Q9NQW8 (CNGB3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cyclic nucleotide-gated cation channel beta-3

Alternative name(s):
Cone photoreceptor cGMP-gated channel subunit beta
Cyclic nucleotide-gated cation channel modulatory subunit
Cyclic nucleotide-gated channel beta-3
Short name=CNG channel beta-3

Gene names

Name:

CNGB3

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	809 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 cGMP which leads to an opening of the cation channel and thereby causing a depolarization of rod 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 efficiency of the channel when coexpressed with CNGA3 By similarity. Essential for the generation of light-evoked electrical responses in the red-, green- and blue sensitive cones. Ref.3
Subunit structure	Tetramer formed of three CNGA3 and one CNGB3 modulatory subunits. Ref.3 Ref.4
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Expressed specifically in the retina. Ref.1
Involvement in disease	Stargardt disease 1 (STGD1) [MIM:248200]: A common hereditary macular degeneration. It is characterized by decreased central vision, atrophy of the macula and underlying retinal pigment epithelium, and frequent presence of prominent flecks in the posterior pole of the retina. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Achromatopsia 3 (ACHM3) [MIM:262300]: An ocular stationary disorder due to the absence of functioning cone photoreceptors in the retina. It is characterized by total colorblindness, low visual acuity, photophobia and nystagmus. Achromatopsia type 3 patients manifest severe myopia. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.3 Ref.5 Ref.6 Ref.7 Ref.8
Sequence similarities	Belongs to the cyclic nucleotide-gated cation channel (TC 1.A.1.5) family. CNGB3 subfamily. [View classification] Contains 1 cyclic nucleotide-binding domain.
Sequence caution	The sequence AAF80179.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Ion transport Sensory transduction Transport Vision
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Stargardt disease
Domain	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	signal transduction Non-traceable author statement Ref.3. Source: ProtInc transport Non-traceable author statement Ref.3. Source: ProtInc visual perception Traceable author statement Ref.3. Source: ProtInc
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW photoreceptor outer segment Inferred from electronic annotation. Source: Compara
Molecular_function	cGMP binding Inferred from electronic annotation. Source: UniProtKB-KW intracellular cGMP activated cation channel activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9NQW8-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9NQW8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     590-594: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 809	809	Cyclic nucleotide-gated cation channel beta-3		PRO_0000219320
Regions
	Topological domain	1 – 216	216	Cytoplasmic Potential
