ID CNGA1_HUMAN Reviewed; 686 AA. AC P29973; A8K7K6; J3KPZ2; Q16279; Q16485; Q4W5E3; DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot. DT 23-FEB-2022, sequence version 4. DT 24-JUL-2024, entry version 217. DE RecName: Full=Cyclic nucleotide-gated channel alpha-1; DE Short=CNG channel alpha-1; DE Short=CNG-1; DE Short=CNG1 {ECO:0000303|PubMed:11764791}; DE AltName: Full=Cyclic nucleotide-gated channel, photoreceptor; DE AltName: Full=Rod photoreceptor cGMP-gated cation channel subunit alpha {ECO:0000303|PubMed:1372902}; DE AltName: Full=cGMP-gated cation channel alpha-1; GN Name=CNGA1 {ECO:0000303|PubMed:33651975, ECO:0000312|HGNC:HGNC:2148}; GN Synonyms=CNCG, CNCG1; 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]. RC TISSUE=Retina; RX PubMed=1372902; DOI=10.1016/s0021-9258(18)42689-0; RA Pittler S.J., Lee A.K., Altherr M.R., Howard T.A., Seldin M.F., RA Hurwitz R.L., Wasmuth J.J., Baehr W.; RT "Primary structure and chromosomal localization of human and mouse rod RT photoreceptor cGMP-gated cation channel."; RL J. Biol. Chem. 267:6257-6262(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ASN-114. RC TISSUE=Retina; RX PubMed=1379636; DOI=10.1523/jneurosci.12-08-03248.1992; RA Dhallan R.S., Macke J.P., Eddy R.L., Shows T.B., Reed R.R., Yau K.-W., RA Nathans J.; RT "Human rod photoreceptor cGMP-gated channel: amino acid sequence, gene RT structure, and functional expression."; RL J. Neurosci. 12:3248-3256(1992). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Spleen; 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 [4] 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 313-573. 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 [7] RP NOMENCLATURE. RX PubMed=11764791; DOI=10.1126/science.294.5549.2095; RA Bradley J., Frings S., Yau K.W., Reed R.; RT "Nomenclature for ion channel subunits."; RL Science 294:2095-2096(2001). RN [8] RP STRUCTURE BY ELECTRON MICROSCOPY (2.60 ANGSTROMS) OF 140-686, FUNCTION, RP ACTIVITY REGULATION, SUBUNIT, AND MUTAGENESIS OF GLU-361. RX PubMed=33651975; DOI=10.1016/j.neuron.2021.02.007; RA Xue J., Han Y., Zeng W., Wang Y., Jiang Y.; RT "Structural mechanisms of gating and selectivity of human rod CNGA1 RT channel."; RL Neuron 109:1302-1313.e4(2021). RN [9] RP STRUCTURE BY ELECTRON MICROSCOPY (2.61 ANGSTROMS) OF 140-686 IN COMPLEX RP WITH 3',5'-CYCLIC GMP AND 3',5'-CYCLIC AMP, FUNCTION, ACTIVITY REGULATION, RP SUBUNIT, DOMAIN, AND TOPOLOGY. RX PubMed=34699778; DOI=10.1016/j.neuron.2021.10.006; RA Xue J., Han Y., Zeng W., Jiang Y.; RT "Structural mechanisms of assembly, permeation, gating, and pharmacology of RT native human rod CNG channel."; RL Neuron 110:86-95.e5(2022). RN [10] RP VARIANT RP49 PHE-316, VARIANTS GLN-28 AND ASN-114, FUNCTION, AND RP SUBCELLULAR LOCATION. RX PubMed=7479749; DOI=10.1073/pnas.92.22.10177; RA Dryja T.P., Finn J.T., Peng Y.-W., McGee T.L., Berson E.L., Yau K.