CNGA3_HUMAN
ID CNGA3_HUMAN Reviewed; 694 AA.
AC Q16281; E9PF93; Q4VAP7; Q53RD2; Q6ZNA7; Q9UP64;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 04-MAY-2001, sequence version 2.
DT 03-AUG-2022, entry version 201.
DE RecName: Full=Cyclic nucleotide-gated cation channel alpha-3;
DE AltName: Full=Cone photoreceptor cGMP-gated channel subunit alpha;
DE AltName: Full=Cyclic nucleotide-gated channel alpha-3;
DE Short=CNG channel alpha-3;
DE Short=CNG-3;
DE Short=CNG3;
GN Name=CNGA3; Synonyms=CNCG3;
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).
RX PubMed=9517456; DOI=10.1111/j.1460-9568.1997.tb01680.x;
RA Wissinger B., Mueller F., Weyand I., Schuffenhauer S., Thanos S.,
RA Kaupp U.B., Zrenner E.;
RT "Cloning, chromosomal localization and functional expression of the gene
RT encoding the alpha-subunit of the cGMP-gated channel in human cone
RT photoreceptors.";
RL Eur. J. Neurosci. 9:2512-2521(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 320-580.
RX PubMed=7532814; DOI=10.1016/0028-3908(94)90027-2;
RA Distler M., Biel M., Flockerzi V., Hofmann F.;
RT "Expression of cyclic nucleotide-gated cation channels in non-sensory
RT tissues and cells.";
RL Neuropharmacology 33:1275-1282(1994).
RN [6]
RP FUNCTION, AND SUBUNIT.
RX PubMed=10888875; DOI=10.1038/77162;
RA Sundin O.H., Yang J.-M., Li Y., Zhu D., Hurd J.N., Mitchell T.N.,
RA Silva E.D., Maumenee I.H.;
RT "Genetic basis of total colourblindness among the Pingelapese islanders.";
RL Nat. Genet. 25:289-293(2000).
RN [7]
RP SUBUNIT.
RX PubMed=15134637; DOI=10.1016/s0896-6273(04)00225-9;
RA Peng C., Rich E.D., Varnum M.D.;
RT "Subunit configuration of heteromeric cone cyclic nucleotide-gated
RT channels.";
RL Neuron 42:401-410(2004).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 626-669, AND SUBUNIT
RP STOICHIOMETRY.
RX PubMed=21878911; DOI=10.1038/ncomms1466;
RA Shuart N.G., Haitin Y., Camp S.S., Black K.D., Zagotta W.N.;
RT "Molecular mechanism for 3:1 subunit stoichiometry of rod cyclic
RT nucleotide-gated ion channels.";
RL Nat. Commun. 2:457-457(2011).
RN [9]
RP VARIANTS ACHM2 LEU-163; GLN-283; TRP-283; ARG-291; TRP-410; MET-529;
RP LEU-547 AND ARG-557, AND VARIANT MET-153.
RX PubMed=9662398; DOI=10.1038/935;
RA Kohl S., Marx T., Giddings I., Jaegle H., Jacobson S.G.,
RA Apfelstedt-Sylla E., Zrenner E., Sharpe L.T., Wissinger B.;
RT "Total colourblindness is caused by mutations in the gene encoding the
RT alpha-subunit of the cone photoreceptor cGMP-gated cation channel.";
RL Nat. Genet. 19:257-259(1998).
RN [10]
RP VARIANTS ACHM2 VAL-162; LEU-163; CYS-181; TYR-182; PHE-186; TYR-191;
RP LYS-194; TRP-223; ARG-224; ASN-260; ASP-267; CYS-277; HIS-277; TRP-283;
RP GLN-283; ARG-291; ILE-312 DEL; PRO-341; SER-369; SER-372; SER-380; THR-406;
RP TRP-410; CYS-427; TRP-436; SER-471; VAL-485; SER-510; GLU-513; GLU-516;
RP THR-522; ASP-525; MET-529; LEU-547; ARG-557; HIS-563; MET-565; HIS-569;
RP CYS-573 AND LYS-593.
RX PubMed=11536077; DOI=10.1086/323613;
RA Wissinger B., Gamer D., Jaegle H., Giorda R., Marx T., Mayer S.,
RA Tippmann S., Broghammer M., Jurklies B., Rosenberg T., Jacobson S.G.,
RA Sener E.C., Tatlipinar S., Hoyng C.B., Castellan C., Bitoun P.,
RA Andreasson S., Rudolph G., Kellner U., Lorenz B., Wolff G.,
RA Verellen-Dumoulin C., Schwartz M., Cremers F.P.M., Apfelstedt-Sylla E.,
RA Zrenner E., Salati R., Sharpe L.T., Kohl S.;
RT "CNGA3 mutations in hereditary cone photoreceptor disorders.";
RL Am. J. Hum. Genet. 69:722-737(2001).
RN [11]
RP VARIANTS ACHM2 TRP-223; TRP-436; LEU-547; ARG-548 AND HIS-569.
RX PubMed=14757870; DOI=10.1136/jmg.2003.011437;
RA Johnson S., Michaelides M., Aligianis I.A., Ainsworth J.R., Mollon J.D.,
RA Maher E.R., Moore A.T., Hunt D.M.;
RT "Achromatopsia caused by novel mutations in both CNGA3 and CNGB3.";
RL J. Med. Genet. 41:E20-E20(2004).
