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CNGA2

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Target not currently curated in GtoImmuPdb

Target id: 395

Nomenclature: CNGA2

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 1 664 Xq28 CNGA2 cyclic nucleotide gated channel subunit alpha 2
Mouse 6 1 664 X A7.3 Cnga2 cyclic nucleotide gated channel alpha 2 23
Rat 6 1 664 16q12.4 Cnga2 cyclic nucleotide gated channel subunit alpha 2 12
Previous and Unofficial Names Click here for help
CNGα3 | CNG2 | CNCA | Cncg4 | CNG channel alpha-2 | cyclic nucleotide gated channel 4 | cyclic nucleotide-gated olfactory channel subunit OCNC1 | cyclic nucleotide gated channel alpha 2
Database Links Click here for help
Alphafold Q16280 (Hs), Q62398 (Mm), Q00195 (Rn)
CATH/Gene3D 2.60.120.10
ChEMBL Target CHEMBL4523272 (Rn)
Ensembl Gene ENSG00000183862 (Hs), ENSMUSG00000005864 (Mm), ENSRNOG00000030119 (Rn)
Entrez Gene 1260 (Hs), 12789 (Mm), 25411 (Rn)
Human Protein Atlas ENSG00000183862 (Hs)
KEGG Gene hsa:1260 (Hs), mmu:12789 (Mm), rno:25411 (Rn)
OMIM 300338 (Hs)
Pharos Q16280 (Hs)
RefSeq Nucleotide NM_005140 (Hs), NM_007724 (Mm), NM_012928 (Rn)
RefSeq Protein NP_005131 (Hs), NP_031750 (Mm), NP_037060 (Rn)
UniProtKB Q16280 (Hs), Q62398 (Mm), Q00195 (Rn)
Wikipedia CNGA2 (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
CNGB1b 25
CNGA4 25
Calmodulin 1,17
Functional Characteristics Click here for help
γ = 35 pS
PCa/PNa = 6.8
Ion Selectivity and Conductance Click here for help
Species:  Rat
Rank order:  Ca2+ > K+ > Na+ [35.0 pS]
References:  9,12,16
Activators (Human)
cyclic GMP > cyclic AMP (EC50 ~ 1 μM)

