CNGA2

Target id: 395

Nomenclature: CNGA2

Family: Cyclic nucleotide-regulated channels (CNG)

Gene and Protein Information
Previous and Unofficial Names
Database Links
Associated Proteins
Functional Characteristics
Ion Selectivity and Conductance
Rank order lists
Activators
Gating Inhibitors
Channel Blockers
Tissue Distribution
Functional Assays
Physiological Functions
Phenotypes, Alleles and Disease Models
References
Contributors
How to cite this page

Gene and Protein Information
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
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

Previous and Unofficial Names

Database Links
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

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
γ = 35 pS P_Ca/P_Na = 6.8

Ion Selectivity and Conductance

Species:	Rat
Rank order:	Ca²⁺ > K⁺ > Na⁺ [35.0 pS]
References:	9,12,16

Activators (Human)
cyclic GMP > cyclic AMP (EC₅₀ ~ 1 μM)

Activators (Human)

cyclic GMP > cyclic AMP (EC₅₀ ~ 1 μM)

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Activators

Key to terms and symbols

View all chemical structures

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Ligand		Sp.	Action	Value	Parameter	Concentration range (M)	Holding voltage (mV)	Reference
cyclic GMP		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		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

Key to terms and symbols

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Ligand		Sp.	Action	Value	Parameter	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	4.6	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

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Ligand		Sp.	Action	Value	Parameter	Concentration range (M)	Holding voltage (mV)	Reference
pseudechetoxin		Rn	Antagonist	8.3	pK_i	-	-60.0	6-7
⤷	pK_i 8.3 [6-7] Holding voltage: -60.0 mV
L-(cis)-diltiazem		Rn	Antagonist	2.1	pK_i	-	-40.0 – 40.0	12
⤷	pK_i 2.1 [12] Holding voltage: -40.0 – 40.0 mV
dequalinium		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