-W.; RT "Mutations in the gene encoding the alpha subunit of the rod cGMP-gated RT channel in autosomal recessive retinitis pigmentosa."; RL Proc. Natl. Acad. Sci. U.S.A. 92:10177-10181(1995). RN [11] RP INVOLVEMENT IN RP49. RX PubMed=15570217; RA Zhang Q., Zulfiqar F., Riazuddin S.A., Xiao X., Ahmad Z., Riazuddin S., RA Hejtmancik J.F.; RT "Autosomal recessive retinitis pigmentosa in a Pakistani family mapped to RT CNGA1 with identification of a novel mutation."; RL Mol. Vis. 10:884-889(2004). CC -!- FUNCTION: Pore-forming subunit of the rod cyclic nucleotide-gated CC channel. Mediates rod photoresponses at dim light converting transient CC changes in intracellular cGMP levels into electrical signals. In the CC dark, cGMP levels are high and keep the channel open enabling a steady CC inward current carried by Na(+) and Ca(2+) ions that leads to membrane CC depolarization and neurotransmitter release from synaptic terminals. CC Upon photon absorption cGMP levels decline leading to channel closure CC and membrane hyperpolarization that ultimately slows neurotransmitter CC release and signals the presence of light, the end point of the CC phototransduction cascade. Conducts cGMP- and cAMP-gated ion currents, CC with permeability for monovalent and divalent cations. The selectivity CC for Ca(2+) over Na(+) increases with cGMP concentrations, whereas the CC selectivity among monovalent ions is independent of the cGMP levels. CC {ECO:0000250|UniProtKB:Q00194, ECO:0000269|PubMed:33651975, CC ECO:0000269|PubMed:34699778, ECO:0000269|PubMed:7479749}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Ca(2+)(in) = Ca(2+)(out); Xref=Rhea:RHEA:29671, CC ChEBI:CHEBI:29108; Evidence={ECO:0000250|UniProtKB:Q00194}; CC -!- CATALYTIC ACTIVITY: CC Reaction=Na(+)(in) = Na(+)(out); Xref=Rhea:RHEA:34963, CC ChEBI:CHEBI:29101; Evidence={ECO:0000250|UniProtKB:Q00194}; CC -!- CATALYTIC ACTIVITY: CC Reaction=K(+)(in) = K(+)(out); Xref=Rhea:RHEA:29463, ChEBI:CHEBI:29103; CC Evidence={ECO:0000250|UniProtKB:Q00194}; CC -!- CATALYTIC ACTIVITY: CC Reaction=NH4(+)(in) = NH4(+)(out); Xref=Rhea:RHEA:28747, CC ChEBI:CHEBI:28938; Evidence={ECO:0000250|UniProtKB:Q00194}; CC -!- CATALYTIC ACTIVITY: CC Reaction=Rb(+)(in) = Rb(+)(out); Xref=Rhea:RHEA:78547, CC ChEBI:CHEBI:49847; Evidence={ECO:0000250|UniProtKB:Q00194}; CC -!- CATALYTIC ACTIVITY: CC Reaction=Li(+)(in) = Li(+)(out); Xref=Rhea:RHEA:78551, CC ChEBI:CHEBI:49713; Evidence={ECO:0000250|UniProtKB:Q00194}; CC -!- CATALYTIC ACTIVITY: CC Reaction=Cs(+)(in) = Cs(+)(out); Xref=Rhea:RHEA:78555, CC ChEBI:CHEBI:49547; Evidence={ECO:0000250|UniProtKB:Q00194}; CC -!- ACTIVITY REGULATION: Channel opening is activated by cGMP and at a much CC lesser extent by cAMP. Ca(2+) binding concominantly blocks monovalent CC cation currents. Inhibited by L-cis-diltiazem. CC {ECO:0000269|PubMed:33651975, ECO:0000269|PubMed:34699778}. CC -!- SUBUNIT: Forms heterotetrameric channels composed of CNGA1 and CNGB1 CC subunits with 3:1 stoichiometry (PubMed:34699778). May also form cyclic CC nucleotide-activated homotetrameric channels, that are efficiently CC activated by saturating cGMP, but poorly activated by saturating cAMP CC compared to the heterotetramer with CNGB1. The channel binds Ca(2+)- CC bound CALM1 via CaM1 and CaM2 regions of the CNGB1 subunit; this CC interaction modulates the affinity of the channel for cNMPs in response CC to intracellular Ca(2+) levels (By similarity) (PubMed:33651975). CC {ECO:0000250|UniProtKB:Q00194, ECO:0000269|PubMed:33651975, CC ECO:0000269|PubMed:34699778}. CC -!