CAC1H_HUMAN
ID CAC1H_HUMAN Reviewed; 2353 AA.
AC O95180; B5ME00; F8WFD1; O95802; Q8WWI6; Q96QI6; Q96RZ9; Q9NYY4; Q9NYY5;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 19-SEP-2002, sequence version 4.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=Voltage-dependent T-type calcium channel subunit alpha-1H;
DE AltName: Full=Low-voltage-activated calcium channel alpha1 3.2 subunit;
DE AltName: Full=Voltage-gated calcium channel subunit alpha Cav3.2;
GN Name=CACNA1H {ECO:0000312|HGNC:HGNC:1395};
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] (ISOFORM 1), VARIANT ALA-664, FUNCTION, ACTIVITY
RP REGULATION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Heart;
RX PubMed=9670923; DOI=10.1161/01.res.83.1.103;
RA Cribbs L.L., Lee J.-H., Yang J., Satin J., Zhang Y., Daud A.N., Barclay J.,
RA Wiliamson M.P., Fox M., Rees M., Perez-Reyes E.;
RT "Cloning and characterization of alpha1H from human heart, a member of the
RT T-type Ca2+ channel gene family.";
RL Circ. Res. 83:103-109(1998).
RN [2]
RP SEQUENCE REVISION.
RA Cribbs L.L., Lee J.-H., Yang J., Daud A.N., Perez-Reyes E.;
RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION,
RP ACTIVITY REGULATION, VARIANT HIS-2077, AND TISSUE SPECIFICITY.
RC TISSUE=Thyroid carcinoma;
RX PubMed=9930755; DOI=10.1046/j.1471-4159.1999.0720791.x;
RA Williams M.E., Washburn M.S., Hans M., Urrutia A., Brust P.F.,
RA Prodanovich P., Harpold M.M., Stauderman K.A.;
RT "Structure and functional characterization of a novel human low-voltage
RT activated calcium channel.";
RL J. Neurochem. 72:791-799(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT ALA-664, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=11751928; DOI=10.1074/jbc.m105345200;
RA Jagannathan S., Punt E.L., Gu Y., Arnoult C., Sakkas D., Barratt C.L.,
RA Publicover S.J.;
RT "Identification and localization of T-type voltage-operated calcium channel
RT subunits in human male germ cells. Expression of multiple isoforms.";
RL J. Biol. Chem. 277:8449-8456(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS VAL-313 AND
RP HIS-2060.
RX PubMed=11157797; DOI=10.1093/hmg/10.4.339;
RA Daniels R.J., Peden J.F., Lloyd C., Horsley S.W., Clark K., Tufarelli C.,
RA Kearney L., Buckle V.J., Doggett N.A., Flint J., Higgs D.R.;
RT "Sequence, structure and pathology of the fully annotated terminal 2 Mb of
RT the short arm of human chromosome 16.";
RL Hum. Mol. Genet. 10:339-352(2001).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT VAL-313.
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 424-661 AND 838-2373 (ISOFORM 1), AND
RP VARIANTS LEU-640 AND HIS-2077.
RA Mittman S., Agnew W.S.;
RT "Organization and alternative splicing of CACNA1H.";
RL Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP ZINC-BINDING SITES.
RX PubMed=19940152; DOI=10.1074/jbc.m109.067660;
RA Kang H.W., Vitko I., Lee S.S., Perez-Reyes E., Lee J.H.;
RT "Structural determinants of the high affinity extracellular zinc binding
RT site on Cav3.2 T-type calcium channels.";
RL J. Biol. Chem. 285:3271-3281(2010).
RN [9]
RP INTERACTION WITH STAC, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=27149520; DOI=10.1080/19336950.2016.1186318;
RA Rzhepetskyy Y., Lazniewska J., Proft J., Campiglio M., Flucher B.E.,
RA Weiss N.;
RT "A Cav3.2/Stac1 molecular complex controls T-type channel expression at the
RT plasma membrane.";
RL Channels 10:346-354(2016).
RN [10]
RP VARIANTS ECA6 LEU-161; LYS-282; SER-456; SER-499; LEU-648; GLN-744;
RP VAL-748; ASP-773; SER-784; MET-831; SER-848 AND ASN-1463, AND VARIANTS
RP VAL-313; LEU-640; ALA-664; SER-684; CYS-788; HIS-2060; HIS-2077 AND
RP SER-2173.
RX PubMed=12891677; DOI=10.1002/ana.10607;
RA Chen Y., Lu J., Pan H., Zhang Y., Wu H., Xu K., Liu X., Jiang Y., Bao X.,
RA Yao Z., Ding K., Lo W.H., Qiang B., Chan P., Shen Y., Wu X.;
RT "Association between genetic variation of CACNA1H and childhood absence
RT epilepsy.";
RL Ann. Neurol. 54:239-243(2003).
RN [11]
RP VARIANTS EIG6 LEU-618 AND ASP-755, AND FUNCTION.
