Q8IV77 (CNGA4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cyclic nucleotide-gated cation channel alpha-4

Alternative name(s):
Cyclic nucleotide-gated channel alpha-4
Short name=CNG channel alpha-4
Short name=CNG-4
Short name=CNG4

Gene names

Name:

CNGA4

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	575 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Second messenger, cAMP, causes the opening of cation-selective cyclic nucleotide-gated (CNG) channels and depolarization of the neuron (olfactory sensory neurons, OSNs). CNGA4 is the modulatory subunit of this channel which is known to play a central role in the transduction of odorant signals and subsequent adaptation. By accelerating the calcium-mediated negative feedback in olfactory signaling it allows rapid adaptation to odor stimulation and extends its range of odor detection By similarity.
Enzyme regulation	Calcium-calmodulin exerts its inhibitory effect in cAMP sensitivity by binding to IQ-like motif of CNGA4 and preferably binds to the channel in the closed state. Inhibition by PIP3 of the CNG channel probably occurs via CGNA2 binding. Ref.5
Subunit structure	Heterotetramer composed of two subunits of CNGA2, one of CNGA4 and one of CNGB1b. The complex forms the cyclic nucleotide-gated (CNG) channel of olfactory sensory neurons. Ref.4
Subcellular location	Membrane; Multi-pass membrane protein Potential.
Domain	The C-terminal coiled-coil domain mediates trimerization of CNGA subunits By similarity.
Sequence similarities	Belongs to the cyclic nucleotide-gated cation channel (TC 1.A.1.5) family. CNGA4 subfamily. [View classification] Contains 1 cyclic nucleotide-binding domain.
Sequence caution	The sequence AAH40277.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence AK122736 differs from that shown. Reason: Frameshift at position 154.

Ontologies

Keywords
Biological process	Ion transport Olfaction Sensory transduction Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil Transmembrane Transmembrane helix
Ligand	Nucleotide-binding cAMP cAMP-binding
Molecular function	Ion channel Ligand-gated ion channel
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	response to stimulus Inferred from electronic annotation. Source: UniProtKB-KW sensory perception of smell Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	cAMP binding Inferred from electronic annotation. Source: UniProtKB-KW ion channel activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q8IV77-1)

