Nomenclature: CNGA1

Family: Cyclic nucleotide-regulated channels

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates. 

Contents

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 690 4p12 CNGA1 cyclic nucleotide gated channel alpha 1 4,17
Mouse 6 1 684 5 C3.2 Cnga1 cyclic nucleotide gated channel alpha 1 17
Rat 6 1 683 14p11 Cnga1 cyclic nucleotide gated channel alpha 1 1,5
Previous and Unofficial Names
CNCG
CNCG1
RCNCa
RCNCα
CNG1
RCNC1
CNGα1
HCN
CNG channel alpha-1
CNG-1
cGMP-gated cation channel alpha-1
cyclic nucleotide gated channel alpha 1
cyclic nucleotide-gated cation channel
cyclic nucleotide-gated cation channel 1
cyclic nucleotide-gated channel alpha-1
cyclic nucleotide-gated channel, photoreceptor
rod photoreceptor cGMP-gated channel subunit alpha
Database Links
Ensembl Gene
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
Orphanet Gene
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Not determined
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
CNGB1a 19
Garp1/Garp2 14
Grb14 10
Functional Characteristics
γ = 25-30 pS
PCa/PNa = 3.1
Ion Selectivity and Conductance
Species:  Human
Rank order:  Ca2+ > Na+ = K+ > Li+ > Rb+ > Cs+ [25.0 - 30.0 pS]
References:  3-4,13
Activators (Human)
cGMP (EC50 ~ 30 μM) >> cAMP
Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
cGMP Hs Agonist 4.07 – 4.22 (median: 4.16) pKi - -60.0 – 60.0 2,4,6-7,9,16,22
pKi 4.07 – 4.22 (median: 4.16) (8.5x10-5 – 6x10-5 (median: 6.9x10-5) M) [2,4,6-7,9,16,22]
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 Affinity Units Concentration range (M) Holding voltage (mV) Reference
L-(cis)-diltiazem Hs Antagonist 4.0 pKi - -80.0 – 80.0 3
pKi 4.0 (1x10-4 M) [3]
Holding voltage: -80.0 – 80.0 mV
H-8 Rn Antagonist 3.5 pIC50 - 100.0 20
pIC50 3.5 [20]
Holding voltage: 100.0 mV
View species-specific channel blocker tables
Tissue Distribution
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:  18
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
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
Disease:  Retinitis pigmentosa 49; RP49
OMIM:  613756
Orphanet:  791
References:  6,15,21
Click column headers to sort
Type Species Molecular location Description Reference
Frameshift Human R654fsX 6
Frameshift Human S209fsX 21
Missense Human I384T 8
Missense Human S316F 6
Missense Human R424H 12
Truncation Human K139X 6
Truncation Human R28X 15
Truncation Human E76X 6

REFERENCES

1. Barnstable CJ. (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. U.S.A.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. Nature362 (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. U.S.A.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 ONE6 (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. Neuron14 (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, Pfeifer A, Gerstner A, Yau KW, Biel M. (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. 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]

19. 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. Neuron34 (2): 197-207. [PMID:11970862]

20. 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]

21. 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]

22. Zheng J, Trudeau MC, Zagotta WN. (2002) Rod cyclic nucleotide-gated channels have a stoichiometry of three CNGA1 subunits and one CNGB1 subunit. Neuron36 (5): 891-6. [PMID:12467592]

To cite this database page, please use the following:

Elvir Becirovic, Martin Biel.
Cyclic nucleotide-regulated channels: CNGA1. Last modified on 23/09/2013. Accessed on 22/10/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=394.

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