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Database: UniProt
Entry: CAC1A_HUMAN
LinkDB: CAC1A_HUMAN
Original site: CAC1A_HUMAN 
ID   CAC1A_HUMAN             Reviewed;        2505 AA.
AC   O00555; J3KP41; P78510; P78511; Q16290; Q92690; Q99790; Q99791;
AC   Q99792; Q99793; Q9NS88; Q9UDC4;
DT   15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT   15-JUL-1999, sequence version 2.
DT   27-SEP-2017, entry version 185.
DE   RecName: Full=Voltage-dependent P/Q-type calcium channel subunit alpha-1A;
DE   AltName: Full=Brain calcium channel I;
DE            Short=BI;
DE   AltName: Full=Calcium channel, L type, alpha-1 polypeptide isoform 4;
DE   AltName: Full=Voltage-gated calcium channel subunit alpha Cav2.1;
GN   Name=CACNA1A; Synonyms=CACH4, CACN3, CACNL1A4;
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] (ISOFORMS 1 AND 2), FUNCTION, AND
RP   SUBCELLULAR LOCATION.
RC   TISSUE=Neuron;
RX   PubMed=10049321; DOI=10.1016/S0006-3495(99)77300-5;
RA   Hans M., Urrutia A., Deal C., Brust P.F., Stauderman K., Ellis S.B.,
RA   Harpold M.M., Johnson E.C., Williams M.E.;
RT   "Structural elements in domain IV that influence biophysical and
RT   pharmacological properties of human alpha1A-containing high-voltage-
RT   activated calcium channels.";
RL   Biophys. J. 76:1384-1400(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 3), VARIANTS FHM1
RP   GLN-192; MET-666; ALA-714 AND LEU-1810, VARIANT THR-454, AND
RP   INVOLVEMENT IN EA2.
RC   TISSUE=Cerebellum;
RX   PubMed=8898206; DOI=10.1016/S0092-8674(00)81373-2;
RA   Ophoff R.A., Terwindt G.M., Vergouwe M.N., van Eijk R., Oefner P.J.,
RA   Hoffman S.M.G., Lamerdin J.E., Mohrenweiser H.W., Bulman D.E.,
RA   Ferrari M., Haan J., Lindhout D., van Ommen G.-J.B., Hofker M.H.,
RA   Ferrari M.D., Frants R.R.;
RT   "Familial hemiplegic migraine and episodic ataxia type-2 are caused by
RT   mutations in the Ca2+ channel gene CACNL1A4.";
RL   Cell 87:543-552(1996).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), NUCLEOTIDE SEQUENCE [MRNA] OF
RP   1313-2505 (ISOFORMS 1; 2; 3 AND 6), ALTERNATIVE SPLICING, AND
RP   INVOLVEMENT IN SCA6.
RC   TISSUE=Brain;
RX   PubMed=8988170; DOI=10.1038/ng0197-62;
RA   Zhuchenko O., Bailey J., Bonnen P.E., Ashizawa T., Stockton D.W.,
RA   Amos C., Dobyns W.B., Subramony S.H., Zoghbi H.Y., Lee C.C.;
RT   "Autosomal dominant cerebellar ataxia (SCA6) associated with small
RT   polyglutamine expansions in the alpha 1A-voltage-dependent calcium
RT   channel.";
RL   Nat. Genet. 15:62-69(1997).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 8), VARIANT SER-1105, AND
RP   FUNCTION.
RC   TISSUE=Cerebellum;
RX   PubMed=10753886; DOI=10.1074/jbc.275.15.10893;
RA   Toru S., Murakoshi T., Ishikawa K., Saegusa H., Fujigasaki H.,
RA   Uchihara T., Nagayama S., Osanai M., Mizusawa H., Tanabe T.;
RT   "Spinocerebellar ataxia type 6 mutation alters P-type calcium channel
RT   function.";
RL   J. Biol. Chem. 275:10893-10898(2000).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15057824; DOI=10.1038/nature02399;
RA   Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J.,
RA   Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA   Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA   Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA   Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA   Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA   Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA   Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA   Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA   Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA   Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA   Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA   Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA   Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA   Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA   Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA   Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA   Rubin E.M., Lucas S.M.;
RT   "The DNA sequence and biology of human chromosome 19.";
RL   Nature 428:529-535(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1693-1807.
RC   TISSUE=Lung carcinoma;
RX   PubMed=7823133;
RA   Barry E.L.R., Viglione M.P., Kim Y.I., Froehner S.C.;
RT   "Expression and antibody inhibition of P-type calcium channels in
RT   human small-cell lung carcinoma cells.";
RL   J. Neurosci. 15:274-283(1995).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1702-1822, AND TISSUE SPECIFICITY.
RC   TISSUE=Lung carcinoma;
RX   PubMed=1335101; DOI=10.1016/S0025-6196(12)61144-6;
RA   Oguro-Okano M., Griesmann G.E., Wieben E.D., Slaymaker S.J.,
RA   Snutch T.P., Lennon V.A.;
RT   "Molecular diversity of neuronal-type calcium channels identified in
RT   small cell lung carcinoma.";
RL   Mayo Clin. Proc. 67:1150-1159(1992).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 2038-2258 (ISOFORMS 1/2/3/4).
RC   TISSUE=Frontal cortex;
RX   PubMed=8525433; DOI=10.1007/BF02255782;
RA   Margolis R.L., Breschel T.S., Li S.H., Kidwai A.S., Antonarakis S.E.,
RA   McInnis M.G., Ross C.A.;
RT   "Characterization of cDNA clones containing CCA trinucleotide repeats
RT   derived from human brain.";
RL   Somat. Cell Mol. Genet. 21:279-284(1995).
RN   [9]
RP   INTERACTION WITH CABP1.
RX   PubMed=11865310; DOI=10.1038/nn805;
RA   Lee A., Westenbroek R.E., Haeseleer F., Palczewski K., Scheuer T.,
RA   Catterall W.A.;
RT   "Differential modulation of Ca(v)2.1 channels by calmodulin and Ca2+-
RT   binding protein 1.";
RL   Nat. Neurosci. 5:210-217(2002).
RN   [10]
RP   X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 1955-1975.
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).
RN   [11]
RP   VARIANT SCA6 ARG-293.
RX   PubMed=9345107; DOI=10.1086/301613;
RA   Yue Q., Jen J.C., Nelson S.F., Baloh R.W.;
RT   "Progressive ataxia due to a missense mutation in a calcium-channel
RT   gene.";
RL   Am. J. Hum. Genet. 61:1078-1087(1997).
RN   [12]
RP   POLYMORPHISM, AND INVOLVEMENT IN SCA6 AND EA2.
RX   PubMed=9302278; DOI=10.1093/hmg/6.11.1973;
RA   Jodice C., Mantuano E., Veneziano L., Trettel F., Sabbadini G.,
RA   Calandriello L., Francia A., Spadaro M., Pierelli F., Salvi F.,
RA   Ophoff R.A., Frants R.R., Frontali M.;
RT   "Episodic ataxia type 2 (EA2) and spinocerebellar ataxia type 6 (SCA6)
RT   due to CAG repeat expansion in the CACNA1A gene on chromosome 19p.";
RL   Hum. Mol. Genet. 6:1973-1978(1997).
RN   [13]
RP   VARIANT EA2 HIS-1661.
RX   PubMed=10987655; DOI=10.1007/s004390051099;
RA   Friend K.L., Crimmins D., Phan T.G., Sue C.M., Colley A., Fung V.S.,
RA   Morris J.G., Sutherland G.R., Richards R.I.;
RT   "Detection of a novel missense mutation and second recurrent mutation
RT   in the CACNA1A gene in individuals with EA-2 and FHM.";
RL   Hum. Genet. 105:261-265(1999).
RN   [14]
RP   VARIANT VAL-993, AND VARIANT FHM1 LEU-1456.
RX   PubMed=10408532; DOI=10.1212/WNL.53.1.26;
RA   Carrera P., Piatti M., Stenirri S., Grimaldi L.M., Marchioni E.,
RA   Curcio M., Righetti P.G., Ferrari M., Gelfi C.;
RT   "Genetic heterogeneity in Italian families with familial hemiplegic
RT   migraine.";
RL   Neurology 53:26-33(1999).