RN [12]
RP CHARACTERIZATION OF VARIANTS ACHM2 CYS-277; SER-471 AND HIS-563.
RX PubMed=15743887; DOI=10.1152/ajpcell.00490.2004;
RA Liu C., Varnum M.D.;
RT "Functional consequences of progressive cone dystrophy-associated mutations
RT in the human cone photoreceptor cyclic nucleotide-gated channel CNGA3
RT subunit.";
RL Am. J. Physiol. 289:C187-C198(2005).
RN [13]
RP VARIANTS ACHM2 TRP-223; SER-249; ASP-263; CYS-277; PRO-341; PRO-401;
RP TRP-410; CYS-427; TRP-436; MET-529; MET-565 AND LYS-590, AND VARIANTS
RP LEU-48 AND MET-153.
RX PubMed=15712225; DOI=10.1002/humu.20142;
RA Nishiguchi K.M., Sandberg M.A., Gorji N., Berson E.L., Dryja T.P.;
RT "Cone cGMP-gated channel mutations and clinical findings in patients with
RT achromatopsia, macular degeneration, and other hereditary cone diseases.";
RL Hum. Mutat. 25:248-258(2005).
RN [14]
RP VARIANTS ACHM2 LYS-228; CYS-277; GLN-283; TRP-439; THR-469; LEU-547 AND
RP ARG-557, AND CHARACTERIZATION OF VARIANTS ACHM2 LYS-228; GLN-283; ARG-291;
RP TRP-439; THR-469; LEU-547; ARG-557 AND LYS-590.
RX PubMed=18521937; DOI=10.1002/humu.20790;
RG Achromatopsia clinical study group;
RA Reuter P., Koeppen K., Ladewig T., Kohl S., Baumann B., Wissinger B.;
RT "Mutations in CNGA3 impair trafficking or function of cone cyclic
RT nucleotide-gated channels, resulting in achromatopsia.";
RL Hum. Mutat. 29:1228-1236(2008).
RN [15]
RP VARIANT MET-527.
RX PubMed=21901789; DOI=10.1002/humu.21587;
RA Wang X., Wang H., Cao M., Li Z., Chen X., Patenia C., Gore A., Abboud E.B.,
RA Al-Rajhi A.A., Lewis A.R., Lupski J.R., Mardon G., Zhang K., Muzny D.,
RA Gibbs R.A., Chen R.;
RT "Whole-exome sequencing identifies ALMS1, IQCB1, CNGA3, and MYO7A mutations
RT in patients with Leber congenital amaurosis.";
RL Hum. Mutat. 32:1450-1459(2011).
RN [16]
RP VARIANT CYS-335.
RX PubMed=23033978; DOI=10.1056/nejmoa1206524;
RA de Ligt J., Willemsen M.H., van Bon B.W., Kleefstra T., Yntema H.G.,
RA Kroes T., Vulto-van Silfhout A.T., Koolen D.A., de Vries P., Gilissen C.,
RA del Rosario M., Hoischen A., Scheffer H., de Vries B.B., Brunner H.G.,
RA Veltman J.A., Vissers L.E.;
RT "Diagnostic exome sequencing in persons with severe intellectual
RT disability.";
RL N. Engl. J. Med. 367:1921-1929(2012).
RN [17]
RP VARIANTS ASP-120; LYS-198; ILE-224; MET-247; ARG-258; SER-330; PHE-334;
RP HIS-533; ASN-570 AND HIS-646, AND VARIANTS ACHM2 CYS-171; TRP-223; GLN-223;
RP ASN-260; LYS-274; HIS-277; CYS-277; PRO-278; TRP-283; SER-322; TRP-436;
RP GLN-436; TRP-439; MET-529; 543-ASP--SER-545 DEL AND LYS-590.
RX PubMed=24903488; DOI=10.1001/jamaophthalmol.2014.1032;
RA Li S., Huang L., Xiao X., Jia X., Guo X., Zhang Q.;
RT "Identification of CNGA3 mutations in 46 Families: common cause of
RT achromatopsia and cone-rod dystrophies in Chinese patients.";
RL JAMA Ophthalmol. 132:1076-1083(2014).
RN [18]
RP VARIANTS ACHM2 ASP-323 AND HIS-569.
RX PubMed=26493561; DOI=10.1186/s12967-015-0694-7;
RA Li F.F., Huang X.F., Chen J., Yu X.D., Zheng M.Q., Lu F., Jin Z.B.,
RA Gan D.K.;
RT "Identification of novel mutations by targeted exome sequencing and the
RT genotype-phenotype assessment of patients with achromatopsia.";
RL J. Transl. Med. 13:334-334(2015).
CC -!- FUNCTION: Visual signal transduction is mediated by a G-protein coupled
CC cascade using cGMP as second messenger. This protein can be activated
CC by cyclic GMP which leads to an opening of the cation channel and
CC thereby causing a depolarization of cone photoreceptors. Induced a
CC flickering channel gating, weakened the outward rectification in the
CC presence of extracellular calcium, increased sensitivity for L-cis
CC diltiazem and enhanced the cAMP efficacy of the channel when
CC coexpressed with CNGB3 (By similarity). Essential for the generation of
CC light-evoked electrical responses in the red-, green- and blue
CC sensitive cones. {ECO:0000250, ECO:0000269|PubMed:10888875}.
