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CNGA1

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Target not currently curated in GtoImmuPdb

Target id: 394

Nomenclature: CNGA1

Family: Cyclic nucleotide-regulated channels (CNG)

Contents:

Gene and Protein Information Click here for help
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 690 4p12 CNGA1 cyclic nucleotide gated channel subunit alpha 1 4,17
Mouse 6 1 684 5 38.44 cM Cnga1 cyclic nucleotide gated channel alpha 1 17
Rat 6 1 683 14p11 Cnga1 cyclic nucleotide gated channel subunit alpha 1 1,5
Previous and Unofficial Names Click here for help
CNCG | CNCG1 | cGMP-gated cation channel alpha-1 | CNG channel alpha-1 | cyclic nucleotide-gated channel, photoreceptor | rod photoreceptor cGMP-gated channel subunit alpha | CNG1
Database Links Click here for help
Alphafold P29973 (Hs), P29974 (Mm), Q62927 (Rn)
CATH/Gene3D 2.60.120.10
Ensembl Gene ENSG00000198515 (Hs), ENSMUSG00000067220 (Mm), ENSRNOG00000004778 (Rn)
Entrez Gene 1259 (Hs), 12788 (Mm), 85259 (Rn)
Human Protein Atlas ENSG00000198515 (Hs)
KEGG Gene hsa:1259 (Hs), mmu:12788 (Mm), rno:85259 (Rn)
OMIM 123825 (Hs)
Orphanet ORPHA120664 (Hs)
Pharos P29973 (Hs)
RefSeq Nucleotide NM_000087 (Hs), NM_007723 (Mm), NM_053497 (Rn)
RefSeq Protein NP_000078 (Hs), NP_031749 (Mm), NP_445949 (Rn)
UniProtKB P29973 (Hs), P29974 (Mm), Q62927 (Rn)
Wikipedia CNGA1 (Hs)
Associated Proteins Click here for help
Heteromeric Pore-forming Subunits
Name References
Not determined
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
CNGB1a 20
Garp1/Garp2 14
Grb14 10
Functional Characteristics Click here for help
γ = 25-30 pS
PCa/PNa = 3.1
Ion Selectivity and Conductance Click here for help
Species:  Human
Rank order:  Ca2+ > Na+ = K+ > Li+ > Rb+ > Cs+ [25.0 - 30.0 pS]
References:  3-4,13
Activators (Human)
cyclic GMP (EC50 ~ 30 μM) >> cyclic AMP

Download all structure-activity data for this target as a CSV file go icon to follow link

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
cyclic GMP Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Agonist 4.1 – 4.2 pKi - -60.0 – 60.0 2,4,6-7,9,16,23
⤷ pKi 4.1 – 4.2 (Ki 8.5x10-5 – 6x10-5 M) [2,4,6-7,9,16,23]
Holding voltage: -60.0 – 60.0 mV
Activator Comments
Micromolar concentrations of Ni2+ cause an increase in the response of CNGA1 to both cGMP and cAMP [9].
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
L-(cis)-diltiazem Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 4.0 pKi - -80.0 – 80.0 3
⤷ pKi 4.0 (Ki 1x10-4 M) high affinity binding requires presence of CNGB subunits [3]
Holding voltage: -80.0 – 80.0 mV
dequalinium Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 6.7 pIC50 - 0.0 18
⤷ pIC50 6.7 [18]
Holding voltage: 0.0 mV
H-8 Small molecule or natural product Ligand has a PDB structure Rn Antagonist 3.5 pIC50 - 100.0 21
⤷ pIC50 3.5 [21]
Holding voltage: 100.0 mV
View species-specific channel blocker tables
Tissue Distribution Click here for help
Retina.
Species:  Human
Technique:  Northern Blot
References:  4,17
Rod outer segments.
Species:  Mouse
Technique:  Immunohistochemistry
References:  11
Rod photoreceptors (outer segments).
Species:  Mouse
Technique:  Northern Blot
References:  17
Pineal gland.
Species:  Rat
Technique:  In situ hybridisation
References:  19
Eye, pineal gland, pituitary, adrenal gland, spleen, testis.
Species:  Rat
Technique:  Northern Blot
References:  5
Rod outer segments.
Species:  Rat
Technique:  Immunohistochemistry
References:  1
Physiological Functions Click here for help
Together with CNGB1a this subunit forms the native rod CNG channel. This channel mediates the Na+/Ca2+ influx that depolarises rod photoreceptors in the dark ("dark current").
Species:  Rat
Tissue:  Retina.
References: 
Together with CNGB1a this subunit forms the native rod CNG channel. This channel mediates the Na+/Ca2+ influx that depolarises rod photoreceptors in the dark ("dark current").
Species:  Mouse
Tissue:  Retina.
References: 
Together with CNGB1a this subunit forms the native rod CNG channel. This channel mediates the Na+/Ca2+ influx that depolarises rod photoreceptors in the dark ("dark current").
Species:  Human
Tissue:  Retina.
References: 
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Retinitis pigmentosa 49; RP49
Synonyms: Retinitis pigmentosa [Orphanet: ORPHA791] [Disease Ontology: DOID:10584]
Disease Ontology: DOID:10584
OMIM: 613756
Orphanet: ORPHA791
References:  6,15,22
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Frameshift: Deletion Human R654fsX 1-bp del 6
Frameshift: Deletion Human S209fsX26 c.626_627delTA Exon 8 22
Missense Human S316F 6
Missense Human I384T 8
Missense Human R424H 12
Nonsense Human R28X c.82C>T A severe mutation leading to very premature truncation of the protein. 15
Nonsense Human E76X 6
Nonsense Human K139X 6

