P29973 (CNGA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
cGMP-gated cation channel alpha-1

Alternative name(s):
Cyclic nucleotide-gated cation channel 1
Cyclic nucleotide-gated channel alpha-1
Short name=CNG channel alpha-1
Short name=CNG-1
Short name=CNG1
Cyclic nucleotide-gated channel, photoreceptor
Rod photoreceptor cGMP-gated channel subunit alpha

Gene names

Name:	CNGA1
Synonyms:	CNCG, CNCG1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	690 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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 rod photoreceptors.
Subunit structure	Tetramer formed of three CNGA1 and one CNGB1 modulatory subunits By similarity.
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Rod cells in the retina.
Domain	The C-terminal coiled-coil domain mediates homotrimerization of CNGA subunits By similarity.
Involvement in disease	Retinitis pigmentosa 49 (RP49) [MIM:613756]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.8
Sequence similarities	Belongs to the cyclic nucleotide-gated cation channel (TC 1.A.1.5) family. CNGA1 subfamily. [View classification] Contains 1 cyclic nucleotide-binding domain.
Caution	It is uncertain whether Met-1 or Met-5 is the initiator.
Sequence caution	The sequence AAB22778.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Ion transport Sensory transduction Transport Vision
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation Retinitis pigmentosa
Domain	Coiled coil Transmembrane Transmembrane helix
Ligand	Nucleotide-binding cGMP cGMP-binding
Molecular function	Ion channel Ligand-gated ion channel
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	response to stimulus Inferred from electronic annotation. Source: UniProtKB-KW transport Traceable author statement Ref.7. Source: ProtInc visual perception Traceable author statement Ref.7. Source: ProtInc
Cellular_component	integral to plasma membrane Traceable author statement Ref.7. Source: ProtInc
Molecular_function	cGMP binding Inferred from electronic annotation. Source: UniProtKB-KW ion channel activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 690	690	cGMP-gated cation channel alpha-1		PRO_0000219308
Regions
	Topological domain	1 – 164	164	Cytoplasmic Potential
	Transmembrane	165 – 185	21	Helical; Name=H1; Potential
	Topological domain	186 – 198	13	Extracellular Potential
	Transmembrane	199 – 217	19	Helical; Name=H2; Potential
	Topological domain	218 – 241	24	Cytoplasmic Potential
	Transmembrane	242 – 261	20	Helical; Name=H3; Potential
	Topological domain	262 – 299	38	Extracellular Potential
	Transmembrane	300 – 322	23	Helical; Name=H4; Potential
	Topological domain	323 – 374	52	Cytoplasmic Potential
	Transmembrane	375 – 394	20	Helical; Name=H5; Potential
	Topological domain	395 – 478	84	Extracellular Potential
	Transmembrane	479 – 499	21	Helical; Name=H6; Potential
	Topological domain	500 – 690	191	Cytoplasmic Potential
	Nucleotide binding	487 – 609	123	cGMP Potential
	Coiled coil	623 – 666	44	By similarity
Sites
	Binding site	546	1	cGMP Potential
	Binding site	561	1	cGMP Potential
Amino acid modifications
	Glycosylation	425	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	32	1	R → Q. Ref.7		VAR_009295
	Natural variant	118	1	D → N. Ref.7		VAR_009296
	Natural variant	122	1	N → D. Corresponds to variant rs28642966 [ dbSNP | Ensembl ].		VAR_047385
	Natural variant	320	1	S → F in RP49. Ref.7		VAR_009297
Experimental info
	Sequence conflict	35	1	E → V in BAF84710. Ref.3
	Sequence conflict	50	1	S → Y in AAA52010. Ref.1
	Sequence conflict	89	1	L → I in AAA52010. Ref.1
	Sequence conflict	150 – 151	2	EE → HH in AAA52010. Ref.1
	Sequence conflict	209	1	I → V in BAF84710. Ref.3
	Sequence conflict	543	1	Y → T in AAA52010. Ref.1
	Sequence conflict	681 – 682	2	GA → WS in AAA52010. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P29973 [UniParc]. Last modified June 16, 2009. Version 3. Checksum: F1045A210FE33DC0	FASTA	690	79,586
	10 20 30 40 50 60 MKLSMKNNII NTQQSFVTMP NVIVPDIEKE IRRMENGACS SFSEDDDSAS TSEESENENP 70 80 90 100 110 120 HARGSFSYKS LRKGGPSQRE QYLPGAIALF NVNNSSNKDQ EPEEKKKKKK EKKSKSDDKN 130 140 150 160 170 180 ENKNDPEKKK KKKDKEKKKK EEKSKDKKEE EKKEVVVIDP SGNTYYNWLF CITLPVMYNW 190 200 210 220 230 240 TMVIARACFD ELQSDYLEYW LILDYVSDIV YLIDMFVRTR TGYLEQGLLV KEELKLINKY 250 260 270 280 290 300 KSNLQFKLDV LSLIPTDLLY FKLGWNYPEI RLNRLLRFSR MFEFFQRTET RTNYPNIFRI 310 320 330 340 350 360 SNLVMYIVII IHWNACVFYS ISKAIGFGND TWVYPDINDP EFGRLARKYV YSLYWSTLTL 370 380 390 400 410 420 TTIGETPPPV RDSEYVFVVV DFLIGVLIFA TIVGNIGSMI SNMNAARAEF QARIDAIKQY 430 440 450 460 470 480 MHFRNVSKDM EKRVIKWFDY LWTNKKTVDE KEVLKYLPDK LRAEIAINVH LDTLKKVRIF 490 500 510 520 530 540 ADCEAGLLVE LVLKLQPQVY SPGDYICKKG DIGREMYIIK EGKLAVVADD GVTQFVVLSD 550 560 570 580 590 600 GSYFGEISIL NIKGSKAGNR RTANIKSIGY SDLFCLSKDD LMEALTEYPD AKTMLEEKGK 610 620 630 640 650 660 QILMKDGLLD LNIANAGSDP KDLEEKVTRM EGSVDLLQTR FARILAEYES MQQKLKQRLT 670 680 690 KVEKFLKPLI DTEFSSIEGP GAESGPIDST