RN   [15]
RP   VARIANT FHM1 LEU-218.
RX   PubMed=11409427; DOI=10.1002/ana.1031;
RA   Kors E.E., Terwindt G.M., Vermeulen F.L., Fitzsimons R.B.,
RA   Jardine P.E., Heywood P., Love S., van den Maagdenberg A.M., Haan J.,
RA   Frants R.R., Ferrari M.D.;
RT   "Delayed cerebral edema and fatal coma after minor head trauma: role
RT   of the CACNA1A calcium channel subunit gene and relationship with
RT   familial hemiplegic migraine.";
RL   Ann. Neurol. 49:753-760(2001).
RN   [16]
RP   VARIANT EA2 LYS-1756.
RX   PubMed=11176968; DOI=10.1001/archneur.58.2.292;
RA   Denier C., Ducros A., Durr A., Eymard B., Chassande B.,
RA   Tournier-Lasserve E.;
RT   "Missense CACNA1A mutation causing episodic ataxia type 2.";
RL   Arch. Neurol. 58:292-295(2001).
RN   [17]
RP   VARIANTS FHM1 LYS-195; GLN-583; MET-666; GLU-715; GLU-1335; CYS-1384;
RP   TRP-1667; ARG-1683 AND ILE-1695.
RX   PubMed=11439943; DOI=10.1056/NEJM200107053450103;
RA   Ducros A., Denier C., Joutel A., Cecillon M., Lescoat C., Vahedi K.,
RA   Darcel F., Vicaut E., Bousser M.G., Tournier-Lasserve E.;
RT   "The clinical spectrum of familial hemiplegic migraine associated with
RT   mutations in a neuronal calcium channel.";
RL   N. Engl. J. Med. 345:17-24(2001).
RN   [18]
RP   VARIANT EA2 CYS-1403, CHARACTERIZATION OF VARIANT EA2 CYS-1403, AND
RP   FUNCTION.
RX   PubMed=11723274; DOI=10.1212/WNL.57.10.1843;
RA   Jen J., Wan J., Graves M., Yu H., Mock A.F., Coulin C.J., Kim G.,
RA   Yue Q., Papazian D.M., Baloh R.W.;
RT   "Loss-of-function EA2 mutations are associated with impaired
RT   neuromuscular transmission.";
RL   Neurology 57:1843-1848(2001).
RN   [19]
RP   VARIANT EA2 TYR-253.
RX   PubMed=12420090; DOI=10.1007/s00415-002-0860-8;
RA   van den Maagdenberg A.M., Kors E.E., Brunt E.R., van Paesschen W.,
RA   Pascual J., Ravine D., Keeling S., Vanmolkot K.R., Vermeulen F.L.,
RA   Terwindt G.M., Haan J., Frants R.R., Ferrari M.D.;
RT   "Episodic ataxia type 2. Three novel truncating mutations and one
RT   novel missense mutation in the CACNA1A gene.";
RL   J. Neurol. 249:1515-1519(2002).
RN   [20]
RP   VARIANT EA2 LEU-1736, CHARACTERIZATION OF VARIANT EA2 LEU-1736, AND
RP   FUNCTION.
RX   PubMed=15293273; DOI=10.1002/ana.20169;
RA   Spacey S.D., Hildebrand M.E., Materek L.A., Bird T.D., Snutch T.P.;
RT   "Functional implications of a novel EA2 mutation in the P/Q-type
RT   calcium channel.";
RL   Ann. Neurol. 56:213-220(2004).
RN   [21]
RP   VARIANT FHM1 GLN-1346.
RX   PubMed=15032980; DOI=10.1111/j..2004.00187.x;
RA   Alonso I., Barros J., Tuna A., Seixas A., Coutinho P., Sequeiros J.,
RA   Silveira I.;
RT   "A novel R1347Q mutation in the predicted voltage sensor segment of
RT   the P/Q-type calcium-channel alpha-subunit in a family with
RT   progressive cerebellar ataxia and hemiplegic migraine.";
RL   Clin. Genet. 65:70-72(2004).
RN   [22]
RP   VARIANTS EA2 ARG-256; ARG-1482; SER-1490; ILE-1493 AND CYS-2135.
RX   PubMed=15173248; DOI=10.1136/jmg.2003.015396;
RA   Mantuano E., Veneziano L., Spadaro M., Giunti P., Guida S.,
RA   Leggio M.G., Verriello L., Wood N., Jodice C., Frontali M.;
RT   "Clusters of non-truncating mutations of P/Q type Ca2+ channel subunit
RT   Ca(v)2.1 causing episodic ataxia 2.";
RL   J. Med. Genet. 41:E82-E82(2004).
RN   [23]
RP   VARIANTS EA2 TYR-287; ARG-293 AND MET-666.
RX   PubMed=14718690; DOI=10.1212/01.WNL.0000101675.61074.50;
RA   Jen J., Kim G.W., Baloh R.W.;
RT   "Clinical spectrum of episodic ataxia type 2.";
RL   Neurology 62:17-22(2004).
RN   [24]
RP   VARIANTS ASP-918; VAL-993 AND SER-1105.
RX   PubMed=16866717; DOI=10.1111/j.1526-4610.2006.00504.x;
RA   von Brevern M., Ta N., Shankar A., Wiste A., Siegel A., Radtke A.,
RA   Sander T., Escayg A.;
RT   "Migrainous vertigo: mutation analysis of the candidate genes CACNA1A,
RT   ATP1A2, SCN1A, and CACNB4.";
RL   Headache 46:1136-1141(2006).
RN   [25]
RP   VARIANT SCA6 GLN-1664.
RX   PubMed=16325861; DOI=10.1016/j.jns.2005.10.007;
RA   Tonelli A., D'Angelo M.G., Salati R., Villa L., Germinasi C.,
RA   Frattini T., Meola G., Turconi A.C., Bresolin N., Bassi M.T.;
RT   "Early onset, non fluctuating spinocerebellar ataxia and a novel
RT   missense mutation in CACNA1A gene.";
RL   J. Neurol. Sci. 241:13-17(2006).
RN   [26]
RP   VARIANT FHM1 GLN-1346.
RX   PubMed=18400034; DOI=10.1111/j.1399-0004.2008.00996.x;
RA   Stam A.H., Vanmolkot K.R., Kremer H.P., Gartner J., Brown J.,
RA   Leshinsky-Silver E., Gilad R., Kors E.E., Frankhuizen W.S.,
RA   Ginjaar H.B., Haan J., Frants R.R., Ferrari M.D.,
RA   van den Maagdenberg A.M., Terwindt G.M.;
RT   "CACNA1A R1347Q: a frequent recurrent mutation in hemiplegic
RT   migraine.";
RL   Clin. Genet. 74:481-485(2008).
RN   [27]
RP   VARIANT EA2 CYS-248.
RX   PubMed=18602318; DOI=10.1016/j.ejpn.2008.02.011;
RA   Zafeiriou D.I., Lehmann-Horn F., Vargiami E., Teflioudi E.,
RA   Ververi A., Jurkat-Rott K.;
RT   "Episodic ataxia type 2 showing ictal hyperhidrosis with hypothermia
RT   and interictal chronic diarrhea due to a novel CACNA1A mutation.";
RL   Eur. J. Paediatr. Neurol. 13:191-193(2009).
RN   [28]
RP   VARIANT EA2 ASP-638, CHARACTERIZATION OF VARIANT EA2 ASP-638, AND
RP   FUNCTION.
RX   PubMed=19232643; DOI=10.1016/j.jns.2009.01.005;
RA   Cuenca-Leon E., Banchs I., Serra S.A., Latorre P.,
RA   Fernandez-Castillo N., Corominas R., Valverde M.A., Volpini V.,
RA   Fernandez-Fernandez J.M., Macaya A., Cormand B.;
RT   "Late-onset episodic ataxia type 2 associated with a novel loss-of-
RT   function mutation in the CACNA1A gene.";
RL   J. Neurol. Sci. 280:10-14(2009).
RN   [29]
RP   VARIANTS ASP-918 AND VAL-993.