- INTERACTION: CC P29973; Q5ICW4: GRB14; Xeno; NbExp=4; IntAct=EBI-8417095, EBI-7639273; CC P29973; Q9JLM9: Grb14; Xeno; NbExp=2; IntAct=EBI-8417095, EBI-8347358; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:7479749}; CC Multi-pass membrane protein {ECO:0000255}. CC -!- TISSUE SPECIFICITY: Rod cells in the retina. CC -!- DOMAIN: The C-terminal coiled-coil domain mediates homotrimerization of CC CNGA1 subunit. {ECO:0000269|PubMed:34699778}. CC -!- DOMAIN: The cyclic nucleotide-binding domain (CNBD) comprises three CC helices and a beta-roll of eight beta-strands from CNGA1 and CNGB1 CC subunits. Upon cNMP binding transmits the conformational changes to the CC C-linker domain of the S6 helix to open the ion conduction pathway. CC {ECO:0000269|PubMed:34699778}. CC -!- DOMAIN: The ion conduction pathway consists of S5, S6 and pore helices CC from CNGA1 and CNGB1 subunits. It contains a central hydrophobic gate CC that opens upon cNMP binding. {ECO:0000269|PubMed:34699778}. CC -!- DISEASE: Retinitis pigmentosa 49 (RP49) [MIM:613756]: A retinal CC dystrophy belonging to the group of pigmentary retinopathies. Retinitis CC pigmentosa is characterized by retinal pigment deposits visible on CC fundus examination and primary loss of rod photoreceptor cells followed CC by secondary loss of cone photoreceptors. Patients typically have night CC vision blindness and loss of midperipheral visual field. As their CC condition progresses, they lose their far peripheral visual field and CC eventually central vision as well. {ECO:0000269|PubMed:15570217, CC ECO:0000269|PubMed:7479749}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the cyclic nucleotide-gated cation channel (TC CC 1.A.1.5) family. CNGA1 subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA52010.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAF84710.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Mutations of the CNGA1 gene; Note=Retina CC International's Scientific Newsletter; CC URL="https://www.retina-international.org/files/sci-news/cnga1mut.htm"; 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; M84741; AAA52010.1; ALT_INIT; mRNA. DR EMBL; S42457; AAB22778.1; -; mRNA. DR EMBL; AK292021; BAF84710.1; ALT_INIT; mRNA. DR EMBL; AC096749; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC107068; AAY40919.1; -; Genomic_DNA. DR EMBL; CH471069; EAW93048.1; -; Genomic_DNA. DR EMBL; S76062; AAD14206.1; -; Genomic_DNA. DR CCDS; CCDS43226.2; -. DR PIR; A42161; A42161. DR RefSeq; NP_000078.2; NM_000087.3. DR RefSeq; NP_001136036.1; NM_001142564.1. DR RefSeq; XP_005248106.2; XM_005248049.4. DR RefSeq; XP_011511925.1; XM_011513623.2. DR RefSeq; XP_016863201.1; XM_017007712.1. DR PDB; 7LFT; EM; 2.60 A; A/B/C/D=140-686. DR PDB; 7LFW; EM; 2.90 A; A/B/C/D=140-686. DR PDB; 7LFX; EM; 3.10 A; A/B/C/D=140-686. DR PDB; 7LFY; EM; 3.60 A; A/B/C/D=140-686. DR PDB; 7LG1; EM; 2.70 A; A/B/C/D=140-686. DR PDB; 7RH9; EM; 2.61 A; A/C/D=140-686. DR PDB; 7RHG; EM; 2.88 