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Protein

Cyclic nucleotide-gated cation channel alpha-4

Gene

CNGA4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity

Enzyme regulationi

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.1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi348 – 471124cNMPAdd
BLAST

GO - Molecular functioni

  1. cAMP binding Source: UniProtKB-KW
  2. cGMP binding Source: GO_Central
  3. intracellular cAMP activated cation channel activity Source: GO_Central
  4. intracellular cGMP activated cation channel activity Source: GO_Central
  5. voltage-gated potassium channel activity Source: GO_Central

GO - Biological processi

  1. phototransduction, visible light Source: GO_Central
  2. potassium ion transmembrane transport Source: GO_Central
  3. regulation of membrane potential Source: GO_Central
  4. sensory perception of smell Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Ligand-gated ion channel

Keywords - Biological processi

Ion transport, Olfaction, Sensory transduction, Transport

Keywords - Ligandi

cAMP, cAMP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
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 namesi
Name:CNGA4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 11

Organism-specific databases

HGNCiHGNC:2152. CNGA4.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3333CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei34 – 5421Helical; Name=H1Sequence AnalysisAdd
BLAST
Topological domaini55 – 6511ExtracellularSequence AnalysisAdd
BLAST
Transmembranei66 – 8621Helical; Name=H2Sequence AnalysisAdd
BLAST
Topological domaini87 – 11226CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei113 – 13321Helical; Name=H3Sequence AnalysisAdd
BLAST
Topological domaini134 – 16835ExtracellularSequence AnalysisAdd
BLAST
Transmembranei169 – 18921Helical; Name=H4Sequence AnalysisAdd
BLAST
Topological domaini190 – 21728CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei218 – 23417Helical; Name=H5Sequence AnalysisAdd
BLAST
Topological domaini235 – 24410ExtracellularSequence Analysis
Transmembranei245 – 26521Helical; Name=H6Sequence AnalysisAdd
BLAST
Topological domaini266 – 575310CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. integral component of plasma membrane Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi292 – 2921L → E: Loss of inhibition produced by calcium/calmodulin binding. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 575575Cyclic nucleotide-gated cation channel alpha-4PRO_0000317107Add
BLAST

Proteomic databases

PaxDbiQ8IV77.
PRIDEiQ8IV77.

Expressioni

Gene expression databases

BgeeiQ8IV77.
CleanExiHS_CNGA4.
ExpressionAtlasiQ8IV77. baseline.
GenevestigatoriQ8IV77.

Interactioni

Subunit structurei

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.1 Publication

Protein-protein interaction databases

STRINGi9606.ENSP00000369268.

Structurei

3D structure databases

ProteinModelPortaliQ8IV77.
SMRiQ8IV77. Positions 286-466.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili493 – 53644By similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi292 – 30211IQ-typeAdd
BLAST

Domaini

The C-terminal coiled-coil domain mediates trimerization of CNGA subunits.By similarity

Sequence similaritiesi

Contains 1 cyclic nucleotide-binding domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG300831.
GeneTreeiENSGT00760000118772.
HOGENOMiHOG000007898.
HOVERGENiHBG000281.
InParanoidiQ8IV77.
KOiK04951.
OMAiCERGVLE.
OrthoDBiEOG771268.
PhylomeDBiQ8IV77.
TreeFamiTF319048.

Family and domain databases

Gene3Di2.60.120.10. 1 hit.
InterProiIPR018490. cNMP-bd-like.
IPR018488. cNMP-bd_CS.
IPR000595. cNMP-bd_dom.
IPR005821. Ion_trans_dom.
IPR014710. RmlC-like_jellyroll.
[Graphical view]
PfamiPF00027. cNMP_binding. 1 hit.
PF00520. Ion_trans. 1 hit.
[Graphical view]
SMARTiSM00100. cNMP. 1 hit.
[Graphical view]
SUPFAMiSSF51206. SSF51206. 1 hit.
PROSITEiPS00888. CNMP_BINDING_1. 1 hit.
PS00889. CNMP_BINDING_2. 1 hit.
PS50042. CNMP_BINDING_3. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q8IV77-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MSQDTKVKTT ESSPPAPSKA RKLLPVLDPS GDYYYWWLNT MVFPVMYNLI
60 70 80 90 100
ILVCRACFPD LQHGYLVAWL VLDYTSDLLY LLDMVVRFHT GFLEQGILVV
110 120 130 140 150
DKGRISSRYV RTWSFFLDLA SLMPTDVVYV RLGPHTPTLR LNRFLRAPRL
160 170 180 190 200
FEAFDRTETR TAYPNAFRIA KLMLYIFVVI HWNSCLYFAL SRYLGFGRDA
210 220 230 240 250
WVYPDPAQPG FERLRRQYLY SFYFSTLILT TVGDTPPPAR EEEYLFMVGD
260 270 280 290 300
FLLAVMGFAT IMGSMSSVIY NMNTADAAFY PDHALVKKYM KLQHVNRKLE
310 320 330 340 350
RRVIDWYQHL QINKKMTNEV AILQHLPERL RAEVAVSVHL STLSRVQIFQ
360 370 380 390 400
NCEASLLEEL VLKLQPQTYS PGEYVCRKGD IGQEMYIIRE GQLAVVADDG
410 420 430 440 450
ITQYAVLGAG LYFGEISIIN IKGNMSGNRR TANIKSLGYS DLFCLSKEDL
460 470 480 490 500
REVLSEYPQA QTIMEEKGRE ILLKMNKLDV NAEAAEIALQ EATESRLRGL
510 520 530 540 550
DQQLDDLQTK FARLLAELES SALKIAYRIE RLEWQTREWP MPEDLAEADD
560 570
EGEPEEGTSK DEEGRASQEG PPGPE
Length:575
Mass (Da):65,999
Last modified:November 2, 2010 - v3
Checksum:i4249188A8563A461
GO
Isoform 2 (identifier: Q8IV77-2) [UniParc]FASTAAdd to Basket