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure and chromosomal localization of human and mouse rod photoreceptor cGMP-gated cation channel." Pittler S.J., Lee A.K., Altherr M.R., Howard T.A., Seldin M.F., Hurwitz R.L., Wasmuth J.J., Baehr W. J. Biol. Chem. 267:6257-6262(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Retina.
[2]	"Human rod photoreceptor cGMP-gated channel: amino acid sequence, gene structure, and functional expression." Dhallan R.S., Macke J.P., Eddy R.L., Shows T.B., Reed R.R., Yau K.-W., Nathans J. J. Neurosci. 12:3248-3256(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Retina.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Spleen.
[4]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"Expression of cyclic nucleotide-gated cation channels in non-sensory tissues and cells." Distler M., Biel M., Flockerzi V., Hofmann F. Neuropharmacology 33:1275-1282(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 317-577.
[7]	"Mutations in the gene encoding the alpha subunit of the rod cGMP-gated channel in autosomal recessive retinitis pigmentosa." Dryja T.P., Finn J.T., Peng Y.-W., McGee T.L., Berson E.L., Yau K.-W. Proc. Natl. Acad. Sci. U.S.A. 92:10177-10181(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT RP49 PHE-320, VARIANTS GLN-32 AND ASN-118.
[8]	"Autosomal recessive retinitis pigmentosa in a Pakistani family mapped to CNGA1 with identification of a novel mutation." Zhang Q., Zulfiqar F., Riazuddin S.A., Xiao X., Ahmad Z., Riazuddin S., Hejtmancik J.F. Mol. Vis. 10:884-889(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN RP49.
+	Additional computationally mapped references.

Web resources

Mutations of the CNGA1 gene

Retina International's Scientific Newsletter

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	M84741 mRNA. Translation: AAA52010.1. S42457 mRNA. Translation: AAB22778.1. Different initiation. AK292021 mRNA. Translation: BAF84710.1. AC107068 Genomic DNA. Translation: AAY40919.1. CH471069 Genomic DNA. Translation: EAW93048.1. S76062 Genomic DNA. Translation: AAD14206.1.
IPI	IPI00218428.
PIR	A42161.
RefSeq	NP_000078.2. NM_000087.3. NP_001136036.1. NM_001142564.1.
UniGene	Hs.1323.
3D structure databases
ProteinModelPortal	P29973.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-7004260.
STRING	9606.ENSP00000384264.
Protein family/group databases
TCDB	1.A.1.5.3. voltage-gated ion channel (VIC) superfamily.
PTM databases
PhosphoSite	P29973.
Polymorphism databases
DMDM	239938910.
Proteomic databases
PaxDb	P29973.
PRIDE	P29973.
Protocols and materials databases
DNASU	1259.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000358519; ENSP00000351320; ENSG00000198515. ENST00000420489; ENSP00000389881; ENSG00000198515. ENST00000514170; ENSP00000426862; ENSG00000198515. ENST00000544810; ENSP00000443401; ENSG00000198515.
GeneID	1259.
KEGG	hsa:1259.
UCSC	uc003gxt.4. human.
Organism-specific databases
CTD	1259.
GeneCards	GC04M047853.
H-InvDB	HIX0031530. HIX0031590.
HGNC	HGNC:2148. CNGA1.
MIM	123825. gene. 613756. phenotype.
neXtProt	NX_P29973.
Orphanet	791. Retinitis pigmentosa.
PharmGKB	PA26658.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG300025.
HOGENOM	HOG000007898.
HOVERGEN	HBG000281.
InParanoid	P29973.
KO	K04948.
Enzyme and pathway databases
Pathway_Interaction_DB	rhodopsin_pathway. Visual signal transduction: Rods.
Gene expression databases
ArrayExpress	P29973.
Bgee	P29973.
CleanEx	HS_CNGA1.
Genevestigator	P29973.
GermOnline	ENSG00000198515. Homo sapiens.
Family and domain databases
Gene3D	2.60.120.10. 1 hit.
InterPro	IPR018490. cNMP-bd-like. IPR018488. cNMP-bd_CS. IPR000595. cNMP-bd_dom. IPR005821. Ion_trans_dom. IPR014710. RmlC-like_jellyroll. [Graphical view]
Pfam	PF00027. cNMP_binding. 1 hit. PF00520. Ion_trans. 1 hit. [Graphical view]
SMART	SM00100. cNMP. 1 hit. [Graphical view]
SUPFAM	SSF51206. cNMP_binding. 1 hit.
PROSITE	PS00888. CNMP_BINDING_1. 1 hit. PS00889. CNMP_BINDING_2. 1 hit. PS50042. CNMP_BINDING_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL1628476.
GenomeRNAi	1259.
NextBio	5093.
SOURCE	Search...

Entry information

Entry name

CNGA1_HUMAN

Accession

Primary (citable) accession number: P29973
Secondary accession number(s): A8K7K6 , Q16279, Q16485, Q4W5E3

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	June 16, 2009
Last modified:	May 29, 2013
This is version 136 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.