RX PubMed=15048902; DOI=10.1002/ana.20028;
RA Heron S.E., Phillips H.A., Mulley J.C., Mazarib A., Neufeld M.Y.,
RA Berkovic S.F., Scheffer I.E.;
RT "Genetic variation of CACNA1H in idiopathic generalized epilepsy.";
RL Ann. Neurol. 55:595-596(2004).
RN [12]
RP CHARACTERIZATION OF VARIANT ECA6 SER-456, AND FUNCTION.
RX PubMed=24277868; DOI=10.1113/jphysiol.2013.264176;
RA Eckle V.S., Shcheglovitov A., Vitko I., Dey D., Yap C.C., Winckler B.,
RA Perez-Reyes E.;
RT "Mechanisms by which a CACNA1H mutation in epilepsy patients increases
RT seizure susceptibility.";
RL J. Physiol. (Lond.) 592:795-809(2014).
RN [13]
RP VARIANT HALD4 VAL-1549, CHARACTERIZATION OF VARIANT HALD4 VAL-1549,
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=25907736;
RA Scholl U.I., Stoelting G., Nelson-Williams C., Vichot A.A., Choi M.,
RA Loring E., Prasad M.L., Goh G., Carling T., Juhlin C.C., Quack I.,
RA Rump L.C., Thiel A., Lande M., Frazier B.G., Rasoulpour M., Bowlin D.L.,
RA Sethna C.B., Trachtman H., Fahlke C., Lifton R.P.;
RT "Recurrent gain of function mutation in calcium channel CACNA1H causes
RT early-onset hypertension with primary aldosteronism.";
RL Elife 4:E06315-E06315(2015).
RN [14]
RP VARIANT CYS-1970.
RX PubMed=26637798; DOI=10.1016/j.neuron.2015.11.009;
RA D'Gama A.M., Pochareddy S., Li M., Jamuar S.S., Reiff R.E., Lam A.T.,
RA Sestan N., Walsh C.A.;
RT "Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates
RT Multiple Genetic Mechanisms.";
RL Neuron 88:910-917(2015).
RN [15]
RP VARIANTS HALD4 LEU-196; ILE-1549 AND LEU-2083, VARIANT GLU-1951,
RP CHARACTERIZATION OF VARIANTS HALD4 LEU-196; ILE-1549 AND LEU-2083,
RP CHARACTERIZATION OF VARIANT GLU-1951, FUNCTION, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=27729216; DOI=10.1016/j.ebiom.2016.10.002;
RA Daniil G., Fernandes-Rosa F.L., Chemin J., Blesneac I., Beltrand J.,
RA Polak M., Jeunemaitre X., Boulkroun S., Amar L., Strom T.M., Lory P.,
RA Zennaro M.C.;
RT "CACNA1H mutations are associated with different forms of primary
RT aldosteronism.";
RL EBioMedicine 13:225-236(2016).
RN [16]
RP VARIANT GLN-1871.
RX PubMed=28501589; DOI=10.1016/j.clim.2017.05.009;
RA Sadovnick A.D., Traboulsee A.L., Zhao Y., Bernales C.Q., Encarnacion M.,
RA Ross J.P., Yee I.M., Criscuoli M.G., Vilarino-Gueell C.;
RT "Genetic modifiers of multiple sclerosis progression, severity and onset.";
RL Clin. Immunol. 180:100-105(2017).
RN [17]
RP VARIANT TYR-516.
RX PubMed=27864847; DOI=10.1002/humu.23149;
RG Clinical Study Group;
RA Parrini E., Marini C., Mei D., Galuppi A., Cellini E., Pucatti D.,
RA Chiti L., Rutigliano D., Bianchini C., Virdo S., De Vita D., Bigoni S.,
RA Barba C., Mari F., Montomoli M., Pisano T., Rosati A., Guerrini R.;
RT "Diagnostic targeted resequencing in 349 patients with drug-resistant
RT pediatric epilepsies identifies causative mutations in 30 different
RT genes.";
RL Hum. Mutat. 38:216-225(2017).
RN [18]
RP CHARACTERIZATION OF VARIANT ECA6 LEU-648.
RX PubMed=30197081; DOI=10.1016/j.cell.2018.08.019;
RA Meyer K., Kirchner M., Uyar B., Cheng J.Y., Russo G.,
RA Hernandez-Miranda L.R., Szymborska A., Zauber H., Rudolph I.M.,
RA Willnow T.E., Akalin A., Haucke V., Gerhardt H., Birchmeier C., Kuehn R.,
RA Krauss M., Diecke S., Pascual J.M., Selbach M.;
RT "Mutations in disordered regions can cause disease by creating dileucine
RT motifs.";
RL Cell 175:239-253(2018).