RX   PubMed=19429006; DOI=10.1016/j.neulet.2009.01.081;
RA   D'Onofrio M., Ambrosini A., Di Mambro A., Arisi I., Santorelli F.M.,
RA   Grieco G.S., Nicoletti F., Nappi G., Pierelli F., Schoenen J.,
RA   Buzzi M.G.;
RT   "The interplay of two single nucleotide polymorphisms in the CACNA1A
RT   gene may contribute to migraine susceptibility.";
RL   Neurosci. Lett. 453:12-15(2009).
RN   [30]
RP   VARIANT SCA6 THR-405.
RX   PubMed=20682717; DOI=10.1136/jnnp.2008.163402;
RA   Romaniello R., Zucca C., Tonelli A., Bonato S., Baschirotto C.,
RA   Zanotta N., Epifanio R., Righini A., Bresolin N., Bassi M.T.,
RA   Borgatti R.;
RT   "A wide spectrum of clinical, neurophysiological and neuroradiological
RT   abnormalities in a family with a novel CACNA1A mutation.";
RL   J. Neurol. Neurosurg. Psych. 81:840-843(2010).
RN   [31]
RP   VARIANTS EA2 PHE-389; MET-501; THR-798; ARG-897; CYS-1679 AND
RP   ARG-1869.
RX   PubMed=20129625; DOI=10.1016/j.jns.2010.01.010;
RA   Mantuano E., Romano S., Veneziano L., Gellera C., Castellotti B.,
RA   Caimi S., Testa D., Estienne M., Zorzi G., Bugiani M., Rajabally Y.A.,
RA   Barcina M.J., Servidei S., Panico A., Frontali M., Mariotti C.;
RT   "Identification of novel and recurrent CACNA1A gene mutations in
RT   fifteen patients with episodic ataxia type 2.";
RL   J. Neurol. Sci. 291:30-36(2010).
RN   [32]
RP   VARIANT EA2 LYS-388.
RX   PubMed=21696515; DOI=10.1111/j.1442-200X.2011.03390.x;
RA   Nikaido K., Tachi N., Ohya K., Wada T., Tsutsumi H.;
RT   "New mutation of CACNA1A gene in episodic ataxia type 2.";
RL   Pediatr. Int. 53:415-416(2011).
RN   [33]
RP   VARIANT FHM1 PHE-1502 DEL, CHARACTERIZATION OF VARIANT FHM1 PHE-1502
RP   DEL, AND FUNCTION.
RX   PubMed=24836863; DOI=10.1016/j.jns.2014.04.027;
RA   Garcia Segarra N., Gautschi I., Mittaz-Crettol L., Kallay Zetchi C.,
RA   Al-Qusairi L., Van Bemmelen M.X., Maeder P., Bonafe L., Schild L.,
RA   Roulet-Perez E.;
RT   "Congenital ataxia and hemiplegic migraine with cerebral edema
RT   associated with a novel gain of function mutation in the calcium
RT   channel CACNA1A.";
RL   J. Neurol. Sci. 342:69-78(2014).
RN   [34]
RP   VARIANT FHM1 PHE-1502 DEL, CHARACTERIZATION OF VARIANT FHM1 PHE-1502
RP   DEL, FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=26716990; DOI=10.1371/journal.pone.0146035;
RA   Bahamonde M.I., Serra S.A., Drechsel O., Rahman R., Marce-Grau A.,
RA   Prieto M., Ossowski S., Macaya A., Fernandez-Fernandez J.M.;
RT   "A single amino acid deletion (deltaf1502) in the s6 segment of cav2.1
RT   domain iii associated with congenital ataxia increases channel
RT   activity and promotes ca2+ influx.";
RL   PLoS ONE 10:E0146035-E0146035(2015).
RN   [35]
RP   INVOLVEMENT IN EIEE42, AND VARIANTS EIEE42 GLN-101; THR-713 AND
RP   SER-1508.
RX   PubMed=27476654; DOI=10.1016/j.ajhg.2016.06.003;
RG   Epi4K Consortium;
RT   "De novo mutations in SLC1A2 and CACNA1A are important causes of
RT   epileptic encephalopathies.";
RL   Am. J. Hum. Genet. 99:287-298(2016).
RN   [36]
RP   VARIANT EIEE42 ARG-1436.
RX   PubMed=27250579; DOI=10.1002/ajmg.a.37678;
RA   Reinson K., Oiglane-Shlik E., Talvik I., Vaher U., Ounapuu A.,
RA   Ennok M., Teek R., Pajusalu S., Murumets U., Tomberg T., Puusepp S.,
RA   Piirsoo A., Reimand T., Ounap K.;
RT   "Biallelic CACNA1A mutations cause early onset epileptic
RT   encephalopathy with progressive cerebral, cerebellar, and optic nerve
RT   atrophy.";
RL   Am. J. Med. Genet. A 170:2173-2176(2016).
CC   -!- FUNCTION: Voltage-sensitive calcium channels (VSCC) mediate the
CC       entry of calcium ions into excitable cells and are also involved
CC       in a variety of calcium-dependent processes, including muscle
CC       contraction, hormone or neurotransmitter release, gene expression,
CC       cell motility, cell division and cell death. The isoform alpha-1A
CC       gives rise to P and/or Q-type calcium currents. P/Q-type calcium
CC       channels belong to the 'high-voltage activated' (HVA) group and
CC       are blocked by the funnel toxin (Ftx) and by the omega-agatoxin-
CC       IVA (omega-Aga-IVA). They are however insensitive to
CC       dihydropyridines (DHP), and omega-conotoxin-GVIA (omega-CTx-GVIA).
CC       {ECO:0000269|PubMed:10049321, ECO:0000269|PubMed:10753886,
CC       ECO:0000269|PubMed:11723274, ECO:0000269|PubMed:15293273,
CC       ECO:0000269|PubMed:19232643, ECO:0000269|PubMed:24836863,
CC       ECO:0000269|PubMed:26716990}.
CC   -!- SUBUNIT: Voltage-dependent calcium channels are multisubunit
CC       complexes, consisting of alpha-1, alpha-2, beta and delta subunits
CC       in a 1:1:1:1 ratio. The channel activity is directed by the pore-
CC       forming and voltage-sensitive alpha-1 subunit. In many cases, this
CC       subunit is sufficient to generate voltage-sensitive calcium
CC       channel activity. The auxiliary subunits beta and alpha-2/delta
CC       linked by a disulfide bridge regulate the channel activity.
CC       Interact (via C-terminal CDB motif) with CABP1 in the pre- and
CC       postsynaptic membranes.
