CNGA4_HUMAN
ID CNGA4_HUMAN Reviewed; 575 AA.
AC Q8IV77;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2010, sequence version 3.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Cyclic nucleotide-gated cation channel alpha-4;
DE AltName: Full=Cyclic nucleotide-gated channel alpha-4;
DE Short=CNG channel alpha-4;
DE Short=CNG-4;
DE Short=CNG4;
GN Name=CNGA4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP SUBUNIT, AND MUTAGENESIS OF LEU-292.
RX PubMed=15195096; DOI=10.1038/nn1266;
RA Bradley J., Boenigk W., Yau K.-W., Frings S.;
RT "Calmodulin permanently associates with rat olfactory CNG channels under
RT native conditions.";
RL Nat. Neurosci. 7:705-710(2004).
RN [5]
RP ACTIVITY REGULATION.
RX PubMed=17032767; DOI=10.1073/pnas.0603344103;
RA Brady J.D., Rich E.D., Martens J.R., Karpen J.W., Varnum M.D., Brown R.L.;
RT "Interplay between PIP3 and calmodulin regulation of olfactory cyclic
RT nucleotide-gated channels.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:15635-15640(2006).
CC -!- FUNCTION: Second messenger, cAMP, causes the opening of cation-
CC selective cyclic nucleotide-gated (CNG) channels and depolarization of
CC the neuron (olfactory sensory neurons, OSNs). CNGA4 is the modulatory
CC subunit of this channel which is known to play a central role in the
CC transduction of odorant signals and subsequent adaptation. By
CC accelerating the calcium-mediated negative feedback in olfactory
CC signaling it allows rapid adaptation to odor stimulation and extends
CC its range of odor detection (By similarity). {ECO:0000250}.
CC -!- ACTIVITY REGULATION: Calcium-calmodulin exerts its inhibitory effect in
CC cAMP sensitivity by binding to IQ-like motif of CNGA4 and preferably
CC binds to the channel in the closed state. Inhibition by PIP3 of the CNG
CC channel probably occurs via CGNA2 binding.
CC {ECO:0000269|PubMed:17032767}.
CC -!- SUBUNIT: Heterotetramer composed of two subunits of CNGA2, one of CNGA4
CC and one of CNGB1b. The complex forms the cyclic nucleotide-gated (CNG)
CC channel of olfactory sensory neurons. {ECO:0000269|PubMed:15195096}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8IV77-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IV77-2; Sequence=VSP_039919, VSP_039920, VSP_039921;
CC -!- DOMAIN: The C-terminal coiled-coil domain mediates trimerization of
CC CNGA subunits. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the cyclic nucleotide-gated cation channel (TC
CC 1.A.1.5) family. CNGA4 subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH40277.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AK122736; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK122736; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC022762; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC040277; AAH40277.1; ALT_INIT; mRNA.
DR EMBL; BC106935; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC106936; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS31408.1; -. [Q8IV77-1]
DR RefSeq; NP_001032406.1; NM_001037329.3. [Q8IV77-1]
DR AlphaFoldDB; Q8IV77; -.
DR SMR; Q8IV77; -.
DR BioGRID; 107662; 40.
DR STRING; 9606.ENSP00000369268; -.
DR iPTMnet; Q8IV77; -.
DR PhosphoSitePlus; Q8IV77; -.
DR BioMuta; CNGA4; -.
DR DMDM; 311033466; -.
DR MassIVE; Q8IV77; -.
DR PaxDb; Q8IV77; -.
DR PeptideAtlas; Q8IV77; -.
DR PRIDE; Q8IV77; -.
DR Antibodypedia; 58012; 98 antibodies from 21 providers.
DR DNASU; 1262; -.
DR Ensembl; ENST00000379936.3; ENSP00000369268.2; ENSG00000132259.13. [Q8IV77-1]
DR GeneID; 1262; -.
DR KEGG; hsa:1262; -.
DR MANE-Select; ENST00000379936.3; ENSP00000369268.2; NM_001037329.4; NP_001032406.1.
DR UCSC; uc001mco.4; human. [Q8IV77-1]
DR CTD; 1262; -.
DR GeneCards; CNGA4; -.
DR HGNC; HGNC:2152; CNGA4.
DR HPA; ENSG00000132259; Group enriched (fallopian tube, testis).
DR MIM; 609472; gene.
DR neXtProt; NX_Q8IV77; -.
DR OpenTargets; ENSG00000132259; -.
DR VEuPathDB; HostDB:ENSG00000132259; -.
DR eggNOG; KOG0500; Eukaryota.
DR GeneTree; ENSGT00940000159415; -.
DR HOGENOM; CLU_005746_12_0_1; -.
DR InParanoid; Q8IV77; -.
DR OMA; FPDLQHS; -.
DR OrthoDB; 1073751at2759; -.
DR PhylomeDB; Q8IV77; -.
DR TreeFam; TF319048; -.
DR PathwayCommons; Q8IV77; -.
DR Reactome; R-HSA-381753; Olfactory Signaling Pathway.
DR Reactome; R-HSA-5620916; VxPx cargo-targeting to cilium.
DR SignaLink; Q8IV77; -.
DR BioGRID-ORCS; 1262; 11 hits in 1064 CRISPR screens.
DR GeneWiki; Cyclic_nucleotide-gated_channel_alpha_4; -.
DR GenomeRNAi; 1262; -.
DR Pharos; Q8IV77; Tbio.
DR PRO; PR:Q8IV77; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q8IV77; protein.
DR Bgee; ENSG00000132259; Expressed in right uterine tube and 102 other tissues.
DR ExpressionAtlas; Q8IV77; baseline and differential.
DR Genevisible; Q8IV77; HS.
DR GO; GO:0060170; C:ciliary membrane; TAS:Reactome.
DR GO; GO:0030660; C:Golgi-associated vesicle membrane; TAS:Reactome.
DR GO; GO:0017071; C:intracellular cyclic nucleotide activated cation channel complex; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0030552; F:cAMP binding; IEA:UniProtKB-KW.
DR GO; GO:0030553; F:cGMP binding; IBA:GO_Central.
DR GO; GO:0005222; F:intracellular cAMP-activated cation channel activity; IBA:GO_Central.
DR GO; GO:0005223; F:intracellular cGMP-activated cation channel activity; IBA:GO_Central.
DR GO; GO:0044877; F:protein-containing complex binding; IBA:GO_Central.
DR GO; GO:0098655; P:cation transmembrane transport; IBA:GO_Central.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR GO; GO:0007608; P:sensory perception of smell; IEA:UniProtKB-KW.
DR CDD; cd00038; CAP_ED; 1.
DR Gene3D; 2.60.120.10; -; 1.
DR InterPro; IPR032406; CLZ_dom.
DR InterPro; IPR018490; cNMP-bd-like.
DR InterPro; IPR018488; cNMP-bd_CS.
DR InterPro; IPR000595; cNMP-bd_dom.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR014710; RmlC-like_jellyroll.
DR Pfam; PF16526; CLZ; 1.
DR Pfam; PF00027; cNMP_binding; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR SMART; SM00100; cNMP; 1.
DR SUPFAM; SSF51206; SSF51206; 1.
DR PROSITE; PS00888; CNMP_BINDING_1; 1.
DR PROSITE; PS00889; CNMP_BINDING_2; 1.
DR PROSITE; PS50042; CNMP_BINDING_3; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; cAMP; cAMP-binding; Coiled coil; Ion channel;
KW Ion transport; Ligand-gated ion channel; Membrane; Nucleotide-binding;
KW Olfaction; Reference proteome; Sensory transduction; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..575
FT /note="Cyclic nucleotide-gated cation channel alpha-4"
FT /id="PRO_0000317107"
FT TOPO_DOM 1..33
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 34..54
FT /note="Helical; Name=H1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 55..65
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 66..86
FT /note="Helical; Name=H2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 87..112
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 113..133
FT /note="Helical; Name=H3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 134..168
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 169..189
FT /note="Helical; Name=H4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 190..217
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 218..234
FT /note="Helical; Name=H5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 235..244
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 245..265
FT /note="Helical; Name=H6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 266..575
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 538..575
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 493..536
FT /evidence="ECO:0000250"
FT MOTIF 292..302
FT /note="IQ-type"
FT BINDING 348..471
FT /ligand="a nucleoside 3',5'-cyclic phosphate"
FT /ligand_id="ChEBI:CHEBI:58464"
FT VAR_SEQ 1..40
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_039919"
FT VAR_SEQ 424..456
FT /note="NMSGNRRTANIKSLGYSDLFCLSKEDLREVLSE -> GYPSICSRDKDGWGR
FT GEQQSPVLGPDSTSGLNF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_039920"
FT VAR_SEQ 457..575
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_039921"
FT VARIANT 553
FT /note="E -> V (in dbSNP:rs325706)"
FT /id="VAR_038480"
FT MUTAGEN 292
FT /note="L->E: Loss of inhibition produced by
FT calcium/calmodulin binding."
FT /evidence="ECO:0000269|PubMed:15195096"
SQ SEQUENCE 575 AA; 65999 MW; 4249188A8563A461 CRC64;
MSQDTKVKTT ESSPPAPSKA RKLLPVLDPS GDYYYWWLNT MVFPVMYNLI ILVCRACFPD
LQHGYLVAWL VLDYTSDLLY LLDMVVRFHT GFLEQGILVV DKGRISSRYV RTWSFFLDLA
SLMPTDVVYV RLGPHTPTLR LNRFLRAPRL FEAFDRTETR TAYPNAFRIA KLMLYIFVVI
HWNSCLYFAL SRYLGFGRDA WVYPDPAQPG FERLRRQYLY SFYFSTLILT TVGDTPPPAR
EEEYLFMVGD FLLAVMGFAT IMGSMSSVIY NMNTADAAFY PDHALVKKYM KLQHVNRKLE
RRVIDWYQHL QINKKMTNEV AILQHLPERL RAEVAVSVHL STLSRVQIFQ NCEASLLEEL
VLKLQPQTYS PGEYVCRKGD IGQEMYIIRE GQLAVVADDG ITQYAVLGAG LYFGEISIIN
IKGNMSGNRR TANIKSLGYS DLFCLSKEDL REVLSEYPQA QTIMEEKGRE ILLKMNKLDV
NAEAAEIALQ EATESRLRGL DQQLDDLQTK FARLLAELES SALKIAYRIE RLEWQTREWP
MPEDLAEADD EGEPEEGTSK DEEGRASQEG PPGPE