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.

Show »
Length:416
Mass (Da):47,743
Checksum:i1268718DEB5E54E2
GO

Sequence cautioni

The sequence AAH40277.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AK122736 differs from that shown. Reason: Frameshift at position 154. Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti553 – 5531E → V.
Corresponds to variant rs325706 [ dbSNP | Ensembl ].
VAR_038480

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 4040Missing in isoform 2. 1 PublicationVSP_039919Add
BLAST
Alternative sequencei424 – 45633NMSGN…EVLSE → GYPSICSRDKDGWGRGEQQS PVLGPDSTSGLNF in isoform 2. 1 PublicationVSP_039920Add
BLAST
Alternative sequencei457 – 575119Missing in isoform 2. 1 PublicationVSP_039921Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS31408.1. [Q8IV77-1]
RefSeqiNP_001032406.1. NM_001037329.3. [Q8IV77-1]
XP_006718207.1. XM_006718144.1. [Q8IV77-1]
XP_006718209.1. XM_006718146.1. [Q8IV77-2]
UniGeneiHs.434618.

Genome annotation databases

EnsembliENST00000379936; ENSP00000369268; ENSG00000132259. [Q8IV77-1]
GeneIDi1262.
KEGGihsa:1262.
UCSCiuc001mcn.3. human. [Q8IV77-2]
uc001mco.3. human. [Q8IV77-1]

Polymorphism databases

DMDMi311033466.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS31408.1. [Q8IV77-1]
RefSeqiNP_001032406.1. NM_001037329.3. [Q8IV77-1]
XP_006718207.1. XM_006718144.1. [Q8IV77-1]
XP_006718209.1. XM_006718146.1. [Q8IV77-2]
UniGeneiHs.434618.

3D structure databases

ProteinModelPortaliQ8IV77.
SMRiQ8IV77. Positions 286-466.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000369268.

Polymorphism databases

DMDMi311033466.

Proteomic databases

PaxDbiQ8IV77.
PRIDEiQ8IV77.

Protocols and materials databases

DNASUi1262.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000379936; ENSP00000369268; ENSG00000132259. [Q8IV77-1]
GeneIDi1262.
KEGGihsa:1262.
UCSCiuc001mcn.3. human. [Q8IV77-2]
uc001mco.3. human. [Q8IV77-1]

Organism-specific databases

CTDi1262.
GeneCardsiGC11P006255.
H-InvDBHIX0026152.
HGNCiHGNC:2152. CNGA4.
MIMi609472. gene.
neXtProtiNX_Q8IV77.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG300831.
GeneTreeiENSGT00760000118772.
HOGENOMiHOG000007898.
HOVERGENiHBG000281.
InParanoidiQ8IV77.
KOiK04951.
OMAiCERGVLE.
OrthoDBiEOG771268.
PhylomeDBiQ8IV77.
TreeFamiTF319048.

Miscellaneous databases

GeneWikiiCyclic_nucleotide-gated_channel_alpha_4.
GenomeRNAii1262.
NextBioi5107.
PROiQ8IV77.
SOURCEiSearch...

Gene expression databases

BgeeiQ8IV77.
CleanExiHS_CNGA4.
ExpressionAtlasiQ8IV77. baseline.
GenevestigatoriQ8IV77.

Family and domain databases

Gene3Di2.60.120.10. 1 hit.
InterProiIPR018490. cNMP-bd-like.
IPR018488. cNMP-bd_CS.
IPR000595. cNMP-bd_dom.
IPR005821. Ion_trans_dom.
IPR014710. RmlC-like_jellyroll.
[Graphical view]
PfamiPF00027. cNMP_binding. 1 hit.
PF00520. Ion_trans. 1 hit.
[Graphical view]
SMARTiSM00100. cNMP. 1 hit.
[Graphical view]
SUPFAMiSSF51206. SSF51206. 1 hit.
PROSITEiPS00888. CNMP_BINDING_1. 1 hit.
PS00889. CNMP_BINDING_2. 1 hit.
PS50042. CNMP_BINDING_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. 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.

Entry informationi

Entry nameiCNGA4_HUMAN
AccessioniPrimary (citable) accession number: Q8IV77
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 5, 2008
Last sequence update: November 2, 2010
Last modified: February 4, 2015
This is version 97 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.