CC   -!- INTERACTION:
CC       Q8IZP0:ABI1; NbExp=2; IntAct=EBI-766279, EBI-375446;
CC       O94910:ADGRL1; NbExp=2; IntAct=EBI-766279, EBI-3389315;
CC       Q86SJ2:AMIGO2; NbExp=2; IntAct=EBI-766279, EBI-3866830;
CC       Q7Z5H3:ARHGAP22; NbExp=2; IntAct=EBI-766279, EBI-3866859;
CC       P67870:CSNK2B; NbExp=2; IntAct=EBI-766279, EBI-348169;
CC       O75953:DNAJB5; NbExp=2; IntAct=EBI-766279, EBI-5655937;
CC       P28799:GRN; NbExp=2; IntAct=EBI-766279, EBI-747754;
CC       P15822:HIVEP1; NbExp=2; IntAct=EBI-766279, EBI-722264;
CC       Q8N2S1:LTBP4; NbExp=2; IntAct=EBI-766279, EBI-947718;
CC       O00339:MATN2; NbExp=2; IntAct=EBI-766279, EBI-949020;
CC       O75095:MEGF6; NbExp=2; IntAct=EBI-766279, EBI-947597;
CC       Q7Z7M0:MEGF8; NbExp=2; IntAct=EBI-766279, EBI-947617;
CC       Q9UHX1:PUF60; NbExp=2; IntAct=EBI-766279, EBI-1053259;
CC       Q8IXT5:RBM12B; NbExp=2; IntAct=EBI-766279, EBI-3044077;
CC       O95153:TSPOAP1; NbExp=2; IntAct=EBI-766279, EBI-5915931;
CC       Q9BVA1:TUBB2B; NbExp=2; IntAct=EBI-766279, EBI-355665;
CC       P22695:UQCRC2; NbExp=2; IntAct=EBI-766279, EBI-1051424;
CC       P49750:YLPM1; NbExp=2; IntAct=EBI-766279, EBI-712871;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10049321,
CC       ECO:0000269|PubMed:26716990}; Multi-pass membrane protein
CC       {ECO:0000255}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=7;
CC         Comment=Additional isoforms seem to exist.;
CC       Name=1; Synonyms=1A-1, BI-1-GGCAG;
CC         IsoId=O00555-1; Sequence=Displayed;
CC       Name=2; Synonyms=1A-2,BI-1;
CC         IsoId=O00555-2; Sequence=VSP_000875;
CC       Name=3; Synonyms=BI-1(V1);
CC         IsoId=O00555-3; Sequence=VSP_000871, VSP_000875;
CC       Name=4; Synonyms=BI-1(V1)-GGCAG;
CC         IsoId=O00555-4; Sequence=VSP_000871;
CC       Name=5; Synonyms=BI-1(V2);
CC         IsoId=O00555-5; Sequence=VSP_000872, VSP_000875;
CC       Name=6; Synonyms=BI-1(V2)-GGCAG;
CC         IsoId=O00555-6; Sequence=VSP_000872;
CC       Name=8;
CC         IsoId=O00555-8; Sequence=VSP_046165, VSP_046166;
CC   -!- TISSUE SPECIFICITY: Brain specific; mainly found in cerebellum,
CC       cerebral cortex, thalamus and hypothalamus. Expressed in the small
CC       cell lung carcinoma cell line SCC-9. No expression in heart,
CC       kidney, liver or muscle. Purkinje cells contain predominantly P-
CC       type VSCC, the Q-type being a prominent calcium current in
CC       cerebellar granule cells. {ECO:0000269|PubMed:1335101}.
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   -!- POLYMORPHISM: The poly-Gln region of CACNA1A is polymorphic: 6 to
CC       17 repeats in the normal population, expanded to about 21 to 30
CC       repeats in SCA6. Repeat expansion has been reported also in a EA2
CC       family. {ECO:0000269|PubMed:9302278}.
CC   -!- DISEASE: Spinocerebellar ataxia 6 (SCA6) [MIM:183086]:
CC       Spinocerebellar ataxia is a clinically and genetically
CC       heterogeneous group of cerebellar disorders. Patients show
CC       progressive incoordination of gait and often poor coordination of
CC       hands, speech and eye movements, due to degeneration of the
CC       cerebellum with variable involvement of the brainstem and spinal
CC       cord. SCA6 is an autosomal dominant cerebellar ataxia (ADCA),
CC       mainly caused by expansion of a CAG repeat in the coding region of
CC       CACNA1A. There seems to be a correlation between the repeat number
CC       and earlier onset of the disorder. {ECO:0000269|PubMed:16325861,
CC       ECO:0000269|PubMed:20682717, ECO:0000269|PubMed:8988170,
CC       ECO:0000269|PubMed:9302278, ECO:0000269|PubMed:9345107}. Note=The
CC       disease is caused by mutations affecting the gene represented in
CC       this entry.
CC   -!- DISEASE: Migraine, familial hemiplegic, 1 (FHM1) [MIM:141500]: A
CC       subtype of migraine with aura associated with ictal hemiparesis
CC       and, in some families, cerebellar ataxia and atrophy. Migraine is
CC       a disabling symptom complex of periodic headaches, usually
CC       temporal and unilateral. Headaches are often accompanied by
CC       irritability, nausea, vomiting and photophobia, preceded by
CC       constriction of the cranial arteries. Migraine with aura is
CC       characterized by recurrent attacks of reversible neurological
CC       symptoms (aura) that precede or accompany the headache. Aura may
CC       include a combination of sensory disturbances, such as blurred
CC       vision, hallucinations, vertigo, numbness and difficulty in
CC       concentrating and speaking. {ECO:0000269|PubMed:10408532,
CC       ECO:0000269|PubMed:11409427, ECO:0000269|PubMed:11439943,
CC       ECO:0000269|PubMed:15032980, ECO:0000269|PubMed:18400034,
CC       ECO:0000269|PubMed:24836863, ECO:0000269|PubMed:26716990,
CC       ECO:0000269|PubMed:8898206}. Note=The disease is caused by
CC       mutations affecting the gene represented in this entry.
CC   -!- DISEASE: Episodic ataxia 2 (EA2) [MIM:108500]: An autosomal
CC       dominant disorder characterized by acetozolamide-responsive
CC       attacks of ataxia, migraine-like symptoms, interictal nystagmus,
CC       and cerebellar atrophy. {ECO:0000269|PubMed:10987655,
CC       ECO:0000269|PubMed:11176968, ECO:0000269|PubMed:11723274,
CC       ECO:0000269|PubMed:12420090, ECO:0000269|PubMed:14718690,
CC       ECO:0000269|PubMed:15173248, ECO:0000269|PubMed:15293273,
CC       ECO:0000269|PubMed:18602318, ECO:0000269|PubMed:19232643,
CC       ECO:0000269|PubMed:20129625, ECO:0000269|PubMed:21696515,
CC       ECO:0000269|PubMed:8898206, ECO:0000269|PubMed:9302278}. Note=The
CC       disease is caused by mutations affecting the gene represented in
CC       this entry.
CC   -!- DISEASE: Epileptic encephalopathy, early infantile, 42 (EIEE42)
CC       [MIM:617106]: 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. EIEE42
CC       inheritance is autosomal dominant. {ECO:0000269|PubMed:27250579,
CC       ECO:0000269|PubMed:27476654}. Note=The disease is caused by
CC       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. CACNA1A subfamily. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAB49678.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};
CC   -!- WEB RESOURCE: Name=Calcium channel, voltage-dependent, P/Q type,
CC       alpha 1A subunit (CACNA1A); Note=Leiden Open Variation Database
CC       (LOVD);
CC       URL="http://chromium.lovd.nl/LOVD2/home.php?select_db=CACNA1A";
CC   -!- WEB RESOURCE: Name=Familial hemiplegic migraine (FHM) variation
CC       database, calcium channel, voltage-dependent, P/Q type, alpha 1A
CC       subunit (CACNA1A); Note=Leiden Open Variation Database (LOVD);
CC       URL="http://grenada.lumc.nl/LOVD2/FHM/home.php?select_db=CACNA1A";
CC   -!- WEB RESOURCE: Name=Undiagnosed Disease Network; Note=CACNA1A;
CC       URL="https://undiagnosed.hms.harvard.edu/updates/genes-of-interest/cacna1a-gene/";
DR   EMBL; AF004883; AAB61612.1; -; mRNA.
DR   EMBL; AF004884; AAB61613.1; -; mRNA.
DR   EMBL; X99897; CAA68172.1; -; mRNA.
DR   EMBL; Z80114; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; Z80115; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; U79663; AAB49674.1; -; mRNA.
DR   EMBL; U79664; AAB49675.1; -; mRNA.
DR   EMBL; U79665; AAB49676.1; -; mRNA.
DR   EMBL; U79666; AAB64179.1; -; mRNA.
DR   EMBL; U79667; AAB49677.1; -; mRNA.
DR   EMBL; U79668; AAB49678.1; ALT_SEQ; mRNA.
DR   EMBL; AB035727; BAA94766.2; -; mRNA.
DR   EMBL; AC005305; AAC26839.1; -; Genomic_DNA.
DR   EMBL; AC005513; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC008540; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC011446; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC022436; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC026805; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC093062; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC098781; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC124224; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; S76537; AAB33068.1; -; mRNA.
DR   EMBL; U06702; -; NOT_ANNOTATED_CDS; mRNA.
DR   CCDS; CCDS45998.1; -. [O00555-8]
DR   CCDS; CCDS45999.1; -. [O00555-3]
DR   RefSeq; NP_000059.3; NM_000068.3.
DR   RefSeq; NP_001120693.1; NM_001127221.1. [O00555-3]
DR   RefSeq; NP_001120694.1; NM_001127222.1. [O00555-8]
DR   RefSeq; NP_001167551.1; NM_001174080.1.