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 Rn Agonist 5.6 – 5.8 pEC50 - -80.0 – 100.0 2,16,20
⤷ pEC50 5.6 – 5.8 (EC50 2.5x10-6 – 1.74x10-6 M) [2,16,20]
Holding voltage: -80.0 – 100.0 mV
cyclic AMP Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Rn Agonist 4.2 – 4.3 pEC50 - -80.0 – 100.0 2,9,16,20
⤷ pEC50 4.2 – 4.3 (EC50 6.16x10-5 – 4.57x10-5 M) [2,9,16,20]
Holding voltage: -80.0 – 100.0 mV
Gating inhibitors Click here for help
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
PIP3 Small molecule or natural product Rn Antagonist - - 1x10-5 -50.0 – 50.0 5
⤷ Conc range: 1x10-5 M [5]
Holding voltage: -50.0 – 50.0 mV
calmodulin {Sp: Human} Peptide Click here for species-specific activity table Rn Antagonist 7.7 – 8.5 pIC50 - -60.0 10,17
⤷ pIC50 7.7 – 8.5 [10,17]
Holding voltage: -60.0 mV
all-trans-retinal Small molecule or natural product Ligand has a PDB structure Rn Antagonist 4.6 pIC50 - 100.0 11
⤷ pIC50 4.6 [11]
Holding voltage: 100.0 mV
Gating Inhibitor Comments
The calmodulin binding site of CNGA2 is functionally silent in heteromeric CNG channels. Feedback-inhibition of the native olfactory CNG channel by calcium-calmodulin (CaM) is conferred by the CNGA4 and CNGB1b subunits [1,3-4,18-19,24].
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
pseudechetoxin Peptide Rn Antagonist 8.3 pKi - -60.0 6-7
⤷ pKi 8.3 [6-7]
Holding voltage: -60.0 mV
L-(cis)-diltiazem Small molecule or natural product Ligand has a PDB structure Rn Antagonist 2.1 pKi - -40.0 – 40.0 12
⤷ pKi 2.1 [12]
Holding voltage: -40.0 – 40.0 mV
dequalinium Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 5.6 pIC50 - 0.0 22
⤷ pIC50 5.6 [22]
Holding voltage: 0.0 mV
View species-specific channel blocker tables
Tissue Distribution Click here for help
Heart.
Species:  Mouse
Technique:  Immunohistochemistry
References:  23
Olfactory sensory neurons.
Species:  Mouse
Technique:  Immunocytochemistry
References:  18
Olfactory sensory neurons.
Species:  Rat
Technique:  Northern Blot
References:  12
Olfactory sensory neurons, brain.
Species:  Rat
Technique:  Immunocytochemistry
References:  9,15
Hippocampus.
Species:  Rat
Technique:  In situ hybridisation
References:  11
Cochlea
Species:  Rat
Technique:  Immunohistochemistry, RT-PCR
References:  13
Functional Assays Click here for help
Not established.
Species:  None
Tissue: 
Response measured: 
References: 
Physiological Functions Click here for help
Olfactory signal transduction. This subunit forms together with CNGA4 and CNGB1b the native olfactory CNG channel.
Species:  None
Tissue:  Olfactory sensory epithelium.
References:  8,14,21
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Cnga2tm1Mom Cnga2tm1Mom/Y
involves: 129S1/Sv		 MGI:108040  MP:0004811 abnormal neuron physiology PMID: 10798394 
Cnga2tm1Mom Cnga2tm1Mom/Cnga2tm1Mom
involves: 129S1/Sv		 MGI:108040  MP:0004811 abnormal neuron physiology PMID: 10798394 
Cnga2tm1Mom|Olfr160+|Olfr160tm5(Cnga2)Mom Cnga2tm1Mom/Cnga2tm1Mom,Olfr160tm5(Cnga2)Mom/Olfr160+
involves: 129P2/OlaHsd * 129S1/Sv		 MGI:108040  MGI:1931271  MP:0004811 abnormal neuron physiology PMID: 10798394 
Cnga2tm1Mom|Olfr160+|Olfr160tm5(Cnga2)Mom Cnga2tm1Mom/Y,Olfr160tm5(Cnga2)Mom/Olfr160+
involves: 129P2/OlaHsd * 129S1/Sv		 MGI:108040  MGI:1931271  MP:0004811 abnormal neuron physiology PMID: 10798394 
Cnga2tm1Ngai Cnga2tm1Ngai/Cnga2tm1Ngai
involves: 129S1/Sv * FVB/N		 MGI:108040  MP:0001984 abnormal olfaction PMID: 15071119 
Cnga2tm1Mom|Olfr160+|Olfr160tm4Mom Cnga2tm1Mom/Cnga2tm1Mom,Olfr160tm4Mom/Olfr160+
involves: 129P2/OlaHsd * 129S1/Sv		 MGI:108040  MGI:1931271  MP:0000819 abnormal olfactory bulb morphology PMID: 10798394 
Cnga2tm1Mom|Olfr160+|Olfr160tm4Mom Cnga2tm1Mom/Y,Olfr160tm4Mom/Olfr160+
involves: 129P2/OlaHsd * 129S1/Sv		 MGI:108040  MGI:1931271  MP:0000819 abnormal olfactory bulb morphology PMID: 10798394 
Cnga2tm1Gvr Cnga2tm1Gvr/Y
involves: 129 * 129S1/SvImJ * C57BL/6J		 MGI:108040  MP:0000819 abnormal olfactory bulb morphology PMID: 10531436 
Cnga2tm1Gvr Cnga2tm1Gvr/Y
