Cyclic nucleotide-gated (CNG) cation channels are heteromeric complexes made up of principal alpha and modulatory beta subunits. The alpha subunits consist of CNG1-3 and form functional cation channels by themselves. The beta subunits consist of CNG4-6 and, unlike the alpha subunits, do not form functional channels, but rather modify the properties of channels. CNG channels are essential components of olfactory and visual transduction. In olfactory neurons, CNG2, CNG4.3 and CNG5 form Ca2+ permeable channels, which open and depolarize the cell in response to cAMP. In rod photoreceptors, CNG1 and CNG4.1 combine to form Ca ion permeable channels, which give rise to a current in response to cGMP. CNG3 and CNG6 are expressed in cone receptors and may combine to form a native cGMP-activated channel. CNG channels have been implicated in other areas. CNG1 is also expressed in medium-sized and small-sized arteries, suggesting a role for CNG in the regulation of arterial blood pressure and of blood supply to different regions. CNG1, CNG4.1 and CNG4.2 have been detected in the rat pineal gland. CNG2, CNG4.3 and CNG5 are present in GT1 cell lines and may play a role in the secretion of gonadotropin-releasing hormone.
Function:
Visual signal transduction is mediated by a G-protein coupled cascade using cGMP as second messenger. This protein can be activated by cyclic GMP which leads to an opening of the cation channel and thereby causing a depolarization of cone photoreceptors. Induced a flickering channel gating, weakened the outward rectification in the presence of extracellular calcium, increased sensitivity for L-cis diltiazem and enhanced the cAMP efficacy of the channel when coexpressed with CNGB3 (By similarity). Essential for the generation of light-evoked electrical responses in the red-, green- and blue sensitive cones.
Subunit:
Tetramer formed of two CNGA3 and two CNGB3 modulatory subunits.
Subcellular Location:
Membrane; Multi-pass membrane protein.
Tissue Specificity:
Prominently expressed in retina.
Post-translational modifications:
Defects in CNGA3 are the cause of achromatopsia type 2 (ACHM2) [MIM:216900]; also known as total colorblindness or rod monochromacy (RMCH2). ACHM2 is an autosomal recessive condition characterized by day blindness and photophobia. In ACHM2 patients the cones are defective and the subjects see better at night.
Similarity:
Belongs to the cyclic nucleotide-gated cation channel (TC 1.A.1.5) family.
CNGA3 subfamily.
Contains 1 cyclic nucleotide-binding domain.
SWISS:
Q16281
Gene ID:
1261
Database links:
Entrez Gene: 1261 Human
Omim: 600053 Human
SwissProt: Q16281 Human
Unigene: 234785 Human
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