIMDNFEYLT RDSSILGPHH
     LDEFVRVWAE YDRAACGRIH YTEMYEMLTL MSPPLGLGKR CPSKVAYKRL VLMNMPVAED
     MTVHFTSTLM ALIRTALDIK IAKGGADRQQ LDSELQKETL AIWPHLSQKM LDLLVPMPKA
     SDLTVGKIYA AMMIMDYYKQ SKVKKQRQQL EEQKNAPMFQ RMEPSSLPQE IIANAKALPY
     LQQDPVSGLS GRSGYPSMSP LSPQDIFQLA CMDPADDGQF QERQSLEPEV SELKSVQPSN
     HGIYLPSDTQ EHAGSGRASS MPRLTVDPQV VTDPSSMRRS FSTIRDKRSN SSWLEEFSME
     RSSENTYKSR RRSYHSSLRL SAHRLNSDSG HKSDTHRSGG RERGRSKERK HLLSPDVSRC
     NSEERGTQAD WESPERRQSR SPSEGRSQTP NRQGTGSLSE SSIPSVSDTS TPRRSRRQLP
     PVPPKPRPLL SYSSLIRHAG SISPPADGSE EGSPLTSQAL ESNNACLTES SNSPHPQQSQ
     HASPQRYISE PYLALHEDSH ASDCGEEETL TFEAAVATSL GRSNTIGSAP PLRHSWQMPN
     GHYRRRRRGG PGPGMMCGAV NNLLSDTEED DKC
//
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