CC -!- FUNCTION: Voltage-sensitive calcium channel that gives rise to T-type
CC calcium currents. T-type calcium channels belong to the 'low-voltage
CC activated (LVA)' group. A particularity of this type of channel is an
CC opening at quite negative potentials, and a voltage-dependent
CC inactivation (PubMed:9670923, PubMed:9930755, PubMed:27149520). T-type
CC channels serve pacemaking functions in both central neurons and cardiac
CC nodal cells and support calcium signaling in secretory cells and
CC vascular smooth muscle (Probable). They may also be involved in the
CC modulation of firing patterns of neurons (PubMed:15048902). In the
CC adrenal zona glomerulosa, participates in the signaling pathway leading
CC to aldosterone production in response to either AGT/angiotensin II, or
CC hyperkalemia (PubMed:25907736, PubMed:27729216).
CC {ECO:0000269|PubMed:24277868, ECO:0000269|PubMed:25907736,
CC ECO:0000269|PubMed:27149520, ECO:0000269|PubMed:27729216,
CC ECO:0000269|PubMed:9670923, ECO:0000269|PubMed:9930755, ECO:0000305,
CC ECO:0000305|PubMed:15048902}.
CC -!- ACTIVITY REGULATION: Channel activity is strongly inhibited by
CC mibefradil (PubMed:9670923, PubMed:9930755). Channel activity is
CC strongly inhibited by Ni(2+) ions (PubMed:9930755).
CC {ECO:0000269|PubMed:9670923, ECO:0000269|PubMed:9930755}.
CC -!- SUBUNIT: Interacts (via N-terminal cytoplasmic domain) with STAC.
CC {ECO:0000269|PubMed:27149520}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:25907736,
CC ECO:0000269|PubMed:27149520, ECO:0000269|PubMed:27729216,
CC ECO:0000269|PubMed:9670923, ECO:0000269|PubMed:9930755}; Multi-pass
CC membrane protein {ECO:0000305}. Note=Interaction with STAC increases
CC expression at the cell membrane. {ECO:0000269|PubMed:27149520}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=A1H-a;
CC IsoId=O95180-1; Sequence=Displayed;
CC Name=2; Synonyms=A1H-b;
CC IsoId=O95180-2; Sequence=VSP_000949;
CC -!- TISSUE SPECIFICITY: Expressed in the adrenal glomerulosa (at protein
CC level) (PubMed:25907736, PubMed:27729216). In nonneuronal tissues, the
CC highest expression levels are found in the kidney, liver, and heart. In
CC the brain, most abundant in the amygdala, caudate nucleus, and putamen
CC (PubMed:9670923, PubMed:9930755). In the heart, expressed in blood
CC vessels. {ECO:0000269|PubMed:25907736, ECO:0000269|PubMed:27729216,
CC ECO:0000269|PubMed:9670923, ECO:0000269|PubMed:9930755}.
CC -!- TISSUE SPECIFICITY: [Isoform 1]: Expressed in testis, primarily in the
CC germ cells, but not in other portions of the reproductive tract, such
CC as ductus deferens (PubMed:11751928). Expressed in the brain
CC (PubMed:11751928). {ECO:0000269|PubMed:11751928}.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Expressed in testis, primarily in the
CC germ cells, but not in other portions of the reproductive tract, such
CC as ductus deferens (PubMed:11751928). Not expressed in the brain
CC (PubMed:11751928). {ECO:0000269|PubMed:11751928}.
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 -!- PTM: In response to raising of intracellular calcium, the T-type
CC channels are activated by CaM-kinase II.
CC -!- DISEASE: Epilepsy, idiopathic generalized 6 (EIG6) [MIM:611942]: A
CC disorder characterized by recurring generalized seizures in the absence
CC of detectable brain lesions and/or metabolic abnormalities. Generalized
CC seizures arise diffusely and simultaneously from both hemispheres of
CC the brain. {ECO:0000269|PubMed:15048902}. Note=Disease susceptibility
CC may be associated with variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Epilepsy, childhood absence 6 (ECA6) [MIM:611942]: A subtype
CC of idiopathic generalized epilepsy characterized by an onset at age 6-7
CC years, frequent absence seizures (several per day) and bilateral,
CC synchronous, symmetric 3-Hz spike waves on EEG. Tonic-clonic seizures
CC often develop in adolescence. Absence seizures may either remit or
CC persist into adulthood. {ECO:0000269|PubMed:12891677,
CC ECO:0000269|PubMed:24277868, ECO:0000269|PubMed:30197081}. Note=Disease
CC susceptibility is associated with variants affecting the gene
CC represented in this entry.
CC -!- DISEASE: Hyperaldosteronism, familial, 4 (HALD4) [MIM:617027]: A form
CC of familial hyperaldosteronism, a disorder characterized by
CC hypertension, elevated aldosterone levels despite low plasma renin
CC activity, and abnormal adrenal steroid production. There is significant
CC phenotypic heterogeneity, and some individuals never develop
CC hypertension. {ECO:0000269|PubMed:25907736,
CC ECO:0000269|PubMed:27729216}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the calcium channel alpha-1 subunit (TC
CC 1.A.1.11) family. CACNA1H subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK61268.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=CAC42094.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AF051946; AAC67239.3; -; mRNA.