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

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
Cnga2^tm1Mom	Cnga2^tm1Mom/Y involves: 129S1/Sv	MGI:108040	MP:0004811	abnormal neuron physiology	PMID: 10798394
Cnga2^tm1Mom	Cnga2^tm1Mom/Cnga2^tm1Mom involves: 129S1/Sv	MGI:108040	MP:0004811	abnormal neuron physiology	PMID: 10798394
Cnga2^tm1Mom\|Olfr160⁺\|Olfr160^{tm5(Cnga2)Mom}	Cnga2^tm1Mom/Cnga2^tm1Mom,Olfr160^{tm5(Cnga2)Mom}/Olfr160⁺ involves: 129P2/OlaHsd * 129S1/Sv	MGI:108040 MGI:1931271	MP:0004811	abnormal neuron physiology	PMID: 10798394
Cnga2^tm1Mom\|Olfr160⁺\|Olfr160^{tm5(Cnga2)Mom}	Cnga2^tm1Mom/Y,Olfr160^{tm5(Cnga2)Mom}/Olfr160⁺ involves: 129P2/OlaHsd * 129S1/Sv	MGI:108040 MGI:1931271	MP:0004811	abnormal neuron physiology	PMID: 10798394
Cnga2^tm1Ngai	Cnga2^tm1Ngai/Cnga2^tm1Ngai involves: 129S1/Sv * FVB/N	MGI:108040	MP:0001984	abnormal olfaction	PMID: 15071119
Cnga2^tm1Mom\|Olfr160⁺\|Olfr160^tm4Mom	Cnga2^tm1Mom/Cnga2^tm1Mom,Olfr160^tm4Mom/Olfr160⁺ involves: 129P2/OlaHsd * 129S1/Sv	MGI:108040 MGI:1931271	MP:0000819	abnormal olfactory bulb morphology	PMID: 10798394
Cnga2^tm1Mom\|Olfr160⁺\|Olfr160^tm4Mom	Cnga2^tm1Mom/Y,Olfr160^tm4Mom/Olfr160⁺ involves: 129P2/OlaHsd * 129S1/Sv	MGI:108040 MGI:1931271	MP:0000819	abnormal olfactory bulb morphology	PMID: 10798394
Cnga2^tm1Gvr	Cnga2^tm1Gvr/Y involves: 129 * 129S1/SvImJ * C57BL/6J	MGI:108040	MP:0000819	abnormal olfactory bulb morphology	PMID: 10531436
Cnga2^tm1Gvr	Cnga2^tm1Gvr/Y involves: 129 * 129S1/SvImJ * C57BL/6J	MGI:108040	MP:0005236	abnormal olfactory nerve morphology	PMID: 10531436
Cnga2⁺\|Cnga2^tm1Reed	Cnga2^tm1Reed/Cnga2⁺ involves: 129/Sv * BALB/cJ	MGI:108040	MP:0006092	abnormal olfactory neuron morphology	PMID: 11257220
Cnga2^tm1Mom\|Olfr160⁺\|Olfr160^tm4Mom	Cnga2^tm1Mom/Cnga2^tm1Mom,Olfr160^tm4Mom/Olfr160⁺ involves: 129P2/OlaHsd * 129S1/Sv	MGI:108040 MGI:1931271	MP:0006092	abnormal olfactory neuron morphology	PMID: 10798394
Cnga2^tm1Mom\|Olfr160⁺\|Olfr160^tm4Mom	Cnga2^tm1Mom/Y,Olfr160^tm4Mom/Olfr160⁺ involves: 129P2/OlaHsd * 129S1/Sv	MGI:108040 MGI:1931271	MP:0006092	abnormal olfactory neuron morphology	PMID: 10798394
Cnga2^tm1Ngai	Cnga2^tm1Ngai/Cnga2^tm1Ngai involves: 129S1/Sv * FVB/N	MGI:108040	MP:0001983	abnormal olfactory system physiology	PMID: 15071119
Cnga2^tm1Ngai	Cnga2^tm1Ngai/Y involves: 129S1/Sv	MGI:108040	MP:0001983	abnormal olfactory system physiology	PMID: 8893025
Cnga2^tm1Reed	Cnga2^tm1Reed/Y involves: 129/Sv * BALB/cJ	MGI:108040	MP:0001983	abnormal olfactory system physiology	PMID: 11257220
Cnga2^tm1Mom	Cnga2^tm1Mom/Y involves: 129S1/Sv	MGI:108040	MP:0001983	abnormal olfactory system physiology	PMID: 10798394
Cnga2^tm1Mom	Cnga2^tm1Mom/Cnga2^tm1Mom involves: 129S1/Sv	MGI:108040	MP:0001983	abnormal olfactory system physiology	PMID: 10798394
Cnga2^tm1Mom\|Olfr160⁺\|Olfr160^{tm5(Cnga2)Mom}	Cnga2^tm1Mom/Cnga2^tm1Mom,Olfr160^{tm5(Cnga2)Mom}/Olfr160⁺ involves: 129P2/OlaHsd * 129S1/Sv	MGI:108040 MGI:1931271	MP:0001983	abnormal olfactory system physiology	PMID: 10798394
Cnga2^tm1Mom\|Olfr160⁺\|Olfr160^{tm5(Cnga2)Mom}	Cnga2^tm1Mom/Y,Olfr160^{tm5(Cnga2)Mom}/Olfr160⁺ involves: 129P2/OlaHsd * 129S1/Sv	MGI:108040 MGI:1931271	MP:0001983	abnormal olfactory system physiology	PMID: 10798394
Cnga2^tm2Reed	Cnga2^tm2Reed/Y involves: 129/Sv * BALB/cJ	MGI:108040	MP:0001983	abnormal olfactory system physiology	PMID: 11257220
Cnga2^tm1Reed	Cnga2^tm1Reed/Y involves: 129/Sv * BALB/cJ	MGI:108040	MP:0010055	abnormal sensory neuron physiology	PMID: 11257220
Cnga2^tm2Reed	Cnga2^tm2Reed/Y involves: 129/Sv * BALB/cJ	MGI:108040	MP:0010055	abnormal sensory neuron physiology	PMID: 11257220
Cnga2^tm1Mom\|Olfr151^tm2Mom\|Olfr151^tm4Mom	Cnga2^tm1Mom/Cnga2^tm1Mom,Olfr151^tm2Mom/Olfr151^tm4Mom involves: 129P2/OlaHsd * C57BL/6	MGI:108040 MGI:2661338	MP:0000967	abnormal sensory neuron projections	PMID: 15186781
Cnga2^tm1Ngai	Cnga2^tm1Ngai/Y involves: 129S1/Sv	MGI:108040	MP:0004512	anosmia	PMID: 8893025
Cnga2^tm1Gvr	Cnga2^tm1Gvr/Cnga2^tm1Gvr involves: 129 * C57BL/6	MGI:108040	MP:0002922	decreased post-tetanic potentiation	PMID: 9636130
Cnga2^tm1Gvr	Cnga2^tm1Gvr/Y involves: 129 * C57BL/6	MGI:108040	MP:0002922	decreased post-tetanic potentiation	PMID: 9636130
Cnga2^tm1Gvr	Cnga2^tm1Gvr/Cnga2^tm1Gvr involves: 129 * C57BL/6	MGI:108040	MP:0002058	neonatal lethality	PMID: 9636130
Cnga2^tm1Gvr	Cnga2^tm1Gvr/Y involves: 129 * C57BL/6	MGI:108040	MP:0002058	neonatal lethality	PMID: 9636130
Cnga2^tm1Gvr	Cnga2^tm1Gvr/Y involves: 129 * 129S1/SvImJ * C57BL/6J	MGI:108040	MP:0002058	neonatal lethality	PMID: 10531436
Cnga2^tm1Mom	Cnga2^tm1Mom/Y involves: 129S1/Sv	MGI:108040	MP:0001732	postnatal growth retardation	PMID: 10798394
Cnga2^tm1Mom	Cnga2^tm1Mom/Cnga2^tm1Mom involves: 129S1/Sv	MGI:108040	MP:0001732	postnatal growth retardation	PMID: 10798394
Cnga2^tm1Ngai	Cnga2^tm1Ngai/Y involves: 129S1/Sv	MGI:108040	MP:0002082	postnatal lethality	PMID: 8893025
Cnga2^tm1Mom	Cnga2^tm1Mom/Y involves: 129S1/Sv	MGI:108040	MP:0002082	postnatal lethality	PMID: 10798394
Cnga2^tm1Mom	Cnga2^tm1Mom/Cnga2^tm1Mom involves: 129S1/Sv	MGI:108040	MP:0002082	postnatal lethality	PMID: 10798394
Cnga2^tm1Gvr	Cnga2^tm1Gvr/Cnga2^tm1Gvr involves: 129 * C57BL/6	MGI:108040	MP:0001473	reduced long term potentiation	PMID: 9636130
Cnga2^tm1Gvr	Cnga2^tm1Gvr/Y involves: 129 * C57BL/6	MGI:108040	MP:0001473	reduced long term potentiation	PMID: 9636130
Cnga2^tm1Gvr	Cnga2^tm1Gvr/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]