involves: 129 * 129S1/SvImJ * C57BL/6J		 MGI:108040  MP:0005236 abnormal olfactory nerve morphology PMID: 10531436 
Cnga2+|Cnga2tm1Reed Cnga2tm1Reed/Cnga2+
involves: 129/Sv * BALB/cJ		 MGI:108040  MP:0006092 abnormal olfactory neuron morphology PMID: 11257220 
Cnga2tm1Mom|Olfr160+|Olfr160tm4Mom Cnga2tm1Mom/Cnga2tm1Mom,Olfr160tm4Mom/Olfr160+
involves: 129P2/OlaHsd * 129S1/Sv		 MGI:108040  MGI:1931271  MP:0006092 abnormal olfactory neuron morphology PMID: 10798394 
Cnga2tm1Mom|Olfr160+|Olfr160tm4Mom Cnga2tm1Mom/Y,Olfr160tm4Mom/Olfr160+
involves: 129P2/OlaHsd * 129S1/Sv		 MGI:108040  MGI:1931271  MP:0006092 abnormal olfactory neuron morphology PMID: 10798394 
Cnga2tm1Ngai Cnga2tm1Ngai/Cnga2tm1Ngai
involves: 129S1/Sv * FVB/N		 MGI:108040  MP:0001983 abnormal olfactory system physiology PMID: 15071119 
Cnga2tm1Ngai Cnga2tm1Ngai/Y
involves: 129S1/Sv		 MGI:108040  MP:0001983 abnormal olfactory system physiology PMID: 8893025 
Cnga2tm1Reed Cnga2tm1Reed/Y
involves: 129/Sv * BALB/cJ		 MGI:108040  MP:0001983 abnormal olfactory system physiology PMID: 11257220 
Cnga2tm1Mom Cnga2tm1Mom/Y
involves: 129S1/Sv		 MGI:108040  MP:0001983 abnormal olfactory system physiology PMID: 10798394 
Cnga2tm1Mom Cnga2tm1Mom/Cnga2tm1Mom
involves: 129S1/Sv		 MGI:108040  MP:0001983 abnormal olfactory system physiology PMID: 10798394 
Cnga2tm1Mom|Olfr160+|Olfr160tm5(Cnga2)Mom Cnga2tm1Mom/Cnga2tm1Mom,Olfr160tm5(Cnga2)Mom/Olfr160+
involves: 129P2/OlaHsd * 129S1/Sv		 MGI:108040  MGI:1931271  MP:0001983 abnormal olfactory system physiology PMID: 10798394 
Cnga2tm1Mom|Olfr160+|Olfr160tm5(Cnga2)Mom Cnga2tm1Mom/Y,Olfr160tm5(Cnga2)Mom/Olfr160+
involves: 129P2/OlaHsd * 129S1/Sv		 MGI:108040  MGI:1931271  MP:0001983 abnormal olfactory system physiology PMID: 10798394 
Cnga2tm2Reed Cnga2tm2Reed/Y
involves: 129/Sv * BALB/cJ		 MGI:108040  MP:0001983 abnormal olfactory system physiology PMID: 11257220 
Cnga2tm1Reed Cnga2tm1Reed/Y
involves: 129/Sv * BALB/cJ		 MGI:108040  MP:0010055 abnormal sensory neuron physiology PMID: 11257220 
Cnga2tm2Reed Cnga2tm2Reed/Y
involves: 129/Sv * BALB/cJ		 MGI:108040  MP:0010055 abnormal sensory neuron physiology PMID: 11257220 
Cnga2tm1Mom|Olfr151tm2Mom|Olfr151tm4Mom Cnga2tm1Mom/Cnga2tm1Mom,Olfr151tm2Mom/Olfr151tm4Mom
involves: 129P2/OlaHsd * C57BL/6		 MGI:108040  MGI:2661338  MP:0000967 abnormal sensory neuron projections PMID: 15186781 
Cnga2tm1Ngai Cnga2tm1Ngai/Y
involves: 129S1/Sv		 MGI:108040  MP:0004512 anosmia PMID: 8893025 
Cnga2tm1Gvr Cnga2tm1Gvr/Cnga2tm1Gvr
involves: 129 * C57BL/6		 MGI:108040  MP:0002922 decreased post-tetanic potentiation PMID: 9636130 
Cnga2tm1Gvr Cnga2tm1Gvr/Y
involves: 129 * C57BL/6		 MGI:108040  MP:0002922 decreased post-tetanic potentiation PMID: 9636130 
Cnga2tm1Gvr Cnga2tm1Gvr/Cnga2tm1Gvr
involves: 129 * C57BL/6		 MGI:108040  MP:0002058 neonatal lethality PMID: 9636130 
Cnga2tm1Gvr Cnga2tm1Gvr/Y
involves: 129 * C57BL/6		 MGI:108040  MP:0002058 neonatal lethality PMID: 9636130 
Cnga2tm1Gvr Cnga2tm1Gvr/Y
involves: 129 * 129S1/SvImJ * C57BL/6J		 MGI:108040  MP:0002058 neonatal lethality PMID: 10531436 
Cnga2tm1Mom Cnga2tm1Mom/Y
involves: 129S1/Sv		 MGI:108040  MP:0001732 postnatal growth retardation PMID: 10798394 
Cnga2tm1Mom Cnga2tm1Mom/Cnga2tm1Mom
involves: 129S1/Sv		 MGI:108040  MP:0001732 postnatal growth retardation PMID: 10798394 
Cnga2tm1Ngai Cnga2tm1Ngai/Y
involves: 129S1/Sv		 MGI:108040  MP:0002082 postnatal lethality PMID: 8893025 
Cnga2tm1Mom Cnga2tm1Mom/Y
involves: 129S1/Sv		 MGI:108040  MP:0002082 postnatal lethality PMID: 10798394 
Cnga2tm1Mom Cnga2tm1Mom/Cnga2tm1Mom
involves: 129S1/Sv		 MGI:108040  MP:0002082 postnatal lethality PMID: 10798394 
Cnga2tm1Gvr Cnga2tm1Gvr/Cnga2tm1Gvr
involves: 129 * C57BL/6		 MGI:108040  MP:0001473 reduced long term potentiation PMID: 9636130 
Cnga2tm1Gvr Cnga2tm1Gvr/Y
involves: 129 * C57BL/6		 MGI:108040  MP:0001473 reduced long term potentiation PMID: 9636130 
Cnga2tm1Gvr Cnga2tm1Gvr/Y
involves: 129 * 129S1/SvImJ * C57BL/6J		 MGI:108040  MP:0002741 small olfactory bulb PMID: 10531436 