DR EMBL; AF073931; AAD17668.1; -; mRNA.
DR EMBL; AJ420779; CAD12646.1; -; mRNA.
DR EMBL; AE006466; AAK61268.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL031703; CAC42094.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AC120498; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF223562; AAF60162.1; -; Genomic_DNA.
DR EMBL; AF223563; AAF60163.1; -; Genomic_DNA.
DR CCDS; CCDS45375.1; -. [O95180-1]
DR CCDS; CCDS45376.1; -. [O95180-2]
DR RefSeq; NP_001005407.1; NM_001005407.1. [O95180-2]
DR RefSeq; NP_066921.2; NM_021098.2. [O95180-1]
DR AlphaFoldDB; O95180; -.
DR SMR; O95180; -.
DR BioGRID; 114426; 11.
DR IntAct; O95180; 6.
DR MINT; O95180; -.
DR STRING; 9606.ENSP00000334198; -.
DR BindingDB; O95180; -.
DR ChEMBL; CHEMBL1859; -.
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; DB09061; Cannabidiol.
DR DrugBank; DB00568; Cinnarizine.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB00153; Ergocalciferol.
DR DrugBank; DB01023; Felodipine.
DR DrugBank; DB04841; Flunarizine.
DR DrugBank; DB00270; Isradipine.
DR DrugBank; DB09238; Manidipine.
DR DrugBank; DB14009; Medical Cannabis.
DR DrugBank; DB01388; Mibefradil.
DR DrugBank; DB14011; Nabiximols.
DR DrugBank; DB01115; Nifedipine.
DR DrugBank; DB01054; Nitrendipine.
DR DrugBank; DB00421; Spironolactone.
DR DrugBank; DB09089; Trimebutine.
DR DrugBank; DB00661; Verapamil.
DR DrugBank; DB00909; Zonisamide.
DR DrugCentral; O95180; -.
DR GuidetoPHARMACOLOGY; 536; -.
DR TCDB; 1.A.1.11.5; the voltage-gated ion channel (vic) superfamily.
DR GlyGen; O95180; 3 sites.
DR iPTMnet; O95180; -.
DR PhosphoSitePlus; O95180; -.
DR BioMuta; CACNA1H; -.
DR jPOST; O95180; -.
DR MassIVE; O95180; -.
DR PaxDb; O95180; -.
DR PeptideAtlas; O95180; -.
DR PRIDE; O95180; -.
DR ProteomicsDB; 50690; -. [O95180-1]
DR ProteomicsDB; 50691; -. [O95180-2]
DR ABCD; O95180; 1 sequenced antibody.
DR Antibodypedia; 22964; 309 antibodies from 32 providers.
DR DNASU; 8912; -.
DR Ensembl; ENST00000348261.11; ENSP00000334198.7; ENSG00000196557.13. [O95180-1]
DR Ensembl; ENST00000358590.8; ENSP00000351401.4; ENSG00000196557.13. [O95180-2]
DR Ensembl; ENST00000565831.6; ENSP00000455840.1; ENSG00000196557.13. [O95180-2]
DR GeneID; 8912; -.
DR KEGG; hsa:8912; -.
DR MANE-Select; ENST00000348261.11; ENSP00000334198.7; NM_021098.3; NP_066921.2.
DR UCSC; uc002cks.4; human. [O95180-1]
DR CTD; 8912; -.
DR DisGeNET; 8912; -.
DR GeneCards; CACNA1H; -.
DR HGNC; HGNC:1395; CACNA1H.
DR HPA; ENSG00000196557; Tissue enhanced (ovary).
DR MalaCards; CACNA1H; -.
DR MIM; 607904; gene.
DR MIM; 611942; phenotype.
DR MIM; 617027; phenotype.
DR neXtProt; NX_O95180; -.
DR OpenTargets; ENSG00000196557; -.
DR Orphanet; 64280; Childhood absence epilepsy.
DR PharmGKB; PA380; -.
DR VEuPathDB; HostDB:ENSG00000196557; -.
DR eggNOG; KOG2302; Eukaryota.
DR GeneTree; ENSGT00940000156666; -.
DR HOGENOM; CLU_000540_2_0_1; -.
DR InParanoid; O95180; -.
DR OMA; RCLIAVY; -.
DR OrthoDB; 172471at2759; -.
DR PhylomeDB; O95180; -.
DR TreeFam; TF313555; -.
DR PathwayCommons; O95180; -.
DR Reactome; R-HSA-419037; NCAM1 interactions.
DR SignaLink; O95180; -.
DR SIGNOR; O95180; -.
DR BioGRID-ORCS; 8912; 12 hits in 1067 CRISPR screens.
DR ChiTaRS; CACNA1H; human.
DR GeneWiki; CACNA1H; -.
DR GenomeRNAi; 8912; -.
DR Pharos; O95180; Tclin.
