CAC1A_HUMAN
ID CAC1A_HUMAN Reviewed; 2506 AA.
AC O00555; J3KP41; P78510; P78511; Q16290; Q92690; Q99790; Q99791; Q99792;
AC Q99793; Q9NS88; Q9UDC4;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 12-SEP-2018, sequence version 3.
DT 03-AUG-2022, entry version 215.
DE RecName: Full=Voltage-dependent P/Q-type calcium channel subunit alpha-1A {ECO:0000305};
DE AltName: Full=Brain calcium channel I {ECO:0000303|PubMed:8988170};
DE Short=BI {ECO:0000303|PubMed:8988170};
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 {ECO:0000312|HGNC:HGNC:1388}; Synonyms=CACH4, CACN3, CACNL1A4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, AND SUBCELLULAR
RP 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-665; ALA-713 AND LEU-1809, VARIANT THR-453, AND INVOLVEMENT IN
RP 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., Ferrari M.,
RA Haan J., Lindhout D., van Ommen G.-J.B., Hofker M.H., Ferrari M.D.,
RA 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 1312-2506 (ISOFORMS 1; 2; 3 AND 6), ALTERNATIVE SPLICING, AND INVOLVEMENT
RP 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., Amos C.,
RA 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 1), VARIANT SER-1104, AND 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., Uchihara T.,
RA 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., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., 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 1692-1806.
RC TISSUE=Lung carcinoma;
RX PubMed=7823133; DOI=10.1523/jneurosci.15-01-00274.1995;
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 human
RT small-cell lung carcinoma cells.";
RL J. Neurosci. 15:274-283(1995).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1701-1821, 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., Snutch T.P.,
RA Lennon V.A.;
RT "Molecular diversity of neuronal-type calcium channels identified in small
RT cell lung carcinoma.";
RL Mayo Clin. Proc. 67:1150-1159(1992).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2037-2257 (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 1954-1974.
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 Ca2+/calmodulin:
RT high-resolution mechanistic implications for channel 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 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) due
RT 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-1660.
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 in
RT the CACNA1A gene in individuals with EA-2 and FHM.";
RL Hum. Genet. 105:261-265(1999).
RN [14]
RP VARIANT VAL-992, AND VARIANT FHM1 LEU-1455.
RX PubMed=10408532; DOI=10.1212/wnl.53.1.26;
RA Carrera P., Piatti M., Stenirri S., Grimaldi L.M., Marchioni E., Curcio M.,
RA 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 INVOLVEMENT IN EA2, AND VARIANT EA2 1545-ARG--CYS-2506 DEL.
RX PubMed=10408533; DOI=10.1212/wnl.53.1.34;
RA Jen J., Yue Q., Nelson S.F., Yu H., Litt M., Nutt J., Baloh R.W.;
RT "A novel nonsense mutation in CACNA1A causes episodic ataxia and
RT hemiplegia.";
RL Neurology 53:34-37(1999).
RN [16]
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., Jardine P.E.,
RA Heywood P., Love S., van den Maagdenberg A.M., Haan J., Frants R.R.,
RA Ferrari M.D.;
RT "Delayed cerebral edema and fatal coma after minor head trauma: role of the
RT CACNA1A calcium channel subunit gene and relationship with familial
RT hemiplegic migraine.";
RL Ann. Neurol. 49:753-760(2001).
RN [17]
RP VARIANT EA2 LYS-1755.
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 [18]
RP VARIANTS FHM1 LYS-195; GLN-582; MET-665; GLU-714; GLU-1334; CYS-1383;
RP TRP-1666; ARG-1682 AND ILE-1694.
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 [19]
RP VARIANT EA2 CYS-1402, CHARACTERIZATION OF VARIANT EA2 CYS-1402, 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., Yue Q.,
RA Papazian D.M., Baloh R.W.;
RT "Loss-of-function EA2 mutations are associated with impaired neuromuscular
RT transmission.";
RL Neurology 57:1843-1848(2001).
RN [20]
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 novel
RT missense mutation in the CACNA1A gene.";
RL J. Neurol. 249:1515-1519(2002).
RN [21]
RP VARIANT EA2 LEU-1735, CHARACTERIZATION OF VARIANT EA2 LEU-1735, 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 calcium
RT channel.";
RL Ann. Neurol. 56:213-220(2004).
RN [22]
RP VARIANT FHM1 GLN-1345.
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 the
RT P/Q-type calcium-channel alpha-subunit in a family with progressive
RT cerebellar ataxia and hemiplegic migraine.";
RL Clin. Genet. 65:70-72(2004).
RN [23]
RP VARIANTS EA2 ARG-256; ARG-1481; SER-1489; ILE-1492 AND CYS-2134.
RX PubMed=15173248; DOI=10.1136/jmg.2003.015396;
RA Mantuano E., Veneziano L., Spadaro M., Giunti P., Guida S., Leggio M.G.,
RA 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 [24]
RP VARIANTS EA2 TYR-287; ARG-293 AND MET-665.
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 [25]
RP VARIANTS ASP-917; VAL-992 AND SER-1104.
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 [26]
RP VARIANT SCA6 GLN-1663.
RX PubMed=16325861; DOI=10.1016/j.jns.2005.10.007;
RA Tonelli A., D'Angelo M.G., Salati R., Villa L., Germinasi C., Frattini T.,
RA Meola G., Turconi A.C., Bresolin N., Bassi M.T.;
RT "Early onset, non fluctuating spinocerebellar ataxia and a novel missense
RT mutation in CACNA1A gene.";
RL J. Neurol. Sci. 241:13-17(2006).
RN [27]
RP VARIANT FHM1 GLN-1345.
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., Ginjaar H.B.,
RA Haan J., Frants R.R., Ferrari M.D., van den Maagdenberg A.M.,
RA Terwindt G.M.;
RT "CACNA1A R1347Q: a frequent recurrent mutation in hemiplegic migraine.";
RL Clin. Genet. 74:481-485(2008).
RN [28]
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., Ververi A.,
RA Jurkat-Rott K.;
RT "Episodic ataxia type 2 showing ictal hyperhidrosis with hypothermia and
RT interictal chronic diarrhea due to a novel CACNA1A mutation.";
RL Eur. J. Paediatr. Neurol. 13:191-193(2009).
