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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:Q14028
Protein Name:CNGB1
Length:1251
Molecular Weight:139678.00
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_001129111.1    NP_001288.3   
Entrez Gene ID: 1258   
Pfam: PF00027   
OMIM: 600724  gene+phenotype
KEGG: hsa:1258   

Gene Ontology

GO:0017071 C:intracellular cyclic nucleotide activated c...
GO:0030552 F:cAMP binding
GO:0005222 F:intracellular cAMP activated cation channel...
GO:0006811 P:ion transport
GO:0007608 P:sensory perception of smell

References (10)

[1] “A new subunit of the cyclic nucleotide-gated cation channel in retinal rods.”  Chen T.-Y.et.al.   7682292
[2] “cDNA, gene structure, and chromosomal localization of human GAR1 (CNCG3L), a homolog of the third subunit of bovine photoreceptor cGMP-gated channel.”  Ardell M.D.et.al.   7590744
[3] “The beta subunit of human rod photoreceptor cGMP-gated cation channel is generated from a complex transcription unit.”  Ardell M.D.et.al.   8766832
[4] “Identification of a domain on the beta-subunit of the rod cGMP-gated cation channel that mediates inhibition by calcium-calmodulin.”  Grunwald M.E.et.al.   9535905
[5] “The sequence and analysis of duplication-rich human chromosome 16.”  Martin J.et.al.   15616553
[6] “Genomic organization of the human rod photoreceptor cGMP-gated cation channel beta-subunit gene.”  Ardell M.D.et.al.   10717482
[7] “Calmodulin permanently associates with rat olfactory CNG channels under native conditions.”  Bradley J.et.al.   15195096
[8] “The glutamic acid-rich protein-2 (GARP2) is a high affinity rod photoreceptor phosphodiesterase (PDE6)-binding protein that modulates its catalytic properties.”  Pentia D.C.et.al.   16407240
[9] “Glutamic acid-rich proteins of rod photoreceptors are natively unfolded.”  Batra-Safferling R.et.al.   16280326
[10] “Segregation of a mutation in CNGB1 encoding the beta-subunit of the rod cGMP-gated channel in a family with autosomal recessive retinitis pigmentosa.”  Bareil C.et.al.   11379879

External Searches:

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MLGWVQRVLP QPPGTPRKTK MQEEEEVEPE PEMEAEVEPE PNPEEAETES ESMPPEESFK 
61:	EEEVAVADPS PQETKEAALT STISLRAQGA EISEMNSPSR RVLTWLMKGV EKVIPQPVHS 
121:	ITEDPAQILG HGSTGDTGCT DEPNEALEAQ DTRPGLRLLL WLEQNLERVL PQPPKSSEVW 
181:	RDEPAVATGA ASDPAPPGRP QEMGPKLQAR ETPSLPTPIP LQPKEEPKEA PAPEPQPGSQ 
241:	AQTSSLPPTR DPARLVAWVL HRLEMALPQP VLHGKIGEQE PDSPGICDVQ TISILPGGQV 
301:	EPDLVLEEVE PPWEDAHQDV STSPQGTEVV PAYEEENKAV EKMPRELSRI EEEKEDEEEE 
361:	EEEEEEEEEE EVTEVLLDSC VVSQVGVGQS EEDGTRPQST SDQKLWEEVG EEAKKEAEEK 
421:	AKEEAEEVAE EEAEKEPQDW AETKEEPEAE AEAASSGVPA TKQHPEVQVE DTDADSCPLM 
481:	AEENPPSTVL PPPSPAKSDT LIVPSSASGT HRKKLPSEDD EAEELKALSP AESPVVAWSD 
541:	PTTPKDTDGQ DRAASTASTN SAIINDRLQE LVKLFKERTE KVKEKLIDPD VTSDEESPKP 
601:	SPAKKAPEPA PDTKPAEAEP VEEEHYCDML CCKFKHRPWK KYQFPQSIDP LTNLMYVLWL 
661:	FFVVMAWNWN CWLIPVRWAF PYQTPDNIHH WLLMDYLCDL IYFLDITVFQ TRLQFVRGGD 
721:	IITDKKDMRN NYLKSRRFKM DLLSLLPLDF LYLKVGVNPL LRLPRCLKYM AFFEFNSRLE 
781:	SILSKAYVYR VIRTTAYLLY SLHLNSCLYY WASAYQGLGS THWVYDGVGN SYIRCYYFAV 
841:	KTLITIGGLP DPKTLFEIVF QLLNYFTGVF AFSVMIGQMR DVVGAATAGQ TYYRSCMDST 
901:	VKYMNFYKIP KSVQNRVKTW YEYTWHSQGM LDESELMVQL PDKMRLDLAI DVNYNIVSKV 
961:	ALFQGCDRQM IFDMLKRLRS VVYLPNDYVC KKGEIGREMY IIQAGQVQVL GGPDGKSVLV 
1021:	TLKAGSVFGE ISLLAVGGGN RRTANVVAHG FTNLFILDKK DLNEILVHYP ESQKLLRKKA 
1081:	RRMLRSNNKP KEEKSVLILP PRAGTPKLFN AALAMTGKMG GKGAKGGKLA HLRARLKELA 
1141:	ALEAAAKQQE LVEQAKSSQD VKGEEGSAAP DQHTHPKEAA TDPPAPRTPP EPPGSPPSSP 
1201:	PPASLGRPEG EEEGPAEPEE HSVRICMSPG PEPGEQILSV KMPEEREEKA E