CNGA4

Target not currently curated in GtoImmuPdb

Target id: 397

Nomenclature: CNGA4

Family: Cyclic nucleotide-regulated channels (CNG)

Gene and Protein Information
Species	TM	P Loops	AA	Chromosomal Location	Gene Symbol	Gene Name	Reference
Human	6	1	575	11p15.4	CNGA4	cyclic nucleotide gated channel subunit alpha 4
Mouse	6	1	575	7 E3	Cnga4	cyclic nucleotide gated channel alpha 4	1
Rat	6	1	575	1q32	Cnga4	cyclic nucleotide gated channel subunit alpha 4	3,8

Previous and Unofficial Names
CNG5 \| CNGB2 \| CNCA2 \| cyclic nucleotide gated channel beta 2 \| Cgn2 \| CNG channel alpha-4 \| CNG4 \| cyclic nucleotide-gated olfactory channel subunit OCNC2 \| olfactory cyclic nucleotide-gated channel \| cyclic nucleotide gated channel alpha 4

Database Links
Alphafold	Q8IV77 (Hs), Q3UW12 (Mm), Q64359 (Rn)
CATH/Gene3D	2.60.120.10
ChEMBL Target	CHEMBL4523657 (Rn)
Ensembl Gene	ENSG00000132259 (Hs), ENSMUSG00000030897 (Mm), ENSRNOG00000017609 (Rn)
Entrez Gene	1262 (Hs), 233649 (Mm), 85258 (Rn)
Human Protein Atlas	ENSG00000132259 (Hs)
KEGG Gene	hsa:1262 (Hs), mmu:233649 (Mm), rno:85258 (Rn)
OMIM	609472 (Hs)
Pharos	Q8IV77 (Hs)
RefSeq Nucleotide	NM_001037329 (Hs), NM_001033317 (Mm), NM_053496 (Rn)
RefSeq Protein	NP_001032406 (Hs), NP_001028489 (Mm), NP_445948 (Rn)
UniProtKB	Q8IV77 (Hs), Q3UW12 (Mm), Q64359 (Rn)
Wikipedia	CNGA4 (Hs)

Associated Proteins

Heteromeric Pore-forming Subunits
Name	References
Not determined

Auxiliary Subunits
Name	References
Not determined

Other Associated Proteins
Name	References
CNGB1b	12
CNGA2	12
Calmodulin	2

Activator Comments
CNGA4 confers increased sensitivity to cAMP [3,6,8]. Together with CNGA2, CNGA4 confers sensitivity to cGMP [11].

Tissue Distribution

Vomeronasal organ.

Species:	Mouse
Technique:	Northern Blot
References:	1

Olfactory epithelium.

Species:	Mouse
Technique:	Immunohistochemistry
References:	9

Olfactory bulb, brain, cortex, cerebellum.

Species:	Rat
Technique:	RT-PCR
References:	3

Olfactory epithelium.

Species:	Rat
Technique:	Immunohistochemistry
References:	6

Olfactory epithelium.

Species:	Rat
Technique:	In situ hybridisation
References:	3,6,8

Hippocampus.

Species:	Rat
Technique:	In situ hybridisation
References:	5

Physiological Functions

This subunit increases the cAMP sensitivity of the native olfactory CNG channel.

Species:	None
Tissue:	Olfactory epithelium.
References:	3-4,8,10

Together with CNGB1b, this subunit confers fast odor adaptation in olfactory sensory neurons.

Species:	Mouse
Tissue:	Olfactory epithelium.
References:	3-4,8,10

This subunit is important for odor discrimination and adaptation in mice.

Species:	Mouse
Tissue:	Olfactory epithelium.
References:	7

Together with CNGB1b, this subunit is needed for ciliary targeting of the olfactory CNG channel.

Species:	Mouse
Tissue:	Olfactory epithelium.
References:	9

Phenotypes, Alleles and Disease Models

Mouse data from MGI

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Allele	Composition & genetic background	Accession	Phenotype Id	Phenotype	Reference
Cnga4^tm1Reed	Cnga4^tm1Reed/Cnga4^tm1Reed involves: 129/Sv	MGI:2664099	MP:0009562	abnormal odor adaptation	PMID: 11739959
Cnga4^tm1Reed	Cnga4^tm1Reed/Cnga4^tm1Reed involves: 129/Sv	MGI:2664099	MP:0001983	abnormal olfactory system physiology	PMID: 11739959

References

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1. Berghard A, Buck LB, Liman ER. (1996) Evidence for distinct signaling mechanisms in two mammalian olfactory sense organs. Proc Natl Acad Sci USA, 93 (6): 2365-9. [PMID:8637879]

2. 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]

3. 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]

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

5. Bradley J, Zhang Y, Bakin R, Lester HA, Ronnett GV, Zinn K. (1997) Functional expression of the heteromeric "olfactory" cyclic nucleotide-gated channel in the hippocampus: a potential effector of synaptic plasticity in brain neurons. J Neurosci, 17 (6): 1993-2005. [PMID:9045728]

6. 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]

7. Kelliher KR, Ziesmann J, Munger SD, Reed RR, Zufall F. (2003) Importance of the CNGA4 channel gene for odor discrimination and adaptation in behaving mice. Proc Natl Acad Sci USA, 100 (7): 4299-304. [PMID:12649326]

8. 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]

9. 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]

10. 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]

11. 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]

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