RN [29]
RP VARIANT EA2 ASP-637, CHARACTERIZATION OF VARIANT EA2 ASP-637, AND FUNCTION.
RX PubMed=19232643; DOI=10.1016/j.jns.2009.01.005;
RA Cuenca-Leon E., Banchs I., Serra S.A., Latorre P., Fernandez-Castillo N.,
RA Corominas R., Valverde M.A., Volpini V., Fernandez-Fernandez J.M.,
RA Macaya A., Cormand B.;
RT "Late-onset episodic ataxia type 2 associated with a novel loss-of-function
RT mutation in the CACNA1A gene.";
RL J. Neurol. Sci. 280:10-14(2009).
RN [30]
RP VARIANTS ASP-917 AND VAL-992.
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., Buzzi M.G.;
RT "The interplay of two single nucleotide polymorphisms in the CACNA1A gene
RT may contribute to migraine susceptibility.";
RL Neurosci. Lett. 453:12-15(2009).
RN [31]
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., Zanotta N.,
RA Epifanio R., Righini A., Bresolin N., Bassi M.T., 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 [32]
RP VARIANTS EA2 PHE-389; MET-500; THR-797; ARG-896; CYS-1678 AND ARG-1868.
RX PubMed=20129625; DOI=10.1016/j.jns.2010.01.010;
RA Mantuano E., Romano S., Veneziano L., Gellera C., Castellotti B., Caimi S.,
RA Testa D., Estienne M., Zorzi G., Bugiani M., Rajabally Y.A., Barcina M.J.,
RA Servidei S., Panico A., Frontali M., Mariotti C.;
RT "Identification of novel and recurrent CACNA1A gene mutations in fifteen
RT patients with episodic ataxia type 2.";
RL J. Neurol. Sci. 291:30-36(2010).
RN [33]
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 [34]
RP VARIANT FHM1 PHE-1501 DEL, CHARACTERIZATION OF VARIANT FHM1 PHE-1501 DEL,
RP 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 associated
RT with a novel gain of function mutation in the calcium channel CACNA1A.";
RL J. Neurol. Sci. 342:69-78(2014).
RN [35]
RP VARIANT FHM1 PHE-1501 DEL, CHARACTERIZATION OF VARIANT FHM1 PHE-1501 DEL,
RP 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 activity and
RT promotes ca2+ influx.";
RL PLoS ONE 10:E0146035-E0146035(2015).
RN [36]
RP INVOLVEMENT IN DEE42, AND VARIANTS DEE42 GLN-101; THR-712 AND SER-1507.
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 epileptic
RT encephalopathies.";
RL Am. J. Hum. Genet. 99:287-298(2016).
RN [37]
RP VARIANT DEE42 ARG-1435.
RX PubMed=27250579; DOI=10.1002/ajmg.a.37678;
RA Reinson K., Oiglane-Shlik E., Talvik I., Vaher U., Ounapuu A., Ennok M.,
RA Teek R., Pajusalu S., Murumets U., Tomberg T., Puusepp S., Piirsoo A.,
RA Reimand T., Ounap K.;
RT "Biallelic CACNA1A mutations cause early onset epileptic encephalopathy
RT with progressive cerebral, cerebellar, and optic nerve atrophy.";
RL Am. J. Med. Genet. A 170:2173-2176(2016).
RN [38]
RP VARIANTS SCA6 GLN-582; TYR-1337 AND 1545-ARG--CYS-2506 DEL.
RX PubMed=29053796; DOI=10.1093/brain/awx251;
RA Nibbeling E.A.R., Duarri A., Verschuuren-Bemelmans C.C., Fokkens M.R.,
RA Karjalainen J.M., Smeets C.J.L.M., de Boer-Bergsma J.J., van der Vries G.,
RA Dooijes D., Bampi G.B., van Diemen C., Brunt E., Ippel E., Kremer B.,
RA Vlak M., Adir N., Wijmenga C., van de Warrenburg B.P.C., Franke L.,
RA Sinke R.J., Verbeek D.S.;
RT "Exome sequencing and network analysis identifies shared mechanisms
RT underlying spinocerebellar ataxia.";
RL Brain 140:2860-2878(2017).
RN [39]
RP VARIANT FHM1 GLN-582.
RX PubMed=28900389; DOI=10.3389/fncel.2017.00263;
RA Khaiboullina S.F., Mendelevich E.G., Shigapova L.H., Shagimardanova E.,
RA Gazizova G., Nikitin A., Martynova E., Davidyuk Y.N., Bogdanov E.I.,
RA Gusev O., van den Maagdenberg A.M.J.M., Giniatullin R.A., Rizvanov A.A.;
RT "Cerebellar Atrophy and Changes in Cytokines Associated with the CACNA1A
RT R583Q Mutation in a Russian Familial Hemiplegic Migraine Type 1 Family.";
RL Front. Cell. Neurosci. 11:263-263(2017).
RN [40]
RP VARIANTS GLN-1663 AND PRO-1672, AND CHARACTERIZATION OF VARIANTS GLN-1663
RP AND PRO-1672.
RX PubMed=28742085; DOI=10.1371/journal.pgen.1006905;
RG Members of the UDN;
RA Luo X., Rosenfeld J.A., Yamamoto S., Harel T., Zuo Z., Hall M.,
RA Wierenga K.J., Pastore M.T., Bartholomew D., Delgado M.R., Rotenberg J.,
RA Lewis R.A., Emrick L., Bacino C.A., Eldomery M.K., Coban Akdemir Z.,
RA Xia F., Yang Y., Lalani S.R., Lotze T., Lupski J.R., Lee B., Bellen H.J.,
RA Wangler M.F.;
RT "Clinically severe CACNA1A alleles affect synaptic function and
RT neurodegeneration differentially.";
RL PLoS Genet. 13:E1006905-E1006905(2017).
RN [41]
RP VARIANT ASN-1633.
