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1.A.1.5.3
Heterotetrameric (3A:1B) rod photoreceptor cyclic GMP-gated cation channel, CNGA1 or CNCG or CNCG1 (Zhong et al., 2002) of 686 aas and 6 TMSs. Cyclic nucleotides are required to open the channel. Gating is proposed to be initiated by an anticlockwise rotation of the N-terminal region of the C-linker, which is then, transmitted through the S6 transmembrane helices to the P-helix, and in turn from this to the pore lumen, which opens from 2 to 5 Å, thus allowing for ion permeation (Giorgetti et al. 2005). Defects produce channelopathies (Biel & Michalakis, 2007). A ring of four glutamate residues (Glu363) in the outer vestibule, and a ring of four threonines (Thr360) in the inner vestibule of the pore of CNGA1 channels constitute binding sites for permeating ions (Marchesi et al., 2012).  The tetraspanning peripherin-2 (TC# 8.A.40.1.2) links rhodopsin to this cyclic nucleotide-dependent channel in the outer segments of rod photoreceptors.  The G266D retinitis pigmentosa mutation in TMS 4 of rhodopsin abolishes binding of peripherin-2 and prevents association with the CNGA1/CNGB1a subunits present in the complex (Becirovic et al. 2014).  External protons cause inactivation (Marchesi et al. 2015). CNG transmembrane domains have dynamic structures, undergoing conformational rearrangements (Maity et al. 2015).  Moreover, structural heterogeneity of CNGA1 channels has been demonstrated (Maity et al. 2016). The structural basis of calmodulin (CaM) modulation of the rod cyclic nucleotide-gated channel has been elucidated by cryoEM. CaM is a constitutive subunit of the rod channel that ensures high sensitivity in dim light (Barret et al. 2023).

Accession Number:P29973
Protein Name:CNGA1
Length:690
Molecular Weight:79586.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:6
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate cation, inorganic cation

Cross database links:

RefSeq: NP_000078.2    NP_001136036.1   
Entrez Gene ID: 1259   
Pfam: PF00027    PF00520   
OMIM: 123825  gene
268000  phenotype
KEGG: hsa:1259   

Gene Ontology

GO:0005887 C:integral to plasma membrane
GO:0030553 F:cGMP binding
GO:0005216 F:ion channel activity
GO:0006811 P:ion transport
GO:0050896 P:response to stimulus
GO:0055085 P:transmembrane transport
GO:0007601 P:visual perception

References (7)

[1] “Primary structure and chromosomal localization of human and mouse rod photoreceptor cGMP-gated cation channel.”  Pittler S.J.et.al.   1372902
[2] “Human rod photoreceptor cGMP-gated channel: amino acid sequence, gene structure, and functional expression.”  Dhallan R.S.et.al.   1379636
[3] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[4] “Generation and annotation of the DNA sequences of human chromosomes 2 and 4.”  Hillier L.W.et.al.   15815621
[5] “Expression of cyclic nucleotide-gated cation channels in non-sensory tissues and cells.”  Distler M.et.al.   7532814
[6] “Mutations in the gene encoding the alpha subunit of the rod cGMP-gated channel in autosomal recessive retinitis pigmentosa.”  Dryja T.P.et.al.   7479749
[7] “Autosomal recessive retinitis pigmentosa in a Pakistani family mapped to CNGA1 with identification of a novel mutation.”  Zhang Q.et.al.   15570217

External Searches:

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MKLSMKNNII NTQQSFVTMP NVIVPDIEKE IRRMENGACS SFSEDDDSAS TSEESENENP 
61:	HARGSFSYKS LRKGGPSQRE QYLPGAIALF NVNNSSNKDQ EPEEKKKKKK EKKSKSDDKN 
121:	ENKNDPEKKK KKKDKEKKKK EEKSKDKKEE EKKEVVVIDP SGNTYYNWLF CITLPVMYNW 
181:	TMVIARACFD ELQSDYLEYW LILDYVSDIV YLIDMFVRTR TGYLEQGLLV KEELKLINKY 
241:	KSNLQFKLDV LSLIPTDLLY FKLGWNYPEI RLNRLLRFSR MFEFFQRTET RTNYPNIFRI 
301:	SNLVMYIVII IHWNACVFYS ISKAIGFGND TWVYPDINDP EFGRLARKYV YSLYWSTLTL 
361:	TTIGETPPPV RDSEYVFVVV DFLIGVLIFA TIVGNIGSMI SNMNAARAEF QARIDAIKQY 
421:	MHFRNVSKDM EKRVIKWFDY LWTNKKTVDE KEVLKYLPDK LRAEIAINVH LDTLKKVRIF 
481:	ADCEAGLLVE LVLKLQPQVY SPGDYICKKG DIGREMYIIK EGKLAVVADD GVTQFVVLSD 
541:	GSYFGEISIL NIKGSKAGNR RTANIKSIGY SDLFCLSKDD LMEALTEYPD AKTMLEEKGK 
601:	QILMKDGLLD LNIANAGSDP KDLEEKVTRM EGSVDLLQTR FARILAEYES MQQKLKQRLT 
661:	KVEKFLKPLI DTEFSSIEGP GAESGPIDST