Nomenclature: CNGA2

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 1 664 Xq27 CNGA2 cyclic nucleotide gated channel alpha 2
Mouse 6 1 664 X A6 Cnga2 cyclic nucleotide gated channel alpha 2 22
Rat 6 1 664 Xq37 Cnga2 cyclic nucleotide gated channel alpha 2 12
Previous and Unofficial Names
CNG2
CNGα3
OCNC1
CNCA1
CNCA
OCNCa
OCNCALPHA
FLJ46312
Cncg4
OLFCH
CNG channel alpha-2
CNG-2
cyclic nucleotide gated channel 4
cyclic nucleotide-gated cation channel 2
cyclic nucleotide-gated channel alpha-2
cyclic nucleotide-gated olfactory channel
cyclic nucleotide-gated olfactory channel subunit OCNC1
Database Links
Ensembl Gene
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
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
CNGB1b 24
CNGA4 24
Calmodulin 1,17
Functional Characteristics
γ = 35 pS
PCa/PNa = 6.8
Ion Selectivity and Conductance
Species:  Rat
Rank order:  Ca2+ > K+ > Na+ [35.0 pS]
References:  9,12,16
Activators (Human)
cGMP ~ cAMP (EC50 ~ 1 μM)
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 Rn Agonist 5.6 – 5.76 pEC50 - -80.0 – 100.0 2,16,20
pEC50 5.6 – 5.76 (EC50 2.5x10-6 – 1.74x10-6 M) [2,16,20]
Holding voltage: -80.0 – 100.0 mV
cAMP Rn Agonist 4.21 – 4.34 pEC50 - -80.0 – 100.0 2,9,16,20
pEC50 4.21 – 4.34 (EC50 6.16x10-5 – 4.57x10-5 M) [2,9,16,20]
Holding voltage: -80.0 – 100.0 mV
Gating inhibitors
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
PIP3 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} 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 Rn Antagonist 4.57 pIC50 - 100.0 11
pIC50 4.57 [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 [1,3-4,18-19,23].
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
pseudechetoxin Rn Antagonist 8.3 pKi - -60.0 6-7
pKi 8.3 [6-7]
Holding voltage: -60.0 mV
L-(cis)-diltiazem Rn Antagonist 2.12 pKi - -40.0 – 40.0 12
pKi 2.12 [12]
Holding voltage: -40.0 – 40.0 mV
Tissue Distribution
Heart.
Species:  Mouse
Technique:  Immunohistochemistry
References:  22
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
Not established.
Species:  None
Tissue: 
Response measured: 
References: 
Physiological Functions
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 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

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. U.S.A.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. Science294 (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. U.S.A.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. U.S.A.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. Neuron17 (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. Nature368 (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. U.S.A.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. Nature347 (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. Synapse32 (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. Neuron13 (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. Science266 (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, Hatt H, Yau KW, Biel M. (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. Science294 (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 Signal5 (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. 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]

23. 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. Biochemistry50 (15): 3221-8. [PMID:21413724]

24. Zheng J, Zagotta WN. (2004) Stoichiometry and assembly of olfactory cyclic nucleotide-gated channels. Neuron42 (3): 411-21. [PMID:15134638]

To cite this database page, please use the following:

Elvir Becirovic, Martin Biel.
Cyclic nucleotide-regulated channels: CNGA2. Last modified on 23/09/2013. Accessed on 23/09/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=395.

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