References

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1. Bradley J, Bönigk W, Yau KW, Frings S. (2004) Calmodulin permanently associates with rat olfactory CNG channels under native conditions. Nat Neurosci, 7 (7): 705-10. [PMID:15195096]

2. Bradley J, Li J, Davidson N, Lester HA, Zinn K. (1994) Heteromeric olfactory cyclic nucleotide-gated channels: a subunit that confers increased sensitivity to cAMP. Proc Natl Acad Sci USA, 91 (19): 8890-4. [PMID:7522325]

3. Bradley J, Reisert J, Frings S. (2005) Regulation of cyclic nucleotide-gated channels. Curr Opin Neurobiol, 15 (3): 343-9. [PMID:15922582]

4. Bradley J, Reuter D, Frings S. (2001) Facilitation of calmodulin-mediated odor adaptation by cAMP-gated channel subunits. Science, 294 (5549): 2176-8. [PMID:11739960]

5. Brady JD, Rich ED, Martens JR, Karpen JW, Varnum MD, Brown RL. (2006) Interplay between PIP3 and calmodulin regulation of olfactory cyclic nucleotide-gated channels. Proc Natl Acad Sci USA, 103 (42): 15635-40. [PMID:17032767]

6. Brown RL, Haley TL, West KA, Crabb JW. (1999) Pseudechetoxin: a peptide blocker of cyclic nucleotide-gated ion channels. Proc Natl Acad Sci USA, 96 (2): 754-9. [PMID:9892706]

7. Brown RL, Lynch LL, Haley TL, Arsanjani R. (2003) Pseudechetoxin binds to the pore turret of cyclic nucleotide-gated ion channels. J Gen Physiol, 122 (6): 749-60. [PMID:14638933]

8. Brunet LJ, Gold GH, Ngai J. (1996) General anosmia caused by a targeted disruption of the mouse olfactory cyclic nucleotide-gated cation channel. Neuron, 17 (4): 681-93. [PMID:8893025]

9. Bönigk W, Bradley J, Müller F, Sesti F, Boekhoff I, Ronnett GV, Kaupp UB, Frings S. (1999) The native rat olfactory cyclic nucleotide-gated channel is composed of three distinct subunits. J Neurosci, 19 (13): 5332-47. [PMID:10377344]