RX PubMed=33798445; DOI=10.1016/j.ajhg.2021.03.013;
RA Courage C., Oliver K.L., Park E.J., Cameron J.M., Grabinska K.A., Muona M.,
RA Canafoglia L., Gambardella A., Said E., Afawi Z., Baykan B., Brandt C.,
RA di Bonaventura C., Chew H.B., Criscuolo C., Dibbens L.M., Castellotti B.,
RA Riguzzi P., Labate A., Filla A., Giallonardo A.T., Berecki G.,
RA Jackson C.B., Joensuu T., Damiano J.A., Kivity S., Korczyn A., Palotie A.,
RA Striano P., Uccellini D., Giuliano L., Andermann E., Scheffer I.E.,
RA Michelucci R., Bahlo M., Franceschetti S., Sessa W.C., Berkovic S.F.,
RA Lehesjoki A.E.;
RT "Progressive myoclonus epilepsies-Residual unsolved cases have marked
RT genetic heterogeneity including dolichol-dependent protein glycosylation
RT pathway genes.";
RL Am. J. Hum. Genet. 108:722-738(2021).
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-1A gives rise to P and/or Q-
CC type calcium currents. P/Q-type calcium channels belong to the 'high-
CC voltage activated' (HVA) group and are specifically blocked by the
CC spider omega-agatoxin-IVA (AC P54282) (By similarity). They are however
CC insensitive to dihydropyridines (DHP). {ECO:0000250|UniProtKB:P54282,
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 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 (via C-terminal CDB motif)
CC with CABP1 in the pre- and postsynaptic membranes. Interacts with the
CC spider omega-agatoxin-IVA (AC P30288). {ECO:0000250|UniProtKB:P54282,
CC ECO:0000269|PubMed:11865310}.
CC -!- INTERACTION:
CC O00555; Q8IZP0: ABI1; NbExp=2; IntAct=EBI-766279, EBI-375446;
CC O00555; O94910: ADGRL1; NbExp=2; IntAct=EBI-766279, EBI-3389315;
CC O00555; Q86SJ2: AMIGO2; NbExp=2; IntAct=EBI-766279, EBI-3866830;
CC O00555; Q7Z5H3: ARHGAP22; NbExp=2; IntAct=EBI-766279, EBI-3866859;
CC O00555; P67870: CSNK2B; NbExp=2; IntAct=EBI-766279, EBI-348169;
CC O00555; O75953: DNAJB5; NbExp=2; IntAct=EBI-766279, EBI-5655937;
CC O00555; P28799: GRN; NbExp=2; IntAct=EBI-766279, EBI-747754;
CC O00555; P15822: HIVEP1; NbExp=2; IntAct=EBI-766279, EBI-722264;
CC O00555; Q8N2S1: LTBP4; NbExp=2; IntAct=EBI-766279, EBI-947718;
CC O00555; O00339: MATN2; NbExp=2; IntAct=EBI-766279, EBI-949020;
CC O00555; O75095: MEGF6; NbExp=2; IntAct=EBI-766279, EBI-947597;
CC O00555; Q7Z7M0: MEGF8; NbExp=2; IntAct=EBI-766279, EBI-947617;
CC O00555; Q9UHX1: PUF60; NbExp=2; IntAct=EBI-766279, EBI-1053259;
CC O00555; Q8IXT5: RBM12B; NbExp=2; IntAct=EBI-766279, EBI-3044077;
CC O00555; O95153: TSPOAP1; NbExp=2; IntAct=EBI-766279, EBI-5915931;
CC O00555; Q9BVA1: TUBB2B; NbExp=2; IntAct=EBI-766279, EBI-355665;
CC O00555; P22695: UQCRC2; NbExp=2; IntAct=EBI-766279, EBI-1051424;
CC O00555; 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=6;
CC Comment=Additional isoforms seem to exist.;
CC Name=1; Synonyms=1A-1, BI-1-GGCAG {ECO:0000303|PubMed:8988170};
CC IsoId=O00555-8; Sequence=Displayed;
CC Name=2; Synonyms=1A-2, BI-1 {ECO:0000303|PubMed:8988170};
CC IsoId=O00555-2; Sequence=VSP_059675, VSP_059676, VSP_059677,
CC VSP_059681;
CC Name=3; Synonyms=BI-1(V1) {ECO:0000303|PubMed:8988170};
CC IsoId=O00555-3; Sequence=VSP_059675, VSP_059678, VSP_059679,
CC VSP_059681;
CC Name=4; Synonyms=BI-1(V1)-GGCAG {ECO:0000303|PubMed:8988170};
CC IsoId=O00555-4; Sequence=VSP_059675, VSP_059678, VSP_059679,
CC VSP_059682;
CC Name=5; Synonyms=BI-1(V2) {ECO:0000303|PubMed:8988170};
CC IsoId=O00555-5; Sequence=VSP_059675, VSP_059680, VSP_059681;
CC Name=6; Synonyms=BI-1(V2)-GGCAG {ECO:0000303|PubMed:8988170};
CC IsoId=O00555-6; Sequence=VSP_059675, VSP_059680, VSP_059682;
CC -!- TISSUE SPECIFICITY: Brain specific; mainly found in cerebellum,
CC cerebral cortex, thalamus and hypothalamus. Expressed in the small cell
CC lung carcinoma cell line SCC-9. No expression in heart, kidney, liver
CC or muscle. Purkinje cells contain predominantly P-type VSCC, the Q-type
CC being a prominent calcium current in cerebellar granule cells.
CC {ECO:0000269|PubMed:1335101}.
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 -!- POLYMORPHISM: The poly-Gln region of CACNA1A is polymorphic: 6 to 17
CC repeats in the normal population, expanded to about 21 to 30 repeats in
CC SCA6. Repeat expansion has been reported also in a EA2 family.
CC {ECO:0000269|PubMed:9302278}.
CC -!- DISEASE: Spinocerebellar ataxia 6 (SCA6) [MIM:183086]: Spinocerebellar
CC ataxia is a clinically and genetically heterogeneous group of
CC cerebellar disorders. Patients show progressive incoordination of gait
CC and often poor coordination of hands, speech and eye movements, due to
CC degeneration of the cerebellum with variable involvement of the
CC brainstem and spinal cord. SCA6 is an autosomal dominant cerebellar
CC ataxia (ADCA), mainly caused by expansion of a CAG repeat in the coding
CC region of CACNA1A. There seems to be a correlation between the repeat
CC number and earlier onset of the disorder. {ECO:0000269|PubMed:16325861,
CC ECO:0000269|PubMed:20682717, ECO:0000269|PubMed:29053796,
CC ECO:0000269|PubMed:8988170, ECO:0000269|PubMed:9302278,
CC ECO:0000269|PubMed:9345107}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Migraine, familial hemiplegic, 1 (FHM1) [MIM:141500]: A
CC subtype of migraine with aura associated with ictal hemiparesis and, in
CC some families, cerebellar ataxia and atrophy. Migraine is a disabling
CC symptom complex of periodic headaches, usually temporal and unilateral.
