Nomenclature: CNGA4

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 1 575 11p15.4 CNGA4 cyclic nucleotide gated channel alpha 4
Mouse 6 1 575 7 E3 Cnga4 cyclic nucleotide gated channel alpha 4 1
Rat 6 1 575 1q33 Cnga4 cyclic nucleotide gated channel alpha 4 3,8
Previous and Unofficial Names
OCNC2
CNG5
CNGα4
CNGB2
CNCA2
OCNCb
cyclic nucleotide gated channel beta 2
Cgn2
rOCNC2
CNCalpha4, CNG5
CNG channel alpha-4
CNG-4
CNG4
cyclic nucleotide gated cation channel
cyclic nucleotide-gated cation channel alpha 4
cyclic nucleotide-gated cation channel alpha-4
cyclic nucleotide-gated channel alpha-4
cyclic nucleotide-gated olfactory channel subunit OCNC2
olfactory cyclic nucleotide-gated channel
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 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
Cnga4tm1Reed Cnga4tm1Reed/Cnga4tm1Reed
involves: 129/Sv
MGI:2664099  MP:0009562 abnormal odor adaptation PMID: 11739959 
Cnga4tm1Reed Cnga4tm1Reed/Cnga4tm1Reed
involves: 129/Sv
MGI:2664099  MP:0001983 abnormal olfactory system physiology PMID: 11739959 

REFERENCES

1. Berghard A, Buck LB, Liman ER. (1996) Evidence for distinct signaling mechanisms in two mammalian olfactory sense organs. Proc. Natl. Acad. Sci. U.S.A.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. U.S.A.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. U.S.A.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. Neuron13 (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, 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]

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. Science294 (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 Signal5 (232): ra48. [PMID:22786723]

12. 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: CNGA4. Last modified on 23/09/2013. Accessed on 23/09/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=397.

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