CC -!- SUBUNIT: Tetramer formed of three CNGA3 and one CNGB3 modulatory
CC subunits. {ECO:0000269|PubMed:10888875, ECO:0000269|PubMed:15134637,
CC ECO:0000269|PubMed:21878911}.
CC -!- INTERACTION:
CC Q16281; Q9NYP9: MIS18A; NbExp=3; IntAct=EBI-1642108, EBI-1104552;
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q16281-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q16281-2; Sequence=VSP_042525;
CC Name=3;
CC IsoId=Q16281-3; Sequence=VSP_057075;
CC -!- TISSUE SPECIFICITY: Prominently expressed in retina.
CC -!- DOMAIN: The C-terminal coiled-coil domain mediates homotrimerization of
CC CNGA subunits.
CC -!- DISEASE: Achromatopsia 2 (ACHM2) [MIM:216900]: An autosomal recessive,
CC ocular stationary disorder due to the absence of functioning cone
CC photoreceptors in the retina. It is characterized by total
CC colorblindness, low visual acuity, photophobia and nystagmus.
CC {ECO:0000269|PubMed:11536077, ECO:0000269|PubMed:14757870,
CC ECO:0000269|PubMed:15712225, ECO:0000269|PubMed:15743887,
CC ECO:0000269|PubMed:18521937, ECO:0000269|PubMed:24903488,
CC ECO:0000269|PubMed:26493561, ECO:0000269|PubMed:9662398}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the cyclic nucleotide-gated cation channel (TC
CC 1.A.1.5) family. CNGA3 subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Mutations of the CNGA3 gene; Note=Retina
CC International's Scientific Newsletter;
CC URL="https://www.retina-international.org/files/sci-news/cnga3mut.htm";
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DR EMBL; AF065314; AAC17440.1; -; mRNA.
DR EMBL; AK131300; BAD18468.1; -; mRNA.
DR EMBL; AC092675; AAY24181.1; -; Genomic_DNA.
DR EMBL; BC096298; AAH96298.1; -; mRNA.
DR EMBL; BC096299; AAH96299.1; -; mRNA.
DR EMBL; BC096300; AAH96300.1; -; mRNA.
DR EMBL; S76069; AAD14208.1; -; Genomic_DNA.
DR CCDS; CCDS2034.1; -. [Q16281-1]
DR CCDS; CCDS42719.1; -. [Q16281-2]
DR PIR; I78560; I78560.
DR PIR; S74179; S74179.
DR RefSeq; NP_001073347.1; NM_001079878.1. [Q16281-2]
DR RefSeq; NP_001289.1; NM_001298.2. [Q16281-1]
DR PDB; 3SWY; X-ray; 1.90 A; A/B/C=626-669.
DR PDB; 7RHS; EM; 2.93 A; A/B/C=1-694.
DR PDBsum; 3SWY; -.
DR PDBsum; 7RHS; -.
DR AlphaFoldDB; Q16281; -.
DR SMR; Q16281; -.
DR BioGRID; 107661; 33.
DR IntAct; Q16281; 28.
DR STRING; 9606.ENSP00000377140; -.
DR GuidetoPHARMACOLOGY; 396; -.
DR TCDB; 1.A.1.5.12; the voltage-gated ion channel (vic) superfamily.
DR iPTMnet; Q16281; -.
DR PhosphoSitePlus; Q16281; -.
DR BioMuta; CNGA3; -.
DR DMDM; 13959682; -.
DR MassIVE; Q16281; -.
DR PaxDb; Q16281; -.
DR PeptideAtlas; Q16281; -.
DR PRIDE; Q16281; -.
DR ProteomicsDB; 20054; -.
DR ProteomicsDB; 60848; -. [Q16281-1]
DR ProteomicsDB; 60849; -. [Q16281-2]
DR Antibodypedia; 47515; 130 antibodies from 22 providers.
DR DNASU; 1261; -.
DR Ensembl; ENST00000272602.7; ENSP00000272602.2; ENSG00000144191.12. [Q16281-1]
DR Ensembl; ENST00000436404.6; ENSP00000410070.2; ENSG00000144191.12. [Q16281-2]
DR GeneID; 1261; -.
DR KEGG; hsa:1261; -.
DR MANE-Select; ENST00000272602.7; ENSP00000272602.2; NM_001298.3; NP_001289.1.
DR UCSC; uc002syt.4; human. [Q16281-1]
DR CTD; 1261; -.
DR DisGeNET; 1261; -.
DR GeneCards; CNGA3; -.
DR GeneReviews; CNGA3; -.
DR HGNC; HGNC:2150; CNGA3.
DR HPA; ENSG00000144191; Tissue enhanced (brain, pituitary gland, retina).
DR MalaCards; CNGA3; -.
DR MIM; 216900; phenotype.
DR MIM; 600053; gene.
DR neXtProt; NX_Q16281; -.
DR OpenTargets; ENSG00000144191; -.
DR Orphanet; 49382; Achromatopsia.
DR Orphanet; 1872; Cone rod dystrophy.