DR PRO; PR:O95180; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; O95180; protein.
DR Bgee; ENSG00000196557; Expressed in lower esophagus muscularis layer and 96 other tissues.
DR ExpressionAtlas; O95180; baseline and differential.
DR Genevisible; O95180; HS.
DR GO; GO:0016021; C:integral component of membrane; IDA:BHF-UCL.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005891; C:voltage-gated calcium channel complex; TAS:ProtInc.
DR GO; GO:0001518; C:voltage-gated sodium channel complex; IBA:GO_Central.
DR GO; GO:0008332; F:low voltage-gated calcium channel activity; IDA:BHF-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0097110; F:scaffold protein binding; IPI:BHF-UCL.
DR GO; GO:0005244; F:voltage-gated ion channel activity; IDA:UniProtKB.
DR GO; GO:0005248; F:voltage-gated sodium channel activity; IBA:GO_Central.
DR GO; GO:0032342; P:aldosterone biosynthetic process; IMP:UniProtKB.
DR GO; GO:0070509; P:calcium ion import; IDA:BHF-UCL.
DR GO; GO:0032870; P:cellular response to hormone stimulus; IEP:UniProtKB.
DR GO; GO:0035865; P:cellular response to potassium ion; IEP:UniProtKB.
DR GO; GO:0034651; P:cortisol biosynthetic process; IMP:UniProtKB.
DR GO; GO:0098662; P:inorganic cation transmembrane transport; IDA:UniProtKB.
DR GO; GO:0086010; P:membrane depolarization during action potential; IBA:GO_Central.
DR GO; GO:0006936; P:muscle contraction; TAS:ProtInc.
DR GO; GO:0007517; P:muscle organ development; NAS:ProtInc.
DR GO; GO:0007520; P:myoblast fusion; TAS:ProtInc.
DR GO; GO:0019228; P:neuronal action potential; IBA:GO_Central.
DR GO; GO:2000344; P:positive regulation of acrosome reaction; IMP:UniProtKB.
DR GO; GO:0045956; P:positive regulation of calcium ion-dependent exocytosis; IBA:GO_Central.
DR GO; GO:0008016; P:regulation of heart contraction; TAS:ProtInc.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0042391; P:regulation of membrane potential; IDA:BHF-UCL.
DR Gene3D; 1.20.120.350; -; 4.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR005445; VDCC_T_a1.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR Pfam; PF00520; Ion_trans; 4.
DR PRINTS; PR01629; TVDCCALPHA1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Calcium channel; Calcium transport;
KW Cell membrane; Disease variant; Epilepsy; Glycoprotein; Ion channel;
KW Ion transport; Membrane; Metal-binding; Reference proteome; Repeat;
KW Transmembrane; Transmembrane helix; Transport; Voltage-gated channel; Zinc.
FT CHAIN 1..2353
FT /note="Voltage-dependent T-type calcium channel subunit
FT alpha-1H"
FT /id="PRO_0000053954"
FT TOPO_DOM 1..100
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 101..119
FT /note="Helical; Name=S1 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 120..141
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 142..160
FT /note="Helical; Name=S2 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 161..169
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 170..184
FT /note="Helical; Name=S3 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 185..193
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 194..212
FT /note="Helical; Name=S4 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 213..232
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 233..253
FT /note="Helical; Name=S5 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 254..394
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 395..419
FT /note="Helical; Name=S6 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 420..793
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 794..814
FT /note="Helical; Name=S1 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 815..827
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 828..849
FT /note="Helical; Name=S2 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 850..855
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 856..874
FT /note="Helical; Name=S3 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 875..882
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 883..906
FT /note="Helical; Name=S4 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 907..917
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 918..938