A; A/C/D=140-686. DR PDB; 7RHH; EM; 3.31 A; A/C/D=140-686. DR PDB; 7RHI; EM; 3.31 A; A/C/D=140-686. DR PDB; 7RHJ; EM; 2.88 A; A/C/D=140-686. DR PDB; 7RHK; EM; 3.27 A; A/C/D=140-686. DR PDB; 7RHL; EM; 3.03 A; A/C/D=140-686. DR PDBsum; 7LFT; -. DR PDBsum; 7LFW; -. DR PDBsum; 7LFX; -. DR PDBsum; 7LFY; -. DR PDBsum; 7LG1; -. DR PDBsum; 7RH9; -. DR PDBsum; 7RHG; -. DR PDBsum; 7RHH; -. DR PDBsum; 7RHI; -. DR PDBsum; 7RHJ; -. DR PDBsum; 7RHK; -. DR PDBsum; 7RHL; -. DR AlphaFoldDB; P29973; -. DR EMDB; EMD-23306; -. DR EMDB; EMD-23307; -. DR EMDB; EMD-23308; -. DR EMDB; EMD-23309; -. DR EMDB; EMD-23310; -. DR EMDB; EMD-24458; -. DR EMDB; EMD-24460; -. DR EMDB; EMD-24461; -. DR EMDB; EMD-24462; -. DR EMDB; EMD-24463; -. DR EMDB; EMD-24464; -. DR EMDB; EMD-24465; -. DR SMR; P29973; -. DR BioGRID; 107659; 39. DR IntAct; P29973; 2. DR STRING; 9606.ENSP00000384264; -. DR DrugBank; DB04209; Dequalinium. DR DrugCentral; P29973; -. DR GuidetoPHARMACOLOGY; 394; -. DR TCDB; 1.A.1.5.3; the voltage-gated ion channel (vic) superfamily. DR GlyCosmos; P29973; 1 site, No reported glycans. DR GlyGen; P29973; 1 site. DR iPTMnet; P29973; -. DR PhosphoSitePlus; P29973; -. DR BioMuta; CNGA1; -. DR DMDM; 239938910; -. DR jPOST; P29973; -. DR MassIVE; P29973; -. DR PaxDb; 9606-ENSP00000384264; -. DR PeptideAtlas; P29973; -. DR Antibodypedia; 23791; 102 antibodies from 24 providers. DR DNASU; 1259; -. DR Ensembl; ENST00000402813.9; ENSP00000384264.5; ENSG00000198515.16. DR Ensembl; ENST00000420489.7; ENSP00000389881.3; ENSG00000198515.16. DR Ensembl; ENST00000514170.7; ENSP00000426862.3; ENSG00000198515.16. DR GeneID; 1259; -. DR KEGG; hsa:1259; -. DR MANE-Select; ENST00000514170.7; ENSP00000426862.3; NM_001379270.1; NP_001366199.1. DR UCSC; uc003gxt.5; human. DR AGR; HGNC:2148; -. DR CTD; 1259; -. DR DisGeNET; 1259; -. DR GeneCards; CNGA1; -. DR GeneReviews; CNGA1; -. DR HGNC; HGNC:2148; CNGA1. DR HPA; ENSG00000198515; Tissue enriched (retina). DR MalaCards; CNGA1; -. DR MIM; 123825; gene. DR MIM; 613756; phenotype. DR neXtProt; NX_P29973; -. DR OpenTargets; ENSG00000198515; -. DR Orphanet; 791; Retinitis pigmentosa. DR PharmGKB; PA26658; -. DR VEuPathDB; HostDB:ENSG00000198515; -. DR eggNOG; KOG0500; Eukaryota. DR GeneTree; ENSGT00940000156074; -. DR HOGENOM; CLU_005746_12_0_1; -. DR InParanoid; P29973; -. DR OMA; IYYNWLF; -. DR OrthoDB; 74296at2759; -. DR PhylomeDB; P29973; -. DR TreeFam; TF319048; -. DR PathwayCommons; P29973; -. DR Reactome; R-HSA-2485179; Activation of the phototransduction cascade. DR Reactome; R-HSA-2514859; Inactivation, recovery and regulation of the phototransduction cascade. DR SignaLink; P29973; -. DR BioGRID-ORCS; 1259; 27 hits in 1143 CRISPR screens. DR ChiTaRS; CNGA1; human. DR GeneWiki; Cyclic_nucleotide-gated_channel_alpha_1; -. DR GenomeRNAi; 1259; -. DR Pharos; P29973; Tchem. DR PRO; PR:P29973; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; P29973; Protein. DR Bgee; ENSG00000198515; Expressed in lower esophagus mucosa and 120 other cell types or tissues. DR ExpressionAtlas; P29973; baseline and differential. DR GO; GO:0017071; C:intracellular cyclic nucleotide activated cation channel