DR PharmGKB; PA26660; -.
DR VEuPathDB; HostDB:ENSG00000144191; -.
DR eggNOG; KOG0500; Eukaryota.
DR GeneTree; ENSGT00940000158737; -.
DR HOGENOM; CLU_005746_12_0_1; -.
DR InParanoid; Q16281; -.
DR OMA; CGRTERA; -.
DR OrthoDB; 1073751at2759; -.
DR PhylomeDB; Q16281; -.
DR TreeFam; TF319048; -.
DR PathwayCommons; Q16281; -.
DR SignaLink; Q16281; -.
DR BioGRID-ORCS; 1261; 15 hits in 1068 CRISPR screens.
DR GeneWiki; Cyclic_nucleotide-gated_channel_alpha_3; -.
DR GenomeRNAi; 1261; -.
DR Pharos; Q16281; Tchem.
DR PRO; PR:Q16281; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q16281; protein.
DR Bgee; ENSG00000144191; Expressed in ventricular zone and 84 other tissues.
DR Genevisible; Q16281; HS.
DR GO; GO:0043194; C:axon initial segment; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0097386; C:glial cell projection; IEA:Ensembl.
DR GO; GO:0017071; C:intracellular cyclic nucleotide activated cation channel complex; IBA:GO_Central.
DR GO; GO:0043204; C:perikaryon; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:1902495; C:transmembrane transporter complex; IDA:UniProtKB.
DR GO; GO:0030553; F:cGMP binding; IMP:UniProtKB.
DR GO; GO:0005222; F:intracellular cAMP-activated cation channel activity; IBA:GO_Central.
DR GO; GO:0005223; F:intracellular cGMP-activated cation channel activity; IMP:UniProtKB.
DR GO; GO:0015276; F:ligand-gated ion channel activity; TAS:ProtInc.
DR GO; GO:0008022; F:protein C-terminus binding; IEA:Ensembl.
DR GO; GO:0044877; F:protein-containing complex binding; IBA:GO_Central.
DR GO; GO:0098655; P:cation transmembrane transport; IBA:GO_Central.
DR GO; GO:0006812; P:cation transport; IMP:UniProtKB.
DR GO; GO:0098659; P:inorganic cation import across plasma membrane; IEA:Ensembl.
DR GO; GO:0051591; P:response to cAMP; IEA:Ensembl.
DR GO; GO:0031960; P:response to corticosteroid; IEA:Ensembl.
DR GO; GO:0032026; P:response to magnesium ion; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0007601; P:visual perception; TAS:ProtInc.
DR CDD; cd00038; CAP_ED; 1.
DR Gene3D; 2.60.120.10; -; 1.
DR InterPro; IPR032406; CLZ_dom.
DR InterPro; IPR018490; cNMP-bd-like.
DR InterPro; IPR018488; cNMP-bd_CS.
DR InterPro; IPR000595; cNMP-bd_dom.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR014710; RmlC-like_jellyroll.
DR Pfam; PF16526; CLZ; 1.
DR Pfam; PF00027; cNMP_binding; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR SMART; SM00100; cNMP; 1.
DR SUPFAM; SSF51206; SSF51206; 1.
DR PROSITE; PS00888; CNMP_BINDING_1; 1.
DR PROSITE; PS00889; CNMP_BINDING_2; 1.
DR PROSITE; PS50042; CNMP_BINDING_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; cGMP; cGMP-binding; Coiled coil;
KW Disease variant; Ion channel; Ion transport; Leber congenital amaurosis;
KW Ligand-gated ion channel; Membrane; Nucleotide-binding; Reference proteome;
KW Sensory transduction; Transmembrane; Transmembrane helix; Transport;
KW Vision.