FT /note="Helical; Name=S5 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 939..990
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 991..1015
FT /note="Helical; Name=S6 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1016..1290
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1291..1313
FT /note="Helical; Name=S1 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1314..1331
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1332..1352
FT /note="Helical; Name=S2 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1353..1362
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1363..1382
FT /note="Helical; Name=S3 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1383..1396
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1397..1418
FT /note="Helical; Name=S4 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1419..1428
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1429..1452
FT /note="Helical; Name=S5 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1453..1529
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1530..1555
FT /note="Helical; Name=S6 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1556..1616
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1617..1637
FT /note="Helical; Name=S1 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1638..1651
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1652..1673
FT /note="Helical; Name=S2 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1674..1680
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1681..1699
FT /note="Helical; Name=S3 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1700..1713
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1714..1737
FT /note="Helical; Name=S4 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1738..1751
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1752..1772
FT /note="Helical; Name=S5 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1773..1835
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1836..1863
FT /note="Helical; Name=S6 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1864..2353
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 87..422
FT /note="I"
FT REPEAT 779..1018
FT /note="II"
FT REPEAT 1281..1558
FT /note="III"
FT REPEAT 1602..1863
FT /note="IV"
FT REGION 1..64
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 490..571
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 621..646
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 708..772
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1083..1217
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1885..1911
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1989..2009
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2021..2255
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2269..2353
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 503..534
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 728..745
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1156..1184
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2021..2040
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2049..2063
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 140
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 189
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 191
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT SITE 378
FT /note="Calcium ion selectivity and permeability"
FT /evidence="ECO:0000250"
FT SITE 974
FT /note="Calcium ion selectivity and permeability"
FT /evidence="ECO:0000250"
FT SITE 1504
FT /note="Calcium ion selectivity and permeability"
FT /evidence="ECO:0000250"
FT SITE 1808
FT /note="Calcium ion selectivity and permeability"
FT /evidence="ECO:0000250"
FT CARBOHYD 192
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 271
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1466
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1587..1593
FT /note="STFPSPE -> K (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11751928"
FT /id="VSP_000949"
FT VARIANT 161
FT /note="F -> L (in ECA6; dbSNP:rs119454947)"
FT /evidence="ECO:0000269|PubMed:12891677"
FT /id="VAR_045935"