DR   RefSeq; NP_075461.2; NM_023035.2.
DR   UniGene; Hs.501632; -.
DR   PDB; 3BXK; X-ray; 2.55 A; B/D=1955-1975.
DR   PDBsum; 3BXK; -.
DR   ProteinModelPortal; O00555; -.
DR   SMR; O00555; -.
DR   BioGrid; 107227; 100.
DR   CORUM; O00555; -.
DR   IntAct; O00555; 92.
DR   STRING; 9606.ENSP00000353362; -.
DR   BindingDB; O00555; -.
DR   ChEMBL; CHEMBL4266; -.
DR   DrugBank; DB01244; Bepridil.
DR   DrugBank; DB00836; Loperamide.
DR   DrugBank; DB00230; Pregabalin.
DR   DrugBank; DB00421; Spironolactone.
DR   DrugBank; DB00661; Verapamil.
DR   TCDB; 1.A.1.11.27; the voltage-gated ion channel (vic) superfamily.
DR   iPTMnet; O00555; -.
DR   PhosphoSitePlus; O00555; -.
DR   BioMuta; CACNA1A; -.
DR   MaxQB; O00555; -.
DR   PaxDb; O00555; -.
DR   PeptideAtlas; O00555; -.
DR   PRIDE; O00555; -.
DR   DNASU; 773; -.
DR   Ensembl; ENST00000360228; ENSP00000353362; ENSG00000141837. [O00555-8]
DR   Ensembl; ENST00000635895; ENSP00000490323; ENSG00000141837. [O00555-2]
DR   Ensembl; ENST00000637276; ENSP00000489777; ENSG00000141837. [O00555-5]
DR   Ensembl; ENST00000638009; ENSP00000489913; ENSG00000141837. [O00555-3]
DR   GeneID; 773; -.
DR   KEGG; hsa:773; -.
DR   UCSC; uc002mwy.5; human. [O00555-1]
DR   CTD; 773; -.
DR   DisGeNET; 773; -.
DR   EuPathDB; HostDB:ENSG00000141837.18; -.
DR   GeneCards; CACNA1A; -.
DR   GeneReviews; CACNA1A; -.
DR   HGNC; HGNC:1388; CACNA1A.
DR   HPA; HPA064258; -.
DR   MalaCards; CACNA1A; -.
DR   MIM; 108500; phenotype.
DR   MIM; 141500; phenotype.
DR   MIM; 183086; phenotype.
DR   MIM; 601011; gene.
DR   MIM; 617106; phenotype.
DR   neXtProt; NX_O00555; -.
DR   OpenTargets; ENSG00000141837; -.
DR   Orphanet; 2131; Alternating hemiplegia of childhood.
DR   Orphanet; 71518; Benign paroxysmal torticollis of infancy.
DR   Orphanet; 569; Familial or sporadic hemiplegic migraine.
DR   Orphanet; 97; Familial paroxysmal ataxia.
DR   Orphanet; 98758; Spinocerebellar ataxia type 6.
DR   PharmGKB; PA26007; -.
DR   eggNOG; KOG2301; Eukaryota.
DR   eggNOG; ENOG410XNP6; LUCA.
DR   GeneTree; ENSGT00830000128247; -.
DR   HOGENOM; HOG000231530; -.
DR   HOVERGEN; HBG050763; -.
DR   InParanoid; O00555; -.
DR   KO; K04344; -.
DR   PhylomeDB; O00555; -.
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; CACNA1A; human.
DR   EvolutionaryTrace; O00555; -.
DR   GeneWiki; Cav2.1; -.
DR   GenomeRNAi; 773; -.
DR   PRO; PR:O00555; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   Bgee; ENSG00000141837; -.
DR   ExpressionAtlas; O00555; baseline and differential.
DR   Genevisible; O00555; HS.
DR   GO; GO:0042995; C:cell projection; IDA:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0016021; C:integral component of membrane; TAS:UniProtKB.
DR   GO; GO:0043025; C:neuronal cell body; ISS:ARUK-UCL.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0005891; C:voltage-gated calcium channel complex; IEA:InterPro.
DR   GO; GO:0005262; F:calcium channel activity; TAS:Reactome.
DR   GO; GO:0008331; F:high voltage-gated calcium channel activity; IDA:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0019905; F:syntaxin binding; IDA:UniProtKB.
DR   GO; GO:0005245; F:voltage-gated calcium channel activity; IDA:UniProtKB.
DR   GO; GO:0070588; P:calcium ion transmembrane transport; IDA:UniProtKB.
DR   GO; GO:0008219; P:cell death; IDA:UniProtKB.
DR   GO; GO:0051899; P:membrane depolarization; TAS:Reactome.
DR   GO; GO:0086010; P:membrane depolarization during action potential; IBA:GO_Central.
DR   GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IDA:UniProtKB.
DR   GO; GO:0050796; P:regulation of insulin secretion; TAS:Reactome.
DR   InterPro; IPR005448; CACNA1A.
DR   InterPro; IPR031649; GPHH_dom.
DR   InterPro; IPR005821; Ion_trans_dom.
DR   InterPro; IPR014873; VDCC_a1su_IQ.
DR   InterPro; IPR002077; VDCCAlpha1.
DR   PANTHER; PTHR10037:SF249; PTHR10037:SF249; 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; PR01632; PQVDCCALPHA1.
DR   SMART; SM01062; Ca_chan_IQ; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Calcium; Calcium channel;
KW   Calcium transport; Cell membrane; Complete proteome; Disease mutation;
KW   Disulfide bond; Epilepsy; Glycoprotein; Ion channel; Ion transport;
KW   Membrane; Metal-binding; Neurodegeneration; Phosphoprotein;
KW   Polymorphism; Reference proteome; Repeat; Spinocerebellar ataxia;
KW   Transmembrane; Transmembrane helix; Transport;
KW   Triplet repeat expansion; Voltage-gated channel.
FT   CHAIN         1   2505       Voltage-dependent P/Q-type calcium
FT                                channel subunit alpha-1A.
FT                                /FTId=PRO_0000053916.
FT   TOPO_DOM      1     98       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM     99    117       Helical; Name=S1 of repeat I.
FT                                {ECO:0000255}.
FT   TOPO_DOM    118    135       Extracellular. {ECO:0000255}.
FT   TRANSMEM    136    155       Helical; Name=S2 of repeat I.
FT                                {ECO:0000255}.
FT   TOPO_DOM    156    167       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    168    185       Helical; Name=S3 of repeat I.
FT                                {ECO:0000255}.
FT   TOPO_DOM    186    190       Extracellular. {ECO:0000255}.
FT   TRANSMEM    191    209       Helical; Name=S4 of repeat I.
FT                                {ECO:0000255}.
FT   TOPO_DOM    210    228       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    229    248       Helical; Name=S5 of repeat I.
FT                                {ECO:0000255}.
FT   TOPO_DOM    249    335       Extracellular. {ECO:0000255}.
FT   TRANSMEM    336    360       Helical; Name=S6 of repeat I.
FT                                {ECO:0000255}.
FT   TOPO_DOM    361    487       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    488    506       Helical; Name=S1 of repeat II.
FT                                {ECO:0000255}.
FT   TOPO_DOM    507    521       Extracellular. {ECO:0000255}.
FT   TRANSMEM    522    541       Helical; Name=S2 of repeat II.
FT                                {ECO:0000255}.
FT   TOPO_DOM    542    549       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    550    568       Helical; Name=S3 of repeat II.
FT                                {ECO:0000255}.
FT   TOPO_DOM    569    578       Extracellular. {ECO:0000255}.
FT   TRANSMEM    579    597       Helical; Name=S4 of repeat II.
FT                                {ECO:0000255}.
FT   TOPO_DOM    598    616       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    617    636       Helical; Name=S5 of repeat II.
FT                                {ECO:0000255}.
FT   TOPO_DOM    637    689       Extracellular. {ECO:0000255}.
FT   TRANSMEM    690    714       Helical; Name=S6 of repeat II.
FT                                {ECO:0000255}.
FT   TOPO_DOM    715   1242       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM   1243   1261       Helical; Name=S1 of repeat III.