FT CHAIN 1..694
FT /note="Cyclic nucleotide-gated cation channel alpha-3"
FT /id="PRO_0000219317"
FT TOPO_DOM 1..166
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 167..187
FT /note="Helical; Name=H1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 188..199
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 200..220
FT /note="Helical; Name=H2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 221..252
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 253..273
FT /note="Helical; Name=H3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 274..302
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 303..323
FT /note="Helical; Name=H4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 324..378
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 379..399
FT /note="Helical; Name=H5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 400..481
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 482..502
FT /note="Helical; Name=H6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 503..694
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 109..152
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 662..694
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 626..669
FT COMPBIAS 109..125
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 482..605
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT BINDING 549
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /evidence="ECO:0000255"
FT BINDING 564
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..71
FT /note="MAKINTQYSHPSRTHLKVKTSDRDLNRAENGLSRAHSSSEETSSVLQPGIAM
FT ETRGLADSGQGSFTGQGIA -> METRGLADSGQGSFTGQGIARFGRIQKKSQPEKVVR
FT AASRGRPLIGWTQWCAEDGGDESEMALAGSPGCSSGPQG (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057075"
FT VAR_SEQ 132..150
FT /note="SAWPLAKCNTNTSNNTEEE -> R (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_042525"
FT VARIANT 48
FT /note="P -> L (in dbSNP:rs62156348)"
FT /evidence="ECO:0000269|PubMed:15712225"
FT /id="VAR_047565"
FT VARIANT 120
FT /note="N -> D (in dbSNP:rs199859850)"
FT /evidence="ECO:0000269|PubMed:24903488"
FT /id="VAR_071435"
FT VARIANT 153
FT /note="T -> M (in dbSNP:rs34314205)"
FT /evidence="ECO:0000269|PubMed:15712225,
FT ECO:0000269|PubMed:9662398"
FT /id="VAR_010902"
FT VARIANT 162
FT /note="D -> V (in ACHM2; dbSNP:rs747447519)"
FT /evidence="ECO:0000269|PubMed:11536077"
FT /id="VAR_047566"
FT VARIANT 163
FT /note="P -> L (in ACHM2; dbSNP:rs104893612)"
FT /evidence="ECO:0000269|PubMed:11536077,
FT ECO:0000269|PubMed:9662398"
FT /id="VAR_010903"
FT VARIANT 171
FT /note="W -> C (in ACHM2; also found in patients with cone-
FT rod dystrophy; dbSNP:rs762773298)"
FT /evidence="ECO:0000269|PubMed:24903488"
FT /id="VAR_071436"
FT VARIANT 181
FT /note="Y -> C (in ACHM2)"
FT /evidence="ECO:0000269|PubMed:11536077"
FT /id="VAR_047567"
FT VARIANT 182
FT /note="N -> Y (in ACHM2)"
FT /evidence="ECO:0000269|PubMed:11536077"
FT /id="VAR_047568"
FT VARIANT 186
FT /note="L -> F (in ACHM2)"
FT /evidence="ECO:0000269|PubMed:11536077"
FT /id="VAR_047569"
FT VARIANT 191
FT /note="C -> Y (in ACHM2; dbSNP:rs761554853)"
FT /evidence="ECO:0000269|PubMed:11536077"
FT /id="VAR_047570"
FT VARIANT 194
FT /note="E -> K (in ACHM2)"
FT /evidence="ECO:0000269|PubMed:11536077"
FT /id="VAR_047571"
FT VARIANT 198
FT /note="E -> K (in dbSNP:rs2271041)"
FT /evidence="ECO:0000269|PubMed:24903488"
FT /id="VAR_021963"
FT VARIANT 223
FT /note="R -> Q (in ACHM2; dbSNP:rs762668060)"
FT /evidence="ECO:0000269|PubMed:24903488"
FT /id="VAR_071438"
FT VARIANT 223
FT /note="R -> W (in ACHM2; also found in patients with cone-
FT rod dystrophy; dbSNP:rs138958917)"
FT /evidence="ECO:0000269|PubMed:11536077,
FT ECO:0000269|PubMed:14757870, ECO:0000269|PubMed:15712225,
FT ECO:0000269|PubMed:24903488"
FT /id="VAR_047572"
FT VARIANT 224
FT /note="T -> I (probable disease-associated variant found in
FT patients with cone-rod dystrophy)"
FT /evidence="ECO:0000269|PubMed:24903488"
FT /id="VAR_071439"
FT VARIANT 224
FT /note="T -> R (in ACHM2)"
FT /evidence="ECO:0000269|PubMed:11536077"
FT /id="VAR_047573"
FT VARIANT 228
FT /note="E -> K (in ACHM2; unknown pathological significance;
FT the dose-response relationship for cGMP-activation is not
FT significantly different from that of wild-type CNGA3; the
