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 27-MAR-2024, entry version 224. 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}; GN 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, TRANSPORTER RP ACTIVITY, AND 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-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, FUNCTION, AND RP TRANSPORTER ACTIVITY. 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 INTERACTION WITH TSPOAP1. RX PubMed=33539324; DOI=10.1172/jci140625; RA Mencacci N.E., Brockmann M.M., Dai J., Pajusalu S., Atasu B., Campos J., RA Pino G., Gonzalez-Latapi P., Patzke C., Schwake M., Tucci A., Pittman A., RA Simon-Sanchez J., Carvill G.L., Balint B., Wiethoff S., Warner T.T., RA Papandreou A., Soo A., Rein R., Kadastik-Eerme L., Puusepp S., Reinson K., RA Tomberg T., Hanagasi H., Gasser T., Bhatia K.P., Kurian M.A., Lohmann E., RA Ounap K., Rosenmund C., Suedhof T.C., Wood N.W., Krainc D., Acuna C.; RT "Biallelic variants in TSPOAP1, encoding the active-zone protein RIMBP1, RT cause autosomal recessive dystonia."; RL J. Clin. Invest. 131:0-0(2021). RN [11] 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 [12] 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 [13] 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 [14] 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 [15] 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 [16] 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 [17] 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 [18] 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 [19] 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 [20] RP VARIANT EA2 CYS-1402, CHARACTERIZATION OF VARIANT EA2 CYS-1402, FUNCTION, RP AND TRANSPORTER ACTIVITY. 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 [21] 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 [22] RP VARIANT EA2 LEU-1735, CHARACTERIZATION OF VARIANT EA2 LEU-1735, FUNCTION, RP AND TRANSPORTER ACTIVITY. 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 [23] 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 [24] 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 [25] 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 [26] 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 [27] 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 [28] 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 [29] 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 [30] RP VARIANT EA2 ASP-637, CHARACTERIZATION OF VARIANT EA2 ASP-637, FUNCTION, AND RP TRANSPORTER ACTIVITY. 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 [31] 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 [32] 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 [33] 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 [34] 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 [35] RP VARIANT FHM1 PHE-1501 DEL, CHARACTERIZATION OF VARIANT FHM1 PHE-1501 DEL, RP FUNCTION, AND TRANSPORTER ACTIVITY. 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 [36] RP VARIANT FHM1 PHE-1501 DEL, CHARACTERIZATION OF VARIANT FHM1 PHE-1501 DEL, RP FUNCTION, TRANSPORTER ACTIVITY, 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 [37] 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 [38] 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 [39] 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 [40] 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 [41] 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 [42] 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 -!- CATALYTIC ACTIVITY: CC Reaction=Ca(2+)(in) = Ca(2+)(out); Xref=Rhea:RHEA:29671, CC ChEBI:CHEBI:29108; Evidence={ECO:0000269|PubMed:10049321, CC ECO:0000269|PubMed:10753886, ECO:0000269|PubMed:11723274, CC ECO:0000269|PubMed:15293273, ECO:0000269|PubMed:19232643, CC ECO:0000269|PubMed:24836863, 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). Interacts with TSPOAP1 CC (PubMed:33539324). {ECO:0000250|UniProtKB:P54282, CC ECO:0000269|PubMed:11865310, ECO:0000269|PubMed:33539324}. 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 CC (TC 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/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 102. DR CORUM; O00555; -. DR IntAct; O00555; 92. DR MINT; O00555; -. DR STRING; 9606.ENSP00000489829; -. DR BindingDB; O00555; -. 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; DB09235; Efonidipine. 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; DB00622; Nicardipine. DR DrugBank; DB01054; Nitrendipine. 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 GlyCosmos; O00555; 1 site, No reported glycans. 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; 9606-ENSP00000353362; -. DR PeptideAtlas; 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; 114 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 AGR; HGNC:1388; -. 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; 1110761at2759; -. 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; 19 hits in 1172 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 185 other cell types or tissues. DR ExpressionAtlas; O00555; baseline and differential. DR GO; GO:0042995; C:cell projection; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0016020; C: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: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:1904645; P:response to amyloid-beta; IDA:ARUK-UCL. DR Gene3D; 1.10.287.70; -; 4. DR Gene3D; 6.10.250.2180; -; 1. DR Gene3D; 6.10.250.2500; -; 1. DR Gene3D; 1.20.120.350; Voltage-gated potassium channels. Chain C; 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 PANTHER; PTHR45628; VOLTAGE-DEPENDENT CALCIUM CHANNEL TYPE A SUBUNIT ALPHA-1; 1. DR PANTHER; PTHR45628:SF3; VOLTAGE-DEPENDENT P_Q-TYPE CALCIUM CHANNEL SUBUNIT ALPHA-1A; 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. DR SUPFAM; SSF81324; Voltage-gated potassium channels; 4. DR Genevisible; O00555; HS. 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|UniProtKB:P27884" 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|UniProtKB:P27884" 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; decreased voltage-gated calcium FT channel activity; 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 voltage-gated calcium FT channel activity; 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; uncertain significance; FT 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; FT AAB49674/AAB49675/AAB49676/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 //