FT                                {ECO:0000255}.
FT   TOPO_DOM   1262   1277       Extracellular. {ECO:0000255}.
FT   TRANSMEM   1278   1297       Helical; Name=S2 of repeat III.
FT                                {ECO:0000255}.
FT   TOPO_DOM   1298   1309       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM   1310   1328       Helical; Name=S3 of repeat III.
FT                                {ECO:0000255}.
FT   TOPO_DOM   1329   1339       Extracellular. {ECO:0000255}.
FT   TRANSMEM   1340   1358       Helical; Name=S4 of repeat III.
FT                                {ECO:0000255}.
FT   TOPO_DOM   1359   1377       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM   1378   1397       Helical; Name=S5 of repeat III.
FT                                {ECO:0000255}.
FT   TOPO_DOM   1398   1484       Extracellular. {ECO:0000255}.
FT   TRANSMEM   1485   1509       Helical; Name=S6 of repeat III.
FT                                {ECO:0000255}.
FT   TOPO_DOM   1510   1564       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM   1565   1593       Helical; Name=S1 of repeat IV.
FT                                {ECO:0000255}.
FT   TOPO_DOM   1594   1598       Extracellular. {ECO:0000255}.
FT   TRANSMEM   1599   1618       Helical; Name=S2 of repeat IV.
FT                                {ECO:0000255}.
FT   TOPO_DOM   1619   1626       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM   1627   1645       Helical; Name=S3 of repeat IV.
FT                                {ECO:0000255}.
FT   TOPO_DOM   1646   1652       Extracellular. {ECO:0000255}.
FT   TRANSMEM   1653   1671       Helical; Name=S4 of repeat IV.
FT                                {ECO:0000255}.
FT   TOPO_DOM   1672   1690       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM   1691   1710       Helical; Name=S5 of repeat IV.
FT                                {ECO:0000255}.
FT   TOPO_DOM   1711   1782       Extracellular. {ECO:0000255}.
FT   TRANSMEM   1783   1807       Helical; Name=S6 of repeat IV.
FT                                {ECO:0000255}.
FT   TOPO_DOM   1808   2505       Cytoplasmic. {ECO:0000255}.
FT   REPEAT       85    363       I.
FT   REPEAT      473    717       II.
FT   REPEAT     1231   1514       III.
FT   REPEAT     1551   1814       IV.
FT   CA_BIND    1840   1851       {ECO:0000250}.
FT   REGION      383    400       Binding to the beta subunit.
FT                                {ECO:0000250}.
FT   COMPBIAS     13     18       Poly-Gly.
FT   COMPBIAS    727    732       Poly-Glu.
FT   COMPBIAS   1002   1007       Poly-Arg.
FT   COMPBIAS   1204   1207       Poly-Glu.
FT   COMPBIAS   2211   2220       Poly-His.
FT   COMPBIAS   2221   2224       Poly-Pro.
FT   COMPBIAS   2314   2324       Poly-Gln.
FT   SITE        318    318       Calcium ion selectivity and permeability.
FT                                {ECO:0000250}.
FT   SITE        668    668       Calcium ion selectivity and permeability.
FT                                {ECO:0000250}.
FT   SITE       1460   1460       Calcium ion selectivity and permeability.
FT                                {ECO:0000250}.
FT   SITE       1649   1649       Binds to omega-Aga-IVA. {ECO:0000250}.
FT   SITE       1756   1756       Calcium ion selectivity and permeability.
FT                                {ECO:0000250}.
FT   MOD_RES     409    409       Phosphothreonine.
FT                                {ECO:0000250|UniProtKB:P97445}.
FT   MOD_RES     448    448       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P97445}.
FT   MOD_RES     451    451       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P97445}.
FT   MOD_RES     750    750       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P97445}.
FT   MOD_RES     753    753       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P97445}.
FT   MOD_RES     790    790       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P97445}.
FT   MOD_RES    1085   1085       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P97445}.
FT   MOD_RES    1094   1094       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P97445}.
FT   MOD_RES    1822   1822       Phosphoserine; by PKA. {ECO:0000255}.
FT   MOD_RES    1984   1984       Phosphothreonine.
FT                                {ECO:0000250|UniProtKB:P97445}.
FT   MOD_RES    2047   2047       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P54282}.
FT   MOD_RES    2065   2065       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P97445}.
FT   MOD_RES    2077   2077       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P54282}.
FT   MOD_RES    2079   2079       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P54282}.
FT   MOD_RES    2120   2120       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P97445}.
FT   MOD_RES    2140   2140       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P54282}.
FT   CARBOHYD    283    283       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   VAR_SEQ     419    419       Missing (in isoform 8).
FT                                {ECO:0000303|PubMed:10753886}.
FT                                /FTId=VSP_046165.
FT   VAR_SEQ    1844   1875       WGRMPYLDMYQMLRHMSPPLGLGKKCPARVAY -> CGRIH
FT                                YKDMYSLLRVISPPLGLGKKCPHRVAC (in isoform 3
FT                                and isoform 4).
FT                                {ECO:0000303|PubMed:8898206,
FT                                ECO:0000303|PubMed:8988170}.
FT                                /FTId=VSP_000871.
FT   VAR_SEQ    2103   2114       Missing (in isoform 5 and isoform 6).
FT                                {ECO:0000303|PubMed:8988170}.
FT                                /FTId=VSP_000872.
FT   VAR_SEQ    2262   2505       Missing (in isoform 2, isoform 3 and
FT                                isoform 5). {ECO:0000303|PubMed:10049321,
FT                                ECO:0000303|PubMed:8898206,
FT                                ECO:0000303|PubMed:8988170}.
FT                                /FTId=VSP_000875.
FT   VAR_SEQ    2314   2314       Q -> QQQ (in isoform 8).
FT                                {ECO:0000303|PubMed:10753886}.
FT                                /FTId=VSP_046166.
FT   VARIANT      21     21       A -> V (in dbSNP:rs15999).
FT                                /FTId=VAR_014456.
FT   VARIANT     101    101       E -> Q (in EIEE42).
FT                                {ECO:0000269|PubMed:27476654}.
FT                                /FTId=VAR_077071.
FT   VARIANT     192    192       R -> Q (in FHM1; dbSNP:rs121908211).
FT                                {ECO:0000269|PubMed:8898206}.
FT                                /FTId=VAR_001491.
FT   VARIANT     195    195       R -> K (in FHM1; dbSNP:rs121908222).
FT                                {ECO:0000269|PubMed:11439943}.
FT                                /FTId=VAR_043820.
FT   VARIANT     218    218       S -> L (in FHM1; dbSNP:rs121908225).
FT                                {ECO:0000269|PubMed:11409427}.
FT                                /FTId=VAR_043821.
FT   VARIANT     248    248       Y -> C (in EA2; dbSNP:rs121908238).
FT                                {ECO:0000269|PubMed:18602318}.
FT                                /FTId=VAR_063683.
FT   VARIANT     253    253       H -> Y (in EA2; dbSNP:rs121908228).
FT                                {ECO:0000269|PubMed:12420090}.
FT                                /FTId=VAR_043822.
FT   VARIANT     256    256       C -> R (in EA2; dbSNP:rs121908231).
FT                                {ECO:0000269|PubMed:15173248}.
FT                                /FTId=VAR_043823.
FT   VARIANT     287    287       C -> Y (in EA2; dbSNP:rs121908236).
FT                                {ECO:0000269|PubMed:14718690}.
FT                                /FTId=VAR_043824.
FT   VARIANT     293    293       G -> R (in EA2 and SCA6;
FT                                dbSNP:rs121908215).
FT                                {ECO:0000269|PubMed:14718690,
FT                                ECO:0000269|PubMed:9345107}.
FT                                /FTId=VAR_043825.
FT   VARIANT     388    388       E -> K (in EA2).
FT                                {ECO:0000269|PubMed:21696515}.
FT                                /FTId=VAR_067342.
FT   VARIANT     389    389       L -> F (in EA2; dbSNP:rs121908239).
FT                                {ECO:0000269|PubMed:20129625}.
FT                                /FTId=VAR_063684.