FT dose-response relationship of the mutant CNGA3 + CNGB3 is
FT similar to that of the wild-type protein; the channel
FT density into the cell membrane is considerably improved by
FT decreasing the cultivation temperature; dbSNP:rs147415641)"
FT /evidence="ECO:0000269|PubMed:18521937"
FT /id="VAR_047574"
FT VARIANT 247
FT /note="T -> M (in dbSNP:rs148616345)"
FT /evidence="ECO:0000269|PubMed:24903488"
FT /id="VAR_071440"
FT VARIANT 249
FT /note="F -> S (in ACHM2)"
FT /evidence="ECO:0000269|PubMed:15712225"
FT /id="VAR_047575"
FT VARIANT 258
FT /note="P -> R (probable disease-associated variant found in
FT patients with cone-rod dystrophy)"
FT /evidence="ECO:0000269|PubMed:24903488"
FT /id="VAR_071441"
FT VARIANT 260
FT /note="D -> N (in ACHM2; also found in patients with cone-
FT rod dystrophy; dbSNP:rs374258471)"
FT /evidence="ECO:0000269|PubMed:11536077,
FT ECO:0000269|PubMed:24903488"
FT /id="VAR_047576"
FT VARIANT 263
FT /note="Y -> D (in ACHM2; dbSNP:rs943314733)"
FT /evidence="ECO:0000269|PubMed:15712225"
FT /id="VAR_047577"
FT VARIANT 267
FT /note="G -> D (in ACHM2; dbSNP:rs781673067)"
FT /evidence="ECO:0000269|PubMed:11536077"
FT /id="VAR_047578"
FT VARIANT 274
FT /note="R -> K (in ACHM2)"
FT /evidence="ECO:0000269|PubMed:24903488"
FT /id="VAR_071442"
FT VARIANT 277
FT /note="R -> C (in ACHM2; also found in patients with cone-
FT rod dystrophy; does not form functional homomeric or
FT heteromeric channels; dbSNP:rs104893620)"
FT /evidence="ECO:0000269|PubMed:11536077,
FT ECO:0000269|PubMed:15712225, ECO:0000269|PubMed:15743887,
FT ECO:0000269|PubMed:18521937, ECO:0000269|PubMed:24903488"
FT /id="VAR_047579"
FT VARIANT 277
FT /note="R -> H (in ACHM2; also found in patients with cone-
FT rod dystrophy; dbSNP:rs778114016)"
FT /evidence="ECO:0000269|PubMed:11536077,
FT ECO:0000269|PubMed:24903488"
FT /id="VAR_047580"
FT VARIANT 278
FT /note="L -> P (in ACHM2; dbSNP:rs763421555)"
FT /evidence="ECO:0000269|PubMed:24903488"
FT /id="VAR_071443"
FT VARIANT 283
FT /note="R -> Q (in ACHM2; does not reveal any detectable
FT calcium influx upon agonist application at 37 degrees
FT Celsius; the channel function could be restored by
FT incubating the transfected cells at 27 degrees Celsius; the
FT dose-response relationship for cGMP-activation is not
FT significantly different from that of wild-type CNGA3; the
FT dose-response relationship of the mutant CNGA3 + CNGB3 is
FT similar to that of the wild-type protein; a substantial
FT reduction of macroscopic cGMP maximum current to only one-
FT third of the mean value for wild-type CNGA3 + CNGB3 is
FT observed for the mutant CNGA3 + CNGB3; the channel density
FT into the cell membrane is considerably improved by
FT decreasing the cultivation temparature; dbSNP:rs104893614)"
FT /evidence="ECO:0000269|PubMed:11536077,
FT ECO:0000269|PubMed:18521937, ECO:0000269|PubMed:9662398"
FT /id="VAR_010904"
FT VARIANT 283
FT /note="R -> W (in ACHM2; also found in patients with cone-
FT rod dystrophy; dbSNP:rs104893613)"
FT /evidence="ECO:0000269|PubMed:11536077,
FT ECO:0000269|PubMed:24903488, ECO:0000269|PubMed:9662398"
FT /id="VAR_010905"
FT VARIANT 291
FT /note="T -> R (in ACHM2; does not reveal any detectable
FT calcium influx upon agonist application at 37 degrees
FT Celsius; the channel function could be restored by
FT incubating the transfected cells at 27 degrees Celsius; the
FT K(1/2) value is shifted toward a higher cGMP concentration
FT by a factor of 1.8; no positive influence of the CNGB3
FT subunit in the cGMP sensitivity is observed; a substantial
FT reduction of macroscopic cGMP maximum current to only one-
FT third of the mean value for wild-type CNGA3 + CNGB3 is
FT observed for the mutant CNGA3 + CNGB3; the channel density
FT into the cell membrane is considerably improved by
FT decreasing the cultivation temparature; dbSNP:rs104893616)"
FT /evidence="ECO:0000269|PubMed:11536077,
FT ECO:0000269|PubMed:18521937, ECO:0000269|PubMed:9662398"
FT /id="VAR_010906"
FT VARIANT 312
FT /note="Missing (in ACHM2)"
FT /evidence="ECO:0000269|PubMed:11536077"
FT /id="VAR_047581"
FT VARIANT 322
FT /note="F -> S (in ACHM2)"
FT /evidence="ECO:0000269|PubMed:24903488"
FT /id="VAR_071444"
FT VARIANT 323
FT /note="A -> D (in ACHM2)"