complex; IBA:GO_Central. DR GO; GO:0042622; C:photoreceptor outer segment membrane; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0120200; C:rod photoreceptor outer segment; ISS:UniProtKB. DR GO; GO:0005262; F:calcium channel activity; IEA:UniProtKB-KW. DR GO; GO:0030552; F:cAMP binding; IDA:UniProtKB. DR GO; GO:0030553; F:cGMP binding; IDA:UniProtKB. DR GO; GO:0005222; F:intracellularly cAMP-activated cation channel activity; IDA:UniProtKB. DR GO; GO:0005223; F:intracellularly cGMP-activated cation channel activity; IDA:UniProtKB. DR GO; GO:0044877; F:protein-containing complex binding; IBA:GO_Central. DR GO; GO:0005272; F:sodium channel activity; IEA:UniProtKB-KW. DR GO; GO:0006816; P:calcium ion transport; ISS:UniProtKB. DR GO; GO:0098655; P:monoatomic cation transmembrane transport; IBA:GO_Central. DR GO; GO:0006814; P:sodium ion transport; ISS:UniProtKB. DR GO; GO:0007601; P:visual perception; TAS:ProtInc. DR CDD; cd00038; CAP_ED; 1. DR Gene3D; 1.10.287.70; -; 1. DR Gene3D; 1.20.5.170; -; 1. DR Gene3D; 1.10.287.630; Helix hairpin bin; 1. DR Gene3D; 2.60.120.10; Jelly Rolls; 1. DR InterPro; IPR032406; CLZ_dom. DR InterPro; IPR050866; CNG_Cation_Channel. DR InterPro; IPR018488; cNMP-bd_CS. DR InterPro; IPR000595; cNMP-bd_dom. DR InterPro; IPR018490; cNMP-bd_dom_sf. DR InterPro; IPR005821; Ion_trans_dom. DR InterPro; IPR014710; RmlC-like_jellyroll. DR PANTHER; PTHR45638; CYCLIC NUCLEOTIDE-GATED CATION CHANNEL SUBUNIT A; 1. DR PANTHER; PTHR45638:SF9; CYCLIC NUCLEOTIDE-GATED CHANNEL ROD PHOTORECEPTOR SUBUNIT ALPHA; 1. 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; cAMP-binding domain-like; 1. DR SUPFAM; SSF81324; Voltage-gated potassium channels; 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; Calcium; Calcium channel; Calcium transport; cAMP; KW cAMP-binding; Cell membrane; cGMP; cGMP-binding; Coiled coil; KW Disease variant; Glycoprotein; Ion channel; Ion transport; KW Ligand-gated ion channel; Membrane; Nucleotide-binding; Reference proteome; KW Retinitis pigmentosa; Sensory transduction; Sodium; Sodium channel; KW Sodium transport; Transmembrane; Transmembrane helix; Transport; Vision. FT CHAIN 1..686 FT /note="Cyclic nucleotide-gated channel alpha-1" FT /id="PRO_0000219308" FT TOPO_DOM 1..165 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 166..187 FT /note="Helical; Name=S1" FT /evidence="ECO:0000269|PubMed:34699778, FT ECO:0007744|PDB:7RH9" FT TOPO_DOM 188..197 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 198..218 FT /note="Helical; Name=S2" FT /evidence="ECO:0000269|PubMed:34699778, FT ECO:0007744|PDB:7RH9" FT TOPO_DOM 219..243 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 244..262 FT /note="Helical; Name=S3" FT /evidence="ECO:0000269|PubMed:34699778, FT ECO:0007744|PDB:7RH9" FT TOPO_DOM 263..267 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 268..286 FT /note="Helical; Name=S4" FT /evidence="ECO:0000269|PubMed:34699778, FT ECO:0007744|PDB:7RH9" FT TOPO_DOM 287..293 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 294..317 FT /note="Helical; Name=S5" FT /evidence="ECO:0000269|PubMed:34699778, FT ECO:0007744|PDB:7RH9" FT TOPO_DOM 