CC Headaches are often accompanied by irritability, nausea, vomiting and
CC photophobia, preceded by constriction of the cranial arteries. Migraine
CC with aura is characterized by recurrent attacks of reversible
CC neurological symptoms (aura) that precede or accompany the headache.
CC Aura may 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:28900389, ECO:0000269|PubMed:8898206}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Episodic ataxia 2 (EA2) [MIM:108500]: An autosomal dominant
CC disorder characterized by acetozolamide-responsive attacks of ataxia,
CC migraine-like symptoms, interictal nystagmus, and cerebellar atrophy.
CC {ECO:0000269|PubMed:10408533, 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 variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Developmental and epileptic encephalopathy 42 (DEE42)
CC [MIM:617106]: A form of epileptic encephalopathy, a heterogeneous group
CC of severe early-onset epilepsies characterized by refractory seizures,
CC neurodevelopmental impairment, and poor prognosis. Development is
CC normal prior to seizure onset, after which cognitive and motor delays
CC become apparent. DEE42 inheritance is autosomal dominant.
CC {ECO:0000269|PubMed:27250579, ECO:0000269|PubMed:27476654}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC 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, alpha
CC 1A subunit (CACNA1A); Note=Leiden Open Variation Database (LOVD);
CC URL="https://databases.lovd.nl/shared/genes/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="https://grenada.lumc.nl/LSDB_list/lsdbs/CACNA1A";
CC -!- WEB RESOURCE: Name=Undiagnosed Disease Network; Note=CACNA1A;
CC URL="https://undiagnosed.hms.harvard.edu/updates/genes-of-interest/cacna1a-gene/";
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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 CCDS; CCDS82301.1; -. [O00555-2]
DR RefSeq; NP_000059.3; NM_000068.3. [O00555-2]
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 PDB; 3BXK; X-ray; 2.55 A; B/D=1954-1974.
DR PDBsum; 3BXK; -.
DR AlphaFoldDB; O00555; -.
DR BMRB; O00555; -.
DR SMR; O00555; -.
DR BioGRID; 107227; 100.
DR CORUM; O00555; -.
DR IntAct; O00555; 93.
DR MINT; O00555; -.
DR STRING; 9606.ENSP00000353362; -.
DR ChEMBL; CHEMBL4266; -.
DR DrugBank; DB09231; Benidipine.
DR DrugBank; DB01244; Bepridil.
DR DrugBank; DB13746; Bioallethrin.
DR DrugBank; DB11148; Butamben.
DR DrugBank; DB11093; Calcium citrate.
DR DrugBank; DB11348; Calcium Phosphate.
DR DrugBank; DB14481; Calcium phosphate dihydrate.
DR DrugBank; DB09232; Cilnidipine.
DR DrugBank; DB06446; Dotarizine.
DR DrugBank; DB06751; Drotaverine.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB00153; Ergocalciferol.
DR DrugBank; DB09236; Lacidipine.
DR DrugBank; DB00825; Levomenthol.
DR DrugBank; DB00836; Loperamide.
DR DrugBank; DB00653; Magnesium sulfate.
DR DrugBank; DB09238; Manidipine.
DR DrugBank; DB00252; Phenytoin.
DR DrugBank; DB00421; Spironolactone.
DR DrugBank; DB09089; Trimebutine.
DR DrugBank; DB00661; Verapamil.
DR DrugBank; DB06283; Ziconotide.
DR DrugCentral; O00555; -.
DR TCDB; 1.A.1.11.27; the voltage-gated ion channel (vic) superfamily.
DR GlyGen; O00555; 1 site.
DR iPTMnet; O00555; -.
DR PhosphoSitePlus; O00555; -.
DR BioMuta; CACNA1A; -.
DR jPOST; O00555; -.
DR MassIVE; O00555; -.
DR MaxQB; O00555; -.
DR PaxDb; O00555; -.
DR PeptideAtlas; O00555; -.
DR PRIDE; O00555; -.
DR ProteomicsDB; 47967; -. [O00555-2]
DR ProteomicsDB; 47968; -. [O00555-3]
DR ProteomicsDB; 47969; -. [O00555-4]
DR ProteomicsDB; 47970; -. [O00555-5]
DR ProteomicsDB; 47971; -. [O00555-6]
DR Antibodypedia; 26386; 94 antibodies from 22 providers.
DR DNASU; 773; -.
DR Ensembl; ENST00000360228.11; ENSP00000353362.5; ENSG00000141837.22. [O00555-8]
DR Ensembl; ENST00000637276.1; ENSP00000489777.1; ENSG00000141837.22. [O00555-5]
DR Ensembl; ENST00000637432.1; ENSP00000490617.1; ENSG00000141837.22. [O00555-2]
DR Ensembl; ENST00000638009.2; ENSP00000489913.1; ENSG00000141837.22. [O00555-3]
DR GeneID; 773; -.
DR KEGG; hsa:773; -.
DR MANE-Select; ENST00000360228.11; ENSP00000353362.5; NM_001127222.2; NP_001120694.1.
DR UCSC; uc002mwy.5; human. [O00555-8]
DR CTD; 773; -.
DR DisGeNET; 773; -.
DR GeneCards; CACNA1A; -.
DR GeneReviews; CACNA1A; -.
DR HGNC; HGNC:1388; CACNA1A.
DR HPA; ENSG00000141837; Tissue enriched (brain).
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; 2382; Lennox-Gastaut syndrome.
DR Orphanet; 442835; Non-specific early-onset epileptic encephalopathy.
DR Orphanet; 98758; Spinocerebellar ataxia type 6.
DR PharmGKB; PA26007; -.
DR VEuPathDB; HostDB:ENSG00000141837; -.
DR eggNOG; KOG2301; Eukaryota.
DR GeneTree; ENSGT00940000156518; -.
DR HOGENOM; CLU_000540_1_0_1; -.
DR InParanoid; O00555; -.
DR OMA; KRMCQHR; -.
DR OrthoDB; 172471at2759; -.
DR PhylomeDB; O00555; -.
DR TreeFam; TF312805; -.