10. Chen TY, Yau KW. (1994) Direct modulation by Ca(2+)-calmodulin of cyclic nucleotide-activated channel of rat olfactory receptor neurons. Nature, 368 (6471): 545-8. [PMID:7511217]

11. Dean DM, Nguitragool W, Miri A, McCabe SL, Zimmerman AL. (2002) All-trans-retinal shuts down rod cyclic nucleotide-gated ion channels: a novel role for photoreceptor retinoids in the response to bright light?. Proc Natl Acad Sci USA, 99 (12): 8372-7. [PMID:12034887]

12. Dhallan RS, Yau KW, Schrader KA, Reed RR. (1990) Primary structure and functional expression of a cyclic nucleotide-activated channel from olfactory neurons. Nature, 347 (6289): 184-7. [PMID:1697649]

13. Drescher MJ, Barretto RL, Chaturvedi D, Beisel KW, Hatfield JS, Khan KM, Drescher DG. (2002) Expression of subunits for the cAMP-sensitive 'olfactory' cyclic nucleotide-gated ion channel in the cochlea: implications for signal transduction. Brain Res Mol Brain Res, 98 (1-2): 1-14. [PMID:11834291]

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

15. Kingston PA, Zufall F, Barnstable CJ. (1999) Widespread expression of olfactory cyclic nucleotide-gated channel genes in rat brain: implications for neuronal signalling. Synapse, 32 (1): 1-12. [PMID:10188632]

16. Liman ER, Buck LB. (1994) A second subunit of the olfactory cyclic nucleotide-gated channel confers high sensitivity to cAMP. Neuron, 13 (3): 611-21. [PMID:7522482]

17. Liu M, Chen TY, Ahamed B, Li J, Yau KW. (1994) Calcium-calmodulin modulation of the olfactory cyclic nucleotide-gated cation channel. Science, 266 (5189): 1348-54. [PMID:7526466]

18. Michalakis S, Reisert J, Geiger H, Wetzel C, Zong X, Bradley J, Spehr M, Hüttl S, Gerstner A, Pfeifer A et al.. (2006) Loss of CNGB1 protein leads to olfactory dysfunction and subciliary cyclic nucleotide-gated channel trapping. J Biol Chem, 281 (46): 35156-66. [PMID:16980309]

19. Munger SD, Lane AP, Zhong H, Leinders-Zufall T, Yau KW, Zufall F, Reed RR. (2001) Central role of the CNGA4 channel subunit in Ca2+-calmodulin-dependent odor adaptation. Science, 294 (5549): 2172-5. [PMID:11739959]

20. Nache V, Zimmer T, Wongsamitkul N, Schmauder R, Kusch J, Reinhardt L, Bönigk W, Seifert R, Biskup C, Schwede F et al.. (2012) Differential regulation by cyclic nucleotides of the CNGA4 and CNGB1b subunits in olfactory cyclic nucleotide-gated channels. Sci Signal, 5 (232): ra48. [PMID:22786723]

21. Pifferi S, Boccaccio A, Menini A. (2006) Cyclic nucleotide-gated ion channels in sensory transduction. FEBS Lett, 580 (12): 2853-9. [PMID:16631748]

22. Rosenbaum T, Gordon-Shaag A, Islas LD, Cooper J, Munari M, Gordon SE. (2004) State-dependent block of CNG channels by dequalinium. J Gen Physiol, 123 (3): 295-304. [PMID:14981138]

23. Ruiz ML, London B, Nadal-Ginard B. (1996) Cloning and characterization of an olfactory cyclic nucleotide-gated channel expressed in mouse heart. J Mol Cell Cardiol, 28 (7): 1453-61. [PMID:8841933]

24. Ungerer N, Mücke N, Broecker J, Keller S, Frings S, Möhrlen F. (2011) Distinct binding properties distinguish LQ-type calmodulin-binding domains in cyclic nucleotide-gated channels. Biochemistry, 50 (15): 3221-8. [PMID:21413724]

25. Zheng J, Zagotta WN. (2004) Stoichiometry and assembly of olfactory cyclic nucleotide-gated channels. Neuron, 42 (3): 411-21. [PMID:15134638]

Contributors

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