FT /evidence="ECO:0000269|PubMed:26493561"
FT /id="VAR_075493"
FT VARIANT 330
FT /note="F -> S (probable disease-associated variant found in
FT patients with cone-rod dystrophy)"
FT /evidence="ECO:0000269|PubMed:24903488"
FT /id="VAR_071445"
FT VARIANT 334
FT /note="S -> F (probable disease-associated variant found in
FT patients with cone-rod dystrophy)"
FT /evidence="ECO:0000269|PubMed:24903488"
FT /id="VAR_071446"
FT VARIANT 335
FT /note="W -> C"
FT /evidence="ECO:0000269|PubMed:23033978"
FT /id="VAR_069398"
FT VARIANT 341
FT /note="S -> P (in ACHM2; dbSNP:rs1227761587)"
FT /evidence="ECO:0000269|PubMed:11536077,
FT ECO:0000269|PubMed:15712225"
FT /id="VAR_047582"
FT VARIANT 369
FT /note="T -> S (in ACHM2; dbSNP:rs766637612)"
FT /evidence="ECO:0000269|PubMed:11536077"
FT /id="VAR_047583"
FT VARIANT 372
FT /note="P -> S (in ACHM2; dbSNP:rs1464167194)"
FT /evidence="ECO:0000269|PubMed:11536077"
FT /id="VAR_047584"
FT VARIANT 380
FT /note="F -> S (in ACHM2)"
FT /evidence="ECO:0000269|PubMed:11536077"
FT /id="VAR_047585"
FT VARIANT 401
FT /note="S -> P (in ACHM2; dbSNP:rs916035276)"
FT /evidence="ECO:0000269|PubMed:15712225"
FT /id="VAR_047586"
FT VARIANT 406
FT /note="M -> T (in ACHM2; dbSNP:rs1553450734)"
FT /evidence="ECO:0000269|PubMed:11536077"
FT /id="VAR_047587"
FT VARIANT 410
FT /note="R -> W (in ACHM2; dbSNP:rs137852608)"
FT /evidence="ECO:0000269|PubMed:11536077,
FT ECO:0000269|PubMed:15712225, ECO:0000269|PubMed:9662398"
FT /id="VAR_010910"
FT VARIANT 427
FT /note="R -> C (in ACHM2; dbSNP:rs141386891)"
FT /evidence="ECO:0000269|PubMed:11536077,
FT ECO:0000269|PubMed:15712225"
FT /id="VAR_047588"
FT VARIANT 436
FT /note="R -> Q (in ACHM2; dbSNP:rs767083685)"
FT /evidence="ECO:0000269|PubMed:24903488"
FT /id="VAR_071447"
FT VARIANT 436
FT /note="R -> W (in ACHM2; also found in patients with cone-
FT rod dystrophy; dbSNP:rs104893621)"
FT /evidence="ECO:0000269|PubMed:11536077,
FT ECO:0000269|PubMed:14757870, ECO:0000269|PubMed:15712225,
FT ECO:0000269|PubMed:24903488"
FT /id="VAR_047589"
FT VARIANT 439
FT /note="R -> W (in ACHM2; also found in patients with cone-
FT rod dystrophy; does not reveal any detectable calcium
FT influx upon agonist application at 37 degrees Celsius;
FT dbSNP:rs749842881)"
FT /evidence="ECO:0000269|PubMed:18521937,
FT ECO:0000269|PubMed:24903488"
FT /id="VAR_047590"
FT VARIANT 469
FT /note="A -> T (in ACHM2; the dose-response relationship for
FT cGMP-activation is shifted toward a lower cGMP
FT concentration; the left shift in the dose-response
FT relationship of the mutant CNGA3 is less distinctive than
FT in homomeric channels with this mutation indicating a
FT partial rescue effect of the CNGB3 subunit; is in large
FT part located in the cell membrane at 37 and 27 degrees
FT Celsius; dbSNP:rs117522010)"
FT /evidence="ECO:0000269|PubMed:18521937"
FT /id="VAR_047591"
FT VARIANT 471
FT /note="N -> S (in ACHM2; mutant CNGA3 alone or together
FT with the CNGB3 subunit exhibit an increase in apparent
FT affinity for cGMP and an increase in the relative agonist
FT efficacy of cAMP compared with cGMP; cell surface
FT expression levels is unchanged; dbSNP:rs373954146)"
FT /evidence="ECO:0000269|PubMed:11536077,
FT ECO:0000269|PubMed:15743887"
FT /id="VAR_047592"
FT VARIANT 485
FT /note="D -> V (in ACHM2)"
FT /evidence="ECO:0000269|PubMed:11536077"
FT /id="VAR_047593"
FT VARIANT 510
FT /note="C -> S (in ACHM2; dbSNP:rs908111816)"
FT /evidence="ECO:0000269|PubMed:11536077"
FT /id="VAR_047594"
FT VARIANT 513
FT /note="G -> E (in ACHM2)"
FT /evidence="ECO:0000269|PubMed:11536077"
FT /id="VAR_047595"
FT VARIANT 516
FT /note="G -> E (in ACHM2)"
FT /evidence="ECO:0000269|PubMed:11536077"
FT /id="VAR_047596"
FT VARIANT 522
FT /note="I -> T (in ACHM2)"
FT /evidence="ECO:0000269|PubMed:11536077"
FT /id="VAR_047597"
FT VARIANT 525
FT /note="G -> D (in ACHM2)"
FT /evidence="ECO:0000269|PubMed:11536077"
FT /id="VAR_047598"
FT VARIANT 527
FT /note="L -> M (found in a patient with Leber congenital
FT amaurosis; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:21901789"
FT /id="VAR_066860"
FT VARIANT 529
FT /note="V -> M (in ACHM2; also found in patients with cone-
FT rod dystrophy; dbSNP:rs104893619)"
FT /evidence="ECO:0000269|PubMed:11536077,
FT ECO:0000269|PubMed:15712225, ECO:0000269|PubMed:24903488,