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: Q8IV77-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-40: Missing.
     424-456: NMSGNRRTANIKSLGYSDLFCLSKEDLREVLSE → GYPSICSRDKDGWGRGEQQSPVLGPDSTSGLNF
     457-575: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 575	575	Cyclic nucleotide-gated cation channel alpha-4		PRO_0000317107
Regions
	Topological domain	1 – 33	33	Cytoplasmic Potential
	Transmembrane	34 – 54	21	Helical; Name=H1; Potential
	Topological domain	55 – 65	11	Extracellular Potential
	Transmembrane	66 – 86	21	Helical; Name=H2; Potential
	Topological domain	87 – 112	26	Cytoplasmic Potential
	Transmembrane	113 – 133	21	Helical; Name=H3; Potential
	Topological domain	134 – 168	35	Extracellular Potential
	Transmembrane	169 – 189	21	Helical; Name=H4; Potential
	Topological domain	190 – 217	28	Cytoplasmic Potential
	Transmembrane	218 – 234	17	Helical; Name=H5; Potential
	Topological domain	235 – 244	10	Extracellular Potential
	Transmembrane	245 – 265	21	Helical; Name=H6; Potential
	Topological domain	266 – 575	310	Cytoplasmic Potential
	Nucleotide binding	348 – 471	124	cNMP
	Coiled coil	493 – 536	44	By similarity
	Motif	292 – 302	11	IQ-type
Natural variations
	Alternative sequence	1 – 40	40	Missing in isoform 2.		VSP_039919
	Alternative sequence	424 – 456	33	NMSGN…EVLSE → GYPSICSRDKDGWGRGEQQS PVLGPDSTSGLNF in isoform 2.		VSP_039920
	Alternative sequence	457 – 575	119	Missing in isoform 2.		VSP_039921
	Natural variant	553	1	E → V. Corresponds to variant rs325706 [ dbSNP | Ensembl ].		VAR_038480
Experimental info
	Mutagenesis	292	1	L → E: Loss of inhibition produced by calcium/calmodulin binding. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 2, 2010. Version 3. Checksum: 4249188A8563A461	FASTA	575	65,999
	10 20 30 40 50 60 MSQDTKVKTT ESSPPAPSKA RKLLPVLDPS GDYYYWWLNT MVFPVMYNLI ILVCRACFPD 70 80 90 100 110 120 LQHGYLVAWL VLDYTSDLLY LLDMVVRFHT GFLEQGILVV DKGRISSRYV RTWSFFLDLA 130 140 150 160 170 180 SLMPTDVVYV RLGPHTPTLR LNRFLRAPRL FEAFDRTETR TAYPNAFRIA KLMLYIFVVI 190 200 210 220 230 240 HWNSCLYFAL SRYLGFGRDA WVYPDPAQPG FERLRRQYLY SFYFSTLILT TVGDTPPPAR 250 260 270 280 290 300 EEEYLFMVGD FLLAVMGFAT IMGSMSSVIY NMNTADAAFY PDHALVKKYM KLQHVNRKLE 310 320 330 340 350 360 RRVIDWYQHL QINKKMTNEV AILQHLPERL RAEVAVSVHL STLSRVQIFQ NCEASLLEEL 370 380 390 400 410 420 VLKLQPQTYS PGEYVCRKGD IGQEMYIIRE GQLAVVADDG ITQYAVLGAG LYFGEISIIN 430 440 450 460 470 480 IKGNMSGNRR TANIKSLGYS DLFCLSKEDL REVLSEYPQA QTIMEEKGRE ILLKMNKLDV 490 500 510 520 530 540 NAEAAEIALQ EATESRLRGL DQQLDDLQTK FARLLAELES SALKIAYRIE RLEWQTREWP 550 560 570 MPEDLAEADD EGEPEEGTSK DEEGRASQEG PPGPE
	Isoform 2 [UniParc]. Checksum: 1268718DEB5E54E2	FASTA	416	47,743
	10 20 30 40 50 60 MVFPVMYNLI ILVCRACFPD LQHGYLVAWL VLDYTSDLLY LLDMVVRFHT GFLEQGILVV 70 80 90 100 110 120 DKGRISSRYV RTWSFFLDLA SLMPTDVVYV RLGPHTPTLR LNRFLRAPRL FEAFDRTETR 130 140 150 160 170 180 TAYPNAFRIA KLMLYIFVVI HWNSCLYFAL SRYLGFGRDA WVYPDPAQPG FERLRRQYLY 190 200 210 220 230 240 SFYFSTLILT TVGDTPPPAR EEEYLFMVGD FLLAVMGFAT IMGSMSSVIY NMNTADAAFY 250 260 270 280 290 300 PDHALVKKYM KLQHVNRKLE RRVIDWYQHL QINKKMTNEV AILQHLPERL RAEVAVSVHL 310 320 330 340 350 360 STLSRVQIFQ NCEASLLEEL VLKLQPQTYS PGEYVCRKGD IGQEMYIIRE GQLAVVADDG 370 380 390 400 410 ITQYAVLGAG LYFGEISIIN IKGGYPSICS RDKDGWGRGE QQSPVLGPDS TSGLNF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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] (ISOFORM 1).
[2]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Brain and Lung.
[4]	"Calmodulin permanently associates with rat olfactory CNG channels under native conditions." Bradley J., Boenigk W., Yau K.-W., Frings S. Nat. Neurosci. 7:705-710(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT, MUTAGENESIS OF LEU-292.
[5]	"Interplay between PIP3 and calmodulin regulation of olfactory cyclic nucleotide-gated channels." Brady J.D., Rich E.D., Martens J.R., Karpen J.W., Varnum M.D., Brown R.L. Proc. Natl. Acad. Sci. U.S.A. 103:15635-15640(2006) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK122736 mRNA. No translation available. AC022762 Genomic DNA. No translation available. BC040277 mRNA. Translation: AAH40277.1. Different initiation. BC106935 mRNA. No translation available. BC106936 mRNA. No translation available.
IPI	IPI00216905. IPI00970995.
RefSeq	NP_001032406.1. NM_001037329.3.
UniGene	Hs.434618.
3D structure databases
ProteinModelPortal	Q8IV77.
SMR	Q8IV77. Positions 286-465.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000369268.
Polymorphism databases
DMDM	311033466.
Proteomic databases
PaxDb	Q8IV77.
PRIDE	Q8IV77.
Protocols and materials databases
DNASU	1262.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000379936; ENSP00000369268; ENSG00000132259.
GeneID	1262.
KEGG	hsa:1262.
UCSC	uc001mcn.3. human. uc001mco.3. human.
Organism-specific databases
CTD	1262.
GeneCards	GC11P006255.
H-InvDB	HIX0026152.
HGNC	HGNC:2152. CNGA4.
MIM	609472. gene.
neXtProt	NX_Q8IV77.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG300831.
HOGENOM	HOG000007898.
HOVERGEN	HBG000281.
InParanoid	Q8IV77.
KO	K04951.
OMA	VGHEMYI.
OrthoDB	EOG4229JG.
Gene expression databases
ArrayExpress	Q8IV77.
Bgee	Q8IV77.
CleanEx	HS_CNGA4.
Genevestigator	Q8IV77.
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	1262.
NextBio	5107.
SOURCE	Search...

Entry information

Entry name

CNGA4_HUMAN

Accession

Primary (citable) accession number: Q8IV77

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 5, 2008
Last sequence update:	November 2, 2010
Last modified:	May 1, 2013
This is version 81 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.