	Transmembrane	217 – 237	21	Helical; Name=H1; Potential
	Topological domain	238 – 250	13	Extracellular Potential
	Transmembrane	251 – 271	21	Helical; Name=H2; Potential
	Topological domain	272 – 302	31	Cytoplasmic Potential
	Transmembrane	303 – 323	21	Helical; Name=H3; Potential
	Topological domain	324 – 359	36	Extracellular Potential
	Transmembrane	360 – 380	21	Helical; Name=H4; Potential
	Topological domain	381 – 417	37	Cytoplasmic Potential
	Transmembrane	418 – 438	21	Helical; Name=H5; Potential
	Topological domain	439 – 504	66	Extracellular Potential
	Transmembrane	505 – 525	21	Helical; Name=H6; Potential
	Topological domain	526 – 809	284	Cytoplasmic Potential
	Nucleotide binding	532 – 676	145	cGMP By similarity
Sites
	Binding site	592	1	cGMP By similarity
	Binding site	604	1	cGMP By similarity
Amino acid modifications
	Glycosylation	468	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	590 – 594	5	Missing in isoform 2.		VSP_009742
	Natural variant	25	1	R → H. Ref.8		VAR_047606
	Natural variant	27	1	N → S. Ref.8 Corresponds to variant rs35807406 [ dbSNP | Ensembl ].		VAR_047607
	Natural variant	107	1	G → R in ACHM3; uncertain pathogenicity. Ref.8		VAR_047608
	Natural variant	148	1	K → E in ACHM3. Ref.5		VAR_047609
	Natural variant	156	1	S → F in ACHM3. Ref.7		VAR_047610
	Natural variant	199	1	E → K in ACHM3; uncertain pathogenicity. Ref.8		VAR_047611
	Natural variant	203	1	R → Q in ACHM3; uncertain pathogenicity. Ref.8 Corresponds to variant rs16916632 [ dbSNP | Ensembl ].		VAR_025524
	Natural variant	234	1	C → W. Ref.1 Corresponds to variant rs6471482 [ dbSNP | Ensembl ].		VAR_018109
	Natural variant	298	1	T → P. Ref.1 Ref.8 Corresponds to variant rs4961206 [ dbSNP | Ensembl ].		VAR_018110
	Natural variant	307	1	I → V. Ref.6 Ref.8 Corresponds to variant rs13265557 [ dbSNP | Ensembl ].		VAR_024418
	Natural variant	309	1	P → L in ACHM3. Ref.7		VAR_047612
	Natural variant	403	1	R → Q in macular degeneration. Ref.8		VAR_047613
	Natural variant	435	1	S → F in ACHM3. Ref.1 Ref.3 Ref.7		VAR_018111
	Natural variant	466	1	M → T in ACHM3; uncertain pathogenicity. Ref.8 Corresponds to variant rs35010099 [ dbSNP | Ensembl ].		VAR_047614
	Natural variant	469	1	Y → D in STGD1. Ref.8 Corresponds to variant rs35365413 [ dbSNP | Ensembl ].		VAR_047615
	Natural variant	494	1	D → N in ACHM3; uncertain pathogenicity. Ref.8		VAR_047616
	Natural variant	513	1	D → Y in ACHM3; uncertain pathogenicity. Ref.8		VAR_047617
	Natural variant	525	1	F → N in ACHM3; requires 2 nucleotide substitutions. Ref.6		VAR_047618
	Natural variant	558	1	G → C in ACHM3. Ref.8		VAR_047619
	Natural variant	595	1	L → F in ACHM3. Ref.8		VAR_047620
	Natural variant	672	1	T → P in ACHM3; uncertain pathogenicity. Ref.8		VAR_047621
	Natural variant	720 – 726	7	Missing in ACHM3.		VAR_047622
	Natural variant	750	1	P → S. Corresponds to variant rs3735971 [ dbSNP | Ensembl ].		VAR_025525
	Natural variant	755	1	E → G. Ref.1 Ref.8 Corresponds to variant rs3735972 [ dbSNP | Ensembl ].		VAR_018112