318..340 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 341..375 FT /note="Helical; Name=P-helix" FT /evidence="ECO:0000269|PubMed:34699778, FT ECO:0007744|PDB:7RH9" FT TRANSMEM 376..400 FT /note="Helical; Name=S6" FT /evidence="ECO:0000269|PubMed:34699778, FT ECO:0007744|PDB:7RH9" FT TOPO_DOM 401..686 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT REGION 31..75 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 87..149 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 291..399 FT /note="Ion conduction pathway" FT /evidence="ECO:0000305|PubMed:34699778" FT REGION 358..361 FT /note="Selectivity filter" FT /evidence="ECO:0000305|PubMed:34699778" FT REGION 401..477 FT /note="C-linker" FT /evidence="ECO:0000305|PubMed:34699778" FT REGION 481..601 FT /note="Cyclic nucleotide-binding domain" FT /evidence="ECO:0000305|PubMed:34699778, FT ECO:0007744|PDB:7RHI" FT COILED 619..673 FT /evidence="ECO:0000269|PubMed:34699778" FT COMPBIAS 94..127 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 135..149 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 541 FT /ligand="3',5'-cyclic GMP" FT /ligand_id="ChEBI:CHEBI:57746" FT /evidence="ECO:0000269|PubMed:34699778, FT ECO:0007744|PDB:7RHH" FT BINDING 544 FT /ligand="3',5'-cyclic GMP" FT /ligand_id="ChEBI:CHEBI:57746" FT /evidence="ECO:0000269|PubMed:34699778, FT ECO:0007744|PDB:7RHH" FT BINDING 557 FT /ligand="3',5'-cyclic AMP" FT /ligand_id="ChEBI:CHEBI:58165" FT /evidence="ECO:0000269|PubMed:34699778, FT ECO:0007744|PDB:7RHG" FT BINDING 557 FT /ligand="3',5'-cyclic GMP" FT /ligand_id="ChEBI:CHEBI:57746" FT /evidence="ECO:0000269|PubMed:34699778, FT ECO:0007744|PDB:7RHH" FT BINDING 558 FT /ligand="3',5'-cyclic AMP" FT /ligand_id="ChEBI:CHEBI:58165" FT /evidence="ECO:0000269|PubMed:34699778, FT ECO:0007744|PDB:7RHG" FT BINDING 558 FT /ligand="3',5'-cyclic GMP" FT /ligand_id="ChEBI:CHEBI:57746" FT /evidence="ECO:0000269|PubMed:34699778, FT ECO:0007744|PDB:7RHH" FT SITE 385 FT /note="Central gate" FT /evidence="ECO:0000305|PubMed:34699778" FT SITE 389 FT /note="Central gate" FT /evidence="ECO:0000305|PubMed:34699778" FT CARBOHYD 325 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000250|UniProtKB:Q00194" FT VARIANT 28 FT /note="R -> Q (in dbSNP:rs76537883)" FT /evidence="ECO:0000269|PubMed:7479749" FT /id="VAR_009295" FT VARIANT 114 FT /note="D -> N (in dbSNP:rs28642966)" FT /evidence="ECO:0000269|PubMed:1379636, FT ECO:0000269|PubMed:7479749" FT /id="VAR_009296" FT VARIANT 118 FT /note="N -> D (in dbSNP:rs28642966)" FT /id="VAR_047385" FT VARIANT 316 FT /note="S -> F (in RP49; dbSNP:rs62625014)" FT /evidence="ECO:0000269|PubMed:7479749" FT /id="VAR_009297" FT MUTAGEN 361 FT /note="E->Q: Renders the channel voltage-gated in the FT presence of saturated concentrations of cGMP." FT /evidence="ECO:0000269|PubMed:33651975" FT CONFLICT 1 FT /note="M -> MKLSM (in Ref. 3; BAF84710 and 1; AAA52010)" FT /evidence="ECO:0000305" FT CONFLICT 31 FT /note="E -> V (in Ref. 3; BAF84710)" FT /evidence="ECO:0000305" FT CONFLICT 46 FT /note="S -> Y (in Ref. 1; AAA52010)" FT /evidence="ECO:0000305" FT CONFLICT 85 FT /note="L -> I (in Ref. 