FT VARIANT 196
FT /note="S -> L (in HALD4; changed calcium channel activity;
FT increased aldosterone production in response to potassium
FT ion stimulation; increased expression of genes involved in
FT aldosterone biosynthesis, with the strongest effect
FT observed on CYP11B2 expression in response to potassium ion
FT stimulation; dbSNP:rs780596901)"
FT /evidence="ECO:0000269|PubMed:27729216"
FT /id="VAR_077064"
FT VARIANT 282
FT /note="E -> K (in ECA6; dbSNP:rs119454948)"
FT /evidence="ECO:0000269|PubMed:12891677"
FT /id="VAR_045936"
FT VARIANT 313
FT /note="M -> V (in dbSNP:rs36117280)"
FT /evidence="ECO:0000269|PubMed:11157797,
FT ECO:0000269|PubMed:12891677, ECO:0000269|PubMed:15616553"
FT /id="VAR_045937"
FT VARIANT 456
FT /note="C -> S (in ECA6; results in increased T-current
FT amplitude and lower threshold for spikes generation;
FT results in increased neuronal excitability)"
FT /evidence="ECO:0000269|PubMed:12891677,
FT ECO:0000269|PubMed:24277868"
FT /id="VAR_045938"
FT VARIANT 499
FT /note="G -> S (in ECA6; dbSNP:rs560915333)"
FT /evidence="ECO:0000269|PubMed:12891677"
FT /id="VAR_045939"
FT VARIANT 516
FT /note="H -> Y (found in a patient with drug-resistant focal
FT epilepsy; unknown pathological significance;
FT dbSNP:rs1057519554)"
FT /evidence="ECO:0000269|PubMed:27864847"
FT /id="VAR_078237"
FT VARIANT 618
FT /note="P -> L (in EIG6; dbSNP:rs60734921)"
FT /evidence="ECO:0000269|PubMed:15048902"
FT /id="VAR_066986"
FT VARIANT 640
FT /note="P -> L (in dbSNP:rs61734410)"
FT /evidence="ECO:0000269|PubMed:12891677, ECO:0000269|Ref.7"
FT /id="VAR_045940"
FT VARIANT 648
FT /note="P -> L (in ECA6; creates a dileucine internalization
FT motif that promotes recruitment of clathrin;
FT dbSNP:rs1288484976)"
FT /evidence="ECO:0000269|PubMed:12891677,
FT ECO:0000269|PubMed:30197081"
FT /id="VAR_045941"
FT VARIANT 664
FT /note="V -> A (in dbSNP:rs4984636)"
FT /evidence="ECO:0000269|PubMed:11751928,
FT ECO:0000269|PubMed:12891677, ECO:0000269|PubMed:9670923"
FT /id="VAR_045942"
FT VARIANT 684
FT /note="P -> S (in dbSNP:rs762185083)"
FT /evidence="ECO:0000269|PubMed:12891677"
FT /id="VAR_045943"
FT VARIANT 744
FT /note="R -> Q (in ECA6; dbSNP:rs373764821)"
FT /evidence="ECO:0000269|PubMed:12891677"
FT /id="VAR_045944"
FT VARIANT 748
FT /note="A -> V (in ECA6; dbSNP:rs770371468)"
FT /evidence="ECO:0000269|PubMed:12891677"
FT /id="VAR_045945"
FT VARIANT 755
FT /note="G -> D (in EIG6; dbSNP:rs142306293)"
FT /evidence="ECO:0000269|PubMed:15048902"
FT /id="VAR_066987"
FT VARIANT 773
FT /note="G -> D (in ECA6; dbSNP:rs267606697)"
FT /evidence="ECO:0000269|PubMed:12891677"
FT /id="VAR_045946"
FT VARIANT 784
FT /note="G -> S (in ECA6; dbSNP:rs779526640)"
FT /evidence="ECO:0000269|PubMed:12891677"
FT /id="VAR_045947"
FT VARIANT 788
FT /note="R -> C (in dbSNP:rs3751664)"
FT /evidence="ECO:0000269|PubMed:12891677"
FT /id="VAR_045948"
FT VARIANT 812
FT /note="V -> M (in dbSNP:rs28365119)"
FT /id="VAR_045949"
FT VARIANT 831
FT /note="V -> M (in ECA6; dbSNP:rs119454949)"
FT /evidence="ECO:0000269|PubMed:12891677"
FT /id="VAR_045950"
FT VARIANT 848
FT /note="G -> S (in ECA6; dbSNP:rs374272094)"
FT /evidence="ECO:0000269|PubMed:12891677"
FT /id="VAR_045951"
FT VARIANT 1463
FT /note="D -> N (in ECA6; dbSNP:rs542245543)"
FT /evidence="ECO:0000269|PubMed:12891677"
FT /id="VAR_045952"
FT VARIANT 1549
FT /note="M -> I (in HALD4; changed calcium channel activity;
FT increased aldosterone production in response to potassium
FT ion stimulation; increased expression of genes involved in
FT aldosterone biosynthesis, with the strongest effect
FT observed on CYP11B2 expression in response to potassium ion
FT stimulation)"
FT /evidence="ECO:0000269|PubMed:27729216"
FT /id="VAR_077065"
FT VARIANT 1549
FT /note="M -> V (in HALD4; changed calcium channel activity;
FT dbSNP:rs786205050)"
FT /evidence="ECO:0000269|PubMed:25907736"
FT /id="VAR_077066"
FT VARIANT 1871
FT /note="R -> Q (in dbSNP:rs58124832)"
FT /evidence="ECO:0000269|PubMed:28501589"
FT /id="VAR_061104"
FT VARIANT 1951
FT /note="V -> E (probable disease-associated variant
FT responsible for primary aldosteronism found in a patient