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 2, 2010. Version 2. Checksum: D16EE71A6149BDB5	FASTA	809	92,167
	10 20 30 40 50 60 MFKSLTKVNK VKPIGENNEN EQSSRRNEEG SHPSNQSQQT TAQEENKGEE KSLKTKSTPV 70 80 90 100 110 120 TSEEPHTNIQ DKLSKKNSSG DLTTNPDPQN AAEPTGTVPE QKEMDPGKEG PNSPQNKPPA 130 140 150 160 170 180 APVINEYADA QLHNLVKRMR QRTALYKKKL VEGDLSSPEA SPQTAKPTAV PPVKESDDKP 190 200 210 220 230 240 TEHYYRLLWF KVKKMPLTEY LKRIKLPNSI DSYTDRLYLL WLLLVTLAYN WNCCFIPLRL 250 260 270 280 290 300 VFPYQTADNI HYWLIADIIC DIIYLYDMLF IQPRLQFVRG GDIIVDSNEL RKHYRTSTKF 310 320 330 340 350 360 QLDVASIIPF DICYLFFGFN PMFRANRMLK YTSFFEFNHH LESIMDKAYI YRVIRTTGYL 370 380 390 400 410 420 LFILHINACV YYWASNYEGI GTTRWVYDGE GNEYLRCYYW AVRTLITIGG LPEPQTLFEI 430 440 450 460 470 480 VFQLLNFFSG VFVFSSLIGQ MRDVIGAATA NQNYFRACMD DTIAYMNNYS IPKLVQKRVR 490 500 510 520 530 540 TWYEYTWDSQ RMLDESDLLK TLPTTVQLAL AIDVNFSIIS KVDLFKGCDT QMIYDMLLRL 550 560 570 580 590 600 KSVLYLPGDF VCKKGEIGKE MYIIKHGEVQ VLGGPDGTKV LVTLKAGSVF GEISLLAAGG 610 620 630 640 650 660 GNRRTANVVA HGFANLLTLD KKTLQEILVH YPDSERILMK KARVLLKQKA KTAEATPPRK 670 680 690 700 710 720 DLALLFPPKE ETPKLFKTLL GGTGKASLAR LLKLKREQAA QKKENSEGGE EEGKENEDKQ 730 740 750 760 770 780 KENEDKQKEN EDKGKENEDK DKGREPEEKP LDRPECTASP IAVEEEPHSV RRTVLPRGTS 790 800 RQSLIISMAP SAEGGEEVLT IEVKEKAKQ
	Isoform 2 [UniParc]. Checksum: 803A5D65F2CEBDE2	FASTA	804	91,633
	10 20 30 40 50 60 MFKSLTKVNK VKPIGENNEN EQSSRRNEEG SHPSNQSQQT TAQEENKGEE KSLKTKSTPV 70 80 90 100 110 120 TSEEPHTNIQ DKLSKKNSSG DLTTNPDPQN AAEPTGTVPE QKEMDPGKEG PNSPQNKPPA 130 140 150 160 170 180 APVINEYADA QLHNLVKRMR QRTALYKKKL VEGDLSSPEA SPQTAKPTAV PPVKESDDKP 190 200 210 220 230 240 TEHYYRLLWF KVKKMPLTEY LKRIKLPNSI DSYTDRLYLL WLLLVTLAYN WNCCFIPLRL 250 260 270 280 290 300 VFPYQTADNI HYWLIADIIC DIIYLYDMLF IQPRLQFVRG GDIIVDSNEL RKHYRTSTKF 310 320 330 340 350 360 QLDVASIIPF DICYLFFGFN PMFRANRMLK YTSFFEFNHH LESIMDKAYI YRVIRTTGYL 370 380 390 400 410 420 LFILHINACV YYWASNYEGI GTTRWVYDGE GNEYLRCYYW AVRTLITIGG LPEPQTLFEI 430 440 450 460 470 480 VFQLLNFFSG VFVFSSLIGQ MRDVIGAATA NQNYFRACMD DTIAYMNNYS IPKLVQKRVR 490 500 510 520 530 540 TWYEYTWDSQ RMLDESDLLK TLPTTVQLAL AIDVNFSIIS KVDLFKGCDT QMIYDMLLRL 550 560 570 580 590 600 KSVLYLPGDF VCKKGEIGKE MYIIKHGEVQ VLGGPDGTKV LVTLKAGSVL LAAGGGNRRT 610 620 630 640 650 660 ANVVAHGFAN LLTLDKKTLQ EILVHYPDSE RILMKKARVL LKQKAKTAEA TPPRKDLALL 670 680 690 700 710 720 FPPKEETPKL FKTLLGGTGK ASLARLLKLK REQAAQKKEN SEGGEEEGKE NEDKQKENED 730 740 750 760 770 780 KQKENEDKGK ENEDKDKGRE PEEKPLDRPE CTASPIAVEE EPHSVRRTVL PRGTSRQSLI 790 800 ISMAPSAEGG EEVLTIEVKE KAKQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mutations in the CNGB3 gene encoding the beta-subunit of the cone photoreceptor cGMP-gated channel are responsible for achromatopsia (ACHM3) linked to chromosome 8Q21." Kohl S., Baumann B., Broghammer M., Jaegle H., Sieving P., Kellner U., Spegal R., Anastasi M., Zrenner E., Sharpe L.T., Wissinger B. Hum. Mol. Genet. 9:2107-2116(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, VARIANT ACHM3 PHE-435, VARIANTS TRP-234; PRO-298 AND GLY-755.
[2]	"DNA sequence and analysis of human chromosome 8." Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S. Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"Genetic basis of total colourblindness among the Pingelapese islanders." Sundin O.H., Yang J.-M., Li Y., Zhu D., Hurd J.N., Mitchell T.N., Silva E.D., Maumenee I.H. Nat. Genet. 25:289-293(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 114-809 (ISOFORM 2), FUNCTION, SUBUNIT, VARIANT ACHM3 PHE-435. Tissue: Retina.
[4]	"Molecular mechanism for 3:1 subunit stoichiometry of rod cyclic nucleotide-gated ion channels." Shuart N.G., Haitin Y., Camp S.S., Black K.D., Zagotta W.N. Nat. Commun. 2:457-457(2011) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT.