FT   VARIANT     405    405       A -> T (in SCA6; dbSNP:rs121908245).
FT                                {ECO:0000269|PubMed:20682717}.
FT                                /FTId=VAR_063685.
FT   VARIANT     454    454       A -> T (in dbSNP:rs41276886).
FT                                {ECO:0000269|PubMed:8898206}.
FT                                /FTId=VAR_063686.
FT   VARIANT     501    501       T -> M (in EA2; dbSNP:rs121908240).
FT                                {ECO:0000269|PubMed:20129625}.
FT                                /FTId=VAR_063687.
FT   VARIANT     583    583       R -> Q (in FHM1; dbSNP:rs121908217).
FT                                {ECO:0000269|PubMed:11439943}.
FT                                /FTId=VAR_043826.
FT   VARIANT     638    638       G -> D (in EA2; reduces P/Q current
FT                                densities; dbSNP:rs121908246).
FT                                {ECO:0000269|PubMed:19232643}.
FT                                /FTId=VAR_063688.
FT   VARIANT     666    666       T -> M (in FHM1 and EA2;
FT                                dbSNP:rs121908212).
FT                                {ECO:0000269|PubMed:11439943,
FT                                ECO:0000269|PubMed:14718690,
FT                                ECO:0000269|PubMed:8898206}.
FT                                /FTId=VAR_001492.
FT   VARIANT     713    713       A -> T (in EIEE42).
FT                                {ECO:0000269|PubMed:27476654}.
FT                                /FTId=VAR_077072.
FT   VARIANT     714    714       V -> A (in FHM1; dbSNP:rs121908213).
FT                                {ECO:0000269|PubMed:8898206}.
FT                                /FTId=VAR_001493.
FT   VARIANT     715    715       D -> E (in FHM1; dbSNP:rs121908218).
FT                                {ECO:0000269|PubMed:11439943}.
FT                                /FTId=VAR_043827.
FT   VARIANT     732    732       E -> A (in dbSNP:rs16019).
FT                                /FTId=VAR_059221.
FT   VARIANT     798    798       M -> T (in EA2; dbSNP:rs121908241).
FT                                {ECO:0000269|PubMed:20129625}.
FT                                /FTId=VAR_063689.
FT   VARIANT     897    897       P -> R (in EA2; dbSNP:rs121908242).
FT                                {ECO:0000269|PubMed:20129625}.
FT                                /FTId=VAR_063690.
FT   VARIANT     914    914       P -> S (in dbSNP:rs16020).
FT                                /FTId=VAR_014458.
FT   VARIANT     918    918       E -> D (in dbSNP:rs16022).
FT                                {ECO:0000269|PubMed:16866717,
FT                                ECO:0000269|PubMed:19429006}.
FT                                /FTId=VAR_014459.
FT   VARIANT     993    993       E -> V (in dbSNP:rs16023).
FT                                {ECO:0000269|PubMed:10408532,
FT                                ECO:0000269|PubMed:16866717,
FT                                ECO:0000269|PubMed:19429006}.
FT                                /FTId=VAR_043828.
FT   VARIANT    1015   1015       E -> K (in dbSNP:rs16024).
FT                                /FTId=VAR_014461.
FT   VARIANT    1105   1105       G -> S (in dbSNP:rs16027).
FT                                {ECO:0000269|PubMed:10753886,
FT                                ECO:0000269|PubMed:16866717}.
FT                                /FTId=VAR_014462.
FT   VARIANT    1173   1173       P -> L (in dbSNP:rs16028).
FT                                /FTId=VAR_059222.
FT   VARIANT    1335   1335       K -> E (in FHM1; dbSNP:rs121908223).
FT                                {ECO:0000269|PubMed:11439943}.
FT                                /FTId=VAR_043829.
FT   VARIANT    1346   1346       R -> Q (in FHM1; with progressive
FT                                cerebellar ataxia; dbSNP:rs121908230).
FT                                {ECO:0000269|PubMed:15032980,
FT                                ECO:0000269|PubMed:18400034}.
FT                                /FTId=VAR_043830.
FT   VARIANT    1384   1384       Y -> C (in FHM1; dbSNP:rs121908219).
FT                                {ECO:0000269|PubMed:11439943}.
FT                                /FTId=VAR_043831.
FT   VARIANT    1403   1403       F -> C (in EA2; loss of function;
FT                                dbSNP:rs121908227).
FT                                {ECO:0000269|PubMed:11723274}.
FT                                /FTId=VAR_043832.
FT   VARIANT    1436   1436       W -> R (in EIEE42).
FT                                {ECO:0000269|PubMed:27250579}.
FT                                /FTId=VAR_077073.
FT   VARIANT    1456   1456       V -> L (in FHM1; dbSNP:rs121908237).
FT                                {ECO:0000269|PubMed:10408532}.
FT                                /FTId=VAR_043833.
FT   VARIANT    1482   1482       G -> R (in EA2; dbSNP:rs121908232).
FT                                {ECO:0000269|PubMed:15173248}.
FT                                /FTId=VAR_043834.
FT   VARIANT    1490   1490       F -> S (in EA2; dbSNP:rs121908233).
FT                                {ECO:0000269|PubMed:15173248}.
FT                                /FTId=VAR_043835.
FT   VARIANT    1493   1493       V -> I (in EA2; dbSNP:rs121908234).
FT                                {ECO:0000269|PubMed:15173248}.
FT                                /FTId=VAR_043836.
FT   VARIANT    1502   1502       Missing (in FHM1; increased high voltage-
FT                                gated calcium channel activity).
FT                                {ECO:0000269|PubMed:24836863,
FT                                ECO:0000269|PubMed:26716990}.
FT                                /FTId=VAR_077074.
FT   VARIANT    1508   1508       A -> S (in EIEE42).
FT                                {ECO:0000269|PubMed:27476654}.
FT                                /FTId=VAR_077075.
FT   VARIANT    1661   1661       R -> H (in EA2; dbSNP:rs121908216).
FT                                {ECO:0000269|PubMed:10987655}.
FT                                /FTId=VAR_043837.
FT   VARIANT    1664   1664       R -> Q (in SCA6; dbSNP:rs121908247).
FT                                {ECO:0000269|PubMed:16325861}.
FT                                /FTId=VAR_063691.
FT   VARIANT    1667   1667       R -> W (in FHM1; dbSNP:rs121908220).
FT                                {ECO:0000269|PubMed:11439943}.
FT                                /FTId=VAR_043838.
FT   VARIANT    1679   1679       R -> C (in EA2; dbSNP:rs121908243).
FT                                {ECO:0000269|PubMed:20129625}.
FT                                /FTId=VAR_063692.
FT   VARIANT    1683   1683       W -> R (in FHM1; dbSNP:rs121908221).
FT                                {ECO:0000269|PubMed:11439943}.
FT                                /FTId=VAR_043839.
FT   VARIANT    1695   1695       V -> I (in FHM1; dbSNP:rs121908224).
FT                                {ECO:0000269|PubMed:11439943}.
FT                                /FTId=VAR_063706.
FT   VARIANT    1736   1736       H -> L (in EA2; changed high voltage-
FT                                gated calcium channel activity;
FT                                dbSNP:rs121908229).
FT                                {ECO:0000269|PubMed:15293273}.
FT                                /FTId=VAR_043840.
FT   VARIANT    1756   1756       E -> K (in EA2; dbSNP:rs121908226).
FT                                {ECO:0000269|PubMed:11176968}.
FT                                /FTId=VAR_043841.
FT   VARIANT    1810   1810       I -> L (in FHM1; dbSNP:rs121908214).
FT                                {ECO:0000269|PubMed:8898206}.
FT                                /FTId=VAR_001494.
FT   VARIANT    1869   1869       C -> R (in EA2; dbSNP:rs121908244).
FT                                {ECO:0000269|PubMed:20129625}.
FT                                /FTId=VAR_063693.
FT   VARIANT    2135   2135       R -> C (in EA2; dbSNP:rs121908235).
FT                                {ECO:0000269|PubMed:15173248}.
FT                                /FTId=VAR_043842.
FT   VARIANT    2394   2394       P -> S (in dbSNP:rs16056).