References

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1. Barnstable CJ, Wei J-Y. (1995) Isolation and characterization of the alpha-subunit of the rat rod photoreceptor cGMP-gated cation channel. J Mol Neurosci, 6 (4): 289-302. [PMID:8860239]

2. Chen TY, Illing M, Molday LL, Hsu YT, Yau KW, Molday RS. (1994) Subunit 2 (or beta) of retinal rod cGMP-gated cation channel is a component of the 240-kDa channel-associated protein and mediates Ca(2+)-calmodulin modulation. Proc Natl Acad Sci USA, 91 (24): 11757-61. [PMID:7526403]

3. Chen TY, Peng YW, Dhallan RS, Ahamed B, Reed RR, Yau KW. (1993) A new subunit of the cyclic nucleotide-gated cation channel in retinal rods. Nature, 362 (6422): 764-7. [PMID:7682292]

4. Dhallan RS, Macke JP, Eddy RL, Shows TB, Reed RR, Yau KW, Nathans J. (1992) Human rod photoreceptor cGMP-gated channel: amino acid sequence, gene structure, and functional expression. J Neurosci, 12 (8): 3248-56. [PMID:1379636]

5. Ding C, Potter ED, Qiu W, Coon SL, Levine MA, Guggino SE. (1997) Cloning and widespread distribution of the rat rod-type cyclic nucleotide-gated cation channel. Am J Physiol, 272 (4 Pt 1): C1335-44. [PMID:9142860]

6. Dryja TP, Finn JT, Peng YW, McGee TL, Berson EL, Yau KW. (1995) Mutations in the gene encoding the alpha subunit of the rod cGMP-gated channel in autosomal recessive retinitis pigmentosa. Proc Natl Acad Sci USA, 92 (22): 10177-81. [PMID:7479749]

7. Finn JT, Krautwurst D, Schroeder JE, Chen TY, Reed RR, Yau KW. (1998) Functional co-assembly among subunits of cyclic-nucleotide-activated, nonselective cation channels, and across species from nematode to human. Biophys J, 74 (3): 1333-45. [PMID:9512030]

8. González-del Pozo M, Borrego S, Barragán I, Pieras JI, Santoyo J, Matamala N, Naranjo B, Dopazo J, Antiñolo G. (2011) Mutation screening of multiple genes in Spanish patients with autosomal recessive retinitis pigmentosa by targeted resequencing. PLoS ONE, 6 (12): e27894. [PMID:22164218]

9. Gordon SE, Zagotta WN. (1995) A histidine residue associated with the gate of the cyclic nucleotide-activated channels in rod photoreceptors. Neuron, 14 (1): 177-83. [PMID:7530019]