DR PathwayCommons; O00555; -.
DR Reactome; R-HSA-112308; Presynaptic depolarization and calcium channel opening.
DR Reactome; R-HSA-422356; Regulation of insulin secretion.
DR SignaLink; O00555; -.
DR SIGNOR; O00555; -.
DR BioGRID-ORCS; 773; 18 hits in 1077 CRISPR screens.
DR ChiTaRS; CACNA1A; human.
DR EvolutionaryTrace; O00555; -.
DR GeneWiki; Cav2.1; -.
DR GenomeRNAi; 773; -.
DR Pharos; O00555; Tchem.
DR PRO; PR:O00555; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; O00555; protein.
DR Bgee; ENSG00000141837; Expressed in cerebellar hemisphere and 184 other tissues.
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:0045202; C:synapse; IEA:GOC.
DR GO; GO:0005891; C:voltage-gated calcium channel complex; IBA:GO_Central.
DR GO; GO:0001540; F:amyloid-beta binding; IC:ARUK-UCL.
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:0098703; P:calcium ion import across plasma membrane; IBA:GO_Central.
DR GO; GO:0070588; P:calcium ion transmembrane transport; IDA:UniProtKB.
DR GO; GO:0008219; P:cell death; IDA:UniProtKB.
DR GO; GO:1904646; P:cellular response to amyloid-beta; IDA:ARUK-UCL.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IDA:ARUK-UCL.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IDA:UniProtKB.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:1904645; P:response to amyloid-beta; IDA:ARUK-UCL.
DR Gene3D; 1.20.120.350; -; 4.
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 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; 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; Disease variant; Disulfide bond;
KW Epilepsy; Glycoprotein; Ion channel; Ion transport; Membrane;
KW Metal-binding; Neurodegeneration; Phosphoprotein; Reference proteome;
KW Repeat; Spinocerebellar ataxia; Transmembrane; Transmembrane helix;
KW Transport; Triplet repeat expansion; Voltage-gated channel.
FT CHAIN 1..2506
FT /note="Voltage-dependent P/Q-type calcium channel subunit
FT alpha-1A"
FT /id="PRO_0000053916"
FT TOPO_DOM 1..98
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 99..117
FT /note="Helical; Name=S1 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 118..135
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 136..155
FT /note="Helical; Name=S2 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 156..167
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 168..185
FT /note="Helical; Name=S3 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 186..190
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 191..209
FT /note="Helical; Name=S4 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 210..228
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 229..248
FT /note="Helical; Name=S5 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 249..335
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 336..360
FT /note="Helical; Name=S6 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 361..486
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 487..505
FT /note="Helical; Name=S1 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 506..520
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 521..540
FT /note="Helical; Name=S2 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 541..548
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 549..567
FT /note="Helical; Name=S3 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 568..577
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 578..596
FT /note="Helical; Name=S4 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 597..615
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 616..635
FT /note="Helical; Name=S5 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 636..688
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 689..713
FT /note="Helical; Name=S6 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 714..1241
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1242..1260
FT /note="Helical; Name=S1 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1261..1276
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1277..1296
FT /note="Helical; Name=S2 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1297..1308
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1309..1327
FT /note="Helical; Name=S3 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1328..1338
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1339..1357
FT /note="Helical; Name=S4 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1358..1376
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1377..1396
FT /note="Helical; Name=S5 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1397..1483
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1484..1508
FT /note="Helical; Name=S6 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1509..1563
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1564..1592
FT /note="Helical; Name=S1 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1593..1597
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1598..1617
FT /note="Helical; Name=S2 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1618..1625
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1626..1644