FT                                /FTId=VAR_014463.
FT   CONFLICT    725    725       K -> KVEA (in Ref. 1; AAB61613/AAB61612).
FT                                {ECO:0000305}.
FT   CONFLICT    896    896       G -> D (in Ref. 2; CAA68172 and 4;
FT                                BAA94766). {ECO:0000305}.
FT   CONFLICT    953    953       D -> N (in Ref. 4; BAA94766).
FT                                {ECO:0000305}.
FT   CONFLICT    964    964       R -> S (in Ref. 4; BAA94766).
FT                                {ECO:0000305}.
FT   CONFLICT   1207   1207       E -> EE (in Ref. 2; CAA68172).
FT                                {ECO:0000305}.
FT   CONFLICT   1313   1315       WNI -> ILP (in Ref. 3; AAB49674/AAB49675/
FT                                AAB49676/AAB49677/AAB49678).
FT                                {ECO:0000305}.
FT   CONFLICT   1459   1459       G -> A (in Ref. 2; CAA68172).
FT                                {ECO:0000305}.
FT   CONFLICT   1604   1604       V -> A (in Ref. 2; CAA68172).
FT                                {ECO:0000305}.
FT   CONFLICT   1617   1617       V -> A (in Ref. 2; CAA68172).
FT                                {ECO:0000305}.
FT   CONFLICT   1651   1651       G -> GNP (in Ref. 1; AAB61613/AAB61612).
FT                                {ECO:0000305}.
FT   CONFLICT   1693   1693       P -> A (in Ref. 6; AAB33068).
FT                                {ECO:0000305}.
FT   CONFLICT   2038   2038       E -> G (in Ref. 8; U06702).
FT                                {ECO:0000305}.
FT   CONFLICT   2314   2314       Q -> QQ (in Ref. 3; AAB49676).
FT                                {ECO:0000305}.
FT   HELIX      1956   1970       {ECO:0000244|PDB:3BXK}.
SQ   SEQUENCE   2505 AA;  282365 MW;  2F2F378ACE02FD56 CRC64;
     MARFGDEMPA RYGGGGSGAA AGVVVGSGGG RGAGGSRQGG QPGAQRMYKQ SMAQRARTMA
     LYNPIPVRQN CLTVNRSLFL FSEDNVVRKY AKKITEWPPF EYMILATIIA NCIVLALEQH
     LPDDDKTPMS ERLDDTEPYF IGIFCFEAGI KIIALGFAFH KGSYLRNGWN VMDFVVVLTG
     ILATVGTEFD LRTLRAVRVL RPLKLVSGIP SLQVVLKSIM KAMIPLLQIG LLLFFAILIF
     AIIGLEFYMG KFHTTCFEEG TDDIQGESPA PCGTEEPART CPNGTKCQPY WEGPNNGITQ
     FDNILFAVLT VFQCITMEGW TDLLYNSNDA SGNTWNWLYF IPLIIIGSFF MLNLVLGVLS
     GEFAKERERV ENRRAFLKLR RQQQIERELN GYMEWISKAE EVILAEDETD GEQRHPFDGA
     LRRTTIKKSK TDLLNPEEAE DQLADIASVG SPFARASIKS AKLENSTFFH KKERRMRFYI
     RRMVKTQAFY WTVLSLVALN TLCVAIVHYN QPEWLSDFLY YAEFIFLGLF MSEMFIKMYG
     LGTRPYFHSS FNCFDCGVII GSIFEVIWAV IKPGTSFGIS VLRALRLLRI FKVTKYWASL
     RNLVVSLLNS MKSIISLLFL LFLFIVVFAL LGMQLFGGQF NFDEGTPPTN FDTFPAAIMT
     VFQILTGEDW NEVMYDGIKS QGGVQGGMVF SIYFIVLTLF GNYTLLNVFL AIAVDNLANA
     QELTKDEQEE EEAANQKLAL QKAKEVAEVS PLSAANMSIA VKEQQKNQKP AKSVWEQRTS
     EMRKQNLLAS REALYNEMDP DERWKAAYTR HLRPDMKTHL DRPLVVDPQE NRNNNTNKSR
     AAEPTVDQRL GQQRAEDFLR KQARYHDRAR DPSGSAGLDA RRPWAGSQEA ELSREGPYGR
     ESDHHAREGS LEQPGFWEGE AERGKAGDPH RRHVHRQGGS RESRSGSPRT GADGEHRRHR
     AHRRPGEEGP EDKAERRARH REGSRPARGG EGEGEGPDGG ERRRRHRHGA PATYEGDARR
     EDKERRHRRR KENQGSGVPV SGPNLSTTRP IQQDLGRQDP PLAEDIDNMK NNKLATAESA
     APHGSLGHAG LPQSPAKMGN STDPGPMLAI PAMATNPQNA ASRRTPNNPG NPSNPGPPKT
     PENSLIVTNP SGTQTNSAKT ARKPDHTTVD IPPACPPPLN HTVVQVNKNA NPDPLPKKEE
     EKKEEEEDDR GEDGPKPMPP YSSMFILSTT NPLRRLCHYI LNLRYFEMCI LMVIAMSSIA
     LAAEDPVQPN APRNNVLRYF DYVFTGVFTF EMVIKMIDLG LVLHQGAYFR DLWNILDFIV
     VSGALVAFAF TGNSKGKDIN TIKSLRVLRV LRPLKTIKRL PKLKAVFDCV VNSLKNVFNI
     LIVYMLFMFI FAVVAVQLFK GKFFHCTDES KEFEKDCRGK YLLYEKNEVK ARDREWKKYE
     FHYDNVLWAL LTLFTVSTGE GWPQVLKHSV DATFENQGPS PGYRMEMSIF YVVYFVVFPF
     FFVNIFVALI IITFQEQGDK MMEEYSLEKN ERACIDFAIS AKPLTRHMPQ NKQSFQYRMW
     QFVVSPPFEY TIMAMIALNT IVLMMKFYGA SVAYENALRV FNIVFTSLFS LECVLKVMAF
     GILNYFRDAW NIFDFVTVLG SITDILVTEF GNNFINLSFL RLFRAARLIK LLRQGYTIRI
     LLWTFVQSFK ALPYVCLLIA MLFFIYAIIG MQVFGNIGID VEDEDSDEDE FQITEHNNFR
     TFFQALMLLF RSATGEAWHN IMLSCLSGKP CDKNSGILTR ECGNEFAYFY FVSFIFLCSF
     LMLNLFVAVI MDNFEYLTRD SSILGPHHLD EYVRVWAEYD PAAWGRMPYL DMYQMLRHMS
     PPLGLGKKCP ARVAYKRLLR MDLPVADDNT VHFNSTLMAL IRTALDIKIA KGGADKQQMD
     AELRKEMMAI WPNLSQKTLD LLVTPHKSTD LTVGKIYAAM MIMEYYRQSK AKKLQAMREE
     QDRTPLMFQR MEPPSPTQEG GPGQNALPST QLDPGGALMA HESGLKESPS WVTQRAQEMF
     QKTGTWSPEQ GPPTDMPNSQ PNSQSVEMRE MGRDGYSDSE HYLPMEGQGR AASMPRLPAE
     NQRRRGRPRG NNLSTISDTS PMKRSASVLG PKARRLDDYS LERVPPEENQ RHHQRRRDRS
     HRASERSLGR YTDVDTGLGT DLSMTTQSGD LPSKERDQER GRPKDRKHRQ HHHHHHHHHH
     PPPPDKDRYA QERPDHGRAR ARDQRWSRSP SEGREHMAHR QGSSSVSGSP APSTSGTSTP
     RRGRRQLPQT PSTPRPHVSY SPVIRKAGGS GPPQQQQQQQ QQQQAVARPG RAATSGPRRY
     PGPTAEPLAG DRPPTGGHSS GRSPRMERRV PGPARSESPR ACRHGGARWP ASGPHVSEGP
     PGPRHHGYYR GSDYDEADGP GSGGGEEAMA GAYDAPPPVR HASSGATGRS PRTPRASGPA
     CASPSRHGRR LPNGYYPAHG LARPRGPGSR KGLHEPYSES DDDWC
//
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