10. Gupta VK, Rajala A, Daly RJ, Rajala RV. (2010) Growth factor receptor-bound protein 14: a new modulator of photoreceptor-specific cyclic-nucleotide-gated channel. EMBO Rep, 11 (11): 861-7. [PMID:20890309]

11. Hüttl S, Michalakis S, Seeliger M, Luo DG, Acar N, Geiger H, Hudl K, Mader R, Haverkamp S, Moser M et al.. (2005) Impaired channel targeting and retinal degeneration in mice lacking the cyclic nucleotide-gated channel subunit CNGB1. J Neurosci, 25 (1): 130-8. [PMID:15634774]

12. Jin ZB, Mandai M, Yokota T, Higuchi K, Ohmori K, Ohtsuki F, Takakura S, Itabashi T, Wada Y, Akimoto M et al.. (2008) Identifying pathogenic genetic background of simplex or multiplex retinitis pigmentosa patients: a large scale mutation screening study. J Med Genet, 45 (7): 465-72. [PMID:18310263]

13. Kaupp UB, Seifert R. (2002) Cyclic nucleotide-gated ion channels. Physiol Rev, 82 (3): 769-824. [PMID:12087135]

14. Michalakis S, Zong X, Becirovic E, Hammelmann V, Wein T, Wanner KT, Biel M. (2011) The glutamic acid-rich protein is a gating inhibitor of cyclic nucleotide-gated channels. J Neurosci, 31 (1): 133-41. [PMID:21209198]

15. Paloma E, Martínez-Mir A, García-Sandoval B, Ayuso C, Vilageliu L, Gonzàlez-Duarte R, Balcells S. (2002) Novel homozygous mutation in the alpha subunit of the rod cGMP gated channel (CNGA1) in two Spanish sibs affected with autosomal recessive retinitis pigmentosa. J Med Genet, 39 (10): E66. [PMID:12362048]

16. Paoletti P, Young EC, Siegelbaum SA. (1999) C-Linker of cyclic nucleotide-gated channels controls coupling of ligand binding to channel gating. J Gen Physiol, 113 (1): 17-34. [PMID:9874685]

17. Pittler SJ, Lee AK, Altherr MR, Howard TA, Seldin MF, Hurwitz RL, Wasmuth JJ, Baehr W. (1992) Primary structure and chromosomal localization of human and mouse rod photoreceptor cGMP-gated cation channel. J Biol Chem, 267 (9): 6257-62. [PMID:1372902]

18. Rosenbaum T, Islas LD, Carlson AE, Gordon SE. (2003) Dequalinium: a novel, high-affinity blocker of CNGA1 channels. J Gen Physiol, 121 (1): 37-47. [PMID:12508052]

19. Sautter A, Biel M, Hofmann F. (1997) Molecular cloning of cyclic nucleotide-gated cation channel subunits from rat pineal gland. Brain Res Mol Brain Res, 48 (1): 171-5. [PMID:9379842]

20. Trudeau MC, Zagotta WN. (2002) An intersubunit interaction regulates trafficking of rod cyclic nucleotide-gated channels and is disrupted in an inherited form of blindness. Neuron, 34 (2): 197-207. [PMID:11970862]

21. Wei JY, Cohen ED, Barnstable CJ. (1997) Direct blockade of both cloned rat rod photoreceptor cyclic nucleotide-gated non-selective cation (CNG) channel alpha-subunit and native CNG channels from Xenopus rod outer segments by H-8, a non-specific cyclic nucleotide-dependent protein kinase inhibitor. Neurosci Lett, 233 (1): 37-40. [PMID:9324234]

22. Zhang Q, Zulfiqar F, Riazuddin SA, Xiao X, Ahmad Z, Riazuddin S, Hejtmancik JF. (2004) Autosomal recessive retinitis pigmentosa in a Pakistani family mapped to CNGA1 with identification of a novel mutation. Mol Vis, 10: 884-9. [PMID:15570217]

23. Zheng J, Trudeau MC, Zagotta WN. (2002) Rod cyclic nucleotide-gated channels have a stoichiometry of three CNGA1 subunits and one CNGB1 subunit. Neuron, 36 (5): 891-6. [PMID:12467592]

Contributors

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