FT /note="Helical; Name=S3 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1645..1651
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1652..1670
FT /note="Helical; Name=S4 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1671..1689
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1690..1709
FT /note="Helical; Name=S5 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1710..1781
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1782..1806
FT /note="Helical; Name=S6 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1807..2506
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 85..363
FT /note="I"
FT REPEAT 472..716
FT /note="II"
FT REPEAT 1230..1513
FT /note="III"
FT REPEAT 1550..1813
FT /note="IV"
FT REGION 383..400
FT /note="Binding to the beta subunit"
FT /evidence="ECO:0000250"
FT REGION 818..1220
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1988..2031
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2043..2506
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 827..842
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 852..874
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 893..910
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 917..1033
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1036..1053
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1114..1128
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1139..1161
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1192..1214
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2043..2066
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2107..2123
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2134..2153
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2204..2221
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2222..2258
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2259..2296
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2309..2330
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2489..2506
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 318
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT BINDING 667
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT BINDING 1459
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT SITE 1648
FT /note="Binds to omega-Aga-IVA"
FT /evidence="ECO:0000250"
FT MOD_RES 409
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P97445"
FT MOD_RES 447
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P97445"
FT MOD_RES 450
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P97445"
FT MOD_RES 749
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P97445"
FT MOD_RES 752
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P97445"
FT MOD_RES 789
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P97445"
FT MOD_RES 1084
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P97445"
FT MOD_RES 1093
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P97445"
FT MOD_RES 1983
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P97445"
FT MOD_RES 2046
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P54282"
FT MOD_RES 2064
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P97445"
FT MOD_RES 2076
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P54282"
FT MOD_RES 2078
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P54282"
FT MOD_RES 2119
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P97445"
FT MOD_RES 2139
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P54282"
FT CARBOHYD 283
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 418
FT /note="D -> DG (in isoform 2, isoform 3, isoform 4, isoform
FT 5 and isoform 6)"
FT /id="VSP_059675"
FT VAR_SEQ 724
FT /note="K -> KVEA (in isoform 2)"
FT /id="VSP_059676"
FT VAR_SEQ 1650
FT /note="G -> GNP (in isoform 2)"
FT /id="VSP_059677"
FT VAR_SEQ 1843..1858
FT /note="WGRMPYLDMYQMLRHM -> CGRIHYKDMYSLLRVI (in isoform 3
FT and isoform 4)"
FT /id="VSP_059678"
FT VAR_SEQ 1870..1874
FT /note="ARVAY -> HRVAC (in isoform 3 and isoform 4)"
FT /id="VSP_059679"
FT VAR_SEQ 2102..2113
FT /note="Missing (in isoform 5 and isoform 6)"
FT /id="VSP_059680"
FT VAR_SEQ 2261..2506
FT /note="Missing (in isoform 2, isoform 3 and isoform 5)"
FT /id="VSP_059681"
FT VAR_SEQ 2323..2324
FT /note="Missing (in isoform 4 and isoform 6)"
FT /id="VSP_059682"
FT VARIANT 21
FT /note="A -> V (in dbSNP:rs15999)"
FT /id="VAR_014456"
FT VARIANT 101
FT /note="E -> Q (in DEE42; dbSNP:rs886037944)"
FT /evidence="ECO:0000269|PubMed:27476654"
FT /id="VAR_077071"
FT VARIANT 192
FT /note="R -> Q (in FHM1; dbSNP:rs121908211)"
FT /evidence="ECO:0000269|PubMed:8898206"
FT /id="VAR_001491"
FT VARIANT 195
FT /note="R -> K (in FHM1; dbSNP:rs121908222)"
FT /evidence="ECO:0000269|PubMed:11439943"
FT /id="VAR_043820"
FT VARIANT 218
FT /note="S -> L (in FHM1; dbSNP:rs121908225)"
FT /evidence="ECO:0000269|PubMed:11409427"
FT /id="VAR_043821"
FT VARIANT 248
FT /note="Y -> C (in EA2; dbSNP:rs121908238)"
FT /evidence="ECO:0000269|PubMed:18602318"
FT /id="VAR_063683"
FT VARIANT 253
FT /note="H -> Y (in EA2; dbSNP:rs121908228)"
FT /evidence="ECO:0000269|PubMed:12420090"
FT /id="VAR_043822"
FT VARIANT 256
FT /note="C -> R (in EA2; dbSNP:rs121908231)"
FT /evidence="ECO:0000269|PubMed:15173248"
FT /id="VAR_043823"
FT VARIANT 287
FT /note="C -> Y (in EA2; dbSNP:rs121908236)"
FT /evidence="ECO:0000269|PubMed:14718690"
FT /id="VAR_043824"
FT VARIANT 293
FT /note="G -> R (in EA2 and SCA6; dbSNP:rs121908215)"
FT /evidence="ECO:0000269|PubMed:14718690,
FT ECO:0000269|PubMed:9345107"
FT /id="VAR_043825"
FT VARIANT 388
FT /note="E -> K (in EA2)"
FT /evidence="ECO:0000269|PubMed:21696515"
FT /id="VAR_067342"
FT VARIANT 389
FT /note="L -> F (in EA2; dbSNP:rs121908239)"
FT /evidence="ECO:0000269|PubMed:20129625"
FT /id="VAR_063684"
FT VARIANT 405
FT /note="A -> T (in SCA6; dbSNP:rs121908245)"
FT /evidence="ECO:0000269|PubMed:20682717"
FT /id="VAR_063685"
FT VARIANT 453
FT /note="A -> T (in dbSNP:rs41276886)"
FT /evidence="ECO:0000269|PubMed:8898206"
FT /id="VAR_063686"
FT VARIANT 500
FT /note="T -> M (in EA2; dbSNP:rs121908240)"
FT /evidence="ECO:0000269|PubMed:20129625"
FT /id="VAR_063687"
FT VARIANT 582
FT /note="R -> Q (in FHM1 and SCA6; dbSNP:rs121908217)"
FT /evidence="ECO:0000269|PubMed:11439943,
FT ECO:0000269|PubMed:28900389, ECO:0000269|PubMed:29053796"
FT /id="VAR_043826"
FT VARIANT 637
FT /note="G -> D (in EA2; reduces P/Q current densities;
FT dbSNP:rs121908246)"
FT /evidence="ECO:0000269|PubMed:19232643"
FT /id="VAR_063688"
FT VARIANT 665
FT /note="T -> M (in FHM1 and EA2; dbSNP:rs121908212)"
FT /evidence="ECO:0000269|PubMed:11439943,
FT ECO:0000269|PubMed:14718690, ECO:0000269|PubMed:8898206"
FT /id="VAR_001492"
FT VARIANT 712
FT /note="A -> T (in DEE42; dbSNP:rs886037945)"
FT /evidence="ECO:0000269|PubMed:27476654"
FT /id="VAR_077072"
FT VARIANT 713
FT /note="V -> A (in FHM1; dbSNP:rs121908213)"
FT /evidence="ECO:0000269|PubMed:8898206"
FT /id="VAR_001493"
FT VARIANT 714
FT /note="D -> E (in FHM1; dbSNP:rs121908218)"
FT /evidence="ECO:0000269|PubMed:11439943"
FT /id="VAR_043827"
FT VARIANT 731
FT /note="E -> A (in dbSNP:rs16019)"
FT /id="VAR_059221"
FT VARIANT 797
FT /note="M -> T (in EA2; dbSNP:rs121908241)"
FT /evidence="ECO:0000269|PubMed:20129625"
FT /id="VAR_063689"
FT VARIANT 896
FT /note="P -> R (in EA2; dbSNP:rs121908242)"
FT /evidence="ECO:0000269|PubMed:20129625"
FT /id="VAR_063690"
FT VARIANT 913
FT /note="P -> S (in dbSNP:rs16020)"
FT /id="VAR_014458"
FT VARIANT 917
FT /note="E -> D (in dbSNP:rs16022)"
FT /evidence="ECO:0000269|PubMed:16866717,
FT ECO:0000269|PubMed:19429006"
FT /id="VAR_014459"
FT VARIANT 992
FT /note="E -> V (in dbSNP:rs16023)"
FT /evidence="ECO:0000269|PubMed:10408532,
FT ECO:0000269|PubMed:16866717, ECO:0000269|PubMed:19429006"
FT /id="VAR_043828"
FT VARIANT 1014
FT /note="E -> K (in dbSNP:rs16024)"
FT /id="VAR_014461"
FT VARIANT 1104
FT /note="G -> S (in dbSNP:rs16027)"
FT /evidence="ECO:0000269|PubMed:10753886,
FT ECO:0000269|PubMed:16866717"
FT /id="VAR_014462"
FT VARIANT 1172
FT /note="P -> L (in dbSNP:rs16028)"
FT /id="VAR_059222"
FT VARIANT 1334
FT /note="K -> E (in FHM1; dbSNP:rs121908223)"
FT /evidence="ECO:0000269|PubMed:11439943"
FT /id="VAR_043829"
FT VARIANT 1337
FT /note="D -> Y (in SCA6; dbSNP:rs1568473283)"
FT /evidence="ECO:0000269|PubMed:29053796"
FT /id="VAR_080738"
FT VARIANT 1345
FT /note="R -> Q (in FHM1; with progressive cerebellar ataxia;
FT dbSNP:rs121908230)"
FT /evidence="ECO:0000269|PubMed:15032980,
FT ECO:0000269|PubMed:18400034"
FT /id="VAR_043830"
FT VARIANT 1383
FT /note="Y -> C (in FHM1; dbSNP:rs121908219)"
FT /evidence="ECO:0000269|PubMed:11439943"
FT /id="VAR_043831"
FT VARIANT 1402
FT /note="F -> C (in EA2; loss of function;
FT dbSNP:rs121908227)"
FT /evidence="ECO:0000269|PubMed:11723274"
FT /id="VAR_043832"
FT VARIANT 1435
FT /note="W -> R (in DEE42)"
FT /evidence="ECO:0000269|PubMed:27250579"
FT /id="VAR_077073"
FT VARIANT 1455
FT /note="V -> L (in FHM1; dbSNP:rs121908237)"
FT /evidence="ECO:0000269|PubMed:10408532"
FT /id="VAR_043833"
FT VARIANT 1481
FT /note="G -> R (in EA2; dbSNP:rs121908232)"
FT /evidence="ECO:0000269|PubMed:15173248"
FT /id="VAR_043834"
FT VARIANT 1489
FT /note="F -> S (in EA2; dbSNP:rs121908233)"
FT /evidence="ECO:0000269|PubMed:15173248"
FT /id="VAR_043835"
FT VARIANT 1492
FT /note="V -> I (in EA2; dbSNP:rs121908234)"
FT /evidence="ECO:0000269|PubMed:15173248"
FT /id="VAR_043836"
FT VARIANT 1501
FT /note="Missing (in FHM1; increased high voltage-gated
FT calcium channel activity; dbSNP:rs1131691374)"
FT /evidence="ECO:0000269|PubMed:24836863,
FT ECO:0000269|PubMed:26716990"
FT /id="VAR_077074"
FT VARIANT 1507
FT /note="A -> S (in DEE42; dbSNP:rs886037946)"
FT /evidence="ECO:0000269|PubMed:27476654"
FT /id="VAR_077075"
FT VARIANT 1545..2506
FT /note="Missing (in EA2 and SCA6)"
FT /evidence="ECO:0000269|PubMed:10408533,
FT ECO:0000269|PubMed:29053796"
FT /id="VAR_080739"
FT VARIANT 1633
FT /note="D -> N (found in a patient with late onset
FT progressive myoclonus epilepsy; unknown pathological
FT significance; dbSNP:rs1555740805)"
FT /evidence="ECO:0000269|PubMed:33798445"
FT /id="VAR_085042"
FT VARIANT 1660
FT /note="R -> H (in EA2; dbSNP:rs121908216)"
FT /evidence="ECO:0000269|PubMed:10987655"
FT /id="VAR_043837"
FT VARIANT 1663
FT /note="R -> Q (in SCA6; also found in patients with global
FT developmental delay and congenital ataxia; loss of function
FT observed in the Drosophila homolog; dbSNP:rs121908247)"
FT /evidence="ECO:0000250|UniProtKB:P91645,
FT ECO:0000269|PubMed:16325861, ECO:0000269|PubMed:28742085"
FT /id="VAR_063691"
FT VARIANT 1666
FT /note="R -> W (in FHM1; dbSNP:rs121908220)"
FT /evidence="ECO:0000269|PubMed:11439943"
FT /id="VAR_043838"
FT VARIANT 1672
FT /note="R -> P (also found in patients with global
FT developmental delay and congenital ataxia; gain of function
FT observed in the Drosophila homolog; dbSNP:rs1057519429)"
FT /evidence="ECO:0000250|UniProtKB:P91645,
FT ECO:0000269|PubMed:28742085"
FT /id="VAR_079826"
FT VARIANT 1678
FT /note="R -> C (in EA2; dbSNP:rs121908243)"
FT /evidence="ECO:0000269|PubMed:20129625"
FT /id="VAR_063692"
FT VARIANT 1682
FT /note="W -> R (in FHM1; dbSNP:rs121908221)"
FT /evidence="ECO:0000269|PubMed:11439943"
FT /id="VAR_043839"
FT VARIANT 1694
FT /note="V -> I (in FHM1; dbSNP:rs121908224)"
FT /evidence="ECO:0000269|PubMed:11439943"
FT /id="VAR_063706"
FT VARIANT 1735
FT /note="H -> L (in EA2; changed high voltage-gated calcium
FT channel activity; dbSNP:rs121908229)"
FT /evidence="ECO:0000269|PubMed:15293273"
FT /id="VAR_043840"
FT VARIANT 1755
FT /note="E -> K (in EA2; dbSNP:rs121908226)"
FT /evidence="ECO:0000269|PubMed:11176968"
FT /id="VAR_043841"
FT VARIANT 1809
FT /note="I -> L (in FHM1; dbSNP:rs121908214)"
FT /evidence="ECO:0000269|PubMed:8898206"
FT /id="VAR_001494"
FT VARIANT 1868
FT /note="C -> R (in EA2; dbSNP:rs121908244)"
FT /evidence="ECO:0000269|PubMed:20129625"
FT /id="VAR_063693"
FT VARIANT 2134
FT /note="R -> C (in EA2; dbSNP:rs121908235)"
FT /evidence="ECO:0000269|PubMed:15173248"
FT /id="VAR_043842"
FT VARIANT 2395
FT /note="P -> S (in dbSNP:rs16056)"
FT /id="VAR_014463"
FT CONFLICT 895
FT /note="G -> D (in Ref. 2; CAA68172 and 4; BAA94766)"
FT /evidence="ECO:0000305"
FT CONFLICT 952
FT /note="D -> N (in Ref. 4; BAA94766)"
FT /evidence="ECO:0000305"
FT CONFLICT 963
FT /note="R -> S (in Ref. 4; BAA94766)"
FT /evidence="ECO:0000305"
FT CONFLICT 1206
FT /note="E -> EE (in Ref. 2; CAA68172)"
FT /evidence="ECO:0000305"
FT CONFLICT 1312..1314
FT /note="WNI -> ILP (in Ref. 3; AAB49674/AAB49675/AAB49676/
FT AAB49677/AAB49678)"
FT /evidence="ECO:0000305"
FT CONFLICT 1458
FT /note="G -> A (in Ref. 2; CAA68172)"
FT /evidence="ECO:0000305"
FT CONFLICT 1603
FT /note="V -> A (in Ref. 2; CAA68172)"
FT /evidence="ECO:0000305"
FT CONFLICT 1616
FT /note="V -> A (in Ref. 2; CAA68172)"
FT /evidence="ECO:0000305"
FT CONFLICT 1692
FT /note="P -> A (in Ref. 6; AAB33068)"
FT /evidence="ECO:0000305"
FT CONFLICT 2037
FT /note="E -> G (in Ref. 8; U06702)"
FT /evidence="ECO:0000305"
FT CONFLICT 2325
FT /note="Missing (in Ref. 3; AAB49676/AAB49677)"
FT /evidence="ECO:0000305"
FT HELIX 1955..1969
FT /evidence="ECO:0007829|PDB:3BXK"
SQ SEQUENCE 2506 AA; 282564 MW; AEDF4D2A5E49263F 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 GEQRHPFDAL
RRTTIKKSKT DLLNPEEAED QLADIASVGS PFARASIKSA KLENSTFFHK KERRMRFYIR
RMVKTQAFYW TVLSLVALNT LCVAIVHYNQ PEWLSDFLYY AEFIFLGLFM SEMFIKMYGL
GTRPYFHSSF NCFDCGVIIG SIFEVIWAVI KPGTSFGISV LRALRLLRIF KVTKYWASLR
NLVVSLLNSM KSIISLLFLL FLFIVVFALL GMQLFGGQFN FDEGTPPTNF DTFPAAIMTV
FQILTGEDWN EVMYDGIKSQ GGVQGGMVFS IYFIVLTLFG NYTLLNVFLA IAVDNLANAQ
ELTKDEQEEE EAANQKLALQ KAKEVAEVSP LSAANMSIAV KEQQKNQKPA KSVWEQRTSE
MRKQNLLASR EALYNEMDPD ERWKAAYTRH LRPDMKTHLD RPLVVDPQEN RNNNTNKSRA
AEPTVDQRLG QQRAEDFLRK QARYHDRARD PSGSAGLDAR RPWAGSQEAE LSREGPYGRE
SDHHAREGSL EQPGFWEGEA ERGKAGDPHR RHVHRQGGSR ESRSGSPRTG ADGEHRRHRA
HRRPGEEGPE DKAERRARHR EGSRPARGGE GEGEGPDGGE RRRRHRHGAP ATYEGDARRE
DKERRHRRRK ENQGSGVPVS GPNLSTTRPI QQDLGRQDPP LAEDIDNMKN NKLATAESAA
PHGSLGHAGL PQSPAKMGNS TDPGPMLAIP AMATNPQNAA SRRTPNNPGN PSNPGPPKTP
ENSLIVTNPS GTQTNSAKTA RKPDHTTVDI PPACPPPLNH TVVQVNKNAN PDPLPKKEEE
KKEEEEDDRG EDGPKPMPPY SSMFILSTTN PLRRLCHYIL NLRYFEMCIL MVIAMSSIAL
AAEDPVQPNA PRNNVLRYFD YVFTGVFTFE MVIKMIDLGL VLHQGAYFRD LWNILDFIVV
SGALVAFAFT GNSKGKDINT IKSLRVLRVL RPLKTIKRLP KLKAVFDCVV NSLKNVFNIL
IVYMLFMFIF AVVAVQLFKG KFFHCTDESK EFEKDCRGKY LLYEKNEVKA RDREWKKYEF
HYDNVLWALL TLFTVSTGEG WPQVLKHSVD ATFENQGPSP GYRMEMSIFY VVYFVVFPFF
FVNIFVALII ITFQEQGDKM MEEYSLEKNE RACIDFAISA KPLTRHMPQN KQSFQYRMWQ
FVVSPPFEYT IMAMIALNTI VLMMKFYGAS VAYENALRVF NIVFTSLFSL ECVLKVMAFG
ILNYFRDAWN IFDFVTVLGS ITDILVTEFG NNFINLSFLR LFRAARLIKL LRQGYTIRIL
LWTFVQSFKA LPYVCLLIAM LFFIYAIIGM QVFGNIGIDV EDEDSDEDEF QITEHNNFRT
FFQALMLLFR SATGEAWHNI MLSCLSGKPC DKNSGILTRE CGNEFAYFYF VSFIFLCSFL
MLNLFVAVIM DNFEYLTRDS SILGPHHLDE YVRVWAEYDP AAWGRMPYLD MYQMLRHMSP
PLGLGKKCPA RVAYKRLLRM DLPVADDNTV HFNSTLMALI RTALDIKIAK GGADKQQMDA
ELRKEMMAIW PNLSQKTLDL LVTPHKSTDL TVGKIYAAMM IMEYYRQSKA KKLQAMREEQ
DRTPLMFQRM EPPSPTQEGG PGQNALPSTQ LDPGGALMAH ESGLKESPSW VTQRAQEMFQ
KTGTWSPEQG PPTDMPNSQP NSQSVEMREM GRDGYSDSEH YLPMEGQGRA ASMPRLPAEN
QRRRGRPRGN NLSTISDTSP MKRSASVLGP KARRLDDYSL ERVPPEENQR HHQRRRDRSH
RASERSLGRY TDVDTGLGTD LSMTTQSGDL PSKERDQERG RPKDRKHRQH HHHHHHHHHP
PPPDKDRYAQ ERPDHGRARA RDQRWSRSPS EGREHMAHRQ GSSSVSGSPA PSTSGTSTPR
RGRRQLPQTP STPRPHVSYS PVIRKAGGSG PPQQQQQQQQ QQQQQAVARP GRAATSGPRR
YPGPTAEPLA GDRPPTGGHS SGRSPRMERR VPGPARSESP RACRHGGARW PASGPHVSEG
PPGPRHHGYY RGSDYDEADG PGSGGGEEAM AGAYDAPPPV RHASSGATGR SPRTPRASGP
ACASPSRHGR RLPNGYYPAH GLARPRGPGS RKGLHEPYSE SDDDWC