1; AAA52010)" FT /evidence="ECO:0000305" FT CONFLICT 146..147 FT /note="EE -> HH (in Ref. 1; AAA52010)" FT /evidence="ECO:0000305" FT CONFLICT 205 FT /note="I -> V (in Ref. 3; BAF84710)" FT /evidence="ECO:0000305" FT CONFLICT 539 FT /note="Y -> T (in Ref. 1; AAA52010)" FT /evidence="ECO:0000305" FT CONFLICT 677..678 FT /note="GA -> WS (in Ref. 1; AAA52010)" FT /evidence="ECO:0000305" FT HELIX 159..184 FT /evidence="ECO:0007829|PDB:7LFT" FT HELIX 186..191 FT /evidence="ECO:0007829|PDB:7LFT" FT HELIX 193..215 FT /evidence="ECO:0007829|PDB:7LFT" FT HELIX 229..237 FT /evidence="ECO:0007829|PDB:7LFT" FT HELIX 240..249 FT /evidence="ECO:0007829|PDB:7LFT" FT HELIX 252..254 FT /evidence="ECO:0007829|PDB:7RH9" FT HELIX 255..258 FT /evidence="ECO:0007829|PDB:7LFT" FT HELIX 264..273 FT /evidence="ECO:0007829|PDB:7LFT" FT HELIX 274..285 FT /evidence="ECO:0007829|PDB:7LFT" FT HELIX 291..321 FT /evidence="ECO:0007829|PDB:7LFT" FT STRAND 325..329 FT /evidence="ECO:0007829|PDB:7LFT" FT TURN 336..339 FT /evidence="ECO:0007829|PDB:7LFT" FT HELIX 341..356 FT /evidence="ECO:0007829|PDB:7LFT" FT HELIX 368..399 FT /evidence="ECO:0007829|PDB:7LFT" FT HELIX 401..419 FT /evidence="ECO:0007829|PDB:7LFT" FT HELIX 424..439 FT /evidence="ECO:0007829|PDB:7LFT" FT HELIX 446..450 FT /evidence="ECO:0007829|PDB:7LFT" FT STRAND 451..453 FT /evidence="ECO:0007829|PDB:7RHH" FT HELIX 455..472 FT /evidence="ECO:0007829|PDB:7LFT" FT HELIX 475..478 FT /evidence="ECO:0007829|PDB:7LFT" FT HELIX 481..488 FT /evidence="ECO:0007829|PDB:7LFT" FT STRAND 492..494 FT /evidence="ECO:0007829|PDB:7LFT" FT STRAND 501..503 FT /evidence="ECO:0007829|PDB:7LFT" FT STRAND 505..507 FT /evidence="ECO:0007829|PDB:7LG1" FT STRAND 511..517 FT /evidence="ECO:0007829|PDB:7LFT" FT STRAND 520..523 FT /evidence="ECO:0007829|PDB:7LFT" FT STRAND 525..528 FT /evidence="ECO:0007829|PDB:7RH9" FT STRAND 530..534 FT /evidence="ECO:0007829|PDB:7LFT" FT STRAND 539..541 FT /evidence="ECO:0007829|PDB:7LG1" FT TURN 542..545 FT /evidence="ECO:0007829|PDB:7LFT" FT TURN 552..555 FT /evidence="ECO:0007829|PDB:7RH9" FT STRAND 559..565 FT /evidence="ECO:0007829|PDB:7LFT" FT STRAND 569..573 FT /evidence="ECO:0007829|PDB:7LFT" FT HELIX 574..581 FT /evidence="ECO:0007829|PDB:7LFT" FT HELIX 585..600 FT /evidence="ECO:0007829|PDB:7LFT" FT HELIX 622..658 FT /evidence="ECO:0007829|PDB:7RHL" SQ SEQUENCE 686 AA; 79126 MW; E5200D216FC97AF6 CRC64; MKNNIINTQQ SFVTMPNVIV PDIEKEIRRM ENGACSSFSE DDDSASTSEE SENENPHARG SFSYKSLRKG GPSQREQYLP GAIALFNVNN SSNKDQEPEE KKKKKKEKKS KSDDKNENKN DPEKKKKKKD KEKKKKEEKS KDKKEEEKKE VVVIDPSGNT YYNWLFCITL PVMYNWTMVI ARACFDELQS DYLEYWLILD YVSDIVYLID MFVRTRTGYL EQGLLVKEEL KLINKYKSNL QFKLDVLSLI PTDLLYFKLG WNYPEIRLNR LLRFSRMFEF FQRTETRTNY PNIFRISNLV MYIVIIIHWN ACVFYSISKA IGFGNDTWVY PDINDPEFGR LARKYVYSLY WSTLTLTTIG ETPPPVRDSE YVFVVVDFLI GVLIFATIVG NIGSMISNMN AARAEFQARI DAIKQYMHFR NVSKDMEKRV IKWFDYLWTN KKTVDEKEVL KYLPDKLRAE IAINVHLDTL KKVRIFADCE AGLLVELVLK LQPQVYSPGD YICKKGDIGR EMYIIKEGKL AVVADDGVTQ FVVLSDGSYF GEISILNIKG SKAGNRRTAN IKSIGYSDLF CLSKDDLMEA LTEYPDAKTM LEEKGKQILM KDGLLDLNIA NAGSDPKDLE EKVTRMEGSV DLLQTRFARI LAEYESMQQK LKQRLTKVEK FLKPLIDTEF SSIEGPGAES GPIDST //