FT ECO:0000269|PubMed:9662398"
FT /id="VAR_010907"
FT VARIANT 533
FT /note="D -> H (probable disease-associated variant found in
FT patients with cone-rod dystrophy; dbSNP:rs775332304)"
FT /evidence="ECO:0000269|PubMed:24903488"
FT /id="VAR_071448"
FT VARIANT 543..545
FT /note="Missing (in ACHM2)"
FT /evidence="ECO:0000269|PubMed:24903488"
FT /id="VAR_071449"
FT VARIANT 547
FT /note="F -> L (in ACHM2; does not reveal any detectable
FT calcium influx upon agonist application at 37 degrees
FT Celsius; the channel function could be restored by
FT incubating the transfected cells at 27 degrees Celsius; the
FT dose-response relationship for cGMP-activation is shifted
FT toward a lower cGMP concentration; a substantial reduction
FT of macroscopic cGMP maximum current to only one-third of
FT the mean value for wild-type CNGA3 + CNGB3 is observed for
FT the mutant CNGA3 + CNGB3; is in large part located in the
FT cell membrane at 37 and 27 degrees Celsius;
FT dbSNP:rs104893617)"
FT /evidence="ECO:0000269|PubMed:11536077,
FT ECO:0000269|PubMed:14757870, ECO:0000269|PubMed:18521937,
FT ECO:0000269|PubMed:9662398"
FT /id="VAR_010908"
FT VARIANT 548
FT /note="G -> R (in ACHM2; dbSNP:rs781227859)"
FT /evidence="ECO:0000269|PubMed:14757870"
FT /id="VAR_047599"
FT VARIANT 557
FT /note="G -> R (in ACHM2; the K(1/2) value is shifted toward
FT a higher cGMP concentration by a factor of 3.0; no positive
FT influence of the CNGB3 subunit in the cGMP sensitivity is
FT observed; average cGMP maximum current is decreased to half
FT of the mean wild-type value for the mutant CNGA3 + CNGB3;
FT dbSNP:rs104893615)"
FT /evidence="ECO:0000269|PubMed:11536077,
FT ECO:0000269|PubMed:18521937, ECO:0000269|PubMed:9662398"
FT /id="VAR_010909"
FT VARIANT 563
FT /note="R -> H (in ACHM2; mutant CNGA3 alone or together
FT with the CNGB3 subunit exhibit an increase in apparent
FT affinity for cGMP and an increase in the relative agonist
FT efficacy of cAMP compared with cGMP; cell surface
FT expression levels is significantly reduced;
FT dbSNP:rs552069173)"
FT /evidence="ECO:0000269|PubMed:11536077,
FT ECO:0000269|PubMed:15743887"
FT /id="VAR_047600"
FT VARIANT 565
FT /note="T -> M (in ACHM2; dbSNP:rs201747279)"
FT /evidence="ECO:0000269|PubMed:11536077,
FT ECO:0000269|PubMed:15712225"
FT /id="VAR_047601"
FT VARIANT 569
FT /note="R -> H (in ACHM2; dbSNP:rs201782746)"
FT /evidence="ECO:0000269|PubMed:11536077,
FT ECO:0000269|PubMed:14757870, ECO:0000269|PubMed:26493561"
FT /id="VAR_047602"
FT VARIANT 570
FT /note="S -> N (probable disease-associated variant found in
FT patients with cone-rod dystrophy)"
FT /evidence="ECO:0000269|PubMed:24903488"
FT /id="VAR_071450"
FT VARIANT 573
FT /note="Y -> C (in ACHM2)"
FT /evidence="ECO:0000269|PubMed:11536077"
FT /id="VAR_047603"
FT VARIANT 590
FT /note="E -> K (in ACHM2; also found in patients with cone-
FT rod dystrophy; the dose-response relationship for cGMP-
FT activation is shifted toward a lower cGMP concentration;
FT dbSNP:rs763041373)"
FT /evidence="ECO:0000269|PubMed:15712225,
FT ECO:0000269|PubMed:18521937, ECO:0000269|PubMed:24903488"
FT /id="VAR_047604"
FT VARIANT 593
FT /note="E -> K (in ACHM2; dbSNP:rs774676415)"
FT /evidence="ECO:0000269|PubMed:11536077"
FT /id="VAR_047605"
FT VARIANT 646
FT /note="R -> H (in dbSNP:rs141577844)"
FT /evidence="ECO:0000269|PubMed:24903488"
FT /id="VAR_071451"
FT HELIX 626..668
FT /evidence="ECO:0007829|PDB:3SWY"
SQ SEQUENCE 694 AA; 78838 MW; AE00B4EE760D70A0 CRC64;
MAKINTQYSH PSRTHLKVKT SDRDLNRAEN GLSRAHSSSE ETSSVLQPGI AMETRGLADS
GQGSFTGQGI ARLSRLIFLL RRWAARHVHH QDQGPDSFPD RFRGAELKEV SSQESNAQAN
VGSQEPADRG RSAWPLAKCN TNTSNNTEEE KKTKKKDAIV VDPSSNLYYR WLTAIALPVF
YNWYLLICRA CFDELQSEYL MLWLVLDYSA DVLYVLDVLV RARTGFLEQG LMVSDTNRLW
QHYKTTTQFK LDVLSLVPTD LAYLKVGTNY PEVRFNRLLK FSRLFEFFDR TETRTNYPNM
FRIGNLVLYI LIIIHWNACI YFAISKFIGF GTDSWVYPNI SIPEHGRLSR KYIYSLYWST
LTLTTIGETP PPVKDEEYLF VVVDFLVGVL IFATIVGNVG SMISNMNASR AEFQAKIDSI
KQYMQFRKVT KDLETRVIRW FDYLWANKKT VDEKEVLKSL PDKLKAEIAI NVHLDTLKKV
RIFQDCEAGL LVELVLKLRP TVFSPGDYIC KKGDIGKEMY IINEGKLAVV ADDGVTQFVV
LSDGSYFGEI SILNIKGSKS GNRRTANIRS IGYSDLFCLS KDDLMEALTE YPEAKKALEE
KGRQILMKDN LIDEELARAG ADPKDLEEKV EQLGSSLDTL QTRFARLLAE YNATQMKMKQ
RLSQLESQVK GGGDKPLADG EVPGDATKTE DKQQ
