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CNGA1

Family: Cyclic nucleotide-regulated channels

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Associated Proteins
Ion Selectivity and Conductance
Activators
Pore Blockers
Tissue Distribution
Physiological Functions
Clinically-Relevant Mutations and Pathophysiology
References
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 5,14
Mouse 6 1 684 5 C3.2 Cnga1 cyclic nucleotide gated channel alpha 1 14
Rat 6 1 683 14p11 Cnga1 cyclic nucleotide gated channel alpha 1 1,6
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 ENSG00000198515 (Hs), ENSMUSG00000067220 (Mm), ENSRNOG00000004778 (Rn)
Entrez Gene 1259 (Hs), 12788 (Mm), 85259 (Rn)
GeneCards CNGA1 (Hs)
GenitoUrinary Development Molecular Anatomy Project Cnga1 (Mm)
HomoloGene 55432 (Hs)
Human Protein Reference Database 00445 (Hs)
InterPro P29973 (Hs), P29974 (Mm), Q62927 (Rn)
KEGG Gene hsa:1259 (Hs), mmu:12788 (Mm), rno:85259 (Rn)
OMIM 123825 (Hs)
Orphanet Gene ORPHA120664 (Hs)
PharmGKB Gene PA26658 (Hs)
PhosphoSitePlus P29973 (Hs), P29974 (Mm), Q62927 (Rn)
Protein Ontology (PRO) PRO:000000686 (Hs)
RefSeq Nucleotide NM_000087 (Hs), NM_007723 (Mm), NM_053497 (Rn)
RefSeq Protein NP_000078 (Hs), NP_031749 (Mm), NP_445949 (Rn)
TreeFam ENSG00000198515 (Hs), ENSMUSG00000067220 (Mm), ENSRNOG00000004778 (Rn)
UniGene Hs. 1323 (Hs)
UniProt P29973 (Hs), P29974 (Mm), Q62927 (Rn)
Wikipedia CNGA1
Cyclic nucleotide-regulated channels
Search for 3D structures on the PDB
Search by keyword: Cyclic nucleotide-regulated channels CNGA1 Search by accession number: P29973, Q62927, P29974
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Not determined
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
Not determined
Ion Selectivity and Conductance
Species:  Human
Rank order:  Ca2+ > Na+ = K+ > Li+ > Rb+ > Cs+ [25.0 - 30.0 pS]
References:  3,5,11
Activators (Human)
cGMP (EC50 ~ 30 μM) >> cAMP
Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Affinity Units Concentration range (M) Holding voltage (mV) Reference
cGMP Hs 4.07 – 4.22 (median: 4.16) pKi - -60.0 – 60.0 2,5,7-9,13,19
Activator Comments
Micromolar concentrations of Ni2+ cause an increase in the response of CNGA1 to both cGMP and cAMP [9].
Pore Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Affinity Units Concentration range (M) Holding voltage (mV) Reference
L-(cis)-diltiazem Hs 4.0 pKi - -80.0 – 80.0 3
H-8 Rn 3.5 pIC50 - 100.0 16
View species-specific pore blocker tables
Tissue Distribution
Retina.
Species:  Human
Technique:  Northern Blot
References:  5,14
Rod outer segments.
Species:  Mouse
Technique:  Immunohistochemistry
References:  10
Rod photoreceptors (outer segments).
Species:  Mouse
Technique:  Northern Blot
References:  14
Pineal gland.
Species:  Rat
Technique:  In situ hybridisation
References:  15
Eye, pineal gland, pituitary, adrenal gland, spleen, testis.
Species:  Rat
Technique:  Northern Blot
References:  6
Rod outer segments.
Species:  Rat
Technique:  Immunohistochemistry
References:  1
Functional Assays
Not Determined
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+ influs that depolarises rod photoreceptorsin the dark ("dark current").
Species:  Human
Tissue:  Retina.
References: 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Retinitis pigmentosa 49; RP49
OMIM:  613756
Orphanet:  791
References:  7,12,18
Click column headers to sort
Type Species Molecular location Description Reference
Frameshift Human S209fsX 18
Frameshift Human R654fsX 7,12
Missense Human S316F 7
Truncation Human R28X 7,12

REFERENCES

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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. Nature, 362 (6422): 764-7. [PMID:7682292]

4. Colville, CA; Molday, RS. (1996) Primary structure and expression of the human beta-subunit and related proteins of the rod photoreceptor cGMP-gated channel. J. Biol. Chem., 271 (51): 32968-74. [PMID:8955140]

5. 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]

6. 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]

7. 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]

8. 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]

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. 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]

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

12. 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]

13. 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]

14. 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]

15. 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]

16. 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]

17. Weitz, D; Ficek, N; Kremmer, E; Bauer, PJ; Kaupp, UB. (2002) Subunit stoichiometry of the CNG channel of rod photoreceptors. Neuron, 36 (5): 881-9. [PMID:12467591]

18. 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]

19. 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]

20. Zhong, H; Molday, LL; Molday, RS; Yau, KW. (2002) The heteromeric cyclic nucleotide-gated channel adopts a 3A:1B stoichiometry. Nature, 420 (6912): 193-8. [PMID:12432397]

To cite this database page, please use the following:

Martin Biel, Franz Hofmann, U. Benjamin Kaupp.
Cyclic nucleotide-regulated channels: CNGA1. Last modified on 08/03/2013. Accessed on 18/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=394.


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