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Q8IV77 (CNGA4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 92. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length575 AA.
Sequence statusComplete.
Protein existenceEvidence 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.

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 575575Cyclic nucleotide-gated cation channel alpha-4
PRO_0000317107

Regions

Topological domain1 – 3333Cytoplasmic Potential
Transmembrane34 – 5421Helical; Name=H1; Potential
Topological domain55 – 6511Extracellular Potential
Transmembrane66 – 8621Helical; Name=H2; Potential
Topological domain87 – 11226Cytoplasmic Potential
Transmembrane113 – 13321Helical; Name=H3; Potential
Topological domain134 – 16835Extracellular Potential
Transmembrane169 – 18921Helical; Name=H4; Potential
Topological domain190 – 21728Cytoplasmic Potential
Transmembrane218 – 23417Helical; Name=H5; Potential
Topological domain235 – 24410Extracellular Potential
Transmembrane245 – 26521Helical; Name=H6; Potential
Topological domain266 – 575310Cytoplasmic Potential
Nucleotide binding348 – 471124cNMP
Coiled coil493 – 53644 By similarity
Motif292 – 30211IQ-type

Natural variations

Alternative sequence1 – 4040Missing in isoform 2.
VSP_039919
Alternative sequence424 – 45633NMSGN…EVLSE → GYPSICSRDKDGWGRGEQQS PVLGPDSTSGLNF in isoform 2.
VSP_039920
Alternative sequence457 – 575119Missing in isoform 2.
VSP_039921
Natural variant5531E → V.
Corresponds to variant rs325706 [ dbSNP | Ensembl ].
VAR_038480

Experimental info

Mutagenesis2921L → E: Loss of inhibition produced by calcium/calmodulin binding. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 2, 2010. Version 3.
Checksum: 4249188A8563A461

FASTA57565,999
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 1268718DEB5E54E2
Show »

FASTA41647,743

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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.
CCDSCCDS31408.1. [Q8IV77-1]
RefSeqNP_001032406.1. NM_001037329.3. [Q8IV77-1]
XP_006718207.1. XM_006718144.1. [Q8IV77-1]
XP_006718209.1. XM_006718146.1. [Q8IV77-2]
UniGeneHs.434618.

3D structure databases

ProteinModelPortalQ8IV77.
SMRQ8IV77. Positions 286-466.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000369268.

Polymorphism databases

DMDM311033466.

Proteomic databases

PaxDbQ8IV77.
PRIDEQ8IV77.

Protocols and materials databases

DNASU1262.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000379936; ENSP00000369268; ENSG00000132259. [Q8IV77-1]
GeneID1262.
KEGGhsa:1262.
UCSCuc001mcn.3. human. [Q8IV77-2]
uc001mco.3. human. [Q8IV77-1]

Organism-specific databases

CTD1262.
GeneCardsGC11P006255.
H-InvDBHIX0026152.
HGNCHGNC:2152. CNGA4.
MIM609472. gene.
neXtProtNX_Q8IV77.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG300831.
HOGENOMHOG000007898.
HOVERGENHBG000281.
InParanoidQ8IV77.
KOK04951.
OMAHSEALNK.
OrthoDBEOG771268.
PhylomeDBQ8IV77.
TreeFamTF319048.

Gene expression databases

ArrayExpressQ8IV77.
BgeeQ8IV77.
CleanExHS_CNGA4.
GenevestigatorQ8IV77.

Family and domain databases

Gene3D2.60.120.10. 1 hit.
InterProIPR018490. cNMP-bd-like.
IPR018488. cNMP-bd_CS.
IPR000595. cNMP-bd_dom.
IPR005821. Ion_trans_dom.
IPR014710. RmlC-like_jellyroll.
[Graphical view]
PfamPF00027. cNMP_binding. 1 hit.
PF00520. Ion_trans. 1 hit.
[Graphical view]
SMARTSM00100. cNMP. 1 hit.
[Graphical view]
SUPFAMSSF51206. SSF51206. 1 hit.
PROSITEPS00888. CNMP_BINDING_1. 1 hit.
PS00889. CNMP_BINDING_2. 1 hit.
PS50042. CNMP_BINDING_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiCyclic_nucleotide-gated_channel_alpha_4.
GenomeRNAi1262.
NextBio5107.
PROQ8IV77.
SOURCESearch...

Entry information

Entry nameCNGA4_HUMAN
AccessionPrimary (citable) accession number: Q8IV77
Entry history
Integrated into UniProtKB/Swiss-Prot: February 5, 2008
Last sequence update: November 2, 2010
Last modified: July 9, 2014
This is version 92 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM