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Q8IV77

- CNGA4_HUMAN

UniProt

Q8IV77 - CNGA4_HUMAN

Protein

Cyclic nucleotide-gated cation channel alpha-4

Gene

CNGA4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 93 (01 Oct 2014)
      Sequence version 3 (02 Nov 2010)
      Previous versions | rss
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    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: RefGenome
    3. intracellular cAMP activated cation channel activity Source: RefGenome
    4. intracellular cGMP activated cation channel activity Source: RefGenome
    5. voltage-gated potassium channel activity Source: RefGenome

    GO - Biological processi

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

    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

    GO - Cellular componenti

    1. integral component of plasma membrane Source: RefGenome

    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

    ArrayExpressiQ8IV77.
    BgeeiQ8IV77.
    CleanExiHS_CNGA4.
    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...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 3333CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini55 – 6511ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini87 – 11226CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini134 – 16835ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini190 – 21728CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini235 – 24410ExtracellularSequence Analysis
    Topological domaini266 – 575310CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei34 – 5421Helical; Name=H1Sequence AnalysisAdd
    BLAST
    Transmembranei66 – 8621Helical; Name=H2Sequence AnalysisAdd
    BLAST
    Transmembranei113 – 13321Helical; Name=H3Sequence AnalysisAdd
    BLAST
    Transmembranei169 – 18921Helical; Name=H4Sequence AnalysisAdd
    BLAST
    Transmembranei218 – 23417Helical; Name=H5Sequence AnalysisAdd
    BLAST
    Transmembranei245 – 26521Helical; Name=H6Sequence AnalysisAdd
    BLAST

    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.
    HOGENOMiHOG000007898.
    HOVERGENiHBG000281.
    InParanoidiQ8IV77.
    KOiK04951.
    OMAiHSEALNK.
    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

    MSQDTKVKTT ESSPPAPSKA RKLLPVLDPS GDYYYWWLNT MVFPVMYNLI    50
    ILVCRACFPD LQHGYLVAWL VLDYTSDLLY LLDMVVRFHT GFLEQGILVV 100
    DKGRISSRYV RTWSFFLDLA SLMPTDVVYV RLGPHTPTLR LNRFLRAPRL 150
    FEAFDRTETR TAYPNAFRIA KLMLYIFVVI HWNSCLYFAL SRYLGFGRDA 200
    WVYPDPAQPG FERLRRQYLY SFYFSTLILT TVGDTPPPAR EEEYLFMVGD 250
    FLLAVMGFAT IMGSMSSVIY NMNTADAAFY PDHALVKKYM KLQHVNRKLE 300
    RRVIDWYQHL QINKKMTNEV AILQHLPERL RAEVAVSVHL STLSRVQIFQ 350
    NCEASLLEEL VLKLQPQTYS PGEYVCRKGD IGQEMYIIRE GQLAVVADDG 400
    ITQYAVLGAG LYFGEISIIN IKGNMSGNRR TANIKSLGYS DLFCLSKEDL 450
    REVLSEYPQA QTIMEEKGRE ILLKMNKLDV NAEAAEIALQ EATESRLRGL 500
    DQQLDDLQTK FARLLAELES SALKIAYRIE RLEWQTREWP MPEDLAEADD 550
    EGEPEEGTSK DEEGRASQEG PPGPE 575
    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 AK122736 differs from that shown. Reason: Frameshift at position 154.
    The sequence AAH40277.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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.
    CCDSi CCDS31408.1. [Q8IV77-1 ]
    RefSeqi NP_001032406.1. NM_001037329.3. [Q8IV77-1 ]
    XP_006718207.1. XM_006718144.1. [Q8IV77-1 ]
    XP_006718209.1. XM_006718146.1. [Q8IV77-2 ]
    UniGenei Hs.434618.

    3D structure databases

    ProteinModelPortali Q8IV77.
    SMRi Q8IV77. Positions 286-466.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9606.ENSP00000369268.

    Polymorphism databases

    DMDMi 311033466.

    Proteomic databases

    PaxDbi Q8IV77.
    PRIDEi Q8IV77.

    Protocols and materials databases

    DNASUi 1262.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000379936 ; ENSP00000369268 ; ENSG00000132259 . [Q8IV77-1 ]
    GeneIDi 1262.
    KEGGi hsa:1262.
    UCSCi uc001mcn.3. human. [Q8IV77-2 ]
    uc001mco.3. human. [Q8IV77-1 ]

    Organism-specific databases

    CTDi 1262.
    GeneCardsi GC11P006255.
    H-InvDB HIX0026152.
    HGNCi HGNC:2152. CNGA4.
    MIMi 609472. gene.
    neXtProti NX_Q8IV77.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG300831.
    HOGENOMi HOG000007898.
    HOVERGENi HBG000281.
    InParanoidi Q8IV77.
    KOi K04951.
    OMAi HSEALNK.
    OrthoDBi EOG771268.
    PhylomeDBi Q8IV77.
    TreeFami TF319048.

    Miscellaneous databases

    GeneWikii Cyclic_nucleotide-gated_channel_alpha_4.
    GenomeRNAii 1262.
    NextBioi 5107.
    PROi Q8IV77.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q8IV77.
    Bgeei Q8IV77.
    CleanExi HS_CNGA4.
    Genevestigatori Q8IV77.

    Family and domain databases

    Gene3Di 2.60.120.10. 1 hit.
    InterProi IPR018490. cNMP-bd-like.
    IPR018488. cNMP-bd_CS.
    IPR000595. cNMP-bd_dom.
    IPR005821. Ion_trans_dom.
    IPR014710. RmlC-like_jellyroll.
    [Graphical view ]
    Pfami PF00027. cNMP_binding. 1 hit.
    PF00520. Ion_trans. 1 hit.
    [Graphical view ]
    SMARTi SM00100. cNMP. 1 hit.
    [Graphical view ]
    SUPFAMi SSF51206. SSF51206. 1 hit.
    PROSITEi PS00888. CNMP_BINDING_1. 1 hit.
    PS00889. CNMP_BINDING_2. 1 hit.
    PS50042. CNMP_BINDING_3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 93 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