[5]	"A frameshift insertion in the cone cyclic nucleotide gated cation channel causes complete achromatopsia in a consanguineous family from a rural isolate." Rojas C.V., Maria L.S., Santos J.L., Cortes F., Alliende M.A. Eur. J. Hum. Genet. 10:638-642(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ACHM3 GLU-148.
[6]	"Achromatopsia caused by novel mutations in both CNGA3 and CNGB3." Johnson S., Michaelides M., Aligianis I.A., Ainsworth J.R., Mollon J.D., Maher E.R., Moore A.T., Hunt D.M. J. Med. Genet. 41:E20-E20(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ACHM3 VAL-307 AND ASN-525.
[7]	"CNGB3 mutations account for 50% of all cases with autosomal recessive achromatopsia." Kohl S., Varsanyi B., Antunes G.A., Baumann B., Hoyng C.B., Jaegle H., Rosenberg T., Kellner U., Lorenz B., Salati R., Jurklies B., Farkas A., Andreasson S., Weleber R.G., Jacobson S.G., Rudolph G., Castellan C., Dollfus H. , Legius E., Anastasi M., Bitoun P., Lev D., Sieving P.A., Munier F.L., Zrenner E., Sharpe L.T., Cremers F.P.M., Wissinger B. Eur. J. Hum. Genet. 13:302-308(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ACHM3 PHE-156; LEU-309; PHE-435 AND 720-GLN--LYS-726 DEL.
[8]	"Cone cGMP-gated channel mutations and clinical findings in patients with achromatopsia, macular degeneration, and other hereditary cone diseases." Nishiguchi K.M., Sandberg M.A., Gorji N., Berson E.L., Dryja T.P. Hum. Mutat. 25:248-258(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MACULAR DEGENERATION GLN-403, VARIANT STGD1 ASP-469, VARIANTS ACHM3 ARG-107; LYS-199; GLN-203; THR-466; ASN-494; TYR-513; CYS-558; PHE-595 AND PRO-672, VARIANTS HIS-25; SER-27; PRO-298; VAL-307 AND GLY-755.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF272900 mRNA. Translation: AAF86274.1. AC013751 Genomic DNA. No translation available. AC090572 Genomic DNA. No translation available. AF228520 mRNA. Translation: AAF80179.1. Different initiation.
IPI	IPI00409767. IPI00746960.
RefSeq	NP_061971.3. NM_019098.4.
UniGene	Hs.154433.
3D structure databases
ProteinModelPortal	Q9NQW8.
SMR	Q9NQW8. Positions 465-636.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000316605.
PTM databases
PhosphoSite	Q9NQW8.
Polymorphism databases
DMDM	311033366.
Proteomic databases
PaxDb	Q9NQW8.
PRIDE	Q9NQW8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000320005; ENSP00000316605; ENSG00000170289.
GeneID	54714.
KEGG	hsa:54714.
UCSC	uc003ydx.3. human. uc010maj.3. human.
Organism-specific databases
CTD	54714.
GeneCards	GC08M087566.
H-InvDB	HIX0034272.
HGNC	HGNC:2153. CNGB3.
MIM	248200. phenotype. 262300. phenotype. 605080. gene.
neXtProt	NX_Q9NQW8.
Orphanet	49382. Achromatopsia. 1871. Progressive cone dystrophy.
PharmGKB	PA26663.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG289446.
HOGENOM	HOG000231425.
HOVERGEN	HBG051038.
InParanoid	Q9NQW8.
KO	K04953.
OMA	NCWFIPL.
OrthoDB	EOG4FJ887.
PhylomeDB	Q9NQW8.
Enzyme and pathway databases
Pathway_Interaction_DB	cone_pathway. Visual signal transduction: Cones.
Gene expression databases
ArrayExpress	Q9NQW8.
Bgee	Q9NQW8.
CleanEx	HS_CNGB3.
Genevestigator	Q9NQW8.
GermOnline	ENSG00000170289. 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
GenomeRNAi	54714.
NextBio	57273.
SOURCE	Search...

Entry information

Entry name

CNGB3_HUMAN

Accession

Primary (citable) accession number: Q9NQW8
Secondary accession number(s): C9JA51, Q9NRE9

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 29, 2004
Last sequence update:	November 2, 2010
Last modified:	May 1, 2013
This is version 103 of the entry and version 2 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.