CNGA4_MOUSE
ID CNGA4_MOUSE Reviewed; 575 AA.
AC Q3UW12; Q08EL1;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 129.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Epididymis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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 [3]
RP FUNCTION.
RX PubMed=11739959; DOI=10.1126/science.1063224;
RA Munger S.D., Lane A.P., Zhong H., Leinders-Zufall T., Yau K.-W., Zufall F.,
RA Reed R.R.;
RT "Central role of the CNGA4 channel subunit in Ca2+-calmodulin-dependent
RT odor adaptation.";
RL Science 294:2172-2175(2001).
RN [4]
RP FUNCTION.
RX PubMed=12649326; DOI=10.1073/pnas.0736071100;
RA Kelliher K.R., Ziesmann J., Munger S.D., Reed R.R., Zufall F.;
RT "Importance of the CNGA4 channel gene for odor discrimination and
RT adaptation in behaving mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:4299-4304(2003).
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. {ECO:0000269|PubMed:11739959,
CC ECO:0000269|PubMed:12649326}.
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 (By similarity).
CC {ECO:0000250}.
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 neurons (By similarity). {ECO:0000250}.
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=Q3UW12-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3UW12-2; Sequence=VSP_030873;
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 ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK136723; BAE23107.1; -; mRNA.
DR EMBL; BC107347; AAI07348.1; -; mRNA.
DR EMBL; BC107348; AAI07349.1; -; mRNA.
DR CCDS; CCDS21650.1; -. [Q3UW12-1]
DR RefSeq; NP_001028489.1; NM_001033317.3. [Q3UW12-1]
DR RefSeq; XP_006507717.1; XM_006507654.2.
DR RefSeq; XP_011240046.1; XM_011241744.2.
DR RefSeq; XP_017177672.1; XM_017322183.1. [Q3UW12-1]
DR AlphaFoldDB; Q3UW12; -.
DR SMR; Q3UW12; -.
DR STRING; 10090.ENSMUSP00000033187; -.
DR TCDB; 1.A.1.5.4; the voltage-gated ion channel (vic) superfamily.
DR PhosphoSitePlus; Q3UW12; -.
DR PaxDb; Q3UW12; -.
DR PRIDE; Q3UW12; -.
DR ProteomicsDB; 283400; -. [Q3UW12-1]
DR ProteomicsDB; 283401; -. [Q3UW12-2]
DR Antibodypedia; 58012; 98 antibodies from 21 providers.
DR DNASU; 233649; -.
DR Ensembl; ENSMUST00000033187; ENSMUSP00000033187; ENSMUSG00000030897. [Q3UW12-1]
DR Ensembl; ENSMUST00000210344; ENSMUSP00000147387; ENSMUSG00000030897. [Q3UW12-2]
DR GeneID; 233649; -.
DR KEGG; mmu:233649; -.
DR UCSC; uc009iyc.1; mouse. [Q3UW12-1]
DR CTD; 1262; -.
DR MGI; MGI:2664099; Cnga4.
DR VEuPathDB; HostDB:ENSMUSG00000030897; -.
DR eggNOG; KOG0500; Eukaryota.
DR GeneTree; ENSGT00940000159415; -.
DR HOGENOM; CLU_005746_12_0_1; -.
DR InParanoid; Q3UW12; -.
DR OMA; FPDLQHS; -.
DR OrthoDB; 1073751at2759; -.
DR PhylomeDB; Q3UW12; -.
DR TreeFam; TF319048; -.
DR Reactome; R-MMU-5620916; VxPx cargo-targeting to cilium.
DR BioGRID-ORCS; 233649; 1 hit in 71 CRISPR screens.
DR PRO; PR:Q3UW12; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q3UW12; protein.
DR Bgee; ENSMUSG00000030897; Expressed in olfactory epithelium and 14 other tissues.
DR Genevisible; Q3UW12; MM.
DR GO; GO:0017071; C:intracellular cyclic nucleotide activated cation channel complex; ISO:MGI.
DR GO; GO:0043204; C:perikaryon; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0030552; F:cAMP binding; IEA:UniProtKB-KW.
DR GO; GO:0030553; F:cGMP binding; ISO:MGI.
DR GO; GO:0005222; F:intracellular cAMP-activated cation channel activity; ISO:MGI.
DR GO; GO:0005223; F:intracellular cGMP-activated cation channel activity; ISO:MGI.
DR GO; GO:0005221; F:intracellular cyclic nucleotide activated cation channel activity; ISO:MGI.
DR GO; GO:0005216; F:ion channel activity; TAS:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
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; IMP:MGI.
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 2: Evidence at transcript 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_0000317108"
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..218
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 219..239
FT /note="Helical; Name=H5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 240..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 536..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 /evidence="ECO:0000250"
FT COMPBIAS 553..568
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 348..471
FT /ligand="a nucleoside 3',5'-cyclic phosphate"
FT /ligand_id="ChEBI:CHEBI:58464"
FT VAR_SEQ 1..103
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_030873"
SQ SEQUENCE 575 AA; 65835 MW; 2E79D58D658D4930 CRC64;
MSQDSKVKTT ESTPPAPTKA RKWLPVLDPS GDYYYWWLNT MVFPIMYNLI IVVCRACFPD
LQHSYLVAWF VLDYTSDLLY LLDIGVRFHT GFLEQGILVV DKSMIASRYV RTWSFLLDLA
SLVPTDAAYV QLGPHIPTLR LNRFLRVPRL FEAFDRTETR TAYPNAFRIA KLMIYIFVVI
HWNSCLYFAL SRYLGFGRDA WVYPDPAQPG FERLRRQYLY SFYFSTLILT TVGDTPLPAR
EEEYLFMVGD FLLAVMGFAT IMGSMSSVIY NMNTADAAFY PDHALVKKYM KLQHVNRRLE
RRVIDWYQHL QINKKMTNEV AILQHLPERL RAEVAVSVHL STLSRVQIFQ NCEASLLEEL
VLKLQPQTYS PGEYVCRKGD IGREMYIIRE GQLAVVADDG VTQYAVLGAG LYFGEISIIN
IKGNMSGNRR TANIKSLGYS DLFCLSKEDL REVLSEYPQA QAVMEEKGRE ILLKMNKLDV
NAEAAEIALQ EATESRLKGL DQQLDDLQTK FARLLAELES SALKIAYRIE RLEWQTREWP
MPDDMGEADD EAEPGEGTSK DGEEKAGQEG PSGLE