FT with aldosterone-producing adenoma; changed Ca(2+) channel
FT activity; dbSNP:rs746967306)"
FT /evidence="ECO:0000269|PubMed:27729216"
FT /id="VAR_077067"
FT VARIANT 1970
FT /note="S -> C (found in a patient with autism; unknown
FT pathological significance; dbSNP:rs1267377730)"
FT /evidence="ECO:0000269|PubMed:26637798"
FT /id="VAR_078702"
FT VARIANT 1974
FT /note="E -> G (in dbSNP:rs3751886)"
FT /id="VAR_033698"
FT VARIANT 2060
FT /note="R -> H (in dbSNP:rs1054644)"
FT /evidence="ECO:0000269|PubMed:11157797,
FT ECO:0000269|PubMed:12891677"
FT /id="VAR_045953"
FT VARIANT 2077
FT /note="R -> H (in dbSNP:rs1054645)"
FT /evidence="ECO:0000269|PubMed:12891677,
FT ECO:0000269|PubMed:9930755, ECO:0000269|Ref.7"
FT /id="VAR_045954"
FT VARIANT 2083
FT /note="P -> L (in HALD4; changed calcium channel activity;
FT dbSNP:rs759924732)"
FT /evidence="ECO:0000269|PubMed:27729216"
FT /id="VAR_077068"
FT VARIANT 2173
FT /note="P -> S (in dbSNP:rs200675829)"
FT /evidence="ECO:0000269|PubMed:12891677"
FT /id="VAR_045955"
FT CONFLICT 7
FT /note="A -> S (in Ref. 5; AC120498)"
FT /evidence="ECO:0000305"
FT CONFLICT 31
FT /note="E -> K (in Ref. 5; AC120498)"
FT /evidence="ECO:0000305"
FT CONFLICT 55
FT /note="A -> S (in Ref. 5; AC120498)"
FT /evidence="ECO:0000305"
FT CONFLICT 94
FT /note="L -> V (in Ref. 5; AC120498)"
FT /evidence="ECO:0000305"
FT CONFLICT 215
FT /note="S -> T (in Ref. 6; CAC42094)"
FT /evidence="ECO:0000305"
FT CONFLICT O95180-2:1587
FT /note="K -> E (in Ref. 4; CAD12646)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2353 AA; 259163 MW; E13E270635173D98 CRC64;
MTEGARAADE VRVPLGAPPP GPAALVGASP ESPGAPGREA ERGSELGVSP SESPAAERGA
ELGADEEQRV PYPALAATVF FCLGQTTRPR SWCLRLVCNP WFEHVSMLVI MLNCVTLGMF
RPCEDVECGS ERCNILEAFD AFIFAFFAVE MVIKMVALGL FGQKCYLGDT WNRLDFFIVV
AGMMEYSLDG HNVSLSAIRT VRVLRPLRAI NRVPSMRILV TLLLDTLPML GNVLLLCFFV
FFIFGIVGVQ LWAGLLRNRC FLDSAFVRNN NLTFLRPYYQ TEEGEENPFI CSSRRDNGMQ
KCSHIPGRRE LRMPCTLGWE AYTQPQAEGV GAARNACINW NQYYNVCRSG DSNPHNGAIN
FDNIGYAWIA IFQVITLEGW VDIMYYVMDA HSFYNFIYFI LLIIVGSFFM INLCLVVIAT
QFSETKQRES QLMREQRARH LSNDSTLASF SEPGSCYEEL LKYVGHIFRK VKRRSLRLYA
RWQSRWRKKV DPSAVQGQGP GHRQRRAGRH TASVHHLVYH HHHHHHHHYH FSHGSPRRPG
PEPGACDTRL VRAGAPPSPP SPGRGPPDAE SVHSIYHADC HIEGPQERAR VAHAAATAAA
SLRLATGLGT MNYPTILPSG VGSGKGSTSP GPKGKWAGGP PGTGGHGPLS LNSPDPYEKI
PHVVGEHGLG QAPGHLSGLS VPCPLPSPPA GTLTCELKSC PYCTRALEDP EGELSGSESG
DSDGRGVYEF TQDVRHGDRW DPTRPPRATD TPGPGPGSPQ RRAQQRAAPG EPGWMGRLWV
TFSGKLRRIV DSKYFSRGIM MAILVNTLSM GVEYHEQPEE LTNALEISNI VFTSMFALEM
LLKLLACGPL GYIRNPYNIF DGIIVVISVW EIVGQADGGL SVLRTFRLLR VLKLVRFLPA
LRRQLVVLVK TMDNVATFCT LLMLFIFIFS ILGMHLFGCK FSLKTDTGDT VPDRKNFDSL
LWAIVTVFQI LTQEDWNVVL YNGMASTSSW AALYFVALMT FGNYVLFNLL VAILVEGFQA
EGDANRSDTD EDKTSVHFEE DFHKLRELQT TELKMCSLAV TPNGHLEGRG SLSPPLIMCT
AATPMPTPKS SPFLDAAPSL PDSRRGSSSS GDPPLGDQKP PASLRSSPCA PWGPSGAWSS
RRSSWSSLGR APSLKRRGQC GERESLLSGE GKGSTDDEAE DGRAAPGPRA TPLRRAESLD
PRPLRPAALP PTKCRDRDGQ VVALPSDFFL RIDSHREDAA ELDDDSEDSC CLRLHKVLEP
YKPQWCRSRE AWALYLFSPQ NRFRVSCQKV ITHKMFDHVV LVFIFLNCVT IALERPDIDP
GSTERVFLSV SNYIFTAIFV AEMMVKVVAL GLLSGEHAYL QSSWNLLDGL LVLVSLVDIV
VAMASAGGAK ILGVLRVLRL LRTLRPLRVI SRAPGLKLVV ETLISSLRPI GNIVLICCAF
FIIFGILGVQ LFKGKFYYCE GPDTRNISTK AQCRAAHYRW VRRKYNFDNL GQALMSLFVL
SSKDGWVNIM YDGLDAVGVD QQPVQNHNPW MLLYFISFLL IVSFFVLNMF VGVVVENFHK
CRQHQEAEEA RRREEKRLRR LERRRRSTFP SPEAQRRPYY ADYSPTRRSI HSLCTSHYLD
LFITFIICVN VITMSMEHYN QPKSLDEALK YCNYVFTIVF VFEAALKLVA FGFRRFFKDR
WNQLDLAIVL LSLMGITLEE IEMSAALPIN PTIIRIMRVL RIARVLKLLK MATGMRALLD
TVVQALPQVG NLGLLFMLLF FIYAALGVEL FGRLECSEDN PCEGLSRHAT FSNFGMAFLT
LFRVSTGDNW NGIMKDTLRE CSREDKHCLS YLPALSPVYF VTFVLVAQFV LVNVVVAVLM
KHLEESNKEA REDAELDAEI ELEMAQGPGS ARRVDADRPP LPQESPGARD APNLVARKVS
VSRMLSLPND SYMFRPVVPA SAPHPRPLQE VEMETYGAGT PLGSVASVHS PPAESCASLQ
IPLAVSSPAR SGEPLHALSP RGTARSPSLS RLLCRQEAVH TDSLEGKIDS PRDTLDPAEP
GEKTPVRPVT QGGSLQSPPR SPRPASVRTR KHTFGQRCVS SRPAAPGGEE AEASDPADEE
VSHITSSACP WQPTAEPHGP EASPVAGGER DLRRLYSVDA QGFLDKPGRA DEQWRPSAEL
GSGEPGEAKA WGPEAEPALG ARRKKKMSPP CISVEPPAED EGSARPSAAE GGSTTLRRRT
PSCEATPHRD SLEPTEGSGA GGDPAAKGER WGQASCRAEH LTVPSFAFEP LDLGVPSGDP
FLDGSHSVTP ESRASSSGAI VPLEPPESEP PMPVGDPPEK RRGLYLTVPQ CPLEKPGSPS
ATPAPGGGAD DPV
